1234iTitle:A global review of value-based care:theory,practice and lessons learnedISBN:978-92-9022-012-1 World Health Organization 2025Some rights reserved.This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence(CC BY-NC-SA 3.0 IGO;https:/creativecommons.org/licenses/by-nc-sa/3.0/igo).Under the terms of this licence,you may copy,redistribute and adapt the work for non-commercial purposes,provided the work is appropriately cited,as indicated below.In any use of this work,there should be no suggestion that WHO endorses any specific organization,products or services.The use of the WHO logo is not permitted.If you adapt the work,then you must license your work under the same or equivalent Creative Commons licence.If you create a translation of this work,you should add the following disclaimer along with the suggested citation:“This translation was not created by the World Health Organization(WHO).WHO is not responsible for the content or 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reuse and to obtain permission from the copyright holder.The risk of claims resulting from infringement of any third-party-owned component in the work rests solely with the user.General disclaimers.The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of WHO concerning the legal status of any country,territory,city or area or of its authorities,or concerning the delimitation of its frontiers or boundaries.Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement.The mention of specific companies or of certain manufacturers products does not imply that they are endorsed or recommended by WHO in preference to others of a similar nature that are not mentioned.Errors and omissions excepted,the names of proprietary products are distinguished by initial capital letters.All reasonable precautions have been taken by WHO to verify the information contained in this publication.However,the published material is being distributed without warranty of any kind,either expressed or implied.The responsibility for the interpretation and use of the material lies with the reader.In no event shall WHO be liable for damages arising from its use.iiiiiContentsFigures.ivTables.vBoxes.viAcknowledgements.viiAcronyms.ixIntroduction.1 The role of publicly subsidized health insurance and Ayushman Bharat Pradhan MantriJan Arogya Yojana(AB PM-JAY)in India.1 The role of National Health Authority(NHA)and its impact as an institution onuniversal health coverage(purchaser).2 The genesis for the review.2 Background on value-based care(VBC).3 Objectives of the review.5 Flow of the document.6 Methods.6Part A.Theory and empirical experience.8 Findings of review.9 Literature review on empirical experience of VBC implementation across the world.9 Conclusions from implementation experience.15 What is value in health?.19 Value in health?.19 What values should be considered in health?.19 Conclusion.21Part B.Implementation experience for each pillar of VBC.22Detailed review of implementation of each pillar of VBC.231.Integrated practice unit.232.Outcome and costs measurement.273.Payment models.354.Integrated care.485.Expansion across geographic areas.536.Information systems for VBC.567.VBC for pharmaceuticals.598.Health technology assessment.60Part C.Reconceptualizing VBC.74 Synthesis of the literature review.75 Critiques of the approach as conceptualized and implemented.81 Re-framing VBC.81Part D.Moving forward with VBC in India.86 Current approach to VBC in PM-JAY.87 Proposed implementation plan for adoption of VBC.90 The implementation arrangements for the plan.94 Conclusion.95References.97ivFiguresFig.1.Global changes and distribution of total health expenditure(THE)(2000-2019).3Fig.2.Framework of key design and implementation elements of bundled payment contract.39Fig.3 Bundled payment model features and dimension in Netherlands and USA and their degree of integration.40Fig.4.System effects of episode-based payment models under Centre for Medicare and Medicaid Services(CMS),USA.42Fig.5.Attributes of pay-for-performance.45Fig.6.Elements of health technology assessment(HTA)institutionalization.63Fig.7.Status of health workforce in rural areas in India.80Fig.8.VBC revised framework.82vTablesTable 1.VBC programmes in the USA.9Table 2.VBC initiatives in United Kingdom.10Table 3.Aspects of value in EU framework on VBC.13Table 4.Key features of an integrated practice unit(IPU).23Table 5.Tiers in outcomes hierarchy.27Table 6.Illustrative applications of patient reported outcome measures(PROMs)and patient reported experience measures(PREMs).30Table 7.Benefits arising from deployment of PROMs and PREMs by level of system engagement.31Table 8.Design and implementation consideration for bundled payments.36Table 9.Performance frameworks in various countries.46Table 10.State experience of implementing integrated care in the USA.51Table 11.Domains of health systems decision making for HTA.60Table 12.Overview of legal frameworks deployed by countries in building their HTA system.64Table 13.Stakeholder elements and roles and responsibilities for HTA.66Table 14.Funding mechanisms for HTA.68Table 15.Examples of successful outcomes-based approaches for value-based pricing for drugs.70Table 16.Summary of findings from VBC literature review.76Table 17.Transition plan from volume-based care to VBC in PM-JAY.87Table 18.Proposed implementation plan for VBC adoption in PM-JAY.90BoxesBox 1.Use of HTA in clinical practice guidelines in Brazil.62viviiAcknowledgementsThe report was prepared by Dr Grace Achungura,Mr Jaidev Singh Anand,Dr Suneet Peepre,Dr Akash Srivastava and Dr Priyanka Pandit of the Health Systems team at the World Health Organization Country Office for India.The team is also grateful to Dr Sudha Chandrashekar(former Executive Director,HPQA Division,National Health Authority)for her valuable input and feedback during the course of this work as well as to Dr Hilde De Graeve,Team Leader,Health Systems,WHO Country Office for India,for her guidance and support during the execution of this review.viiiixAcronymsABDMAyushman Bharat Digital MissionAB-PM-JAYAyushman Bharat Pradhan Mantri Jan Arogya YojanaACAAffordable Care ActACOAccountable Care OrganizationAHRQAgency for Healthcare Research and QualityAPIapplication programming interfaceAPMalternative payment modelsASMRAmelioration du Service Medical RenduATVadditional therapeutic valueBISbeneficiary identification systemBPCIbundled payments for care improvementCADTHCanadian Agency for Drugs and Technologies in HealthCAHPSconsumer assessment of healthcare providers and systemsCDCCentre for Disease ControlCDECentre for Drug EvaluationCEAcost-effectiveness analysisCEOchief executive officerCGHSCentral Government Health SchemeCHOcommunity health officersCHOPChildrens Hospital of PhiladelphiaCJRcomprehensive care for joint replacementCMMICentre for Medicare and Medicaid InnovationCMSCentre for Medicare and Medicaid ServicesCONITECNational Committee for Health Technology IncorporationCOPDchronic obstructive pulmonary disorderCROMsclinician reported outcome measuresDALYdisability-adjusted life yearDGITISDepartment of Management and Incorporation of Health TechnologiesDHRDepartment of Health ResearchDICADutch Institute for Clinical AuditingDMSDell Medical SchoolDRGsdiagnosis related groupsEHCPempaneled health care providerEHRelectronic health recordsERPexternal reference pricingESISEmployee State Insurance SchemeESRD QIPEnd-stage Renal Disease Quality Incentive ProgrammeFFSfee-for-serviceGDPgross domestic productGIRFTgetting it right the first timeGPgeneral practitionerGPPSGeneral Practice Patient SurveyH2Ohealth outcomes observatory HAIhealth care associated infectionsHCXhealth claims exchangexHEFTAHealth Financing and Technology Assessment UnitHEMhospital empanelment moduleHEShospital episode statisticsHIChigh income countryHIEhealth information exchangeHIRAHealth Insurance Review and Assessment ServiceHITAPHealth Intervention and Technology Assessment ProgrammeHOPEhealth outcomes and patient experienceHOSHealth Outcomes SurveyHRQoLhealth related quality of lifeHRRPHospital Readmissions Reduction ProgrammeHTAhealth technology assessmentHTAInHealth Technology Assessment in IndiaHWChealth and wellness centreIAAinnovation assessment algorithmIAPOInternational Association of Patients OrganizationsICHOMInternational Consortium for Health Outcomes MeasurementICSIntegrated Care SystemINNEindividual,node,network and enabling environmentIPPSinpatient prospective payment systemIPUintegrated practice unitIQWIGInstitute for Quality and Efficiency in Health CareISPORInternational Society for Pharmacoeconomics and Outcomes ResearchITinformation technologyLIClow-income countryLMIClow-middle income countryM&Emonitoring and evaluationMCDAmulti-criteria decision analysisMICmiddle income countryMSACMedical Services Advisory CommitteeNECANational Evidence-based Health Care Collaborating AgencyNHANational Health AuthorityNHICNational Health Insurance CorporationNHSNational Health ServiceNICENational Institute for Health and Care ExcellenceNSWNew South WalesOCMoncology care modelOECDOrganization for Economic Co-operation and DevelopmentOOPEout-of-pocket expenditureP4Ppay-for-performancePBACPharmaceutical Benefits Advisory CommitteePBFperformance-based financingPBMAprogram budgeting marginal analysisPCMHpatient-centred medical homePFSphysician fee schedulePHRpersonal health recordPLACProstheses List Advisory CommitteexiPM-ABHIMPradhan Mantri Ayushman Bharat Health Infrastructure MissionPREMspatient reported experience measuresPRISMApreferred reporting items for systematic reviews and meta-analysesPM-JAYPradhan Mantri Jan Arogya YojanaPPEpublic private engagementPRMspatient reported measuresPROMspatient reported outcome measuresPROMISpatient-reported outcomes measurement information systemPSHIpublicly subsidized health insuranceQALYquality-adjusted life yearQoFQuality Outcomes FrameworkR&Dresearch and developmentRBFresults-based financingRSBYRashtriya Swasthya Bima YojanaSHAState Health AgencySHAPEsustaining health care across integrated primary care effortsSHIstatutory health insuranceSOPstandard operating procedureSTFspecial task forceSTGstandard treatment guidelineSUSSistema Unico de SaudeTDABCtime-driven activity based costingTHCtransitional home careTHEtotal health expenditureTMStransaction management systemTVtherapeutic valueUHCuniversal health coverageUKUnited KingdomUMIC upper-middle income countryUTunion territoryVAVeterans Health AdministrationVBCvalued-based careVBHCvalue-based health careVBPvalue-based pricing/purchasingVPHSVictorian Population Health Surveyxii1The role of publicly subsidized health insurance and AB PM-JAY in India Health is a central element of the sustainable development agenda for India.As part of the countrys development agenda,the country has implemented a flagship scheme“Ayushman Bharat”.This scheme is a four-pronged programme for the implementation of:a)Enhanced primary healthcare reform through the health and wellness centres(HWCs),b)Improved financial protection and service coverage for secondary and tertiary care through Pradhan Mantri Jan Arogya Yojana(PM-JAY)scheme for the poor and vulnerable(40%of the total population).c)Improved digital health systems and interoperability through Ayushman Bharat Digital Health Mission(ABDM).d)Improved public health infrastructure for pandemic preparedness and response and for UHC through Pradhan Mantri Ayushman Bharat Health Infrastructure Mission(PM ABHIM).The four pillars work in a cohesive manner to ensure the attainment of UHC.They complement other programmes that are being implemented in the sector.PM-JAY is a publicly subsidized health insurance(PSHI)scheme that focuses on the poor and vulnerable population and provides cashless cover up to approximately US$6000(INR 500 000 in 2024 prices)per annum for the household(approximately 4.5 people).It covers inpatient care for secondary and tertiary care services as well as up to three days of pre-hospitalization and 15 days of post-hospitalization expenses such as diagnostics and medicines1.The implementation of PM-JAY follows a long legacy of implementation of PSHIs including the erstwhile Rashtriya Swasthya Bima Yojana Health Scheme(RSBY),a health insurance cover for individuals or families below the poverty line and workers belonging to unorganised sectors.The scheme offered a coverage of approximately US$350(i.e.INR 30 000)on a floater basis for households for secondary and tertiary services.It covered only inpatient care.The implementation experience of RSBY was critical in shaping the design and implementation of PM-JAY.Other schemes including the Central Government Health Scheme(CGHS)and the Employees State Insurance Scheme(ESIS)also influenced the design of several elements of the scheme.PM-JAY is managed by the National Health Authority(NHA),an agency formed by Gazette Notification Registered No.DL(N)04/0007/2003-18.It is an attached office of the Ministry of Health and Family Welfare(MoHFW)with full functional autonomy.With reference to the governance of the NHA,it is governed by a Governing Board chaired by the Union Minister for Health and Family Welfare.It is headed by a Chief Executive Officer(CEO),an officer of the rank of Secretary to the Government of India,who manages its affairs.The CEO is the ex-Office Member Secretary of the Governing Board.The implementation of PM-JAY is done by NHA in partnership with the State Health Agencies(SHA)that are set up by the states.The scheme is financed by the Union and state governments in a ratio of 60:40 respectively for most states and 90:10 in the case of North and North-eastern states(90%covered by Union)and 100%covered by the Union government in case of Union Territories(UTs).The scheme is also implemented in partnership with public and private health care providers to ensure service coverage and provision is accessible,equitable and of Introduction1.About Pradhan Mantri Jan Arogya Yojana(PM-JAY):https:/PM-JAY.gov.in/about/PM-JAYIntroduction2good quality.Thus far,as of July 2024,the scheme has empaneled 30 174 hospitals of which 17 036(56.5%)hospitals are public and 13 138(43.5%)hospitals are private.The role of National Health Authority and its impact as an institution on UHC(purchaser)As a result of this engagement as purchaser of services from public and private hospitals for secondary and tertiary care for 40%of the population,the NHA has great influence on the quality of services,the efficiency of service delivery and in improving equity in care.These elements of value for money are critical for ensuring UHC.Thus,the NHA,is positioned as an influential stakeholder in the health sector to use its instruments and policy levers to drive value for money.The genesis for the reviewThus far,the NHA has implemented several interventions to drive value for money including:a)To improve the quality of care,NHA has implemented an accreditation system for hospitals empaneled with the scheme with additional incentives above the base package rate to ensure quality services.It has also implemented standard treatment guidelines to drive quality of care according to agreed standards of care.These have been implemented for three years now and have shown some influence on driving improvements in quality of care and claim adjudication.There is however room for improvement in the design and implementation of the guidelines 1.Others include the grievance redressal mechanisms for both beneficiaries and providers.b)Diagnosis related groups(DRGs)pilot that is being implemented by NHA to review alternative payment mechanisms to improve provider reimbursement,payment rates as well as quality and efficiency.c)The process for developing and revising the health benefit package and the price-setting mechanisms that have been implemented by the scheme.These mechanisms have been implemented to drive improvements in service coverage and equity,in quality of care,in efficiency and cost-containment.There is a need however,to improve the process of rationalization and price-setting to achieve policy goals.d)Digital modules relating to beneficiary identification systems(BIS)for beneficiary enrolment and management,hospital empanelment module(HEM)for hospital empanelment and a transaction management system(TMS)for claims adjudications.Currently,interoperability of the system with other information systems in the sector is limited.NHA is also implementing other reforms in strategic purchasing to optimize efficiency and equity,including a value-based care(VBC)pilot that is implementing performance incentives based on robust indicators to improve the quality of care.This document is a synthesis of the global evidence on the implementation of the VBC concept,the evidence of effectiveness and cost-effectiveness of different practices and what lessons India can draw form the global empirical experience to better design the reforms for VBC.Introduction3Background on value-based careIn many contexts around the world,the challenge of increasing health expenditure is a concern.The WHO reports that health expenditure has doubled over the past two decades reaching US$8.5 trillion in 2019 and 9.8%of global gross domestic product,that is,GDP(up from 8.5%in 2000)2.Inequalities in spending between countries have persisted and far outstrip inequality in the distribution of global GDP.For instance,the report shows that high-income countries accounted for nearly 80%of global spending on health(with the USA alone accounting for more than 40%).Across middle-and high-income countries,the share of health spending financed by domestic public sources has risen over the past 20 years,and out-of-pocket spending has reduced.The increasing reliance on public sources of spending has resulted in increasing attention to the rise in health expenditure.This is more so following recent economic shocks globally including the 2008 economic recession and the recent COVID-19 pandemic that caused significant contraction of economies globally.The rise in health expenditure in many countries has been attributed to increasing costs of adoption of health technologies and interventions such as chemotherapy,organ transplant,treatments for rare diseases and genomics,new effective vaccines that do not substitute for those previously on the immunization schedule and thus requiring more investment;increasing healthcare demand because of increasing population as well as the high costs related to care for the elderly.This has prompted concerns regarding financial sustainability and the exploration of policy levers for curbing growth in costs and for improving value for money.Fig.1.Global changes and distribution of THE(2000-2019)Source:Global Health Expenditure DatabaseRecent evidence in OECD countries also shows that there are unwarranted variations in the care provided by providers 3.This variation may be due to underuse of services,overuse of services or supply challenges related to oversupply of low value care and overuse or underuse of effective care.Others have suggested that these variations may result from differences Introduction4in demand for services that are sensitive to the preferences of the patients(preference-sensitive)or that are supply-sensitive resulting in inequities and inefficiencies in health spending 4.These variations occur within and across countries and vary with the type of service.In the United Kingdom,it was estimated that these unwarranted variations in care cost the National Health Service(NHS)at least 5bn of the 55.6bn spent annually by acute hospitalizations 5.Additionally,a multi-country assessment by the OECD showed variation within and across countries for services.The notion of VBC has become increasingly popular globally in many settings as a plausible solution to enable health systems to improve the value of health services offered whilst curbing growth in health expenditure.This notion has been defined as:“Patient value is defined as patient-relevant outcomes,divided by the costs per patient across the full cycle of care to achieve these outcomes.value-based healthcare focuses on maximizing the value of care for patients and reducing the cost of healthcare.”6The concept described by Porter and Teisberg calls for a focus on health outcomes of value to the patient rather than a focus on reducing costs.The framework described by Porter and Teisberg includes six main components 7.These six themes are discussed briefly in this section but will be explored more deeply in the subsequent sessions in Part B.They include:1.a.1.Organize integrated practice unitsThe framework proposes the development of integrated practice units(IPUs)which are organized around a medical condition or a set of closely related conditions(or around defined patient segments for primary care).In these IPUs,care is delivered by a multi-disciplinary team of physicians,nurses,etc.,who provide care across the full care cycle including outpatient,inpatient,rehabilitation,supporting services(such as nutrition,social work,and behavioral health).In these units,patient education,engagement,and follow-up are integrated into care.1.a.2.Measure costs and outcomes for every patientThis component of the framework makes the argument for greater and deliberate measurement of outcomes that are of value to the patient rather than driven by the perspective of the provider.Porter and Teisberg proposed an outcomes hierarchy that accounts for improvements in health status,improvements in the functionality of the patient(across the full care cycle)and the sustainability of the outcomes.It also proposes tracking of healthcare costs across the full care cycle accounting for all resources consumed during the entire care cycle.The proposition is premised on the need for tracking outcomes and costs to understand how outcomes relate to costs to enable providers to re-program and re-allocate health services for greater value for money.1.a.3.Move to bundled payment for the care cycleThis component recognizes the limitations of payment models like fee-for-service(FFS),global budgets,and capitation with regard to incentivizing focus on value and improved outcomes.Global budgets and capitation payments provide lumpsum amounts to providers and should ideally incentivize them to maximize output while saving on spending and reducing costs.This often has deleterious effects of compromising quality of care and encouraging shifting Introduction5of patients from one service provider to another.Other traditional payments have included FFS payments that reimburse providers for every service provided.This often has the effect of encouraging an oversupply of services(which may not be necessary)and may also result in poor quality care.1.a.4.Integrate care delivery across separate facilitiesThis theme is premised on the argument that the traditional organization of services in health facilities is designed to cover everything for everyone and therefore compromising on value for money and efficiency.It therefore argues for organizing services within a network of facilities where each facility covers services of a leaner scope that it is best suited to provide and eliminating or transferring those where they cannot realistically achieve high value.This may entail creating partnerships with facilities best suited to cover those services,for example,community centres or primary care units.1.a.5.Expand excellent services across geographyThis theme addresses services that are provided by some specialized centres that may need to extend service delivery beyond the immediate vicinity of the facility.Targeted geographic expansion is required to ensure that services provided by superior providers(providers providing the best quality care)extend to more patients than they can physically serve.Targeted expansion may include models such as hub-and-spoke models where the provider develops satellite facilities that are staffed by clinicians and other personnel employed by the parent organization.Another model includes the creation of affiliations with similar and smaller clinics in which the facilities and capacities of those clinics are used by the IPU instead of increasing their own capacity.1.a.6.Enable a suitable information technology platformThis enhances the efficacy of the five elements of the framework above.Integrated infor-mation systems should be patient-centric,collect data in a standardized manner and collect all manner of relevant patient information(clinical notes,treatment,laboratory tests,imaging tests,etc.).This data should be able to be retrieved by all relevant parties whilst ensuring data security and privacy for clinical and policymaking use.This shall be explored in greater detail below.Objectives of the reviewa)To review the various conceptualizations of value and VBC globally and in India.b)To review the design and implementation of VBC to identify the models that have demonstrated effectiveness and value for money,design features that have facilitated this as well as enabling and constraining factors.c)To provide options for defining value,a framework for design and implementation of VBC adaptation for India and models for each component of the framework that is suited to the context in which NHA and its stakeholders are operating.d)To propose implementation arrangements and necessary shifts to be considered for the successful implementation of VBC in PM-JAY.Introduction6Flow of the documentThis document is divided into four main sections.The flow of the document is to enable the reader to follow what has been gleaned in the literature thus far on VBC in terms of the lessons that are important for the design,implementation,and evaluation of VBC for UHC to the development of a revised framework of the same,and finally to how the same can be applied to the India health financing landscape for impact.Part A:This section summarizes empirical experience of implementing VBC in the real world from a policy perspective.The main issues of concern addressed by the review include whether the whole framework is adoptable at the national level or even at a state-level and,if so,whether it is best adopted incrementally or as a big-bang reform.It further explores,the common elements countries implement and the reasons behind the same.It also explores the broader systemic concerns that are needed to successfully implement VBC.It also explores the issue of valuation in healthcare and what that means for the implementation of the approach.Lastly it explores the question of what level is best to adopt VBC.Part B:In this section of the document,each element is described in detail and elements that are important including:how that element is implemented with case studies of best practice;what is the real-world evidence of effectiveness,cost-effectiveness and affordability,sustainability,inter alia,what are the challenges or enablers in the implementation of this pillar and finally;what can be said about its scalability and adoption for the long term.Additionally,this section also sheds light on some international experiences and examples of VBC in practice,with detailed country examples provided in the accompanying supplemental report.Part C:It includes a synthesis of findings from the previous sections and proffers our thoughts on a new framing for VBC for UHC and includes a synthesis of lessons for the implementation of VBC.Part D:This section provides recommendations for how India can systematically approach VBC to further its UHC agenda.It also includes suggestions for an implementation roadmap and what is needed for it.MethodsThe assessment was largely a secondary scoping review of the literature.We reviewed literature sourced from:a)Peer-reviewed journal articles were included from electronic databases that included Google Scholar and HINARI/GIFT,PUBMED.We included articles that were published between January 2010 to August 2023.Search terms included“value-based care”,“value-based care”and“health”and“universal health coverage”.b)We searched government documents from government websites including web pages of Ministries of Health and equivalent,purchasing agencies for health insurance schemes in countries and any other agency that is critical for formulating policy documents.Countries that were included in the search were those where peer-reviewed literature had indicated that there was implementation of VBC at a national or subnational level.These included USA,United Kingdom,Netherlands,Norway,Sweden,Finland,Denmark,Australia.Introduction7c)The websites of multilateral organizations and regional bodies were also searched to identify policy documents or strategies on VBC that are being employed,these include the European Union,African Union,World Bank,Asian Development Bank and more.A narrative synthesis of findings was adopted for the review.This included grouping the findings according to themes emerging in the literature on the practical experience of VBC and the issues that emerge regarding motivation for the transition towards,the feasibility of implementation,barriers and facilitators to effective implementation and the sufficiency of the framework given the UHC agenda globally.Introduction8Part ATheory and empirical experience9Findings of the reviewLiterature review on empirical experience of VBC implementation across the worldA recent review assessed the extent of implementation of VBC in 25 countries 8.It concluded that in countries with health spending less than 5%of GDP,there was very little alignment with the pillars of the VBC framework while in contrast,countries with spending higher than 5%tended to have higher alignment to VBC pillars.The former tended to be developing countries,the latter more higher income countries including the USA,United Kingdom,Sweden,Canada,Australia,and Japan.The VBC concept was born in the USA as one of the means to check the growth in health expenditure resulting from uncontrolled FFS payments driven by prioritization of the volume of services produced,instead of the value offered to patients in terms of the outcomes of care.In the wake of healthcare reforms geared towards increasing service coverage and financial protection through the Affordable Care Act(ACA)9,the USA has implemented numerous VBC reforms to improve value for money.The ACA and other associated laws have provided an enabling legal framework and policy framework 10,11 for facilitating the implementation of VBC in the USA.This strategic direction has benefitted from a decade-long experience of implementing and testing over 50 models of VBC including bundled payments,accountable care organizations(ACOs),home-based value programmes and the quality payment programmes 12-15.It has also led to national programmes rolled out based on VBC principles including the programmes shown in Table 1 below:Table 1.VBC programmes in the USAVBC programmeDefinitionHospital Acquired Conditions ProgrammeEncourages hospitals to improve patients safety and reduce the number of conditions people experience during their time in a hospital 16.Hospital Readmissions Reduction Programme(HRRP)Encourages hospitals to improve communication and care coordination to better engage patients and caregivers in discharge plans and,in turn,reduce avoidable readmissions 17.The Hospital Value-Based Purchasing ProgrammeRewards acute care hospitals with incentive payments for the quality of care provided in the inpatient hospital setting using the Inpatient Prospective Payment System(IPPS)based on the quality of care they deliver 18.The End-Stage Renal Disease Quality Incentive Programme(ESRD QIP)Promote high-quality services in renal dialysis facilities by linking a portion of payment directly to facilities performance on quality of care measures 19.The Physician Feedback/Value-Based Payment Modifier(Value Modifier)ProgrammeProvided for differential payment using a value modifier to payments on the Medicare Physician Fee Schedule(PFS)based on the quality of care compared to the cost of care during a performance period 20.Theory and empirical experience10Skilled Nursing Facility Value-Based Purchasing Award incentive payments to skilled nursing facilities(SNFs)through the SNF value-based purchasing programme to encourage SNFs to improve the quality of care(measured by all-cause hospital readmissions)they provide to Medicare beneficiaries 21.Expanded Home Health Value-based Purchasing Home health associations are provided incentives for better quality with efficiency in healthcare provision 22.It is an expansion of the original home health value-based programme that was piloted in nine states.Despite similar motivations for adopting VBC practices in the United Kingdom(UK),the experience varies slightly from that in the USA.The main drivers for VBC in the UK have been increasing evidence of inefficient and inequitable care demonstrated by evidence of unwarranted variations in service access and availability with pockets of overuse of some services,underuse of others and incidences of low-value care.Furthermore,reviews have demonstrated potential cost-savings to the NHS if these inefficiencies are addressed.Though the constitution of the NHS states that The NHS is committed to providing the best value for taxpayers money,there is no agreed consensus on what defines value in the NHS and what VBC in this context means 23.Despite early attention by the National Institute for Health and Care Excellence(NICE)in the UK to improving efficiency in health through institutionalized health technology assessment(HTA)to determine the interventions funded by the NHS,and the development of standard treatment guidelines(STGs),there has been no overarching policy framework that comprehensively addressed the notion of VBC until recently.The drive for VBC commenced with the NHS Wales through the implementation of the“Prudent Health Care”initiative which was a collaborative effort between patients and their providers to improve the quality of care and equity,reduce unwarranted variations in practice,and irrational prescribing 24.VBC has since been used as a vehicle for implementing“Prudent Health Care”within the national policy for“A healthier Wales”25.A national VBC team has also been assembled to implement it.VBC in NHS England has followed a more incremental approach with the NHS implementing discrete programmes at different levels of scale until more recently.Table 2 summarizes some of these initiatives.Table 2.VBC initiatives in the United KingdomVBC initiativeProgramme elementsGetting it right the first time(GIRFT)This is a national programme that was designed in response to the challenge of unwarranted variations in health services 26.Theory and empirical experience11VBC initiativeProgramme elementsIt is premised on improvements in clinical practice and quality without much investment required to make it functional.The implementation of the model includes 40 surgical and medical workstreams and several other cross-cutting,system-wide projects which are led by a prominent clinical specialist.The specialist and team visit the Trusts to discuss the findings of the review and the areas that need improvement.Hospital Episode Statistics(HES)and other relevant registry or professional body data and inputs from a standard questionnaire regarding service or pathways are filled in by Trusts under review.Reports are developed annually on the performance of Trusts.Trusts implement improvements supported by regional teams.Review metrics feed into the Model Hospital portal detailed below.The programme is aligned with the integrated care systems strategy.NHS right careThis is a programme that has been implemented to support health and care systems to improve care quality,population health and system sustainability through three delivery strategies 27:It does this through three modalities i)Direct support clinical commissioning group development and embedding operational support;ii)Facilitative support for example,enhanced commissioning support unit development and promoting and commissioning innovations;iii)Creating the right environment develop via a concordat with other arms-length bodies,monitoring programmatic variations and stakeholder engagement such as with Public Health England.Model health system This is a data-driven model(portal-based)that includes metrics on care quality,responsiveness and productivity across systems,Trusts and hospitals that can be used for benchmarking leading to service improvements 28.Integrated care system(ICS)This is an integral part of the NHS England long-term plan for health.Recent legislation(the Health and Care Act 2022)makes ICSs statutory thus facilitating the implementation of this strategy.The journey to integrate service delivery in England started in 2014 with some pioneer boards and has been scaled up nation-wide following the development of 42 Integrated Care Systems that are integrating care across community trusts and primary care providers as well as specialist hospitals 29.It is aligned with the programmes highlighted above.Atlas of variationA tool developed by the NHS to track and document variations in practice across geographic areas,boards,Trusts and Boards 30.E-products include an interactive tool that can be used to compare practice,compendium atlases and themed atlases,for example,for liver disease.The data is contextualized using a description of the variation and provides options for action.This is used as part of the identification of intervention conditions for the GIRFT programme.Theory and empirical experience12VBC initiativeProgramme elementsShared decision makingIs at the heart of person-centric care in which the individuals and the clinicians work together to understand the diagnosis,tests and treatments,management and support packages so as to make the most of the patients knowledge of themselves and the clinicians expertise to determine the appropriate treatment course 31.Is part of a broader comprehensive model of personalized care(36)that includes five other pillars including i)personalized care and support planning;ii)enabling choice,(including legal rights to choose);iii)social prescribing and community-based support;iv)supported self-management and v)personal health budgets and integrated personal budgets.National Institute for Health and Care Excellence(NICE)This is a national programme that provides evidence-based assessments of health technologies and services using economic and epidemiologic models to drive the adoption of innovations that provide value for money for health in the UK 32.NICE does this through the development of standard treatment guidelines,quality standards and indicators,a clinical knowledge base that has been developed to summarize the evidence on clinical care and Health technology assessments for the British National Formulary.National Consultant Information ProgrammeThis is a portal that has been developed to support consultants in benchmarking their performance on clinical activity and patient outcomes 27.The tool is useful for continuous learning and development for the consultants and is used to improve their practice.The experience in the UK shows barriers that often arise at the policy level,in the implementation of VBC,which include:A.Limited access to comprehensive and good quality data to define and accurately measure outcomes for all conditions.B.The lack of a roadmap that defines the path to VBC and how all the disparate elements implemented by the NHS align and what the anticipated outcomes will be.C.Multi-disciplinary engagement across different stakeholders including patients.This requires evidence-based mechanisms for effective citizen engagement.D.A systemic approach to VBC that places the reforms within an enabling financing,information,and governance environment.E.Better evidence on effectiveness(not efficacy data)that can be used for resource allocation purposes.The implementation of VBC in Australia has taken on a very varied approach with pilots of some programmes in states like Victoria and Western Australia and a state-wide initiative in others such as New South Wales(NSW)33.The government of NSW has implemented a state-wide strategy for the implementation of VBC through the Integrated Care Approach 34.Regarding the implementation of VBC in the EU,there is no overarching strategy for the implementation of VBC.The European Union(EU)has a longstanding Expert Panel on Theory and empirical experience13Investment in Health that has been commissioned to provide non-binding guidance on investing for health 35.The Expert Panel has provided recommendations for improving the value for care by reducing investments in low-value care and increasing investment in high-value care.Central to this is the definition of value.The panel proposes four aspects of value that need to be considered to incorporate the principle of solidarity,which is one of the core values from the European standpoint.Table 3.Aspects of value in EU framework on VBCValue attributeDefinition Allocative value Equitable distribution of resources across all patient groups.Technical valueAchievement of best possible outcomes with available resources.Personal valueAppropriate care to achieve patients personal goals.Societal valueContribution of healthcare to social participation and connectedness.Adapted from:Defining value in Value-Based Healthcare35 The panel has provided some proposals for improving VBC in the European Union including:Creating greater awareness of health as an essential investment for an equal and fair European society and of the centrality of it as a European value to achieving UHC.Develop a long-term strategy for a step-by-step value-based approach towards the change of culture.Support research and development(R&D)of methodologies on appropriateness and unwarranted variation by creating collaborative avenues for research and enabling data creation and sharing.Encouraging health care practitioners to be more aware of value in their practice and discouraging low-value care.Support the creation of learning communities,including communities of health professionals,to bring together the best expertise,experiences,and practices.Encourage and support patient engagement in policymaking and shared decision-making for their care considering their knowledge,experiences,and preferences.Despite the lack of a strategy on VBC,there are some union-wide initiatives that have commenced to further VBC,including the Regulation on Health Technology Assessment(Regulation(EU)2021/2282)36,37.Since 2004,the European Union has instituted a mechanism for joint HTA across the member states 38-40.In 2005,the EU commissioned a network of organizations at the national level to conduct joint assessments for health technology to facilitate ease of market entry of devices and medicines.The EU collaboration on HTA consisted initially of two components that is the HTA network and the EUnetHTA Joint Actions.The HTA Network connected national authorities or bodies responsible for HTA.The network was introduced by Directive 2011/24/EU on the application of patients rights in cross-border healthcare to provide strategic guidance and policy orientation for scientific and technical cooperation.The voluntary network included the participation of all the member states of the EU who were represented by the national HTA organizations or institutions.They set the policy direction for the HTA and included potential areas for collaboration across the member states.More recently,the EU Commission has developed regulation for HTA(Regulation(EU)2021/2282)37 which provides a framework for the establishment of a coordination group of national or regional HTA authorities,a stakeholder network and lays down rules on the involvement in joint clinical assessments and joint scientific consultations Theory and empirical experience14of patients,clinical experts,and other relevant experts 41.It replaces the HTA Network and EUnetHTA and has taken effect since January 2022 and is effectual till January 2025.VBC in Latin America is not as well integrated into the health system design as in Europe and the USA.A few studies have summarized experiences in countries like Argentina,Brazil,Chile,Colombia and Mexico 42.A global review of 25 countries shows that the implementation of VBC in this region is not very advanced,with the exception of Chile and Colombia which are more advanced adopters 8.The study assessed enabling factors and institutional factors for VBC as well as the implementation of outcomes-based care,patient-centred care,bundled/block payments;payment for performance linked to quality and quality standardization.Regarding the presence of enabling factors,Chile was the only Latin American country assessed that had a national strategy for VBC while Colombia was the only country that had a quality standardization mechanism.Colombia and Chile were also the only countries in the region where the Government and/or major payer(s)are actively collecting patient treatment cost data in some areas.There was no such mechanism in Brazil and Mexico.The study highlighted Chile as the only country that is implementing bundled payments in several areas.More recently however,there have been privately-led initiatives to standardize Patient-Reported Outcome Measures(PROMs)in Brazil using the tools available from International Consortium for Health Outcomes Measurement(ICHOM)42-44.This has been initiated by Hospital Israelita Albert Einstein,a private,nonprofit hospital system in So Paulo,Brazil that is implementing VBC comprehensively through the installation of a Value Management Office that works with the medical practice group of the hospital to coordinate care in IPUs and provide necessary training,coordinate outcomes and measure costs through adopting the ICHOM standard sets in low backpain,hip and knee osteoarthritis,breast cancer,and coronary artery disease.It has also begun the development of bundled payments for some conditions as well as coordinating with the financial management section of the hospital to collect data across disease episodes rather than discrete services.VBC elements in Asia are rife but with no comprehensive implementation of the entire framework of VBC envisaged by Porter and Teisberg.The earlier-mentioned review of 25 countries found that in selected countries in Asia such as China,India,Indonesia,and South Korea there are elements of systematic approaches of quality standardization8.The review found that in South Korea and in the United Arab Emirates,there was moderate alignment to VBC with the implementation of systematic approaches of quality standardization as well as implementing outcomes-based care and patient-centred care.In countries like Japan,there was no element of VBC found at the time of the assessment.Asia also has a vibrant HTA element which is not part of VBC per se,but is a critical input in the definition of care pathways 45.This includes countries like Thailand,South Korea,and Taiwan.Early experiences include the implementation of VBC for congenital heart disease in Pakistan 46.The authors describe the feasibility of implementing the agenda including the challenges that emerge in the process.These include the challenges of political buy-in at the provider level.They also highlight the data quality and availability challenges particularly due to poor information systems.The measurement of costs and outcomes is particularly challenging in this context and requires upfront investments in human and financial resources which can affect sustainability.Challenges in defining care pathways as well as the development of IPUs arise from resistance to change as well as the structural challenges due to fragmented service delivery.Theory and empirical experience15There is limited evidence of a comprehensive approach to the implementation of the VBC agenda in Africa.In Kenya,a community-based approach,called MomCare to implementation of VBC for improving maternal child health outcomes has been implemented using a mobile-based digital solution for enabling bundled care payments 47.The cohort-based model includes follow-up of mothers using a care pathway and bundled payments,where outcomes are defined using ICHOM for outcome measures.The mobile-based app enables bi-directional communication between the providers and patients.PROMs data is collected using standardized forms that are filled in through telephone conversations by the providers.The model has shown that VBC is feasible in this context enabled by simple digital solutions and enables delivery of care for mothers at predictable cost per enrollee with improved adherence.There have been several tentative efforts to use and systematize HTA at the country level 48-51 but more recently,at a regional level,the continent of Africa is beginning to systematically address local needs of HTA for health products including vaccines 52-54.The recent endeavor enabled by a specially created unit at the Africa Centre for Disease Control is developing systematic procedures and has begun undertaking assessments on behalf of member states.This has been particularly spurred by the recent COVID-19 pandemic.Conclusions from implementation experienceWe sought to review the implementation experience of VBC as a policy or strategic approach within countries.The literature reviewed has shown that VBC,as a holistic strategy,has had very limited implementation.Much of the implementation experience has come from high-income countries at a national scale in NHS Wales and in some cases at a sub-national level such as NSW in Australia 8,47.Even in these instances,the implementation has been partial,with some elements implemented and not the approach in its entirety.There has been much less implementation in LMICs.The literature shows limited but growing interest in VBC in LMICs as buttressed by the findings from the global survey of 25 countries on the implementation of VBC,even though these contexts need VBC approaches more than the high-income counterparts.The major challenges affecting adoption are weak human resource capacity,as well as information,communication,and technology systems for good data.These affect the measurement of costs and outcomes,the development of IPUs and care pathways and bundled payments.The review highlighted some common themes that emerge across countries that are worth noting,that are critical for successful adoption and implementation of VBC as well as for framing of VBC in general.These are also informed by some of the barriers that were identified in the experience in the UK in implementing VBC.These include:An enabling legal and policy environment:This will help anchor VBC firmly in the health systems policy agenda and is critical for the adoption and scale up of VBC.This was made clear in the implementation experience in the USA and in NHS Wales.The policies or strategies they adopted highlight the key elements and the linkage to broader health goals,identify human and financial resources as well the implementation arrangements,including the roles of different stakeholders.Furthermore,the enactment and enforcement of laws have enabled greater implementation of VBC in some instances.This was evident in the USA,where legal instruments were lever-aged to change payment systems and improve the adoption of electronic health records(EHR).These are also important for driving HTA,and value-based pricing for pharmaceuticals Theory and empirical experience16and diagnostics as elements that we contend,need to be included in the VBC framework.The congruence between different laws and policies regarding each element of the framework must be examined to ensure that synergies are harnessed and there are no conflicts.This includes the designation of roles and responsibilities for the different elements.Confusion in the institutions responsible for different elements can hamper the progress that is realized in implementing VBC.Therefore,a steering team is critical in providing oversight in the congruence of different policy and legal instruments.This also implies that this team should be sufficiently influential within the system as to be get an informed assessment of this congruence and offer solutions that can be practically implemented.A broader agenda for VBC:The empirical experience shows that many countries are including broader definitions of VBC than what Porter and Teisberg propose in the framework.In particular,the empirical experience in the UK,EU and Australia shows that realizing value for money regarding pharmaceutical pricing,is a critical element to address in order to ensure VBC at a system and patient-level.It is therefore important that framing VBC include elements that contribute to pharmaceutical pricing.A transition plan that charts the path for adoption of VBC:As earlier noted,the framework has been implemented to varying degrees in several contexts.No one context has comprehensively implemented the entire framework at either level of the health system.The most common elements of the framework that have been implemented and are documented with evidence are integrated care,bundled payments,outcome measurements and to a lesser extent estimation of the costs,and IPUs.The integrated information systems and to an even lesser extent,the geographical expansion of services,have been adopted.The implication of this is that for any country pursuing an agenda of VBC to improve performance on UHC and patient outcomes,there is need for a transition plan.As has been seen,implementation initially starts with one or a few pillar(s)of the framework being implemented,and usually starts out at the provider level or subnational level.Even the few countries that have scaled up at the national level or state-level started with implementation at a lower level of scale.This transition plan should sequence reforms based on what currently exists,leveraging current reforms and building on them instead of replacing them where possible.It should identify which areas are amenable to immediate change with little cost and sequence them accordingly.It should include clear timelines for execution as well as identifying roles and responsibilities and resources needed(human,financial,IT,etc.).It should be objectives-oriented with clear policy goals and the means identified.It is important to understand that the introduction of VBC into a health system requires an understanding of the interventions that are relevant at different levels of engagement.This ranges from the broader systemic and institutional setup under which VBC will operate(macro),down to the level of the clinician-patient interaction(micro)at the downstream level.Thus,different sets of interventions are necessary when actioning the move towards VBC.Micro level:At the patient-provider interface,the patients clinical pathways and ensuring continuity of care should be paramount.That entails considering the goals and preferences of patients alongside established guidelines.Meso level:A need for optimal allocation of resources and optimization of all interventions across the whole pathway of care,underpinned by a person-centred approach.Theory and empirical experience17 Macro level:Putting in place institutional,regulatory and governance systems and safeguards to steward the actions of all system stakeholders in the general direction of VBC principles.The VBC agenda should be embedded within a broader health system agenda for UHC.The design and implementation of VBC should not be divorced from other reforms in the health system.This is to ensure that the reforms in VBC benefit from any synergies that may already be built in the system and are planned for implementation and that there are no conflicts in the design and implementation of other reforms in health systems.Strategic stakeholder engagement in design and implementation:The health system includes many different actors that are important in the VBC ecosystem.These include but are not limited to health care providers,legislature,Ministries in charge of health,the purchaser(s),beneficiaries,etc.Implementation of VBC requires a comprehensive approach in terms of the stakeholders in the system.To facilitate effective stakeholder engagement,a VBC steering team should be instituted to spearhead the consultations of different stakeholders and involve them in the design of the reforms.The steering team must have the legitimacy and power to convene different stakeholders to deliberate on the reforms.This should ideally include stakeholder mapping and ensuring a shared understanding of VBC across stakeholders.One of the dividends of stakeholder engagement is the identification of the values that should drive the VBC agenda in the country.Value is very much context-driven,largely by prevailing culture and social beliefs and norms as well as the economic status of the context.Within a context,different values may drive the prioritization of services at different times.It is important therefore,to define values for the context by local stakeholders and to include an agreed mechanism for aggregating findings.The implementation experience of VBC in decentralized contexts is varied:The evidence shows that in decentralized contexts like the UK,USA and Australia varied models have been implemented depending on the context.The literature,however,is largely silent on the impact of these varied models on UHC at a population or national level.Regarding some potential barriers in transitioning to VBC,there exists a possibility that over-reliance on decentralized or devolved models may create fragmentation within the system.This may not necessarily pose a problem in the initial pilot or experimentation phase,but it is essential that a more coordinated and streamlined approach to VBC is adopted in the medium to short term.The USA provides an example in which the varied approaches have been used within a more generic framework developed by the Centers for Medicare and Medicaid Services(CMS)and may well be worth emulating.Variations in models are co-developed with CMS and evaluated for impact and to enable learning.The role of champion:The presence of an influential decision-maker is critical for the successful adoption and continued implementation of VBC.The experience in the case of the USA where the Congress provides oversight on the innovation models and makes decisions on the scaleup of programmes is a good example of the role of champions in furthering an enabling legal-policy environment and for securing financing for the initiative.Similarly,in NHS Wales,the involvement of the Minister was a critical enabler in the adoption of VBC for the implementation of the Prudent heath care in Wales.Theory and empirical experience18Human resource capacity for VBC:There is a need to have a dedicated VBC team that interacts with providers and other stakeholders as was shown by the NHS Wales,NHS England as well as the CMS innovations team in the USA.The team works with the stakeholders to monitor service delivery and course-correct during the implementation period to enable the teams to provide more agile and responsive healthcare.The experience in these contexts also shows that a training and awareness-raising plan is needed for the implementation of VBC.This is necessary for every stakeholder and most critical for providers who must adjust to new ways of implementing care in IPUs,across networks,undertake performance measurement,develop awareness of costs,etc.Relatedly,more upstream measures of inculcating the values,understanding and practice of VBC within the medical education system are critical 246.Moving to a system of VBC requires that physicians and physicians-in-training learn to think differently about their role within the larger care team,about what constitutes an effective care solution,and about the importance of measuring the health outcomes that matter most to patients.That learning should begin during medical school.A good example of this is at the University of Texas at Austins Dell Medical School(DMS).At DMS,students study the principles of VBC delivery and are also expected to apply the same during their clinical rotations at the University of Texas Health Austins affiliated clinics.Monitoring and evaluation and learning culture systems:A learning culture is important for entrenching VBC in the system.It is critical to inform the design of the reforms and to adapt to the changing needs of health system.This should be based on a clear M&E plan that deliberately creates evaluation models embedded in the implementation process.This will help enable the VBC team to pick up any lessons for reconfiguration of the scheme.This requires the generation and maintenance of robust,up-to-date and quality information databases for creating the necessary evidence base for decision making.Nurturing structures and processes for continuous M&E at a policy and operational level is also essential to ensure a continuous cycle of improvement based on learning.Public-private engagement:A collaborative approach between private and public actors to further the VBC agenda,including academia and private providers,is critical.Collaborations with the private sector in the US and in Wales have reshaped the VBC agenda and facilitated uptake.These could be used to inform the design of models for payment for outcome measurement and for the design of IPUs.They could also create opportunities for learning from the public sector for the private sector and vice-versa.Active change management strategy:Transitioning to VBC extends beyond solely financial or clinical reforms and requires a cultural shift in the way value is perceived within a health system.The proposition of a change in culture for VBC is highlighted extensively in the literature 55.Thus,a change management plan and strategy are critical for improving the adoption of VBC.What is value in health?One of the major contributions of VBC to the public health discourse has been the broadened understanding of valuing health.The notion has generated debates and fostered greater clarity,albeit with lingering questions on:Theory and empirical experience19a)What is the value in health?b)How is value defined and measured?c)What values are important for decision making in health?d)Whose values are important to consider?e)How should these values be elicited?f)How do values that are seemingly contradictory reconcile to inform fair priority setting?Value in health?It has been said that value like beauty,is in the eyes of the beholder 56.There is no single agreed definition for value.Porter and Teisberg have certainly contributed to the current conceptualization with the framing of value in terms of“patient health outcomes per unit of cost”7.However,value or the values that undergird priority setting in health should account for more than economic criteria for judging the worth of investments in health.Arguments have been made for“socially reflexive and responsible valuing of healthcare that accounts for the socioeconomic and political processes that make a thing valuable for society and its implications”57.In so doing,these arguments recognize that values maybe contextual in nature,drawing from social constructs as well as the need to not only pay attention to social justice(fair distribution of resources)but also pay attention to procedural justice(due process in decision making)to ensure fair and legitimate priority setting processes.These processes,therefore,include consideration of multiple values or decision criteria as well as multiple stakeholders and a means for collating and reconciling differing views and the relative importance of different values.This section synthesizes key issues in the literature on the issues raised in valuing healthcare.What values should be considered in health?The long history of assessing value in care in HTAs and other priority settings has been dominated by concerns for cost-effectiveness and related economic frameworks for technical and allocative efficiency.However,more recently,these have been broadened to incorporate other conceptualizations of value in various jurisdictions.In the EU for instance,the Expert Panel on Effective Ways of Investing in Health,proposes a concept built on four pillars including 35:appropriate care to achieve patients personal goals(personal value),achievement of best possible outcomes with available resources(technical value),equitable resource distribution across all patient groups(allocative value)and contribution of healthcare to social participation and connectedness(societal value).The NICE in the United Kingdom has also defined its principles for valuing care in terms of 32,58:A)Moral principles including respect for autonomy,non-maleficence,beneficence;distributive justice.B)Distributive justice with a particular focus on balancing the tensions between the utilitarian and egalitarian approaches to welfare.The utilitarian approach aims to involve allocating resources to maximize the health of the community while the egalitarian approach involves distributing healthcare resources to allow everyone to have a fair share of the opportunities available,as far as possible.C)Procedural justice ensuring public participation in decision-making as well as ensuring relevance of decisions for most of the population,allows for appeals process(challenge and revision)and processes for public regulation of the process to ensure that it adheres Theory and empirical experience20to all the principles set for procedural justice.D)Evidence-based decision-making that emphasizes clinical and public health effectiveness,cost-effectiveness,individual choice,rare conditions and rule of rescue.E)Avoiding discrimination by race,gender disability,socio-economic status,age,stigma related conditions as well as behavior-related conditions.Recent reviews on value in health have suggested a broad set of values emerging in practice.Cromwell et al in a review of 33 papers,identified that programme effectiveness,equity,affordability,cost-effectiveness,and the number of beneficiaries were the most frequently used decision criteria 59.More recently,Zhang et al found that commonly occurring value categories in different contexts were:health benefits(n=53,96%),affordability(n=45,82%),societal impact(n=42,76%),burden of disease(n=36,65%),quality of evidence(n=32,58%),cost-effectiveness(n=31,56%),ethics and equity(n=27,49%),unmet needs(n=21,38%),and innovation(n=15,27%).In general,the conclusion has been that the criteria and number of values used in decision-making as well as the relative weight accorded to different values varies based on the context,the interventions assessed and may also vary over time in a particular context 60.There are some attempts that have been made to define value frameworks for assessing health technologies that include broader value considerations,which cost-effectiveness analysis(CEA)alone,may not include.These include the efforts of the Second Panel on Cost-Effectiveness that broaden original work done by the Panel of Cost Effectiveness 61.Beyond the recognition of cost and outcome measures(Quality Adjusted Life Years-QALY)in the reference case proposed for CEA,the panel proposes that other values should be considered including patients expectations;legal,ethical,equity,cultural,and political concerns;and pragmatic issues of logistics and feasibility.Most recently,the International Society for Pharmacoeconomics and Outcomes Research(ISPOR)Special Task Force(STF)on US Value Assessments has developed a value framework that defines values that should be used to guide decision-making for new technologies in the USA including medicines and vaccines 62,63.This was spurred by the rising costs of vaccines and medicines.The ISPOR Value Flower includes several criteria related to economic rules of value,social justice including equity as well as other societal values related to externalities of technologies,burden,and severity of disease,etc.Whose values are important to consider?Another issue in valuing care is whose values should be considered.Values may differ with the stakeholder in question.A patient-level valuation of health may contrast with a policymakers valuation of health,with the latters aim being to maximize health at a population level or other efficiency and equity concerns.On the other hand,the patient-level valuation of maximizing individual health outcomes or utility may be at variance with the policy makers valuation.This has been the case in situations like immunization drives,where the individual preference for no vaccination(as a right)may conflict with broader population goals of increasing herd immunity.Traditionally,policymaking considered the policymakers perspective regarding maximizing values important to society.Thus,most priority-setting exercises have included concerns for efficiency or cost-effectiveness,maximizing health gains and equity.However,experiences in countries like the United Kingdom 64 and states like Oregon in the USA 65,66 have highlighted the growing need to incorporate broader perspectives than the policymakers Theory and empirical experience21perspective.Furthermore,public health movements like person-centred care and shared decision-making have emphasized the need to engage citizens in the policymaking process.An interesting issue related to the engagement of citizens is what“citizen”is to be engaged.Should this include patients themselves or should representatives of patient groups be engaged or should the public be engaged 67-70.The emerging themes from the literature indicate that in general,there is an increasing recognition by governments in upper-middle and low-middle income countries,to formally engage multiple stakeholders,including the citizens,in the process of valuing care.The NICE in UK uses the citizens council as a formal mechanism for engaging the public.In other contexts,the government uses other citizen engagement mechanisms including citizens juries or town hall meetings,opinion polls,consultation documents,shared with certain groups on electronic consultations and more 67.Aggregating values in healthConsidering varying perspectives on value in health by stakeholders,the deliberative approaches to priority setting for value have resulted in the evolution of various frameworks for the aggregation of criteria.These frameworks include Assessing Cost-Effectiveness 71;Multi-criteria Decision Analysis(MCDA)72,Evidence and Value:Impact on Decision Makingthe EVIDEM framework 73;and the Programme Budgeting Marginal Analysis(PBMA)74.The frameworks combine technical decision rules-based analyses with the deliberative process involving multiple stakeholders to elicit their criteria for determining the worthiness of investment in a technology or public health intervention.In some of the frameworks,criteria may be weighted to reflect their relative importance in the priority setting process.Weights may be determined through deliberative approaches such as Delphi panels or through quantitative approaches such as discrete choice experiments.ConclusionThe review suggests that there is no one way of eliciting values that are pertinent for prioritizing or measuring health.Values that undergird healthcare systems are necessarily informed by the context,including societal norms and values prevalent therein.Furthermore,the weight that different values carry may vary with the context and therefore systematic mechanisms for arriving at a consensus within a deliberative process are key.Related to VBC,this means that beyond the framework adopted that considers costs and outcomes measured as health benefits such as clinical reported outcome measures(CROMs),patient-reported experience measures(PREMs)and patient-reported outcome measures(PROMs),there may be scope for considering or weighting these against other value considerations including equity,etc.Theory and empirical experience22Part BImplementation experience for each pillar of VBC23Detailed review of the implementation of each pillar of VBCThis section describes with relevant experiences in various contexts,the evidence of implementing the pillars of thematic areas in VBC.This section describes the pillars in detail and then highlights experiences of implementation and the effects of implementing the VBC component in those contexts.Evidence of effectiveness,cost-effectiveness,impact on equity and other factors of importance for the health system is presented from the literature,where available.Some reflection is also made regarding the generalizability of such practices in contexts like India.An essential component of VBC is to move away from silos and paying providers through FFS organized around medical specialties.The aim of VBC is to create integrated health systems by reorganizing service delivery and placing the focus on the patient as the organizing principle of services delivered by the providers and the clinicians 75.Essentially,care is organized around the patients instead of the medical skills of the doctors/physicians.It delivers a full cycle of care which includes patient treatment,education,engagement,and follow-up,outpatient and inpatient services as well as rehabilitative and support services like nutrition and social work 7.Table 4.Key features of an IPU1.An IPU is organized around a medical condition or set of closely related conditions.In primary care,which is by its very nature holistic,IPUs are organized around defined patient segments in terms of their primary and preventive care needs,such as weight loss,atherosclerosis risk reduction,chronic condition management,or smoking cessation.2.Care is delivered by a dedicated,multidisciplinary team whose members devote a significant portion of their time to working together to care for the medical condition.3.Providers identify themselves as part of a common organizational unit and distinct from their specialty department.4.The team takes responsibility for the full cycle of care for the conditions including the responsibility for preparing patients before and after procedures or consultations.The team is also experienced in recognizing variation among patients in their needs and clinical complexity and adjusting care accordingly.5.Patient education,engagement,monitoring,adherence,and follow-up are integrated into team composition and the care model.6.The IPU has a single management and scheduling structure.7.To the extent feasible,the team is co-located in dedicated facilities tailored to the care processes and technology needs.1.Integrated practice unit(IPU)Integrated practice unit248.A physician team captain or a clinical care coordinator(or both)is responsible for overseeing each patients overall care process across time and locations of care,including the patients home.9.The team measures patient outcomes,care processes,and overall costs for each patient using a common measurement platform.10.The team meets formally and informally on a regular basis to discuss outcomes,processes,and technology and employs a structured approach to improving results.11.The team accepts joint overall accountability for outcomes and costs.Source:Integrated Practice Units:A Playbook for Health Care Leaders 76The benefits of IPUs are vast and include:A dedicated medical team consisting of specialist surgeons/physicians working in proper coordination,to provide complete care to patients thus resulting in an ease in access to healthcare.Reduced duplication of investigations by different providers,delays in treatment and lengthy admission processes in various settings as an IPU team is focused on providing care in a collaborated way even if it involves different providers,thus increasing efficiency.Improved healthcare outcomes by establishing new treatment/care pathways and protocols and better monitoring of patients health by the dedicated team consisting of various specialists.Patient awareness and engagement through involving them in their own health decision-making by creating awareness and promoting shared responsibility for their own health.It also covers all the possible complaints of the patient during the cycle,thus increasing patient satisfaction.Aggregating care for a condition within an IPU creates volume,which enables teams to rapidly accumulate and share experience for target patients 7,55,77-79.Some examples of implementing IPUs in practices have been documented in the literature,providing lessons on effectiveness,what conditions are amenable to this model and lessons on factors affecting successful design and implementation.The IPU approach taken by the Virginia Mason Medical Centre in Seattle is an example of IPU in practice.In this case,patients having lower back pain can call a central phone number and can be seen the same day.The“spine team”consists of a board-certified physician and a physical therapist and patients usually visit both on their first visit.Serious cases of back pain with severe causes like malignancy or severe infection are quickly identified and are allowed to enter a process designed to address the specific diagnosis.Patients at Virginia Masons Spine Clinic miss fewer days of work(4.3 versus 9 per episode)and need fewer physical therapy visits(4.4 versus 8.8).In addition,the use of MRI scans to evaluate low back pain has decreased by 23%since the clinics launch in 2005,even as outcomes have improved 7.Integrated practice unit25In primary care,IPUs are multidisciplinary teams which serve patients that require similar primary and preventive care needsfor example,chronic conditions such as diabetes,or frail elderly patients.Usually,for each patient group,the appropriate clinical disciplines and preventive services team and education can be assembled to ensure value for money for the patient and provider.Thus far it has been used for high-risk,high-cost patients through so-called Patient-Centred Medical Homes.However the opportunity to substantially enhance value in primary care is far broader.The West German Headache Centre is an IPU that includes neurologists,physical therapists,and psychologists in one team.The patient sees all the experts they need in a single visit.If diagnostic imaging is needed,it is obtained from a nearby partner provider 78.By restructuring to create an IPU,a West Germanmigraine headache centre was able to lower costs by 20%as well as improve clinical symptoms of patients by 54%.This has enabled them to expand,opening more centres in other cities and developing new programmes for conditions such as vertigo,rheumatoid arthritis,and acute back pain 77.In Netherlands,a collaboration of seven hospitals focusing on VBC(Santeon)introduced a pilot programme at one of the hospitals which involved teams responsible for four medical conditions;they are accountable for the quality outcomes but not for the financial side 55.Consistent with a formal learning system,at each of the hospitals multidisciplinary improvement teams regularly meet to share learnings based on data and develop improvement plans.Both England and Norway,have introduced teams of general practitioners,specialized nurses,physiotherapists,and psychologists to organize care around patients needs in primary care.In specialized care,the governments seek to integrate care along defined standardized clinical patient pathways,such as cancer or mental health,Ibid.Effectiveness of IPUsEvidence from a study focused on evaluating the effectiveness of a Transitional Home Care(THC)programme that applied the IPU concept(THC-IPU)in reducing 30-day readmission for patients with functional dependence,admitted to the Singapore General Hospital,showed a reduction in acute hospital utilization where care was delivered in form of home visits organized through an IPU 80.The study showed that the THC-IPU programme was associated with a reduced likelihood of hospital readmission and emergency department attendance rates at 30 days and up to 90 days after hospital discharge.This suggests a positive contribution from transitional care organized as an IPU.Extending the programme into the pre-hospital discharge phase to include discharge planning is likely to have incremental effectiveness in reducing avoidable hospital readmissions.In an IPU study conducted at a safety net clinic in central Texas,providing musculoskeletal care through an FFS model,it was observed that among the patients undergoing hip or knee replacement,the length of stay was 1.4 days compared to 2.6 days for patients referred to the parallel fee-for-service clinic(p0.001),and 92%were discharged home versus 89%(p=0.46).The IPU increased access and improved short-term surgical outcomes in a population of uninsured and underinsured patients seeking musculoskeletal care,but more studies are required to understand the effectiveness of the IPU model(47).Integrated practice unit26A systematic review of the impact of person-centred interventions for serious physical illness in terms of outcomes and costs reported that in an IPU and modified virtual ward model in Singapore,unplanned readmissions at 30,90 and 180 days were significantly lower in the intervention group than the control group and emergency department attendance were significantly lower at 30,90 and 180 days in the intervention 81.Likewise,an interdisciplinary,collaborative practice intervention involving a primary care physician,a nurse,and a social worker for community-dwelling seniors with chronic illnesses,showed significant changes in the number of hospital admissions per patient per year,percentage of patients with one or more hospital readmissions within 60 days and mean number of visits to all physicians.It also showed fewer attendances at physical,occupational or speech therapy units compared with the control group.However,the change in percentage of patients with one or more visits to the emergency department,the change in proportion of patients with one or more home care visits and the change in number of patients with one or more nursing home placements and emergency visits were not significant.In the same review of the six studies that reported data on costs,five found that person centred care resulted in the reduction of costs of care.Two studies from this review demon-strated that person-centred interventions were effective in reducing pain outcomes,while five studies showed that interventions had no effect on pain and physical symptoms such as fatigue and shortness of breath in chronic obstructive pulmonary disorder(COPD)and heart disease populations(ibid).Mortality was significantly reduced in the community-based integrated care for frail patients with COPD.Mortality was significantly lower in an integrated practice unit and modified virtual ward model(48).A comprehensive care programme with multidisciplinary input for patients with COPD reported a reduction in mortality rates compared with usual care.However,a team intervention for the multimorbid elderly reported that mortality risk at 3-and 6-months follow-up were all non-significant.Conclusion on IPUsIt is clear from both the literature and practice that the successes of IPUs are somewhat mixed(though largely in favor of IPUs),as they work for some conditions whilst they are less favorable for others.This is important in planning the adoption of VBC at any scale and using them for conditions in which they have demonstrated effectiveness.This should be done taking cognizance of the considerable management and staff efforts required,for which restructuring costs and undertaking cost-effectiveness,and budget impact studies are much needed 82.Despite the encouraging evidence,the global implementation of IPUs is very much limited as the changes required to effectively implement them are not aligned to the organizational structure of hospitals where care is organized along the lines of traditional academic disciplines.The reorganization of care from the traditional approach to an IPU model requires concurrent reconfiguration of budgets and authority which is often a barrier to the adoption of this approach 45.Integrated practice unit27Outcomes measurementThe emphasis of this pillar of VBC is to ensure that outcomes of importance to the patient are reported.Porter and Teisberg argue that traditional methods of measuring health status improvements have focused on clinician reported outcomes that often do not cater for the patients experience of care and the outcomes of importance to the patient.They therefore argue that outcomes of importance to the patient should be the focus of outcome measure.They further note that outcomes should be across all relevant specialties,ensuring that accountability for value is shared amongst the providers involved.The outcomes should also be defined for patient groups with similar needs.Principles for determining the group of relevant outcomes to measure for any condition or patient population follows several principles including:Outcomes include health circumstances relevant to patients.They cover both short-term and long-term health,addressing a period that is long enough to encompass the ultimate results of care.It should also include sufficient measurement of risk factors or initial conditions to allow for risk adjustment.Lastly,for any condition or population,multiple outcomes collectively define success.Measuring,reporting,and comparing outcomes are perhaps the most important steps toward rapidly improving outcomes and making good choices about reducing costs.Outcome measurements should include medical conditions and circumstances associated with the patients,as well as sufficient measurements of the associated risk factors.Porter and Teisberg propose an outcomes hierarchy in which the progression in health is contingent on success in the higher tiers of results.The hierarchy is shown in the Table 5 below:Table 5.Tiers in outcomes hierarchyTiersLevelsOutcome dimensionsTier 1-Health status achieved or retainedSurvival-Survival rate in terms of time-Mortality rateDegree of health or recovery-Freedom from disease-Functional statusTier 2-Process of recoveryTime to recovery and time to return to normal activitiesTime needed to complete various phases of care Disutility of care or treatment processAny diagnostic/medication errors,complications,adverse effects,etc.Outcome and costs measurement2.Outcome and costs measurement28TiersLevelsOutcome dimensionsTier 3-Sustainability of healthSustainability of health or recovery and nature of recurrencesRecurrencesLong-term consequences of therapyCare-induced new illnessSource:What Is Value in Health Care?83Different outcomes are described in the literature.These include,Clinician Reported Outcomes Measures(CROMs),Patient Reported Outcomes Measures(PROMs)and Patient Reported Experience Measures(PREMS).Clinician-reported outcomes are measurable changes in a patient or participants symp-toms,overall health,ability to function,quality of life,or survival that require the knowledge and/or judgement of a medical professional to be interpreted and reported.According to the National Centre for Advancing Translational Sciences in the USA,Clinician-reported outcomes(CROMs)include clinically observable signs,behaviors,and clinical manifestations of the disease 56.Biomarkers may aid in measuring CROMs,but changes that only the patient can report,such as pain intensity are not included.These are the traditionally used measures for monitoring progress in the health status of a patient by health providers but do not include the patients perspective on progress in health status.PROMs are directly reported by the patient without interpretation of the patients response by a clinician or anyone else and pertains to the patients health,quality of life,or functional status associated with healthcare or treatment 84.Varying facets of health from a patient perspective may be analyzed(pain,mobility,etc.),owing to which patient involvement becomes an integral part in their development 85.They include PROMs and PREMs.The initial use of PROMs can be traced back to 1975,when Sweden established the nation-wide use of PROMs using disease-specific clinical databases known as quality registers 86,with other countries such as Australia,United Kingdom and USA adopting PROMs into their health systems during the 90s and early 2000s.USA was the first country to implement nationally mandated patient-reported measures,that is,PREMs,beginning with the Consumer Assessment of Health Care Providers and Systems(CAHPS)Health Plan Survey in 1997.This was followed by the implementation of the General Practice Patient Survey(GPPS)in England,which focuses on the experiences of patients with healthcare services provided by general practitioner(GP)practices and dental care 87.The use of PROMs and PREMs to determine quality,financial payments and as tools for gathering performance information have been gaining increased acceptance across health systems in high-income settings.These measures are discussed in detail below:PROMs:PROMs are standardized,validated questionnaires that are completed by patients before,during or after their care episode to ascertain perceptions of their health status,perceived level of impairment,disability and health related quality of life(HRQOL)88.Broadly,there are two basic categories of PROMs 86:General health PROMs:Used to survey patients with any condition.They usually focus on general well-being,mental health and/or quality of life.Condition-specific PROMs:Usually concentrate on the symptoms of a particular disease.They may ask questions about mobility,function,or pain levels in certain areas of the body.Outcome and costs measurement29There exist several generic(Short Form-36 or SF-36,EuroQol-5D or EQ-5D)and disease-specific PROMs,of which the former are used to measure HRQoL.HRQoL is a multidimensional concept encompassing the different assessable aspects of a patients life that can affect physical or mental health such as health risks,functional status,social support and socioeconomic status 89.However,even within such generic PROMs,there exists considerable variation in their length,number of dimensions as well their accessibility vis-vis open source or license-based.Thus,while SF-36 consists of 36 items under eight dimensions,EQ-5D consists of six items under five dimensions(with the former placing emphasis on the dimension of mental health).Additionally,while the Patient-Reported Outcomes Measurements Information System(PROMIS)is a free open-source tool,the others are offered on payment of a license fee 88.Disease-specific PROMs on the other hand,measure outcomes that are important for particular target populations or particular outcome dimensions,be that disease(for example,depression,asthma,etc.),group of patients(for example,children,cancer patients,etc.)or an outcome dimension(for example,pain,mobility,etc.),and are usually not suitable for comparing health status of individuals with different health conditions 90.A large set of disease-specific PROMs are developed through the ICHOM,an international not-for-profit agency committed to using PROMs to unlock the potential of VBC by defining global sets of such measures 91.Despite their different objectives,generic and disease-specific PROMs should be used in a complementary manner to capture the overall quality of care and patient outcomes.PREMs:PREMs focus on the care experience in terms of the service quality and humanitarian aspects of care(dignity,wait time,etc.).They gather information on the process of care as perceived by the patient,rather than the outcomes.Though often conflated with the concept of patient satisfaction,PREMs differ from satisfaction surveys in that they gather more tangible information on how a service can be improved,rather than the patients overall satisfaction level and may be less prone to the influence of patient expectation,known to be influenced by varying factors 92,beyond solely the care experience 93.The difference has been framed in terms of their linkage to process against outcomes respectively,owing to which PREMs are more amenable to objective measures of patient centricity.Methodologically,PREMs typically employ frequency-base response scales(for example,never,sometimes,often always),while patient satisfaction measures use agreement-based response scales(for example,strongly disagree,disagree,etc.),the latter of which is often critiqued for being biased by acquiescence(tendency to agree with an item irrespective of what is being asked)and straight lining(tendency to given identical or near identical responses to consecutive questions)94.PREMs are typically structured around certain dimensions which are recognized as important to patients or in providing patient-centred care.In contexts where they are formulated or used,such as NHS England,Institute of Medicine(USA)and through the International Alliance of Patients Organizations(IAPO),a common theme that emerges in aspects measured includes respecting patients value and preference,coordination,and integration of care,providing adequate information to the patient and their care givers as well as support for accessing care.In NHS England,additional specifics such as patients physical comfort,emotional support and alleviation of fear and anxiety,feature as additional measurement dimensions used 90.Patient experiences can be classified as relational for example,did they feel they were listened to?Or functional,for example,coordination of care 95.They are also informed by societal values and preferences,and therefore development of PREMs necessitates an Outcome and costs measurement30understanding of what matters to the patient.To develop context-relevant and appropriate PREMs,it is essential that experiences that matter to the patient are captured.This involves direct engagement through dialogue and structure or semi-structured interviews with the relevant population,a practice that appears to be standard as part of the development of PREMs in countries such as the UK 96-98.Country examples of using PROMs and PREMs Some illustrative applications of PROMs and PREMs within the VBC framework is provided in the Table 6 below:Table 6.Illustrative applications of PROMs and PREMsCountry PROM#/PREM/Payment Linkages with PROMS-PREMS&Year Laun-chedPurposeUnited KingdomGeneral Practice Patient Survey(GPPS)1998National survey on quality perception and experience from patient perspective in GP settingQuality Outcomes Framework(QoF)&2004Pay for performance(25%)of GP income based on performance across clinical,organizational and patient experienceDepartment of Health PROMs Programme#2009Outcomes measurement for four common elective surgical procedures(later linked to payment under the National Tariff Payment System)USAConsumer Assessment of Health care Providers and Systems(CAHPS)1995A programme by Agency for Healthcare Research and Quality(AHRQ),which works with a consortium of research organizations to generate insight into patient experience of healthcareMedicare Health Outcomes Survey(HOS)#1998First PROM used in Medicare managed care and used in QI activities,programme oversight and pay for performance1.Hospital Value-Based Purchasing Programme&2.Hospital Readmission Reduction Programme&3.Medicare Advantage Quality Bonus&2012Payment-linked programmes using PROMs/PREMs such as Health Outcomes Survey(HOS)and CAHPSAustralia Victorian Population Health Survey(VPHS)#2001VPHS collects information on health status of adults in Victoria StateNSW Health Patient Experience Survey2007Patient experience in public health systemSource:Reproduced from 87Outcome and costs measurement31Additionally in 2013,value-based reimbursement models were introduced in Sweden for spinal surgery,with small performance-based payments(representing approximately 10%of the base payment for an episode of care)linked to improvements in patient-reported pain scores that are compared with national registry outcomes data 99.More recently,PRMs are also being adopted at a wider scale rather than for specific value-based purchasing programmes.Two such emerging examples are the Health Outcomes and Patient Experience(HOPE)platform in Australia 100 and Health Outcomes Observatory(H2O)in the European Union 101.In the USA,they are being used to support the development of person-centred learning health systems 102,which involves continually collecting experiences,priorities and values of patients and their caregivers and feeding them into data systems to monitor ongoing quality improvement and performance benchmarking,accounting for contextual determinants.A noteworthy example is the Veterans Health Administration(VA)in the USA,deployed in the area of mental healthcare,wherein the integration of evidence-informed practice,measurement and quality improvement significantly improved clinical processes and outcomes for persons with mental health issues,including improved access to care 103.Table 7 summarizes the evidence in the literature of the multi-faceted benefits arising from the deployment of PROMs and PREMs:Table 7.Benefits arising from the deployment of PROMs and PREMs by the level of system engagementLevel PurposeType of measureUseMicro Shared decision making andcare in partnership with patientsCondition-specific PROMs Screening Diagnosis Monitoring of disease progression Support of treatment decisions Communication(patient-provider;provider-provider)MesoInformation to drive quality improvement(QI)initiatives PREMs Condition-specific PROMs Identify areas for quality improvement Public reporting to allow informed provider choice Monitoring patient-reported adverse events Comparing providers and organizations or benchmarking them to identify poor performers and learn from good performersMacro Population health monitoring PREMs Generic PROMs(Health-related quality of life)Supportive information for publichealth activities:Prioritization of patient groups,conditions,etc.Designing public health initiatives Monitoring of effects of policy initiativesOutcome and costs measurement32Level PurposeType of measureUseMacro Reimbursement decisionsGeneric and/or condition-specific PROMs Assess the relative effectiveness of treatments and services Assess patient issues associated with condition and treatmentContracting services and payment modelsGeneric PREMs(Pay for performance)or(condi-tion specific)PROMs(meeting minimum thresholds of outcomes)Pay-for-performance Contracting decisionsSource:KCE Report 2018 104Effectiveness of PROMs in improving VBCWith regard to empirical evidence supporting the case for patient-reported measures,evidence indicates that when self-reported symptom monitoring was int
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World Obesity Atlas 2025Overweight,obesity and non-communicable diseases New global,regional and national estimates of the prevalence of overweight and obesity in adults from 2000 to 2030 New estimates for the contribution of high body mass index to leading non-communicable diseases in adults New comparisons of country policy responses and health service preparation Plus 199 national scorecards for adult overweight,non-communicable disease,and policy responsesMarch 2025Source information compiled by Tim Lobstein,Jaynaide Powis,Rachel Thompson and Rachel Jackson-Leach.Additional material from the World Obesity Federation Communications and Policy teams.Design by fuzzylime fuzzylime.co.uk World Obesity Federation 2025.World Obesity Federation 3 Waterhouse Square,138-142 Holborn,London EC1N 2SWwww.worldobesity.org#worldobesityatlas Suggested Citation:World Obesity Federation.World Obesity Atlas 2025.London:World Obesity Federation,2025.https:/data.worldobesity.org/publications/?cat=23 Acknowledgements:The World Obesity Atlas is a non-commercial publication by The World Obesity Federation.The publishers are indebted to the World Health Organization,the NCD Risk Factor Collaboration,The Institute for Health Metrics and Evaluation,the UN Population Division,the Tufts University(Global Dietary Database),and the Food and Agriculture Organization of the UN.None of these organisations is responsible for the use that has been made of their data in the present publication.Eli Lilly and Company and Novo Nordisk have provided funding to partially support the World Obesity Federations 2025 Atlas.Neither Eli Lilly and Company nor Novo Nordisk have had any control or influence over the Atlas content or any materials/activities that were developed as part of this funding.All data are used with the owners permission or with Creative Commons(4)consent.All rights reserved.For further details please see the methods and data sources section in Annex 1.3World Obesity Atlas 2025ContentsList of tables and figures 4Acronyms 5Foreword 6Changing systems,healthier lives:Voices 7Headlines from the World Obesity Atlas 2025 8Section 1:Global overweight and obesity 10Global trends of high BMI in adults 12Numbers and prevalence of high BMI in adults by WHO region 13Numbers and prevalence of high BMI in adults by World Bank income groups 15Lifetime risk of high BMI 17Section 2:Non-communicable diseases and high BMI 21Global trends in NCDs 23The relative importance of high BMI in the likelihood of developing four major NCDs 24Premature deaths and adult years of ill health attributable to high BMI by WHO region 28Premature deaths and years of ill health by World Bank income level 30Section 3:Changing systems,healthier lives 31Health systems 32Healthy environments 34Food systems 36Country comparisons:systems readiness 37World Obesity Day 2025 The time for collective action is now 38Section 4:Country scorecards 61Annexes 263Annex 1:Methods and data sources 264Annex 2:National estimates for the life-time risk of high BMI in adulthood 266References 2724World Obesity Atlas 2025List of tables and figuresTablesTable 1.1:Global estimates and projected numbers and prevalence of men and women(aged 20 )living with high BMI,2010,2015 and 2030Table 1.2:Numbers and prevalence of adults(age 20 )living with high BMI in the African Region,2010,2015 and 2030Table 1.3:Numbers and prevalence of adults(age 20 )living with high BMI in the Region of the Americas,2010,2015 and 2030Table 1.4:Numbers and prevalence of adults(age 20 )living with high BMI in the Eastern Mediterranean Region,2010,2015 and 2030Table 1.5:Numbers and prevalence of adults(age 20 )living with high BMI in the European Region,2010,2015 and 2030Table 1.6:Numbers and prevalence of adults(age 20 )living with high BMI in the South-East Asia Region,2010,2015 and 2030Table 1.7:Numbers and prevalence of adults(age 20 )living with high BMI in the Western Pacific Region,2010,2015 and 2030Table 1.8:Numbers and prevalence of adults(age 20 )living with high BMI in the World Bank Low Income Group,2010,2015 and 2030Table 1.9:Numbers and prevalence of adults(age 20 )living with high BMI in the World Bank Low-Middle Income Group,2010,2015 and 2030Table 1.10:Numbers and prevalence of adults(age 20 )living with high BMI in the World Bank Upper-Middle Income Group,2010,2015 and 2030Table 1.11:Numbers and prevalence of adults(age 20 )living with high BMI in the World Bank High Income Group,2010,2015 and 2030Table 2.1:Ranking of the top 15 risk factors for premature deaths from four major NCDs,2021Table 2.2:Estimated number of premature deaths from NCDs,2021Table 2.3:Ranking of the top 15 risk factors for adult years living with ill health due to four major NCDs,2021Table 2.4:Estimated number(millions)of adult-years living with ill health from NCDs,2021Table 3.1:National Systems Readiness Indicators:Health coverage indicatorsTable 3.2:National Systems Readiness Indicators:Public health system readiness indicatorsTable 3.3:National Systems Readiness Indicators:Policy readiness indicatorsFiguresFigure 1.1:Percentage of men(aged 20 )living with high BMI,2000-2030Figure 1.2:Percentage of women(aged 20 )living with high BMI,2000-20305World Obesity Atlas 2025Figure 1.3:Estimated lifetime risk of high BMI during adulthood for men,2022Figure 1.4:Estimated lifetime risk of high BMI during adulthood for women,2022Figure 1.5:Estimated lifetime risk of BMI 35kg/m2 or higher during adulthood for men,2022Figure 1.6:Estimated lifetime risk of BMI 35kg/m2 or higher during adulthood for women,2022Figure 2.1:Deaths per 100,000 of people aged under 70 years for four NCDs,2010-2021Figure 2.2:Person-years lived with ill health(rate per 100,000 adults over age 20 years),2010-2021Figure 2.3:Estimated impact of high BMI on the number of premature deaths from NCDs,2021Figure 2.4:Estimated impact of high BMI on the number of adult person-years lived with NCD-related ill health,2021Figure 2.5:Regional differences in the numbers of premature deaths attributable to high BMI,2021Figure 2.6:Regional differences in the years of ill health among adults attributable to high BMI,2021Figure 2.7:National income levels and premature deaths attributable to high BMI,2021Figure 2.8:National income levels and years of ill health among adults attributable to high BMI,2021Figure 3.1:Global distribution of untreated type 2 diabetes,2022Figure 3.2:Global barriers to treatmentFigure 3.3:Proportion of men with insufficient physical activity,2022Figure 3.4:Proportion of women with insufficient physical activity,2022Figure 3.5:Estimated health costs due to diets high in processed foods,2024AcronymsBMI Body Mass IndexFAO Food and Agriculture OrganisationGBD Global Burden of DiseaseIHME Institute for Health Metrics and EvaluationNCD Non-Communicable DiseaseNCD-RisC Non Communicable Disease Risk Factor Collaboration NICE National Institute for Health and Care ExcellencePPP Purchasing,Power,ParitySDG Sustainable Development GoalUN United NationsWHO World Health OrganizationWHO-GHO World Health Organization Global Health ObservatoryYLD Years living with disability/ill health6World Obesity Atlas 2025World Obesity Day 2025 comes at a critical time for advancing action on obesity.In September,governments will come together at the Fourth High-level Meeting of the United Nations General Assembly on NCDs and Mental Health to review progress and commit to action for the next phase of the global NCD response.As new data in this Atlas makes clear,the world is off-track to meet global NCD targets.The data also emphasises that prioritising and acting on obesity is a critical opportunity to reduce the global impact of NCDs.The first part of the Atlas presents new global and regional estimates of prevalence of overweight and obesity and major NCDs in adults from 2000 to 2030.On present trends,overweight and obesity will affect nearly 3 billion adults(some 50%of the worlds adult population)by 2030.There are also concerning rises in the number of adults with obesity who will likely need medical intervention in their lifetime,with serious implications for health systems.Obesity is a disease and a major driver of NCDs including some types of cancers,heart disease,stroke,and type 2 diabetes,which are the focus of our analysis in Section 2.Complementing data presented in the 2024 Atlas,the countries where disability and death attributable to overweight and obesity are highest are in the Americas,South-East Asia and the Western Pacific.Once again,our Atlas demonstrates that obesity is truly global,with middle-income countries seeing the biggest increases between now and 2030.The theme of this World Obesity Day Changing Systems,Healthier Lives highlights that behind the global rise in obesity and NCD rates are failing systems:health systems that are ill-equipped to care for people living with obesity and perpetuate bias and stigma;food systems in which corporations produce unhealthy food and then spend billions advertising it to people;and planning and transport systems that discourage people from active travel and being physically active.Looking in depth at policy indicators for the first time,the third part of the Atlas highlights starkly how few countries have systems ready to respond to the growing obesity epidemic.No single intervention can halt the rise of the growing obesity epidemic.This World Obesity Day we are critically examining the systems underlying obesity and NCDs and calling for structural change to create healthier lives for all.We must work together to call for comprehensive change,with people living with obesity leading the way.Many of the same policies to prevent and manage obesity will also help reduce NCDs:both by targeting common risk factors(such as unhealthy diets,lack of physical activity and commercial determinants such as marketing)and by reducing the risks from overweight and obesity.Action on obesity is thus a double duty(win-win)action for healthier lives.The final part of the Atlas showcases WHOs new Technical Package to Stop Obesity with a framework of priority actions and recommended interventions,selected for their proven impact and cost effectiveness in addressing growing obesity rates.The Atlas is completed by a series of national scorecards for 199 countries for adult overweight,non-communicable disease,and policy responses.These serve as a wealth of evidence for advocacy directed at policymakers who have the power to make a difference.ForewordSimn Barquera President,World Obesity FederationJohanna Ralston CEO,World Obesity Federation7World Obesity Atlas 2025Lived experienceYou often hear about the obesity epidemic and how much were a drain on the health care system.And yet I cant get access to the treatments that would help me treat my obesity.There are restrictions and barriers for obesity care that dont exist for other diseases,and thats not right.And that makes it even more difficult for those living with obesity to get the care they need.My call to action for my fellow patients are to speak up and ask for the care.Demand the care that you know you deserve.My call to action for the rest of the society is please treat us as humans.Were human beings.We deserve the same type of access to care as any other disease state.I feel like Ive been working very hard to improve my health,and I need the help of others to change the system which Im working in.Sarah Bramblette Senior advocacy manager for the Obesity Action Coalition(USA)Changing systems,healthier lives:VoicesProfessional experienceIn a country like South Africa,where two-thirds of women are living with overweight and obesity,its still not seen with urgency theres a lot of blaming it on an individual failing,not a system issue.It seems like a tomorrow problem,but the issue is now.In the crisis of obesity,we are waking up as South Africans to what we can do.The bigger issue is that were all working separately what Im excited about is how to get people who worked in other spaces to come together in obesity and the intersection with the non-communicable diseases.My call to action for World Obesity Day 2025 is changing systems and changing lives.When it comes to obesity,inaction will cost us.Itll cost us lives.Itll cost us the economy.Itll cost us across the board.Weve been able to do this before,and we should do it at a systems level,not an individual level.Dr Nomathemba Chandiwana Chief Scientific Officer,Desmond Tutu Health Foundation(South Africa)8World Obesity Atlas 2025Headlines from the World Obesity Atlas 2025On present trends,the world will not meet the World Health Assemblys 2025 targets for the prevention and control of non-communicable diseases(NCDs)which include a halt in the rise in diabetes and obesity and a 25%relative reduction in overall premature mortality from cardiovascular diseases,cancer,diabetes or chronic respiratory diseases,based on 2010 baselines(WHO,2013).Nor is the world likely to meet the Sustainable Development Goals target to reduce by one third premature mortality from non-communicable diseases through prevention and treatment by 2030,agreed at the United Nations Sustainable Development Summit in 2015(UN,2015).The world is off-track to meet global NCD targets.The likelihood of developing an NCD is enhanced by a range of risk factors,including tobacco use,lack of physical activity,poor diet and high body weight,and these risk factors account for more than half of all premature NCD deaths(some 10.7 million in 2021).Of these,1.6 million(15%)of premature deaths were attributable to high body mass index(BMI,a surrogate measure for high body weight)(GBD,2024).This rises to 55%of premature deaths from type 2 diabetes.High BMI is a key driver of NCDs and accounts for 1.6 million premature deaths from NCDs every year.The global burden of premature deaths from NCDs is accompanied by large numbers of people alive but suffering ill health from NCDs.In 2021,a total of 161.1 million years lived in ill health by adults with NCDs were attributable to known risk factors,of which 44.3 million(27%)person-years of ill health were attributed to high BMI(GBD,2024).NCDs result in significant ill health.Over 160 million adult person-years are lost to NCD-related ill health every year and more than 25%of these are due to high BMI.Evidence suggests that a reduction in the prevalence of high BMI in adults is unlikely to be met unless dramatic policy interventions are made.On present trends,high BMI will affect nearly 3 billion adults(some 50%of the worlds adult population)by 2030.This compares with fewer than 2 billion(40%)in 2015 when the SDGs were set,and 1.6 billion(36%)in 2010,the baseline for the WHO targets for NCD reduction.On present trends,high BMI is projected to continue increasing,especially in middle-income countries.The likelihood of having a high BMI rises with age,so by the age of 65 or 70 years,a significant proportion of the population will have experienced overweight or obesity during their lifetime.In the majority of countries(147 out 9World Obesity Atlas 2025of 200)the adult life-time risk of high BMI in 2022 exceeded 50%of the population,and in many countries(62)it exceeded 80%.Looking specifically at a threshold of BMI of 35kg/m2,we estimate that in most countries worldwide,more than 10%of adults will exceed this threshold during their lifetime.In nearly a fifth of all countries,more than 20%of adults will exceed this threshold at some point in their lifetime,based on 2022 figures.These can be considered conservative estimates of the proportion of adults who will likely need medical intervention in their lifetime.Few countries have health systems ready to appropriately address obesity and few countries have sufficient obesity prevention policies.The readiness of countries to address high BMI in their adult population can be assessed using evidence of national health systems ability to provide treatment for obesity and NCDs,to monitor progress towards meeting the national targets,and to introduce nation-wide policies and actions to prevent weight gain across the population.Using eight health system readiness indicators,the latest evidence shows that only 13 countries have all eight indicators of readiness in operation(including monitoring and guidelines).Out of five policy obesity prevention indicators,no country had all five of the policies and actions in place.Overall,only one country(Tonga)said yes to as many as 12 of the 13 combined indicators,while a further five countries(Mexico,India,United Kingdom,Finland and Malaysia)said yes to 11 of the 13 indicators.67 countries had none or only one of the indicators scored as yes.Definition of high BMI and its usage in the AtlasIn this Atlas,the term high BMI includes overweight(BMI 25-30 kg/m2),obesity class I(BMI 30-35 kg/m2),and obesity class II and above(BMI over 35 kg/m2).We have divided obesity into two categories,below and above BMI 35 kg/m2,because BMI 35 kg/m2 is a common threshold for referral for clinical intervention in current guidelines.Although widely used,BMI has well-documented limitations.As a measure of size not health,it is useful as a screening tool at the individual level and for estimating overweight and obesity at a population level.It is not recommended that it be used in isolation as a diagnostic tool in a clinical setting.Section 1 Global overweight and obesity10World Obesity Atlas 202511World Obesity Atlas 2025Section 1:Global overweight and obesityOn present trends,the world will not meet the World Health Assemblys 2025 targets for the prevention and control of non-communicable diseases(NCDs)which include a halt in the rise in diabetes and obesity and a 25%relative reduction in overall premature mortality from cardiovascular diseases,cancer,diabetes or chronic respiratory diseases,based on 2010 baselines(WHO,2013).As previous World Obesity Atlases have reported,NCD and obesity prevalence trends to date suggest that it is unlikely that many countries if any at all will meet these targets.Instead,we have seen rapid rises in overweight and obesity prevalence in many middle-income countries and some evidence of plateaus at a high level in some high-income countries.In this section,we give the global and regional trends in the proportion of adults living with high body mass index(BMI).High BMI includes overweight(BMI 25-30 kg/m2),obesity class I(BMI 30-35 kg/m2),and obesity class II and above(BMI over 35 kg/m2).We have divided obesity into two categories,below and above BMI 35 kg/m2,because BMI 35 kg/m2 is a common threshold for referral for clinical treatment in current guidelines(see e.g.NICE 2024).As we show below,the most recent estimates for global levels of high BMI suggest that nearly 3 billion adults(some 50%of the adult population)will be affected by 2030,the year of the global Sustainable Development Goal(SDG)targets.This compares with fewer than 2 billion(40%)in 2015 when the SDGs were set,and 1.6 billion(36%)in 2010 which is the baseline for the World Health Assembly goals.The likelihood of having a high BMI rises with age so by the age of 65 or 70 years,a significant proportion of the population will have experienced high BMI during their lifetime.In the majority of countries,the adult life-time risk of high BMI exceeded 50%in 2022 and in many countries,it exceeded 80%(see Figures 1.3 and 1.4,and Annex 2).In addition,we present the maximum prevalence of BMI 35kg/m2 or more during adulthood to tell us the estimated lifetime risk of obesity class II and above(Figures 1.5 and 1.6,and Annex 2).For health services where a BMI of 35kg/m2 or greater is currently a condition for referral for medical intervention,these prevalence figures provide a conservative estimate of the proportion of the adult population likely to need medical intervention at some point during their lifetimes,based on 2022 prevalence data.For the majority of countries,this exceeds 10%of all adults,and for around a fifth of all countries,this rises to 20%or more of all adults.In Section 2 we discuss the contribution of high body mass index to the risk of developing NCDs,and the extent to which high prevalence of overweight and obesity contributes to the failure to meet the NCD targets.In Section 3 we discuss the policies and interventions needed to address high BMI and consequential NCDs.Recognising the likelihood that the obesity and NCD targets set by the World Health Assembly are not likely to be met,the World Health Organization has published proposals for accelerated action on obesity,supporting this with technical advice for Member States.These build on the development of policies and actions already underway,which are reviewed in Section 3.12World Obesity Atlas 20251.1 Global trends of high BMI in adultsThe latest estimates by the NCD Risk Factor Collaboration(NCD-RisC)for the prevalence of overweight and obesity worldwide show trends from 1990 through to 2022(NCD-RisC,2024).If there are no significant interventions to alter the trends then they will continue forward to 2030,as we project in Figures 1.1 and 1.2 below.Current trends suggest that by 2030,50%of adult men and women will be living with high BMI.In the same year,17%of men and 22%of women will be living with obesity.Figures 1.1 and 1.2:Percentages of men and women(aged 20 )living with high BMI,2000-2030Men Women200020022004200620082010201220142016201820202022202420262028203002040200020022004200620082010201220142016201820202022202420262028203002040 Key n BMI 25-30 kg/m2 n BMI 3035kg/m2 expected to be living in middle-and lower-income countries(see Tables 1.8 to 1.11).Table 1.1:Global estimates and projected numbers and prevalence of men and women(aged 20 )living with high BMI,2010,2015 and 2030MenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 2010570m 264m 7Qm 2x6m36 15665m 28 3m 8im 36m 39 30966m 3346m 121m 5%1,453m 50%WomenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 2010518m 23 3m 96m 56m 37 15592m 24$4m 103m 58m 40 30834m 2899m 14$4m 8%1,477m 50%Source:NCD-RisC(2024),UN population estimates(2024),and World Obesity Federation projections13World Obesity Atlas 20251.2 Numbers and prevalence of high BMI in adults by WHO regionThe World Health Organization operates through regional offices so we have calculated the number and prevalence of adults living with high BMI in each region,based on the data from the NCD-RisC estimates and the new World Obesity projections up to 2030.Table 1.2:Numbers and prevalence of adults(age 20 )living with high BMI in the African Region,2010,2015 and 2030MenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 201031m15%7.4m4%2.5m1Am20 1538m16%9.8m4%3.3m1Qm21 3067m18!m6%8.2m2m26%WomenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 201040m19m8%9.3m4fm31 1549m20m9.5m5m34 3091m24Gm13)m87m45%Source:NCD-RisC(2024),UN population estimates(2024),and World Obesity Federation projectionsTable 1.3:Numbers and prevalence of adults(age 20 )living with high BMI in the Region of the Americas,2010,2015 and 2030MenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 2010117m38Sm17#m83m63 15126m38bm19)m9!7m66 30144m37m23Qm13(7m73%WomenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 201098m31Um17m123m60 15107m31dm19Im140m64 30131m32m22m2107m75%Source:NCD-RisC(2024),UN population estimates(2024),and World Obesity Federation projections14World Obesity Atlas 2025Table 1.4:Numbers and prevalence of adults(age 20 )living with high BMI in the Eastern Mediterranean Region,2010,2015 and 2030MenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 201053m31 m12%6.6m4m47 1563m33m15%9.9m50m53 3097m37Qm19$m92m65%WomenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 201046m29m17m10m56 1553m304m19!m128m61 3077m31am25Dm182m74%Source:NCD-RisC(2024),UN population estimates(2024),and World Obesity Federation projectionsTable 1.5:Numbers and prevalence of adults(age 20 )living with high BMI in the European Region,2010,2015 and 2030MenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 2010131m41Hm15.3m42m60 15136m41Sm16m5 5m62 30141m40em18%m7#1m65%WomenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 2010101m28Rm14(m81m50 15102m28Tm150m86m51 30103m27Wm158m108m52%Source:NCD-RisC(2024),UN population estimates(2024),and World Obesity Federation projectionsTable 1.6:Numbers and prevalence of adults(age 20 )living with high BMI in the South-East Asia Region,2010,2015 and 2030MenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 201078m14.4m2%2.6m1m16 15107m17m3%3.9m10m20 30221m28Gm6.3m19m35%WomenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 201098m18%m5%6.7m10m24 15127m216m6.2m23m29 30231m30m11&m340m44%Source:NCD-RisC(2024),UN population estimates(2024),and World Obesity Federation projections15World Obesity Atlas 2025Table 1.7:Numbers and prevalence of adults(age 20 )living with high BMI in the Western Pacific Region,2010,2015 and 2030MenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 2010161m25$m4%3.8m19 m30 15195m283m5%6.7m1#5m34 30294m39im9m385m51%WomenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 2010134m20&m4%5.5m16m24 15153m223m5%8.2m14m28 30199m26Wm8!m37m37%Source:NCD-RisC(2024),UN population estimates(2024),and World Obesity Federation projections1.3 Numbers and prevalence of high BMI in adults by World Bank income groups While the WHO regional figures indicate patterns that may reflect cultural as well as economic differences,the World Bank has classified countries into four income levels based on their gross national income per capita.We have calculated the numbers and prevalence of adults living with high BMI for each income level based on the data from the NCD-RisC estimates and the World Obesity projections to 2030.High income countries appear to be showing a plateau in their prevalence of overweight(BMI 25-30 kg/m2)that is not observed in the other income groups.Still,the overall prevalence of high BMI continues to rise in all income groups,with marked rises in the prevalence of obesity class II and above(BMI 35 kg/m2 and above).Table 1.8:Numbers and prevalence of adults(age 20 )living with high BMI in the World Bank Low Income Group,2010,2015 and 2030 MenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 201014.3m13%3.4m3%1.0m1m17 1517m14%4.3m4%1.3m1#m19 3035m17.5m6%4.6m2Qm25%WomenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 201017m15%6.0m5%2.6m2&m22 1522m17%8.0m6%3.6m34m26 3046m22!m10.1m5xm37%Source:NCD-RisC(2024),UN population estimates(2024),and World Obesity Federation projections16World Obesity Atlas 2025Table 1.9:Numbers and prevalence of adults(age 20 )living with high BMI in the World Bank Low-Middle Income Group,2010,2015 and 2030MenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 2010118m17m4%7.1m12m22 15156m198m5.7m1 5m25 30301m28m8)m3A7m39%WomenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 2010134m19Em6 m39m28 15171m22bm8(m4&1m34 30304m295m13fm6P5m48%Source:NCD-RisC(2024),UN population estimates(2024),and World Obesity Federation projectionsTable 1.10:Numbers and prevalence of adults(age 20 )living with high BMI in the World Bank Upper-Middle Income Group,2010,2015 and 2030MenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 2010250m28Xm6.5m222m36 15296m31vm8 m292m41 30424m390m13Qm5a5m57%WomenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 2010230m25m84m445m37 15260m270m19Em55m51 30338m311m15m8X7m54%Source:NCD-RisC(2024),UN population estimates(2024),and World Obesity Federation projectionsTable 1.11:Numbers and prevalence of adults(age 20 )living with high BMI in the World Bank High Income Group,2010,2015 and 2030 MenBMI 25-30 kg/m2BMI 30-35 kg/m2BMI 35 kg/m2All high BMI 2010187m38vm150m6)3m59 15195m38m166m716m61 30205m377m19Wm1069m66%WomenBMI 25-30 kg/m2BMI 30-40%Source:World Obesity Federation analyses of NCD-RisC(2024)data for 2022Figure 1.6:Estimated lifetime risk of BMI 35kg/m2 or higher during adulthood for womenMaximum prevalence(%)of BMI 35kg/m2 or more during adulthood,2022 data Key n 0-10%n 10-20%n 20-30%n 30-40%n 40%Source:World Obesity Federation analyses of NCD-RisC(2024)data for 202220World Obesity Atlas 2025The implications from these analyses are:1)that a larger fraction of the population is affected by obesity and its health consequences than is suggested in studies based on current BMI alone(Stokes et al,2017),and 2)BMI histories should form part of health surveillance of the obesity epidemic for a full evaluation of the effects of obesity on ill health and premature death.Section 2 Non-communicable diseases and high BMI21World Obesity Atlas 202522World Obesity Atlas 2025Section 2:Non-communicable diseases and high BMIOver 17 million people aged under 70 years died from NCDs in 2021,and 11 million of these deaths were attributable to known avoidable risks.A high BMI accounted for 15%of these preventable premature deaths.This rises considerably for specific NCDs,such as type 2 diabetes,for which 55%of preventable premature deaths are attributable to high BMI.Similarly,living with chronic ill health from NCDs is also linked to high BMI:27%of the 161 million adult person-years of avoidable ill health from NCDs in 2021 can be attributed to high BMI.In addition to the World Health Assembly 2025 target of reducing premature mortality from four major NCDs by 25%,the Sustainable Development Goals added a target to reduce by one third premature mortality from non-communicable diseases through prevention and treatment.On present trends,neither target is likely to be met.High BMI plays a significant role in perpetuating the risk of non-communicable disease and it is unlikely that targets will be met without action on overweight and obesity.The 2025 target NCDs are diabetes,cardiovascular disease(including heart disease and stroke),cancers and chronic respiratory diseases.The last is primarily a result of air pollution and tobacco smoking,but the risk of suffering from the other priority NCDs is significantly increased in individuals living with a high BMI.A high BMI is defined as a BMI of 25 kg/m2 or greater.Two measures are reported in this section of the Atlas:1)Premature death(before age 70 years)due to NCDs:Variations between countries and regions may primarily reflect the availability and access to medical interventions alongside the rising incidence of disease.2)Adult years living with disability/ill health(YLD)due to NCDs:Variations between countries may primarily reflect the level of exposure to risk(e.g.the causes of weight gain,poor diet or physical inactivity)alongside improved access to medical interventions.High BMI contributes to a wide range of conditionsIn this Atlas,we focus on four major NCDs:cancers,ischaemic heart disease,stroke,and type 2 diabetes.These key NCDs are the targets for improvement under the World Health Assembly 2025 targets(along with chronic respiratory disease,which is mostly attributable to tobacco use and air pollution).A high BMI is also a risk factor for developing several additional NCDs including liver disease,kidney disease and musculoskeletal disorders(including osteoarthritis and chronic back pain),and contributes to neurological disorders(dementia,Alzheimers)and poor mental health(including depression).High BMI is also a risk factor for communicable diseases:for example,increasing the severity of ill health following infection with SARS-CoV-2.23World Obesity Atlas 20252.1 Global trends in NCDsAs noted,there is little likelihood of meeting the World Health Assemblys global targets for 2025 or the SDG targets for 2030,which require substantial reductions in premature deaths from major NCDs.As Figure 2.1 shows,the trends for death rates(per 100,000 population)for the four NCDs we focus on in this Atlas have remained virtually unchanged since the targets were set.This implies that access to treatment services were not improving significantly during the period shown,or were being overtaken by rising numbers of incidents.Figure 2.1:Deaths per 100,000 of people aged under 70 years for four NCDs,2010-2021 201020112012201320142015201620172018201920202021010203040506070 Key n Cancers n Ischaemic heart disease n Stroke n Type 2 diabetesSource:Institute for Health Metrics(2024)Furthermore,the trends for the numbers of adults living with ill health due to the major NCDs(Figure 2.2)show a similar constant rate per 100,000 adults,with the exception of type 2 diabetes,which shows a significant rise over the period.This suggests that the exposure to the risk factors leading to the development of these diseases has not reduced,and in the case of diabetes is increasing.A failure to adequately address the continued rise in the prevalence of high BMI is likely to be a major contributor to these trends.24World Obesity Atlas 2025Figure 2.2:Person-years lived with ill health(rate per 100,000 adults over age 20 years),2010-2021 2010201120122013201420152016201720182019202020210100200300400500600700 Key n Cancers n Ischaemic heart disease n Stroke n Type 2 diabetesSource:Institute for Health Metrics(2024)2.2 The relative importance of high BMI in the likelihood of developing four major NCDsA paper by Zhou et al(2024)found the number of deaths and years lived with a disease that could have been prevented with reduced prevalence of high BMI more than doubled over the three decades 1990-2021.In this section,we use the same database to look at high BMI and other risk factors for the development of chronic diseases,primarily four of the major NCDs:cancers,ischaemic heart disease,stroke and type 2 diabetes.The tables below show that high BMI ranks among the major risk factors for both premature death(Tables 2.1 and 2.2)and for years lived with ill health(Tables 2.3 and 2.4).It is important to note that the risk factors for disease are not exclusive.This means that(a)the different risk factors may enhance each others effects,and(b)the risk factors may be causally associated with each other.For example,a high BMI raises the likelihood of high blood pressure,while several dietary risks can increase the likelihood of both high blood pressure and high BMI.25World Obesity Atlas 2025Table 2.1:Ranking of the top 15 risk factors for premature deaths from four major NCDs,2021RankCancersIschaemic Heart Disease StrokeType 2 Diabetes 1TobaccoHigh systolic blood pressureHigh systolic blood pressureHigh fasting plasma glucose2High alcohol useHigh LDL cholesterolAir pollutionHigh body-mass index3Air pollutionAir pollutionTobaccoAir pollution4High body-mass indexTobaccoDiet high in sodiumTobacco5Occupational risksDiet low in whole grainsHigh LDL cholesterolDiet high in processed meat6High fasting plasma glucoseHigh body-mass indexKidney dysfunctionNon-optimal temperature7Diet high in red meatHigh fasting plasma glucoseDiet low in fruitsLow physical activity8Diet low in whole grainsKidney dysfunctionHigh fasting plasma glucoseDiet low in whole grains9Diet low in milkDiet low in omega-6 polyunsaturated fatty acidsNon-optimal temperature Diet low in fruits10Diet low in calciumDiet low in fruitsHigh alcohol useDiet high in red meat11Diet high in sodiumDiet low in nuts and seedsHigh body-mass indexDiet high in sugar-sweetened beverages12Drug useDiet low in seafood omega-3 fatty acidsDiet low in fibreHigh alcohol use13Diet low in fruitsDiet high in sodiumDiet low in whole grainsDiet low in vegetables14Diet low in vegetablesDiet low in fibreDiet low in vegetablesDiet low in fibre15Low physical activityNon-optimal temperature Low physical activitySource:Institute for Health Metrics(2024)It is notable how many of the risk factors for premature deaths from cancer,ischaemic heart disease,stroke and type 2 diabetes are causally related to each other,especially to high BMI.It is also striking how much the risk factors overlap across the four NCDs.This reinforces the argument that successful action on global NCDs requires cohesive action across disease groups.Obesity is one of the few NCDs among the ranking of“risk factors”for major NCDs.Therefore,halting and reducing obesity prevalence is critical for achieving global NCD targets.The Institute for Health Metrics and Evaluation has also provided estimates of the extent to which specific numbers of deaths and years with ill health can be attributed to various risk factors,including high BMI.Table 2.2 shows that 15%of all premature NCD deaths which can be attributed to risk factors are attributable to high BMI.This rises to 55%of deaths from type 2 diabetes.26World Obesity Atlas 2025Table 2.2:Estimated number of premature deaths from NCDs,2021DeathsDeaths from known risks of which high BMIHigh BMI as%of deaths from known risksCancers 5.0m2.1m0.2m9%Ischaemic heart disease3.2m3.0m0.5m16%Stroke2.4m2.1m0.1m7%Type 2 Diabetes 0.7m0.7m0.4m55%Other NCDs6.0m2.8m0.4m16%All NCDs17.3m10.7m1.6m15%Source:World Obesity Federation analysis of data from the Institute for Health Metrics(2024)The data in column 4 of Table 2.2(premature deaths attributable to high BMI)can also be shown as a stacked graphic(Figure 2.3).Here,we can see how over 1.6 million premature deaths from NCDs are attributable to high BMI.Figure 2.3:Estimated impact of high BMI on the number of premature deaths from NCDs,2021 00.2M0.4M0.6M0.8M1M1.2M1.4M1.6M Key n Type 2 diabetes n Stroke n Ischaemic heart disease n Cancers n Other NCDsSource:Institute for Health Metrics and Evaluation(2024)(estimates for 2021)As well as looking at the ranking of risk factors for premature deaths from cancers,ischaemic heart disease,stroke and type 2 diabetes,we can also look at the equivalent ranking for years living with ill health due to these diseases.Table 2.3 shows how high BMI features second for both cancers and type 2 diabetes,while also sitting in the top 10 for ischaemic heart disease and stroke.Millions27World Obesity Atlas 2025Table 2.3:Ranking of the top 15 risk factors for adult years living with ill health due to four major NCDs,2021RankCancersIschaemic Heart Disease StrokeType 2 Diabetes 1TobaccoHigh systolic blood pressureHigh systolic blood pressureHigh fasting plasma glucose2High body-mass indexHigh LDL cholesterolHigh LDL cholesterolHigh body-mass index3Diet high in red meatAir pollutionAir pollutionAir pollution4High alcohol useTobaccoTobaccoTobacco5High fasting plasma glucoseHigh fasting plasma glucoseHigh fasting plasma glucoseDiet high in processed meat6Diet low in whole grainsDiet low in whole grainsDiet high in sodiumDiet low in whole grains7Diet low in milkKidney dysfunctionKidney dysfunctionLow physical activity8Occupational risksHigh body-mass indexHigh body-mass indexDiet high in red meat9Air pollutionDiet low in omega-6 polyunsaturated fatty acidsOther environmental risks Diet high in sugar-sweetened beverages10Low physical activityDiet high in sodiumHigh alcohol useDiet low in fruits11Diet high in processed meatDiet low in nuts and seedsDiet low in fruitsHigh alcohol use12Diet low in calciumDiet low in seafood omega-3 fatty acidsDiet low in whole grainsDiet low in fibre13Diet high in sodiumDiet low in fruitsLow physical activityDiet low in vegetables14Other environmental risks Other environmental risks Diet low in fibre15Drug useDiet low in fibreDiet low in vegetablesSource:Institute for Health Metrics(2024)As with the leading risk factors for premature deaths from the listed NCDs,it is notable how many of the risk factors for living with ill health are causally related to each other,especially to high BMI.There is also significant overlap of the major risk factors across the four NCDs again.It is clear that reducing ill health and death from key NCDs requires cohesive action across disease groups.Table 2.4 provides estimates of the extent to which specific numbers of years with ill health can be attributed to various risk factors,including high BMI.Overall,27%of adult years living with ill health from NCDs which can be attributed to risk factors are attributable to high BMI.This rises to 55%of years living with ill health from type 2 diabetes.Figure 2.4 depicts the years living with ill health attributable to high BMI as a stacked graphic and shows how over 40 million adult person-years of ill health from NCDs are attributable to high BMI.28World Obesity Atlas 2025Table 2.4:Estimated number(millions)of adult-years living with ill health from NCDs,2021Years of ill health Years of ill health from known risks of which high BMIHigh BMI as%of ill health from known risksCancers 7.9m2.6m0.4m16%Ischaemic heart disease4.1m3.7m0.5m14%Stroke14.8m12.7m1.1m9%Type 2 Diabetes39.6m39.6m21.8m55%Other NCDs577.8m102.6m20.5m20%All NCDs644.2m161.1m44.3m27%Source:World Obesity Federation analysis of data from the Institute for Health Metrics(2024)Figure 2.4:Estimated impact of high BMI on the number of adult person-years lived with NCD-related ill health,202105M10M15M20M25M30M35M40M45M Key n Type 2 diabetes n Stroke n Ischaemic heart disease n Cancers n Other NCDsSource:Institute for Health Metrics and Evaluation(2024)2.3 Premature deaths and adult years of ill health attributable to high BMI by WHO regionThe number of premature deaths and adult years lived with ill health caused by select NCDs and attributable to high BMI are shown for each WHO region in Figures 2.5 and 2.6.Millions29World Obesity Atlas 2025Figure 2.5:Regional differences in the numbers of premature deaths attributable to high BMI,2021African RegionEastern Mediterranean Region European RegionRegion of the Americas South-East Asia RegionWestern Pacific Region050k100k150k200k250k300k Key n Type 2 diabetes n Stroke n Ischaemic heart disease n Cancers n Other NCDsSource:Institute for Health Metrics and Evaluation(2024)Figure 2.6:Regional differences in the years of ill health among adults attributable to high BMI,2021African RegionEastern Mediterranean Region European RegionRegion of the Americas South-East Asia RegionWestern Pacific Region02M4M6M8M10M Key n Type 2 diabetes n Stroke n Ischaemic heart disease n Cancers n Other NCDsSource:Institute for Health Metrics and Evaluation(2024)ThousandsMillions30World Obesity Atlas 20252.4 Premature deaths and years of ill health by World Bank income levelBy far the greatest number of premature deaths attributable to high BMI are in lower and upper middle-income countries indicating poor levels of treatment available.This is illustrated in Figure 2.7.Figure 2.7:National income levels and premature deaths attributable to high BMI,2021World Bank Low IncomeWorld Bank Lower Middle IncomeWorld Bank Upper Middle IncomeWorld Bank High Income0100k200k300k400k500k600k Key n Type 2 diabetes n Stroke n Ischaemic heart disease n Cancers n Other NCDsSource:Institute for Health Metrics and Evaluation(2024)Figure 2.8 indicates that large numbers of person-years lived with ill health can be attributed to high BMI,especially in upper-middle and high income countries,indicating accessible treatment but poor prevention.Figure 2.8:National income levels and years of ill health among adults attributable to high BMI,2021World Bank Low IncomeWorld Bank Lower Middle IncomeWorld Bank Upper Middle IncomeWorld Bank High Income02M4M6M8M10M12M14M16M18M Key n Type 2 diabetes n Stroke n Ischaemic heart disease n Cancers n Other NCDs Source:Institute for Health Metrics and Evaluation(2024)ThousandsMillionsSection 3 Changing systems,healthier lives31World Obesity Atlas 202532World Obesity Atlas 2025Section 3:Changing systems,healthier livesSections 1 and 2 have outlined the scale of the challenge we face and have emphasised the role of obesity in deaths and diseases related to other major NCDs.It is clear that achieving the WHO and SDG targets for obesity and NCDs requires urgent action both on policy,to address multiple risk factors,as well as in healthcare to ensure people living with obesity and other NCDs can access the services they need.To halt the rise of obesity and associated NCDs,we need to critically examine underlying systems and implement policy and system changes to address the major gaps.This section provides an overview of the types of policies needed to address obesity and NCDs,as well as national level data of the indicators we can use to monitor progress and demand action.The second part presents a new multisector framework from WHO(part of the Technical Package to Stop Obesity)with priority actions and recommended interventions,selected for their proven impact and cost effectiveness,which can help accelerate action on obesity and NCDs.3.1 Health systemsEvidence of health systems readiness to provide access to NCD prevention and management services can be inferred from available data on the rates of premature deaths from NCDs and on the prevalence of type 2 diabetes that is untreated.National estimates of these indicators from the WHO Global Health Observatory are given in the tables at the end of this section.The distribution of untreated Type 2 diabetes across regions can be seen in the map Figure 3.1.This graphic illustrates that the vast majority of the worlds population live in countries where over 30%of type 2 diabetes patients are not being treated for the disease(see data in Table 3.1 at the end of this section).Exceptions to this are Belgium,Costa Rica,Finland,Jordan,Poland and Portugal.This map also shows the differences in access to treatment between countries,with patients in low-and middle-income countries(for example in Africa and Asia)much less likely to be receiving treatment for type 2 diabetes.As shown in Section 1,it is in these regions that obesity,and the prevalence of obesity-related NCDs like type 2 diabetes,are rising fastest.World Obesity Day 2025Underlying the global rise in obesity rates are failing systems:health systems that are ill-equipped to care for people with obesity and perpetuate bias and stigma;food systems where multinational corporations produce unhealthy food and then spend billions advertising it to people;political systems that are based on outdated health data and an oversimplified obesity narrative;planning and transport systems that discourage people from active travel and being physically active.We must work together to call for change to these systems,and people living with obesity are leading this call.33World Obesity Atlas 2025Figure 3.1:Global distribution of untreated type 2 diabetes,2022Percentage of adults with type 2 diabetes who are not being treated Key n 10-30%n 30-40%n 40-50%n 50-60%n 60-70%n 70-80%n 80%Source:WHO Global Health Observatory 2024(data for 2022)In Tables 3.1 and 3.2 we present indicators to understand the capacity of health systems(measured through the UHC NCD Index)as well as the outcomes they deliver(percentage of people with diabetes who are untreated and percentage of people with NCDs dying prematurely).We also document which countries have national guidelines/protocols/standards for the management of overweight/obesity and for NCD management in primary care(see Section 3.4).Data on the coverage of obesity services globally is currently not collected but barriers to access are widespread across countries of all income levels.World Obesitys Management and Advocacy for Providers,Patients and Systems(MAPPS)project found many barriers to treatment that need to be addressed to strengthen health systems to address obesity,see Figure 3.2(Jackson Leach et al,2024).These challenges are now being explored further in the projects second phase that aims to improve understanding of the global obesity policy and care landscape,including an analysis of differences across countries,regions,and income levels.34World Obesity Atlas 2025Figure 3.2:Global barriers to treatment Lack of political will,interest and actionLack of training and trained HCPsHigh cost of out-of-pocket paymentsPoor health literacy and behaviourObesity not recognised as a diseaseLack of financial investment into obesityStigmaFood cost and availabilityCultural norms/traditionsLack of evidence,monitoring and researchLast updated October 2019 by the World Obesity Federation;based on 274 responses3.2 Healthy environmentsRegular physical activity is an important part of obesity prevention and management.It can also decrease the risk of developing hypertension,several types of cancer,osteoporosis,type 2 diabetes,stroke and heart attacks,as well as help prevent dementia and depression(WHO,2018).Yet many people live in environments that do not promote physical activity and globally the world is not meeting minimum physical activity levels(see Figures 3.3 and 3.4).“Physical activity refers to all body movement.Popular ways to be active include walking,cycling,wheeling,sports,active recreation,and play,and can be done at any level of skill and for enjoyment by everybody.Yet,current global estimates show one in three adults and 81%of adolescents do not do enough physical activity.Furthermore,as countries develop economically,levels of inactivity increase and can be as high as 70%,while sitting time and screen time as forms of sedentary time increase due to changing transport patterns,increased use of technology for work and recreation,cultural values.”WHO,2024 WHO recommends a series of actions to change environments in the Global Action Plan on Physical Activity,including:strengthening policies to promote active transport;improving access to public and green open spaces;and providing programmes to support participation in physical activity by all people of diverse abilities(WHO,2024).Implementing tax incentives and subsidies to promote physical activity(for example,tax-free salary sacrifice schemes for bicycles,reduced tax on sporting goods,subsidies for extracurricular physical activity programmes,etc.)can also help enable people to reduce or manage the health risks around obesity and other NCDs.35World Obesity Atlas 2025National estimates of insufficient physical activity for adults are given in the country scorecards at the end of this Atlas.The distribution across regions can be seen in the maps at Figures 3.3 and 3.4.Figure 3.3:Proportion of men with insufficient physical activity,2022 Key n 50%Figure 3.4:Proportion of women with insufficient physical activity,2022 Key n 50%Source:WHO Global Health Observatory 2024(data for 2022)As revealed by these graphics,in countries where there is a gender difference in the percentage of adults with insufficient physical activity,the proportion of women is always higher than men.This highlights the need for gender-responsive policies and programmes,as part of efforts to promote and safeguard the rights of all people,of all ages,that encourage equitable access to engage in regular physical activity,according to ability.In Tables 36World Obesity Atlas 20253.2 and 3.3 we document the existence of national guidelines for physical activity and the management of physical inactivity,as well as if the country has any tax incentives to promote physical activity(also see summary in Section 3.4).3.3 Food systemsThe global rise in obesity since 2010 illustrated in Section 1 is strongly correlated with the increased consumption of unhealthy foods.In particular,it has been linked with the shift to diets high in ultra processed food(UPFs)during the same period and the consumption of sugar-sweetened beverages(Lane et al,2024).Besides increasing the risk of overweight and obesity,recent analyses suggest that the high consumption of sugar-sweetened beverages alone contributes to over 2 million type 2 diabetes cases and over 1 million cardiovascular disease cases annually(Lara-Castor et al,2025).Estimates by the Food and Agriculture Organization(FAO)of the UN suggest that the consequences of consuming diets rich in highly processed foods and low in plant-based foods are costing the world over$6 trillion annually in poor health,along with further costs to the environment and to social well-being(FAO et al,2024).Figure 3.5 shows the impact of diets high in processed foods globally on health costs.Figure 3.5:Estimated health costs due to diets high in processed foods,2024Health costs per capita,in US$purchase-power parity adjustedKey n 1000Source:The State of Food and Agriculture 2024.FAO:Rome,and UN population estimates for 2024.As demonstrated in Table 2.1(excerpt below),many risk factors related to unhealthy diets are associated with premature deaths from NCDs,highlighting the need for strong food system policies that will simultaneously address overweight and obesity.37World Obesity Atlas 2025Top diet-related risk factors for premature deaths from NCDs Diet high in sodium Diet low in whole grains Diet high in processed meat Diet high in sugar-sweetened beverages Diet low in fruit and vegetables3.4 Country comparisons:systems readinessUsing the latest data available,we report on national systems readiness to address obesity through 13 indicators(see below)including:evidence of national health systems ability to provide treatment for obesity and NCDs;to monitor progress towards meeting the national targets;and to implement policies for prevention and management.The full dataset can be found in Tables 3.1 to 3.3.Overall,only one country(Tonga)said yes to as many as 12 of the 13 combined indicators,while a further five countries(Mexico,India,United Kingdom,Finland and Malaysia)said yes to 11 of the 13 indicators.67 countries had none or only one of the 13 indicators scored as yes.3.4a Public health system readiness indicatorsNational guidelines/standards for:National adult survey in the last 5 years on:Management of high BMI:Existence of evidence-based national guidelines/protocols/standards for the management of overweight/obesityOverweight and obesity:Evidence of a recent,national adult risk factor survey covering overweight and obesityPhysical activity:Existence of national guidelines for physical activityUnhealthy diet:Evidence of a recent,national adult risk factor survey covering unhealthy dietManagement of physical inactivity:Existence of evidence-based national guidelines/protocols/standards for the management of physical inactivityPhysical inactivity:Evidence of a recent,national adult risk factor survey covering physical inactivityNCD management in primary care:Existence of evidence-based national guidelines/protocols/standards for the management of major NCDs through a primary care approachSTEPS or health examination:Evidence of a STEPwise approach to NCD risk factor surveillance(STEPS)survey or a comprehensive health examination survey every 5 years We collated the latest data from 2021 across eight indicators(see above)from the WHO Global Health Observatory.Concerningly,a third of the world 67 out of 194 countries had one or less indicator in place.The majority of these countries are in Sub-Saharan Africa alongside those affected by conflict(Pakistan,Syria and Myanmar)and small island developing states where obesity and NCD rates are rising fast.Only 13 countries answered yes to all indicators:Belarus,Bhutan,Canada,China,Finland,Iran,Malaysia,Russian Federation,Tonga,Turkey,Turkmenistan,United Kingdom,and Uzbekistan.However,it is important to note that the existence of guidelines or standards is not the same as implementation.Political,technical and resource challenges may hinder governments capacity to implement recommended actions.38World Obesity Atlas 2025Similarly,evidence of recent surveys does not mean that the data is necessarily utilised by policy makers and there may be a knowledge-action gap.This highlights the important role of civil society in all countries to demand accountability around public health measures to address obesity and NCDs.3.4b Policy readiness indicatorsUsing WHO databases(GIFNA,2024 and Global Health Obeservatory,2024)we collated the latest data(also from 2021)on the existence of five policies to promote healthy diets and physical activity:1)Taxes on SSBs:Existence of tax on sugar-sweetened beverages2)Taxes on HFSS foods:Existence of tax on foods high in fats,saturated fats,sugars or salt3)Subsidies on healthier foods:Existence of price subsidies for healthy foods.4)Restrictions on marketing foods to children:Existence of policies to restrict childrens exposure to the promotional marketing of less healthy foods.5)Taxes to promote physical activity:Existence of tax incentives to promote physical activityWe found that no country had all five of the policies and actions in place and only 17 countries had three or four.Alarmingly,126 countries had either one policy or no policies at all in place to prevent obesity.These countries are mainly low-and middle-income countries.Several OECD countries are also not taking adequate policy action on obesity.On the other hand,most of the 17 countries with three or four policies in place are low-and middle-income:with four out of five indicators India,Mexico,Seychelles,and Tonga;with three out of five indicators Brazil,Brunei Darussalam,Ecuador,Fiji,Finland,Hungary,Latvia,Malaysia,Maldives,Portugal,Samoa,Tuvalu,and United Kingdom.While the existence of multiple policies is to be celebrated,the implementation and effectiveness of food system policies can be hindered by interference from multinational corporations(Slater et al,2024).It is essential that policymaking is free from conflicts of interest between policymakers and the food industry(Cullerton et al,2024).Food industry tactics including lobbying and blocking policies are a major barrier to comprehensive action on obesity in countries of all income levels(Chavez-Ugalde,2021).The fact that countries like Mexico,India and Brazil have food system policies to prevent obesity is testament to the role of civil society in advocating for,and successfully demanding,change.3.5 World Obesity Day 2025 The time for collective action is nowIt is crucial to understand that any number of these policies alone,or those focused on one system alone,will not be enough to reduce obesity and NCDs.As obesity has many complex and often interrelated causes,a comprehensive policy approach catalysing multi-sectoral action across health systems,food systems,communities and the environments in which people live and work is needed.The data presented in this Atlas is intended to help mobilise change across these systems and societies.The rising rates of obesity and NCDs signal the urgent need for coordinated,multi-sectoral action to address this growing public health crisis.The newly launched WHO Technical Package to Stop Obesity(WHO,2025)offers evidence-based interventions designed to enable healthier environments,empower individuals with knowledge and skills,and transform health systems to provide equitable and high-quality services.This comprehensive approach underscores the need to 39World Obesity Atlas 2025address the environmental,societal,and structural determinants of health that contribute to obesity.The package serves as a vital resource for countries seeking to develop integrated responses to obesity prevention and control.At its core,the WHO Technical Package outlines three strategic areas for transformation:1)Adapting environments to enable healthy lifestyles:This pillar focuses on creating supportive environments where healthy choices become easier and more accessible.Key measures include:Promoting breastfeeding and supporting mothers through appropriate policies.Reformulating food products to reduce unhealthy ingredients,such as salt,sugar,and trans fats.Regulating the marketing of unhealthy foods and beverages,especially those targeting children.Establishing and enforcing healthy public food procurement policies,ensuring that schools,hospitals,and public institutions provide nutritious food options.Fostering active environments by creating safe spaces for walking,cycling,and recreational activities.2)Creating knowledge,motivation,and skills for healthy behaviour:Public education and awareness campaigns are critical for promoting healthier behaviours.This strategic area includes:Conducting mass media campaigns to raise awareness about the benefits of a healthy diet and physical activity.Providing community-based programs that empower individuals to adopt healthier lifestyles.Offering tailored educational initiatives for specific groups,such as school-based health programs and workplace wellness initiatives.Supporting healthcare professionals with training and resources to effectively counsel patients on nutrition,physical activity,and weight management.3)Transforming health systems:Strengthening health systems to prevent and manage obesity across the life course is essential.Key actions include:Integrating obesity prevention and management services into primary healthcare settings.Ensuring access to equitable,high-quality care for individuals living with or at risk of obesity.Developing and implementing clinical guidelines for obesity management.Strengthening data systems to monitor and evaluate progress in obesity prevention and care.These interventions collectively form a systems-oriented approach aimed at addressing the root causes of obesity and supporting individuals in leading healthier lives.They highlight the interdependence of health systems,community environments,and individual behaviour in creating lasting change.Implementing this package can help ensure that health services are well-positioned to provide timely,culturally sensitive,and equitable care for those living with or at risk of obesity.As societies confront the growing challenges posed by obesity and its related health impact,the role of a systems approach becomes even more evident.Government,civil society,and private sector must collaborate to align health,agriculture,education,and urban planning policies toward shared health goals.Interventions should be interlinked and mutually reinforcing to ensure sustainable improvements.40World Obesity Atlas 2025World Obesity Day 2025s call to action,Changing systems,healthier lives,emphasises the necessity of pulling together sectors and strategies to implement a holistic and sustained response to obesity.Now more than ever,we need collective,systems-driven solutions to address one of the most pressing public health challenges of our time.Only through bold,transformative action can we create healthier,more equitable environments that support well-being for all.Table 3.1:National Systems Readiness Indicators:Health coverage indicators African RegionUHC NCD index,2021UHC NCD index change,2015-2021%people with diabetes who are untreated,2022%people with NCDs dying aged 70,2019Algeria60.710R6%Angola53.765hnin60.775c%Botswana60.174tY%Burkina Faso54.767r%Burundi59.396wqbo Verde56.775hDmeroon49.145pntral African Republic43.775i%Chad58.546p%Comoros56.057ie%Congo52.474c%Cote dIvoire58.657imocratic Republic of the Congo59.595yb%Equatorial Guinea50.274i%World Obesity Day 2025Addressing obesity is a critical step in reducing the global burden of chronic disease.The time for collective action is now.We need to transform our health systems,so they are better equipped to provide care for people living with obesity,and other related health issues.We need to challenge stigma in all areas of society.We need to transform food systems to deliver healthy diets.We need a built environment that gives people more opportunities to be active.Its time for us to demand change from governments,health systems,food companies,employers and media to fix these failing systems and to end the obesity crisis.41World Obesity Atlas 2025African RegionUHC NCD index,2021UHC NCD index change,2015-2021%people with diabetes who are untreated,2022%people with NCDs dying aged 70,2019Eritrea60.096qV%Eswatini624sY%Ethiopia52.496yU%Gabon53.84U%Gambia57.746f%Ghana70.516f%Guinea58.47h%Guinea-Bissau61.516p%Kenya50.916wq%Lesotho65.784te%Liberia53.056a%Madagascar45.7710wd%Malawi58.779f%Mali67.765h%Mauritania60.56Y%Mauritius61.34DG%Mozambique49.787i%Namibia64.714wT%Niger49.38p%Nigeria62.668ui%Rwanda44.018e%Sao Tome and Principe62.615W%Senegal55.656wa%Seychelles57.34HH%Sierra Leone54.729h%South Africa60.663c%South Sudan59.486wV%Togo56.97xp%Uganda54.56wp%United Republic of Tanzania50.728c%Zambia57.476i%Zimbabwe66.744wbBWorld Obesity Atlas 2025Region of the AmericasUHC NCD index,2021UHC NCD index change,2015-2021%people with diabetes who are untreated,2022%people with NCDs dying aged 70,2019Antigua and Barbuda65.71WA%Argentina61.041E3hamas66.550WUrbados72.180V(lize70.671YQ%Bolivia72.922a5%Brazil75.93GDnada84.0623&%Chile66.54461%Colombia75.763C4%Costa Rica84.983(7%Cuba71.213Q3%Dominica59.961c%n/aDominican Republic74.71SCuador73.221b8%El Salvador79.392E9%Grenada67.681XB%Guatemala625aS%Guyana66.812VR%Haiti63.08-1tW%Honduras79.222IC%Jamaica70.861b6%Mexico67.4348E%Nicaragua80.982FC%Panama73.913Q5%Paraguay67.413FG%Peru70.721f%Saint Kitts and Nevis67.761W%n/aSaint Lucia69.781c7%Saint Vincent and the Grenadines68.621BE%Suriname68.452RGCWorld Obesity Atlas 2025Region of the AmericasUHC NCD index,2021UHC NCD index change,2015-2021%people with diabetes who are untreated,2022%people with NCDs dying aged 70,2019Trinidad and Tobago 63.911aE%United States of America69.71142%Uruguay65.663G%Venezuela)80.334CCstern Mediterranean RegionUHC NCD index,2021UHC NCD index change,2015-2021%people with diabetes who are untreated,2022%people with NCDs dying aged 70,2019Afghanistan64.544vghrain57.312IT%Djibouti58.186w%Egypt62.370TU%Iran68.662aC%Iraq64.021DU%Jordan58.250(G%Kuwait60.415u%Lebanon54.161RB%Libya52.461WT%Morocco57.211bF%Oman58.22SP%Pakistan55.092sY%Qatar62.0625W%Saudi Arabia48.631Ie%Somalia60.566ph%Sudan53.595bU%Syrian Arab Republic65.421IH%Tunisia56.93G8%United Arab Emirates60.631By%Yemen61.592bDWorld Obesity Atlas 2025European RegionUHC NCD index,2021UHC NCD index change,2015-2021%people with diabetes who are untreated,2022%people with NCDs dying aged 70,2019Albania59.834%Andorra65.1129%n/aArmenia50.271p7%Austria68.8249 %Azerbaijan55.281bFlarus61.23D7lgium71.582!%Bosnia and Herzegovina62.37490%Bulgaria59.0940%Croatia61.81B%Cyprus64.8729%Czechia67.8827&nmark53.542A!%Estonia57.84G&%Finland67.022% %France64.911R%Georgia48.930c3%Germany73.4634$%Greece67.5551 %Hungary63.92352%Iceland80.3226!%Ireland65.842F$%Israel71.617$%Italy70.872D%Kazakhstan67.163WG%Kyrgyzstan60.593iT%Latvia58.62P%Lithuania57.653X%Luxembourg68.7542#%Malta75.335%Moldova54.270HH%Monaco69.3420%n/aMontenegro65.9432%Netherlands65.5844EWorld Obesity Atlas 2025European RegionUHC NCD index,2021UHC NCD index change,2015-2021%people with diabetes who are untreated,2022%people with NCDs dying aged 70,2019North Macedonia66.8930%Norway65.9245 %Poland72.75&3%Portugal73.9210 %Romania68.673D1%Russian Federation62.4825%San Marino67.5920%n/aSerbia62.8230%Slovakia66.441B3%Slovenia67.792$%Spain68.3521%Sweden63.844%Switzerland66.72%Turkiye65.960P6%Tajikistan52.951xU%Turkmenistan59.071c%Ukraine64.813V6%United Kingdom68.22H!%Uzbekistan62.970sV%South-East Asia RegionUHC NCD index,2021UHC NCD index change,2015-2021%people with diabetes who are untreated,2022%people with NCDs dying aged 70,2019Bangladesh51.085G%Bhutan47.0948mocratic Peoples Republic of Korea68.622bB%India53.788qT%Indonesia44.072wS%Maldives58.074E6%Myanmar50.38bW%Nepal46.388G%Sri Lanka59.682Y4%Thailand67.233XB%Timor-Leste47.45IFWorld Obesity Atlas 2025Western Pacific RegionUHC NCD index,2021UHC NCD index change,2015-2021%people with diabetes who are untreated,2022%people with NCDs dying aged 70,2019Australia71.87-15#%Brunei Darussalam66.671DTmbodia63.585b%China56.261W7%Cook Islands41.973e%n/aFiji39.082sd%Japan68.743C%Kiribati26.626ur%Laos55.846%Malaysia60.52XH%Marshall Islands36.44-1p%n/aMicronesia(Federated States of)15.82sw%Mongolia63.632e%Nauru43.36V%n/aNew Zealand70.321D$%Niue44.791e%n/aPalau383V%n/aPapua New Guinea36.176wq%Philippines62.053qR%Republic of Korea75.9645(%Samoa34.363XY%Singapore77.371DF%Solomon Islands32.883d%Tonga25.61fI%Tuvalu34.763%n/aVanuatu323h%Vietnam57.64pBGWorld Obesity Atlas 2025Table 3.2:National Systems Readiness Indicators:Public health system readiness indicatorsAfrican Regionnational guidelines/standards for national adult survey in the last 5 years the management of high BMI physical activity the management of physical inactivity.NCD management in primary care covering overweight and obesity.covering unhealthy diet covering physical inactivity STEPS or health examinationAlgeriaNoYesNoYesYesYesYesNoAngolaNon/aNoNoNoNoNoNoBeninNon/aNoYesNoNoNoNoBotswanaNon/aNoYesNoNoNoNoBurkina FasoNon/aNoYesYesYesYesNoBurundiNon/aNoNoNoNoNoNoCabo VerdeNon/aNoNoYesYesYesNoCameroonNon/aNoNoNoNoNoNoCentral African RepublicNon/aNoNoNoNoNoNoChadNon/aNoNoNoNoNoNoComorosNon/aNoNoNoNoNoNoCongoNon/aNoNoNoNoNoNoCote dIvoireNoYesNoNoYesYesYesNoDemocratic Republic of the CongoNon/aNoNoNoNoNoNoEquatorial GuineaNon/aNoNoNoNoNoNoEritreaNon/aNoNoNoNoNoNoEswatiniNon/aNoNoNoNoNoNoEthiopiaYesn/aYesYesNoNoNoNoGabonNon/aNoNoNoNoNoNoGambiaNon/aNoNoNoNoNoNoGhanaNon/aNoYesNoNoNoNoGuineaYesn/aYesNoNoNoNoNoGuinea-BissauNon/aNoNoNoNoNoNoKenyaNoYesYesYesNoNoNoNoLesothoNon/aNoYesNoNoNoNoLiberiaNon/aNoNoNoNoNoNoMadagascarNon/aNoYesNoNoNoNoMalawiNon/aNoYesYesYesYesNoMaliNon/aNoNoNoNoNoNoMauritaniaNon/aNoNoNoNoNoNoMauritiusNon/aNoYesNoNoNoNo48World Obesity Atlas 2025African Regionnational guidelines/standards for national adult survey in the last 5 years the management of high BMI physical activity the management of physical inactivity.NCD management in primary care covering overweight and obesity.covering unhealthy diet covering physical inactivity STEPS or health examinationMozambiqueNon/aNoNoNoNoNoNoNamibiaNon/aNoNoNoNoNoNoNigerNon/aNoNoYesYesYesNoNigeriaNon/aNoNoNoNoNoNoRwandaYesn/aNoYesNoNoNoNoSao Tome and PrincipeNon/aNoNoYesYesYesNoSenegalNon/aNoYesNoNoNoNoSeychellesNon/aNoYesNoNoNoNoSierra LeoneNon/aNoNoNoNoNoNoSouth AfricaNon/aNoYesYesYesNoNoSouth SudanNon/aNoYesNoNoNoNoTanzaniaNoYesNoYesNoNoNoNoTogoNon/aNoNoNoNoNoNoUgandaNon/aNoYesNoNoNoNoZambian/an/aNoYesYesYesYesNoZimbabweNon/aNoNoNoNoNoNoRegion of the Americasnational guidelines/standards for national adult survey in the last 5 years the management of high BMI physical activity the management of physical inactivity.NCD management in primary care covering overweight and obesity.covering unhealthy diet covering physical inactivity STEPS or health examinationAntigua and BarbudaNon/aNoNoNoNoNoNoArgentinaYesn/aYesYesYesYesYesYesBahamasNon/aNoNoYesYesYesNoBarbadosNoYesNoNoNoNoNoNoBelizeNon/aNoNoNon/an/aNoBoliviaNon/aNoYesYesYesYesNoBrazilYesYesYesYesYesYesYesNoCanadaYesYesYesYesYesYesYesYesChileYesYesYesYesYesYesYesNoColombiaYesYesYesYesNoNoNoNoCosta RicaYesn/aYesYesYesYesYesNoCubaYesYesYesYesNoNoNoNoDominicaNon/aNoNoNoNoNoNo49World Obesity Atlas 2025Region of the Americasnational guidelines/standards for national adult survey in the last 5 years the management of high BMI physical activity the management of physical inactivity.NCD management in primary care covering overweight and obesity.covering unhealthy diet covering physical inactivity STEPS or health examinationDominican RepublicYesn/aNoYesYesNoYesNoEcuadorn/aYesn/aNoYesYesYesYesEl SalvadorYesYesYesYesNoNoNoNoGrenadaNon/aNoNoNoNoNoNoGuatemalaYesYesYesYesNoNoNoNoGuyanaNon/aNoNoYesYesYesNoHaitiNon/aNoYesNoNoNoNoHondurasNoDont knowNoNoNoNoNoNoJamaicaYesYesYesYesYesYesYesNoMexicoYesYesYesYesYesYesYesNoNicaraguaNon/aNoYesNoNoNoNoPanamaYesn/aYesNoYesYesYesNoParaguayNon/aNoYesNoNoNoNoPeruYesYesYesNoYesYesNoNoSaint Kitts and NevisNon/aNoYesNoNoNoNoSaint LuciaNon/aNoNoYesYesYesYesSaint Vincent and the GrenadinesNoYesNoYesNoNoNoNoSurinameNon/aNoNoNoNoNoNoTrinidad and Tobagon/an/an/an/aNoNoNoNoUnited States of American/aYesYesYesYesYesYesYesUruguayNoYesYesNoNoNoNoNoVenezuelaNoYesNoYesNoNoNoNoEastern Med.Regionnational guidelines/standards for national adult survey in the last 5 years the management of high BMI physical activity the management of physical inactivity.NCD management in primary care covering overweight and obesity.covering unhealthy diet covering physical inactivity STEPS or health examinationAfghanistanNon/aNoNoYesYesYesNoBahrainYesYesYesYesYesYesYesNoDjiboutiNon/aNoNoNoNoNoNoEgyptn/an/aNoYesYesYesYesYesIranYesYesYesYesYesYesYesYes50World Obesity Atlas 2025Eastern Med.Regionnational guidelines/standards for national adult survey in the last 5 years the management of high BMI physical activity the management of physical inactivity.NCD management in primary care covering overweight and obesity.covering unhealthy diet covering physical inactivity STEPS or health examinationIraqYesNoYesNoNoNoNoNoJordanYesYesYesNoYesYesYesNoKuwaitYesYesYesYesNoNoNoNoLebanonYesn/aNoYesYesYesYesNoLibyaNon/aNoNoNoNoNoNoMoroccoNon/aNoNoYesYesYesYesOmanNoYesNoYesYesYesYesNoPakistanNon/aNoNoYesNoNoNoQatarYesYesYesYesNoNoNoNoSaudi ArabiaYesYesYesYesYesYesYesNoSomaliaNon/aNoNoNoNoNoNoSudanNon/aNoYesYesYesYesYesSyrian Arab RepublicNon/aNoYesNoNoNoNoTunisiaYesYesYesNoYesYesYesNoUnited Arab EmiratesYesYesNoYesYesYesYesYesYemenNon/aNoNoNoNoNoNoEuropean Regionnational guidelines/standards for national adult survey in the last 5 years the management of high BMI physical activity the management of physical inactivity.NCD management in primary care covering overweight and obesity.covering unhealthy diet covering physical inactivity STEPS or health examinationAlbaniaYesn/aYesYesYesYesYesNoAndorraNoYesNoNoNoNoNoNoArmeniaYesYesYesNoYesYesYesYesAustriaNoYesYesNoYesYesYesNoAzerbaijanNoNoYesYesYesYesYesYesBelarusYesYesYesYesYesYesYesYesBelgiumn/an/an/aYesYesNoYesYesBosnia and HerzegovinaYesYesYesYesNoNoNoNoBulgariaYesn/aYesYesYesYesYesNoCroatiaNoYesNoYesYesYesYesNoCyprusn/aYesn/an/an/an/an/an/aCzechiaYesn/aYesYesYesYesYesNoDenmarkYesYesYesYesYesYesYesNo51World Obesity Atlas 2025European Regionnational guidelines/standards for national adult survey in the last 5 years the management of high BMI physical activity the management of physical inactivity.NCD management in primary care covering overweight and obesity.covering unhealthy diet covering physical inactivity STEPS or health examinationEstoniaYesYesYesYesYesNoYesNoFinlandYesYesYesYesYesYesYesYesFranceYesYesYesYesNoNoNoNoGeorgiaYesn/aNoYesYesYesYesYesGermanyYesYesYesYesNoYesYesNoGreeceNoYesNoYesYesYesYesNoHungaryYesn/aNoYesYesYesYesNoIcelandYesYesYesYesYesYesYesNoIrelandYesYesYesYesYesYesYesNoIsraelYesYesYesNoNoNoYesNoItalyYesYesYesNoNoYesYesYesKazakhstanYesn/an/aYesNoNoNoNoKyrgyzstanNoYesNoYesNoNoNoNoLatviaNoYesYesYesYesYesYesNoLithuaniaYesYesYesYesYesYesYesNoLuxembourgNoYesNoYesYesYesYesYesMaltaNoYesNoNoYesYesYesNoMoldovaYesn/aYesYesNoYesNoNoMonacoNon/aNoNoNoNoNoNoMontenegroNon/aNon/aNoNoNoNoNetherlandsYesYesYesYesYesYesYesNoNorth MacedoniaNoYesn/aYesNoNoNoNoNorwayYesYesYesYesNoNoNoNoPolandNoYesNon/aYesYesYesNoPortugalYesYesYesYesNoNoNoNoRomaniaYesYesYesYesYesYesYesNoRussian FederationYesYesYesYesYesYesYesYesSan MarinoNon/aNoNoNoNoNoNoSerbiaYesn/aNoYesYesYesYesNoSlovakiaNon/aNoYesYesYesYesNoSloveniaYesNoYesYesYesYesYesNoSpainYesYesYesYesYesYesYesNoSwedenNoYesYesYesYesYesYesNoSwitzerlandYesYesNoYesYesNoYesNoTurkiyeYesYesYesYesYesYesYesYes52World Obesity Atlas 2025European Regionnational guidelines/standards for national adult survey in the last 5 years the management of high BMI physical activity the management of physical inactivity.NCD management in primary care covering overweight and obesity.covering unhealthy diet covering physical inactivity STEPS or health examinationTajikistanNon/aNoYesNoYesYesYesTurkmenistanYesYesYesYesYesYesYesYesUkraineYesn/aYesYesYesYesYesYesUnited KingdomYesYesYesYesYesYesYesYesUzbekistanYesYesYesYesYesYesYesYesSouth-East Asia Regionnational guidelines/standards for national adult survey in the last 5 years the management of high BMI physical activity the management of physical inactivity.NCD management in primary care covering overweight and obesity.covering unhealthy diet covering physical inactivity STEPS or health examinationBangladeshNon/aNoNoYesYesYesNoBhutanYesYesYesYesYesYesYesYesDemocratic Peoples Republic of KoreaNon/aNoNoNoNoNoYesIndiaYesYesYesYesYesYesYesNoIndonesiaYesYesYesYesYesYesYesNoMaldivesNon/aNoNoNoNoNoNoMyanmarNon/aNoYesNoNoNoNoNepalNon/aNoNoYesYesYesYesSri LankaYesYesYesYesNoNoNoNoThailandYesYesYesYesYesYesYesNoTimor-LesteNon/aNoYesNoNoNoNoWestern Pacific Regionnational guidelines/standards for national adult survey in the last 5 years the management of high BMI physical activity the management of physical inactivity.NCD management in primary care covering overweight and obesity.covering unhealthy diet covering physical inactivity STEPS or health examinationAustraliaYesYesYesYesYesYesYesNoBrunei DarussalamYesYesYesYesNoNoYesNoCambodiaNon/aNoNoYesYesYesYesChinaYesYesYesYesYesYesYesYesCook IslandsNon/aNoNoNoNoNoNoFijiYesYesYesYesNoNoNoNoJapanYesYesYesNoYesYesYesYes53World Obesity Atlas 2025Western Pacific Regionnational guidelines/standards for national adult survey in the last 5 years the management of high BMI physical activity the management of physical inactivity.NCD management in primary care covering overweight and obesity.covering unhealthy diet covering physical inactivity STEPS or health examinationKiribatiNon/aNoNoNoNoNoNoLaosNon/aNoNoNoNoNoNoMalaysiaYesYesYesYesYesYesYesYesMarshall IslandsNon/aNoNoYesYesYesNoMicronesia(Federated States of)Yesn/aYesNoNoNoNoNoMongoliaNoYesNoYesYesYesYesYesNauruNon/aNoNoNoNoNoNoNew ZealandNoYesNoYesYesYesYesNoNiueNoDont knowNoNoNoNoYesNoPalauYesYesYesYesYesYesYesNoPapua New GuineaNon/aNoNoNoNoNoNoPhilippinesYesYesYesNoYesYesYesYesRepublic of KoreaYesYesYesNoYesYesYesNoSamoaNoYesNoYesNoNoNoNoSingaporeYesYesYesYesYesYesYesNoSolomon IslandsNon/aNoNoNoNoNoNoTongaYesYesYesYesYesYesYesYesTuvaluYesn/aYesNoNoNoNoNoVanuatuYesYesYesYesNoNoNoNoVietnamYesn/an/aYesYesYesYesYesTable 3.3:National Systems Readiness Indicators:Policy readiness indicatorsAfrican RegionTaxes on SSBsTaxes on HFSS foodsSubsidies on healthier foodsRestrictions on marketing foods to childrenTax incentives to promote physical activityAlgeriaNoNoNoNoNoAngolaNoNoNoNoNoBeninYesNoNoNoNoBotswanaNoNoNoNoNoBurkina FasoNoNoNoNoNo54World Obesity Atlas 2025African RegionTaxes on SSBsTaxes on HFSS foodsSubsidies on healthier foodsRestrictions on marketing foods to childrenTax incentives to promote physical activityBurundiYesNon/aNon/aCabo VerdeNoNoNoNoNoCameroonNoNoNoNoNoCentral African RepublicNoNoNoNoNoChadYesNon/aNon/aComorosNoNoNoNoNoCongoNoNoNoNoNoCote dIvoireYesNoNoNoNoDemocratic Republic of the CongoYesNon/aNoNoEquatorial Guinean/an/aNoNoNoEritreaNoNoNoNoNoEswatiniNoNoNoNoNoEthiopiaYesYesNoNoNoGabonNoNoNoNoNoGambiaYesNoNoNon/aGhanan/an/an/aNon/aGuineaNoNoNoNoNoGuinea-BissauNoNoNoNoNoKenyaYesNoNoNoNoLesothoNoNoNoNoNoLiberiaYesNoYesNoNoMadagascarYesNoNoNoNoMalawiYesNon/aNon/aMaliYesNoYesNoNoMauritaniaYesYesNoNoNoMauritiusYesYesNoNoNoMozambiqueNoNoNoNoNoNamibiaNoNoNoNoNoNigerYesNoNoNoNoNigeriaYesYesNoNoNoRwandaYesNoNoNoNo55World Obesity Atlas 2025African RegionTaxes on SSBsTaxes on HFSS foodsSubsidies on healthier foodsRestrictions on marketing foods to childrenTax incentives to promote physical activitySao Tome and PrincipeYesNoNoNoNoSenegalYesYesNoNoNoSeychellesYesNoYesYesYesSierra LeoneNoNoNoNoNoSouth AfricaYesNoNoYesNoSouth SudanNoNoNoNoNoTanzaniaYesNoNoNoNoTogoYesNoNoNoNoUgandaYesNoNoNoNoZambiaYesNoNoNoNoZimbabweNoNoNoNoNoRegion of the AmericasTaxes on SSBsTaxes on HFSS foodsSubsidies on healthier foodsRestrictions on marketing foods to childrenTax incentives to promote physical activityAntigua and BarbudaNoNoNoNoNoArgentinaYesNoYesNoNoBahamasNoNoNoNoYesBarbadosYesNoNoNoNoBelizeYesNoNoNoNoBoliviaYesNoNoNoNoBrazilYesNoNoYesYesCanadaNoNoNoYesYesChileYesNoNoYesNoColombiaNoNoNoYesNoCosta RicaYesNoNoYesNoCubaNoNoYesNoNoDominicaYesNoYesNon/aDominican RepublicNoNoNoNoNoEcuadorYesYesNoYesNoEl SalvadorYesNoNoYesNoGrenadaNoNoNoNoNo56World Obesity Atlas 2025Region of the AmericasTaxes on SSBsTaxes on HFSS foodsSubsidies on healthier foodsRestrictions on marketing foods to childrenTax incentives to promote physical activityGuatemalaYesNoNoNoNoGuyanaNoNoNoNoNoHaitiNoNoNoNoNoHondurasYesNoNoNoNoJamaicaNoNoNoNoNoMexicoYesYesNoYesYesNicaraguaYesNoNoNoNoPanamaYesNoNoYesNoParaguayYesNoNoNoNoPeruYesNoNoYesNoSaint Kitts and NevisYesNoNoNoNoSaint LuciaNoNoNoNoNoSaint Vincent and the GrenadinesYesYesNoNoNoSurinameYesNoNoNoNoTrinidad and TobagoNoNoNoNoNoUnited States of AmericaNoNoYesYesNoUruguayYesNoNoYesNoVenezuelaNoNoNon/aNoEastern Mediterranean RegionTaxes on SSBsTaxes on HFSS foodsSubsidies on healthier foodsRestrictions on marketing foods to childrenTax incentives to promote physical activityAfghanistanYesYesNoNoNoBahrainYesNoNoYesNoDjiboutiNoNoNoNoNoEgyptNoNoNoNoNoIranYesNoNoYesNoIraqNoNoNoNoNoJordanNoNoNoNoNoKuwaitNoNoYesYesn/aLebanonNoNoNoNoNo57World Obesity Atlas 2025Eastern Mediterranean RegionTaxes on SSBsTaxes on HFSS foodsSubsidies on healthier foodsRestrictions on marketing foods to childrenTax incentives to promote physical activityLibyaNoNoNoNoNoMoroccoYesNoNoYesNoOmanYesNoNoYesNoPakistanYesNoNoNoNoQatarYesNoNoNoNoSaudi ArabiaYesNoNoYesNoSomaliaNoNoNoNoNoSudanNoNoNoNoNoSyrian Arab RepublicNoNoNoNoNoTunisiaYesYesn/aNon/aUnited Arab EmiratesYesNoNoYesNoYemenn/an/an/aNon/aEuropean RegionTaxes on SSBsTaxes on HFSS foodsSubsidies on healthier foodsRestrictions on marketing foods to childrenTax incentives to promote physical activityAlbaniaYesNoNoYesNoAndorraNoNoNoNoNoArmeniaNoNoNoNoNoAustriaNoNoNoYesNoAzerbaijanNoNoNoYesNoBelarusNoNoNoYesNoBelgiumYesNoNoYesNoBosnia and HerzegovinaNoNoNoYesNoBulgariaNoNoNoYesNoCroatiaYesNoNoYesNoCyprusn/an/an/aNon/aCzechiaNoNoNoYesNoDenmarkNoNoNoYesNoEstoniaNoNoNoYesYesFinlandYesYesNoYesNoFranceYesNoNoYesNo58World Obesity Atlas 2025European RegionTaxes on SSBsTaxes on HFSS foodsSubsidies on healthier foodsRestrictions on marketing foods to childrenTax incentives to promote physical activityGeorgiaNoNoNoNoNoGermanyNoNoNoYesYesGreeceNoNoNoYesNoHungaryYesYesNoYesNoIcelandNoNoNoYesYesIrelandYesNoNoYesNoIsraelNoNoNoYesNoItalyNoNoNoYesYesKazakhstanNoNoNoNoNoKyrgyzstanNoNoNoNoNoLatviaYesNoYesYesNoLithuaniaNoNoNoYesNoLuxembourgNoNoNoYesn/aMaltaNoNoNoYesYesMoldovaNoNoNoYesNoMonacoYesNoNoNoNoMontenegroYesNoNoNoNoNetherlandsNoNoNoYesNoNorth MacedoniaNoNoNoNoNoNorwayNoNoNoYesNoPolandYesNoNoYesNoPortugalYesYesNoYesNoRomaniaNoNoNoNoNoRussian FederationNoNoNoYesNoSan MarinoNoNoNoNoNoSerbiaNoNoNoYesNoSlovakiaNoNoNoNoNoSloveniaNoNoNoYesNoSpainNoNoYesYesNoSwedenNoNoNoYesNoSwitzerlandNoNoNoYesNoTurkiyeYesNoNoYesNo59World Obesity Atlas 2025European RegionTaxes on SSBsTaxes on HFSS foodsSubsidies on healthier foodsRestrictions on marketing foods to childrenTax incentives to promote physical activityTajikistanYesNon/aYesNoTurkmenistann/an/an/aNon/aUkraineNoNoNoNoNoUnited KingdomYesNoNoYesYesUzbekistanNoNoNoYesNoSouth-East Asia RegionTaxes on SSBsTaxes on HFSS foodsSubsidies on healthier foodsRestrictions on marketing foods to childrenTax incentives to promote physical activityBangladeshYesYesNoNoNoBhutanNoNoNoNoNoDemocratic Peoples Republic of KoreaNoNoNoNoNoIndiaYesYesYesYesNoIndonesiaNoNoNoNoNoMaldivesYesYesNoYesNoMyanmarNoNoNoNoNoNepalNoNoNoNoNoSri LankaYesNoNoNoNoThailandYesNoNoYesNoTimor-LesteNoNoNoNoNoWestern Pacific RegionTaxes on SSBsTaxes on HFSS foodsSubsidies on healthier foodsRestrictions on marketing foods to childrenTax incentives to promote physical activityAustraliaNoNoNoYesNoBrunei DarussalamYesYesNoYesNoCambodiaNoNoNoNoNoChinaNoNoNoYesNoCook IslandsYesNoNoYesNoFijiYesYesYesNoNoJapanNoNoNoNoNoKiribatiYesNoNoYesNo60World Obesity Atlas 2025Western Pacific RegionTaxes on SSBsTaxes on HFSS foodsSubsidies on healthier foodsRestrictions on marketing foods to childrenTax incentives to promote physical activityLaosNoNoNoNoNoMalaysiaYesNoNoYesYesMarshall IslandsYesYesNoNoNoMicronesia(Federated States of)YesYesNoNoNoMongoliaNoNoNoYesNoNauruYesYesn/aNon/aNew ZealandNoNoNoNoNoNiueYesNoNoNoNoPalauNoNoNoNoNoPapua New Guinean/an/an/aNon/aPhilippinesYesNoNoYesNoRepublic of KoreaNoNoNoYesNoSamoaYesYesYesNoNoSingaporeNoNoNoYesNoSolomon IslandsYesNoNoNoNoTongaYesYesYesNoYesTuvaluYesYesYesNoNoVanuatuYesYesNoNoNoVietnamNoNoNoNoNoSection 4 Country scorecards61World Obesity Atlas 202562World Obesity Atlas 2025Country indexAfghanistan 64Albania 65Algeria 66American Samoa 67Andorra 68Angola 69Antigua and Barbuda 70Argentina 71Armenia 72Australia 73Austria 74Azerbaijan 75Bahamas 76Bahrain 77Bangladesh 78Barbados 79Belarus 80Belgium 81Belize 82Benin 83Bermuda 84Bhutan 85Bolivia 86Bosnia and Herzegovina 87Botswana 88Brazil 89Brunei Darussalam 90Bulgaria 91Burkina Faso 92Burundi 93Cabo Verde 94Cambodia 95Cameroon 96Canada 97Central African Republic 98Chad 99Chile 100China 101Colombia 102Comoros 103Congo 104Cook Islands 105Costa Rica 106Cote dIvoire 107Croatia 108Cuba 109Cyprus 110Czechia 111Democratic Republic of Congo 112Denmark 113Djibouti 114Dominica 115Dominican Republic 116Ecuador 117Egypt 118El Salvador 119Equatorial Guinea 120Eritrea 121Estonia 122Eswatini 123Ethiopia 124Federated States of Micronesia 125Fiji 126Finland 127France 128Gabon 129Gambia 130Georgia 131Germany 132Ghana 133Greece 134Greenland 135Grenada 136Guatemala 137Guinea 138Guinea-Bissau 139Guyana 140Haiti 141Honduras 142Hungary 143Iceland 144India 145Indonesia 146Iran 147Iraq 148Ireland 149Israel 150Italy 151Jamaica 152Japan 153Jordan 154Kazakhstan 155Kenya 156Kiribati 157Kuwait 158Kyrgyzstan 159Laos 160Latvia 161Lebanon 162Lesotho 163Liberia 164Libya 165Lithuania 16663World Obesity Atlas 2025Luxembourg 167Madagascar 168Malawi 169Malaysia 170Maldives 171Mali 172Malta 173Marshall Islands 174Mauritania 175Mauritius 176Mexico 177Moldova 178Mongolia 179Montenegro 180Morocco 181Mozambique 182Myanmar 183Namibia 184Nauru 185Nepal 186Netherlands 187New Zealand 188Nicaragua 189Niger 190Nigeria 191Niue 192North Korea 193North Macedonia 194Norway 195Oman 196Pakistan 197Palau 198Palestine 199Panama 200Papua New Guinea 201Paraguay 202Peru 203Philippines 204Poland 205Portugal 206Puerto Rico 207Qatar 208Romania 209Russian Federation 210Rwanda 211Saint Kitts and Nevis 212Saint Lucia 213Saint Vincent&the Grenadines 214Samoa 215Sao Tome and Principe 216Saudi Arabia 217Senegal 218Serbia 219Seychelles 220Sierra Leone 221Singapore 222Slovakia 223Slovenia 224Solomon Islands 225Somalia 226South Africa 227South Korea 228South Sudan 229Spain 230Sri Lanka 231Sudan 232Suriname 233Sweden 234Switzerland 235Syrian Arab Republic 236Taiwan 237Tajikistan 238Tanzania 239Thailand 240Timor-Leste 241Togo 242Tokelau 243Tonga 244Trinidad and Tobago 245Tunisia 246Turkey 247Turkmenistan 248Tuvalu 249Uganda 250Ukraine 251United Arab Emirates 252United Kingdom 253United States 254Uruguay 255Uzbekistan 256Vanuatu 257Venezuela 258Vietnam 259Yemen 260Zambia 261Zimbabwe 26264World Obesity Atlas 2025AfghanistanOverweight and obesity prevalence over timeProjected proportion of adults living with high Body Mass Index(25kg/m2 and above)%women with high BMI20002002200420062008201020122014201620182020202220242026202820300204060%men with high BMI200020022004200620082010201220142016201820202022202420262028203002040BMI 25-30BMI 30-35BMI 35 Adult population living with high BMI estimated in 2010,2015 and projected to 2030(inthousands)MenWomenBMI(kg/m2)20102015203020102015203025-301,2601,8304,3301,1801,7704,36030-353505801,7704407702,58035 791405301803401,330All high BMI1,6902,5506,6301,8002,8808,260Totals may not add up due to roundingThe impact of overweight and obesity on other NCDs,2021Number of adults living with disease or suffering premature deaths attributable to high BMIPremature deaths02000400060008000Person years living with ill health050k100kType 2 DiabetesStrokeIschaemic Heart DiseaseCancersOther NCDsNational policies,action and risk factorsNational guidelines for the management of high BMINoNational guidelines for the management of physical inactivityNoNational guidelines for NCD management in primary careNoSurvey of adult overweight and obesity in the last five yearsYesSurvey of adult unhealthy diets in the last five yearsYesSurvey of adult physical inactivity in the last five yearsYesTaxes on sugar-sweetened beveragesYesSugar-sweetened beverage consumption per person per week250-500mlProportion of adults with insufficient physical activity30-40%n/a=status not certain or unavailableSources:Institute for Health Metrics 2024,WHO Global Health Observatory 2024,NCD Risk Factor Collaboration 2024,UN Population Division 2024,Lara-Castor et al 2023(DOI:10.1038/s41467-023-41269-8),World Obesity Federation 2024.Adults with high BMI in 202554ults living with obesity in 202521.9mAdults with high BMI in 20307,702Premature NCD deaths due to highBMI,2021131,366Adult person-years of NCD ill-health due to high BMI,202165World Obesity Atlas 2025AlbaniaOverweight and obesity prevalence over timeProjected proportion of adults living with high Body Mass Index(25kg/m2 and above)%women with high BMI20002002200420062008201020122014201620182020202220242026202820300204060%men with high BMI20002002200420062008201020122014201620182020202220242026202820300204060BMI 25-30BMI 30-35BMI 35 Adult population living with high BMI estimated in 2010,2015 and projected to 2030(inthousands)MenWomenBMI(kg/m2)20102015203020102015203025-3048050046036037035030-2500mlProportion of adults with insufficient physical activity20-30%n/a=status not certain or unavailableSources:Institute for Health Metrics 2024,WHO Global Health Observatory 2024,NCD Risk Factor Collaboration 2024,UN Population Division 2024,Lara-Castor et al 2023(DOI:10.1038/s41467-023-41269-8),World Obesity Federation 2024.Adults with high BMI in 202565ults living with obesity in 202526%1.419mAdults with high BMI in 2030517Premature NCD deaths due to highBMI,202123,077Adult person-years of NCD ill-health due to high BMI,202166World Obesity Atlas 2025AlgeriaOverweight and obesity prevalence over timeProjected proportion of adults living with high Body Mass Index(25kg/m2 and above)%women with high BMI20002002200420062008201020122014201620182020202220242026202820300204060%men with high BMI20002002200420062008201020122014201620182020202220242026202820300204060BMI 25-30BMI 30-35BMI 35 Adult population living with high BMI estimated in 2010,2015 and projected to 2030(inthousands)MenWomenBMI(kg/m2)20102015203020102015203025-303,6204,3306,3803,6904,1505,34030-351,0301,3402,3602,0202,4203,66035 2103308309201,2102,340All high BMI4,8605,9909,5806,6207,79011,330Totals may not add up due to roundingThe impact of overweight and obesity on other NCDs,2021Number of adults living with disease or suffering premature deaths attributable to high BMIPremature deaths05k10kPerson years living with ill health0100k200k300kType 2 DiabetesStrokeIschaemic Heart DiseaseCancersOther NCDsNational policies,action and risk factorsNational guidelines for the management of high BMINoNational guidelines for the management of physical inactivityNoNational guidelines for NCD management in primary careYesSurvey of adult overweight and obesity in the last five yearsYesSurvey of adult unhealthy diets in the last five yearsYesSurvey of adult physical inactivity in the last five yearsYesTaxes on sugar-sweetened beveragesNoSugar-sweetened beverage consumption per person per week1000-2500mlProportion of adults with insufficient physical activity20-30%n/a=status not certain or unavailableSources:Institute for Health Metrics 2024,WHO Global Health Observatory 2024,NCD Risk Factor Collaboration 2024,UN Population Division 2024,Lara-Castor et al 2023(DOI:10.1038/s41467-023-41269-8),World Obesity Federation 2024.Adults with high BMI in 202562ults living with obesity in 202526 .91mAdults with high BMI in 203010,946Premature NCD deaths due to highBMI,2021342,958Adult person-years of NCD ill-health due to high BMI,202167World Obesity Atlas 2025American SamoaOverweight and obesity prevalence over timeProjected proportion of adults living with high Body Mass Index(25kg/m2 and above)%women with high BMI2000200220042006200820102012201420162018202020222024202620282030020406080%men with high BMI2000200220042006200820102012201420162018202020222024202620282030020406080BMI 25-30BMI 30-35BMI 35 Adult population living with high BMI estimated in 2010,2015 and projected to 2030(inthousands)MenWomenBMI(kg/m2)20102015203020102015203025-3033322130-3555444335 666899All high BMI141413141414Totals may not add up due to roundingThe impact of overweight and obesity on other NCDs,2021Number of adults living with disease or suffering premature deaths attributable to high BMIPremature deaths02040Person years living with ill health0200400600800Type 2 DiabetesStrokeIschaemic Heart DiseaseCancersOther NCDsNational policies,action and risk factorsNational guidelines for the management of high BMIn/aNational guidelines for the management of physical inactivityn/aNational guidelines for NCD management in primary caren/aSurvey of adult overweight and obesity in the last five yearsn/aSurvey of adult unhealthy diets in the last five yearsn/aSurvey of adult physical inactivity in the last five yearsn/aTaxes on sugar-sweetened beveragesn/aSugar-sweetened beverage consumption per person per weekn/aProportion of adults with insufficient physical activityn/an/a=status not certain or unavailableSources:Institute for Health Metrics 2024,WHO Global Health Observatory 2024,NCD Risk Factor Collaboration 2024,UN Population Division 2024,Lara-Castor et al 2023(DOI:10.1038/s41467-023-41269-8),World Obesity Federation 2024.Adults with high BMI in 202592ults living with obesity in 202577&,000Adults with high BMI in 203055Premature NCD deaths due to highBMI,2021904Adult person-years of NCD ill-health due to high BMI,202168World Obesity Atlas 2025AndorraOverweight and obesity prevalence over timeProjected proportion of adults living with high Body Mass Index(25kg/m2 and above)%women with high BMI2000200220042006200820102012201420162018202020222024202620282030010203040%men with high BMI20002002200420062008201020122014201620182020202220242026202820300204060BMI 25-30BMI 30-35BMI 35 Adult population living with high BMI estimated in 2010,2015 and projected to 2030(inthousands)MenWomenBMI(kg/m2)20102015203020102015203025-3013111387830-3554633335 113212All high BMI191721131214Totals may not add up due to roundingThe impact of overweight and obesity on other NCDs,2021Number of adults living with disease or suffering premature deaths attributable to high BMIPremature deaths0246810Person years living with ill health0200400600Type 2 DiabetesStrokeIschaemic Heart DiseaseCancersOther NCDsNational policies,action and risk factorsNational guidelines for the management of high BMINoNational guidelines for the management of physical inactivityNoNational guidelines for NCD management in primary careNoSurvey of adult overweight and obesity in the last five yearsNoSurvey of adult unhealthy diets in the last five yearsNoSurvey of adult physical inactivity in the last five yearsNoTaxes on sugar-sweetened beveragesNoSugar-sweetened beverage consumption per person per weekn/aProportion of adults with insufficient physical activity20-30%n/a=status not certain or unavailableSources:Institute for Health Metrics 2024,WHO Global Health Observatory 2024,NCD Risk Factor Collaboration 2024,UN Population Division 2024,Lara-Castor et al 2023(DOI:10.1038/s41467-023-41269-8),World Obesity Federation 2024.Adults with high BMI in 202549ults living with obesity in 2025195,000Adults with high BMI in 203010Premature NCD deaths due to highBMI,2021726Adult person-years of NCD ill-health due to high BMI,202169World Obesity Atlas 2025AngolaOverweight and obesity prevalence over timeProjected proportion of adults living with high Body Mass Index(25kg/m2 and above)%women with high BMI2000200220042006200820102012201420162018202020222024202620282030010203040%men with high BMI200020022004200620082010201220142016201820202022202420262028203001020BMI 25-30BMI 30-35BMI 35 Adult population living with high BMI estimated in 2010,2015 and projected to 2030(inthousands)MenWomenBMI(kg/m2)20102015203020102015203025-307309501,8401,1901,5202,85030-351702305404506101,38035 5178250200290760All high BMI9501,2502,6401,8402,4305,000Totals may not add up due to roundingThe impact of overweight and obesity on other NCDs,2021Number of adults living with disease or suffering premature deaths attributable to high BMIPremature deaths01000200030004000Person years living with ill health020k40k60kType 2 DiabetesStrokeIschaemic Heart DiseaseCancersOther NCDsNational policies,action and risk factorsNational guidelines for the management of high BMINoNational guidelines for the management of physical inactivityNoNational guidelines for NCD management in primary careNoSurvey of adult overweight and obesity in the last five yearsNoSurvey of adult unhealthy diets in the last five yearsNoSurvey of adult physical inactivity in the last five yearsNoTaxes on sugar-sweetened beveragesNoSugar-sweetened beverage consumption per person per week1000-2500mlProportion of adults with insufficient physical activity10-20%n/a=status not certain or unavailableSources:Institute for Health Metrics 2024,WHO Global Health Observatory 2024,NCD Risk Factor Collaboration 2024,UN Population Division 2024,Lara-Castor et al 2023(DOI:10.1038/s41467-023-41269-8),World Obesity Federation 2024.Adults with high BMI in 202534ults living with obesity in 202512%7.62mAdults with high BMI in 20304,680Premature NCD deaths due to highBMI,202166,689Adult person-years of NCD ill-health due to high BMI,202170World Obesity Atlas 2025Antigua and BarbudaOverweight and obesity prevalence over timeProjected proportion of adults living with high Body Mass Index(25kg/m2 and above)%women with high BMI2000200220042006200820102012201420162018202020222024202620282030020406080%men with high BMI20002002200420062008201020122014201620182020202220242026202820300204060BMI 25-30BMI 30-35BMI 35 Adult population living with high BMI estimated in 2010,2015 and projected to 2030(inthousands)MenWomenBMI(kg/m2)20102015203020102015203025-3089119101130-3534667935 1245610All high BMI131521202331Totals may not add up due to roundingThe impact of overweight and obesity on other NCDs,2021Number of adults living with disease or suffering premature deaths attributable to high BMIPremature deaths010203040Person years living with ill health02004006008001000Type 2 DiabetesStrokeIschaemic Heart DiseaseCancersOther NCDsNational policies,action and risk factorsNational guidelines for the management of high BMINoNational guidelines for the management of physical inactivityNoNational guidelines for NCD management in primary careNoSurvey of adult overweight and obesity in the last five yearsNoSurvey of adult unhealthy diets in the last five yearsNoSurvey of adult physical inactivity in the last five yearsNoTaxes on sugar-sweetened beveragesNoSugar-sweetened beverage consumption per person per week10
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All Rights Reserved.1Gen Z:Calling for Healthcare Connection and ChangeJANUARY 2025 All Rights Rese.
2025-03-06
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Market Spotlight Coronary Artery Disease109 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)Market Spotlight:Coronary Artery Disease Last Reviewed:09 Jan,2025 Market Spotlight Coronary Artery Disease209 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)Latest TakeawaysDatamonitor Healthcare estimates that in 2024,there were approximately 237.4 million prevalent cases of coronary artery disease worldwide,and forecasts that number to increase to 252.1 million prevalent cases by 2029.Datamonitor Healthcare estimates that in 2024,there were approximately 5.5 million incident cases of acute coronary syndrome worldwide,and forecasts that number to increase to 5.8 million incident cases by 2029.The approved drugs in the coronary artery disease space target angiotensin converting enzyme,amyloid beta/amyloid plaques,adenosine diphosphate P2Y12 receptor,calcium channel,and coagulation factor X.The majority of marketed drugs are administered via the oral route,with one product being available in an intravenous formulation.The majority of industry-sponsored drugs in active clinical development for coronary artery disease are in Phase II.Therapies in development for coronary artery disease target alpha 2 adrenergic receptor,endothelial lipase,NLRP3/inflammasome,reverse cholesterol transport,stem cells/other cell therapies,and fibroblast growth factor receptor.These drugs are administered via the intravenous,oral,subcutaneous,and percutaneous catheter/injection routes.Market Spotlight Coronary Artery Disease309 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)Disease BackgroundSource:American Heart Association(AHA)01/10/2024 American Heart Association(AHA)12/05/2022 Journal Article 09/12/2007(Maddox et al.)Journal Article 06/01/2005(Bertoni et al.)Journal Article 01/15/2009(Champney et al.)Journal Article 02/04/2013(Deckers)Journal Article 01/03/2011(McManus et al.)Journal Article 07/25/2005(Roe et al.)Journal Article 12/01/2008(Rogers et al.)Journal Article 09/07/2007(Yui et al.)National Institutes of Health(NIH)12/20/2023(Coronary Heart Disease)National Institutes of Health(NIH)12/20/2023(Symptoms)Online Book 02/18/2022(IQWiG)Online Book 02/01/2024(Sweis and Jivan;Angina)Online Book 02/01/2024(Sweis and Jivan;Coronary Artery Disease)Online Book 02/01/2024(Sweis and Jivan;Acute Coronary Syndromes)www.health.gov.au 06/01/2022 Coronary artery disease(CAD),also called ischemic heart disease,occurs due to the narrowing of coronary arteries that supply oxygen-rich blood to the heart.A waxy substance called plaque builds up inside these arteries,leading to atherosclerosis.Plaque builds up within the coronary artery walls until the flow of oxygen-rich blood to the heart muscle is limited.This condition is also called ischemia,which may be chronic or acute.In chronic ischemia,the coronary artery narrows over time,limiting the blood flow to part of the heart muscle,while acute ischemia occurs due to a sudden rupture of plaque and formation of a blood clot.These blood clots can completely or mostly block the flow of blood through the artery,leading to acute myocardial ischemia,which further results in acute coronary syndromes.These include unstable angina,non-ST segment elevation myocardial infarction(NSTEMI),and ST-segment elevation MI(STEMI).If the oxygen-rich blood flow to the heart is blocked or reduced,heart attack or angina can occur.Unstable angina(UA):Of the three acute coronary syndrome(ACS)subtypes,UA is the most difficult to define and diagnose.UA is angina(chest pain)that is new or sudden,and may signal an impending MI.This is in contrast to stable angina,which is chest pain that occurs predictably,typically upon exertion.UA patients may have normal or abnormal ECGs,but do not test positive for biomarkers of cardiac necrosis.Compared with MI patients,UA patients are often significantly less healthy in that they are more likely to have a history of common cardiovascular risk factors such as tobacco use,hypertension,and diabetes mellitus.UA patients tend to have lower mortality rates than MI patients,but it has been argued that favorable mortality outcomes do not necessarily indicate better long-term prognoses because UA patients have similar quality of life scores and rehospitalization rates compared to MI patients after one year.Data show that UA is less common than MI,but this may be because UA is sometimes treated in outpatient settings,which precludes UA cases from being captured upon hospital admission,as MI cases are.Furthermore,as a result of revised definitions,according to which an abnormal value of the most sensitive cardiac biomarkers in a patient with a high clinical suspicion of ACS must be considered to represent myocardial necrosis and thus MI,many ACS patients will be reclassified from UA to NSTEMI.The incidence of NSTEMI will therefore increase significantly,and that of UA will decrease.Myocardial infarction:MIoccurswhentheheartsbloodsupplyisinterrupted,usuallybyablockageofthecoronaryartery.STEMIisanMIinwhichtheSTsegmentonapatientsECGiselevated.ST-segmentelevationisastrongindicationofasuddenlackofbloodgettingtotheheart.Asthenameindicates,NSTEMIisanMIinwhichtheSTsegmentofapatientsECGisnotelevated;theECGmaybenormalormay have other abnormalities indicating MI.STEMI and NSTEMI are not evenly distributed throughout the MI population,and certain types of patients are more prone to one or the other.Studies of MI patients have shown STEMI patients to be about five years younger than NSTEMI patients on average.STEMI patients also tend to be healthier than NSTEMI patients;that is,they are less likely to have a history of hypertension,diabetes mellitus,angina,or stroke.In younger MI patients,STEMI is more common in men,but by the age of 80 years,it is more common in women.Market Spotlight Coronary Artery Disease409 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)The most common symptom of CAD is angina.This is defined as discomfort or chest pain caused by insufficient oxygen and blood flow to the heart muscle.Angina generally occurs during severe emotional stress or exertion,as the heart muscle requires more blood oxygen than can be delivered by the narrowed coronary artery.Usually,pain reduces with rest.The main symptoms of angina include pain and discomfort,which can manifest as burning,tightness,or squeezing of the chest.Pain also occurs in the shoulders,neck,jaw,arms,or back.Other symptoms include breathlessness,cold sweating,dizziness,nausea,weakness,light-headedness,or sleep disturbances.The common risk factors of CAD include high LDL cholesterol,low HDL cholesterol,smoking,high blood pressure,diabetes,lack of physical activity,obesity,lack of social contact,depression,dietary factors,and high levels of lipoprotein and C-reactive protein(CRP)in the blood.The risk of CAD increases with age,and it is more common in men than in women.Family history of early CAD can also be a risk factor if any close relatives have developed CAD before the age of 55 years.Market Spotlight Coronary Artery Disease509 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)TreatmentSource:American Heart Association(AHA)Biomedtracker Journal Article 04/01/2011(Pflieger et al.)National Institutes of Health(NIH)12/20/2023 Online Book 02/18/2022(IQWiG)Prescribing Information 03/02/2015(Caduet)Prescribing Information 05/01/2020(Brilinta)Prescribing Information 06/01/2011(Aceon)UK National Health Service(NHS)01/17/2024 The treatment of CAD involves heart-healthy lifestyle changes,medications,medical procedures or surgery,and cardiac rehabilitation.The main goal of treatment may include relieving symptoms and preventing CAD complications,widening or bypassing the clogged arteries,lowering the risk of forming blood clots,and reducing risk factors for a patient in an effort to delay,stop,or even reverse the plaque buildup.A physician may recommend heart-healthy lifestyle changes such as controlling stress,quitting smoking,physical activity,heart-healthy eating,maintaining a healthy weight,and getting a sufficient amount of good-quality sleep.Medical managementPatients with stable CAD require medical treatment,with the goal of preventing disease progression and recurrent cardiovascular events.Lipid-lowering(such as statins),antihypertensive(such as beta-blockers,calcium channel blockers,and nitrates),and antiplatelet agents(such as aspirin and clopidogrel)are the three essential types of medical therapies for the treatment of CAD.In addition to statins,other medications such as fibrates,nicotinic acid,and ezetimibe can also be used to reduce cholesterol levels.Please note,further coverage of thesedrugsforthetreatmentofdyslipidemiacanbefoundinDatamonitorHealthcaresDisease Analysis:Dyslipidemia.Antiplatelets:Alsoknownasantiaggregants,theyinhibittheplateletsfunctioninthebloodbydelayingthebloodclottingprocess,andprevent the platelets from attaching to the blood vessel walls.Aspirin(acetylsalicylic acid)and Plavix(clopidogrel)are approved in various countries for long-term CAD treatment.Plavix is usually used as an alternative when patients cannot tolerate aspirin.In 2020,the US Food and Drug Administration(FDA)approved aspirin plus Brilinta(ticagrelor)for use in high-risk CAD patients with no prior heart attack or stroke.Brilinta is an oral,reversible agent that inhibits platelet aggregation by blocking the adenosine diphosphate receptor.Statins:Thesearealsoknownas3-hydroxy-3-methyl-glutaryl-CoA(HMG-CoA)reductaseinhibitors.Statinsareusedtoreducethecholesterollevelsintheblood.Thesedrugsaremoreeffectiveinloweringlevelsof“bad”cholesterol,aswellastriglyceridefats.Statinsarealsousedtoincreaselevelsof“good”cholesterol.SomeofthestatinsavailableintheUSareLescol(fluvastatin),Lipitor(atorvastatin),Pravachol(pravastatin),Mevacor(lovastatin),Crestor(rosuvastatin calcium),and Zocor(simvastatin).These drugs are recommended to people with CAD,diabetes,peripheral artery disease,and high LDL cholesterol levels.Moreover,statins can also be used by people who have had a stroke.Beta-blockers:Theseslowtheheartrate,therebyloweringthestrainontheheart,andalsolowerbloodpressure.Beta-blockersareparticularly suitable for individuals with CAD as well as heart failure or high blood pressure,and can be used for relieving or preventing angina(chest pain)symptoms.The most commonly used beta-blockers are metoprolol and bisoprolol.Calcium channel blockers and nitrates:Thesedrugshelptorelieveorpreventanginasymptomsbywideningthebloodvesselsandlowering the heart rate.Calcium channel blockers reduce the blood pressure and also the strain in the chambers of the heart.They are mostly used by individuals who cannot take or tolerate beta-blockers,or who are not getting sufficient relief with the use of beta-blockers.Nitrates are fast-acting drugs which can be used in the form of a spray to treat acute angina attacks.Angiotensin-converting enzyme(ACE)inhibitors and angiotensin II receptor blockers(ARBs):Thesedrugshelpinreducingbloodpressure.Typically,ACE inhibitors are used first as they tend to be effective,but if the patient cannot tolerate ACE inhibitors,ARBs are considered.Medical procedures and surgeryPatients with CAD may need a medical procedure or surgery:Market Spotlight Coronary Artery Disease609 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)Percutaneous coronary intervention(PCI),also known as angioplasty,is a non-surgical procedure which is used to open the narrowed or blocked coronary arteries.Coronary artery bypass grafting(CABG)is a surgical procedure that uses the arteries or veins from other parts of the body to bypass the narrowed coronary arteries.CABG helps in improving the blood flow to the heart,relieving chest pain,and possibly preventing a heart attack.Coronary endarterectomy or transmyocardial laser revascularization is used to treat severe angina associated with coronary heart disease when other treatments do not work or appear too risky.Cardiac rehabilitationPeople with CAD are recommended to participate in a cardiac rehabilitation program.The goal of the program is to increase physical endurance and life expectancy,and to prevent complications.The program usually consists of a combination of learning to manage the condition and its risk factors,physical exercise,and psychological support.The cardiac rehabilitation program may involve specialists from different fields,such as physiotherapy,nutritional sciences,and psychotherapy.Market Spotlight Coronary Artery Disease709 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)EpidemiologySource:Australian Bureau of Statistics(ABS)12/15/2023 Centers for Disease Control and Prevention(CDC)01/02/2017 Datamonitor Healthcare(DMHC)Journal Article 01/14/2016(Krishnan et al.)Journal Article 09/01/2020(Oliveira et al.)Journal Article 04/03/2006(Sani et al.)Journal Article 01/01/2003(Yasser et al.)Journal Article 08/23/2021(Zhao et al.)Journal Article 08/25/2020(Coffey et al.)Journal Article 07/01/2017(Nakamura et al.)Journal Article 02/24/2017(Wang et al.)Journal Article 06/10/2010(Yeh et al.)Public Health Scotland UK National Health Service(NHS)12/04/2018 United Nations Datamonitor Healthcare used historical prevalence data to estimate and forecast the prevalence of coronary artery disease in people aged 20 years and older in the United Nations(UN)world regions(World,Africa,Asia,Europe,Latin America and the Caribbean,Northern America,and Oceania).Datamonitor Healthcare identified several sources for estimates of coronary artery disease prevalence,mainly population-based studies and national surveys describing diagnosed data at a regional level.The data consisted of self-reported prevalence and/or prevalence determined by International Classification of Diseases(ICD)-10 codes.Multiple sources used in this forecast report on prevalence of ischemic heart disease or coronary heart disease instead of coronary artery disease.These terms are used interchangeably with coronary artery disease,and so have been included as a proxy.Data on the incidence of acute coronary syndrome are scarce.Therefore,Datamonitor Healthcare included studies which either reported acute coronary syndrome or acute myocardial infarction/unstable angina.Studies reporting acute coronary syndrome incidence were based on ICD codes or European Society of Cardiology guidelines criteria.For studies which reported myocardial infarction,diagnostic criteria were based on ECG reports or were registry data based on the ICD codes.Region/country-specific data were available for Asia,Europe,Northern America,and Oceania.For Africa and the Latin America and the Caribbean region,the incidence estimate from Asia was applied as this region is most similar regarding population demographics and socioeconomic factors.Tocalculatethenumberofprevalentandincidentcasesforthetwoindicationsinthe202029forecastperiod,DatamonitorHealthcaremultiplied the proportions by the region-specific population estimates from the UN World Population Prospects database.The UN database was chosen as a reliable population denominator;the data include standard sets of demographic indicators.Included are estimated prevalent cases of coronary artery disease in people aged 20 years and over,and estimated incident cases of acutecoronarysyndromeinpeopleaged20yearsandoverduring202029.Evidencesuggeststheseindicationsarerareamongchildrenand young adults;therefore,epidemiological data are also rare.Consequently,children and young adults were excluded from this analysis.Prevalent cases of coronary artery disease,2020-29YearWorldAfricaAsiaEuropeLatin American&the CaribbeanNorthern AmericaOceania2020225,696,00031,111,000145,362,00024,349,0007,995,00015,951,000928,0002021228,634,00032,004,000147,154,00024,348,0008,113,00016,075,000940,0002022231,559,00032,916,000148,923,00024,338,0008,230,00016,199,000925,0002023234,484,00033,852,000150,670,00024,327,0008,345,00016,324,000965,0002024237,424,00034,822,000152,395,00024,319,0008,458,00016,452,000978,000Market Spotlight Coronary Artery Disease809 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)YearWorldAfricaAsiaEuropeLatin American&the CaribbeanNorthern AmericaOceania2025240,390,00035,830,000154,100,00024,318,0008,568,00016,583,000991,0002026243,301,00036,848,000155,756,00024,318,0008,676,00016,699,0001,004,0002027246,230,00037,903,000157,383,00024,324,0008,780,00016,822,0001,018,0002028249,179,00038,996,000158,986,00024,336,0008,882,00016,947,0001,032,0002029252,147,00040,126,000160,569,00024,351,0008,983,00017,073,0001,046,000Note:Totals may not sum due to rounding.Datamonitor Healthcare estimates that in 2024,there were approximately 237.4 million prevalent cases of coronary artery disease in people aged 20 years and over worldwide.Thisnumberisforecastedtoincreasetoapproximately252.1millionprevalentcasesby2029.Asiaisestimatedtohavehadthelargestnumberofprevalentcasesin2024(152.4millioncases),whiletheOceaniaregionisestimatedtohavehadthesmallestnumber(978,000cases).Trends in prevalent cases of coronary artery disease,202029Source:Source:Datamonitor Healthcare;Health Survey for England,2018;Krishnan et al.,2016;National Health Interview Survey,2017;National Health Survey Australia,2018;Oliveira et al.,2020;Sani et al.,2006;Sharaf et al.,2003;United Nations,201Globally,the number of prevalent cases of coronary artery disease among individuals aged 20 years and over is expected to increase by 11.7tween 2020 and 2029.These trends are driven by population demographics,as prevalence proportions were held constant throughout the forecast period.Market Spotlight Coronary Artery Disease909 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)Prevalent cases of coronary artery disease in select regions,by gender,2020RegionMaleFemaleTotalProportion maleAfrica14,660,00016,451,00031,111,00047.12%Asia72,805,00072,557,000145,362,00050.09%Europe15,676,0008,673,00024,349,00064.38%Northern America9,834,0006,117,00015,951,00061.65%Oceania599,000329,000928,00064.58%Note:Gender-specificprevalenceproportionsarenotavailablefortheLatinAmericaandtheCaribbeanregion.Coronary artery disease has a male predominance in Europe,Northern America,and Oceania.Datamonitor Healthcare estimates that in Asia and Africa,coronary artery disease has a similar prevalence in men and women.Incident cases of acute coronary syndrome,2020-29YearWorldAfricaAsiaEuropeLatin American&the CaribbeanNorthern AmericaOceania20205,275,000518,0002,485,0001,240,000341,000584,000107,00020215,330,000533,0002,515,0001,239,000346,000589,000109,00020225,385,000548,0002,544,0001,239,000351,000594,000110,00020235,441,000564,0002,573,0001,238,000355,000598,000112,00020245,497,000580,0002,602,0001,238,000360,000603,000113,00020255,551,000597,0002,630,0001,238,000365,000607,000115,00020265,607,000614,0002,658,0001,238,000369,000612,000116,00020275,662,000632,0002,685,0001,239,000373,000616,000118,00020285,718,000650,0002,711,0001,240,000378,000621,000119,00020295,775,000669,0002,738,0001,240,000382,000625,000121,000Note:Totals may not sum due to rounding.Datamonitor Healthcare estimates that in 2024,there were approximately 5.5 million incident cases of acute coronary syndrome in people aged 20 years and over worldwide.This number is forecasted to increase to approximately 5.8 million incident cases by 2029.Asia is estimated to have had the largest number of incident cases in 2024(2.6 million cases),while the Oceania region is estimated to have had the smallest number(113,000 cases).Globally,the number of incident cases of acute coronary syndrome among individuals aged 20 years and over is expected to increase by 9.6tween 2020 and 2029.These trends are driven by population demographics,as prevalence proportions were held constant throughout the forecast period.Trends in incident cases of acute coronary syndrome,202029Market Spotlight Coronary Artery Disease1009 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)Source:Datamonitor Healthcare;Coffey at al.,2020;Nakamura et al.,2017;Scottish Heart Disease Statistics,2019;United Nations,2019;Wang et al.,2017;Yeh at al.,2010Globally,the number of incident cases of acute coronary syndrome among individuals aged 20 years and over is expected to increase by 9.6tween 2020 and 2029.These trends are driven by population demographics,as prevalence proportions were held constant throughout the forecast period.Market Spotlight Coronary Artery Disease1109 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)Marketed and Pipeline DrugsDrugLead CompanyPartnerIndicationTargetPhaseApproval DateAceonSymplmed Pharmaceuticals LLCAbbVie Inc.(ABBV)XOMA Royalty Corporation(XOMA)Coronary Artery DiseaseAngiotensin Converting Enzyme(ACE)Approved(Generic Competition)08/2005CaduetPfizer Inc.Astellas Pharma,Inc.(4503:JP)Coronary Artery DiseaseCalcium ChannelApproved(Generic Competition)01/2004Sensation 7Fr.IABGetinge ABCoronary Artery DiseaseDevice MiscellaneousApproved01/2007Bx VELOCITY StentCardinal Health,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved05/2000NexStent Carotid StentBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved10/2006NC Quantum Apex PTCA Dilatation CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved08/2012Wiseguide Guide CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved06/1997DURA STAR Rx PTCA Dilatation CatheterCardinal Health,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved08/2007FIRE STAR Rx PTCA Dilatation CatheterCardinal Health,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved08/2007Sprinter OTW Semicompliant Over-the-Wire Balloon Dilatation CatheterMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved06/2004Driver Coronary Stent SystemMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved10/2003WatusiJohnson&JohnsonCoronary Artery DiseaseDevice MiscellaneousApproved04/2006Courier MicrocatheterJohnson&JohnsonCoronary Artery DiseaseDevice MiscellaneousApproved05/2006Market Spotlight Coronary Artery Disease1209 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateApex Dilation CathetersBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved11/2008MuskieTeleflex IncorporatedCoronary Artery DiseaseDevice MiscellaneousApprovedBioFreedomBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved04/2022Inquiry AFocus II CatheterAbbottCoronary Artery DiseaseDevice MiscellaneousApproved11/2004Diamondback 360 Coronary Orbital Atherectomy SystemAbbottOrbusNeich Medical Group Holdings Ltd.(6929)Coronary Artery DiseaseDevice MiscellaneousApproved10/2013Therapy Cool Flex RF Ablation CatheterAbbottCoronary Artery DiseaseDevice MiscellaneousApproved12/2013Eagle Eye PlatinumRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved12/2009Kinetix GuidewireBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved08/2008Sprinter Legend RX Semicompliant Balloon Dilatation CatheterMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved10/2008MinnieTeleflex IncorporatedCoronary Artery DiseaseDevice MiscellaneousApproved01/2009EverCross.035 OTW PTA Dilation CatheterMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved11/2008NanoCrossMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved12/2008SYNERGY Bioabsorbable Polymer StentBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved10/2015Integrity Coronary Stent SystemMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApprovedMarket Spotlight Coronary Artery Disease1309 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateOstial ProMerit Medical Systems Inc.Coronary Artery DiseaseDevice MiscellaneousApproved05/2007NC TREK RX Coronary Dilatation CatheterAbbottCoronary Artery DiseaseDevice MiscellaneousApproved12/2010Linear 7.5 Fr.Intra-Aortic Balloon CatheterGetinge ABCoronary Artery DiseaseDevice MiscellaneousApprovedSAILOR PLUS PTA Balloon CatheterMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved11/2004Submarine PLUS PTA Balloon CatheterMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved11/2004Workhorse PTA Balloon CatheterAngioDynamics,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved09/1999Vista Brite Tip Guiding CatheterCardinal Health,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved08/1996Eagle Eye GoldRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved06/2003Trak Back IIRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved08/1999SpinVision Pullback DeviceRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved12/2005SmartWire IIRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved05/2002FloWire Doppler Guide WireRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved03/1991Avanar F/XRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved06/2000RevolutionRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved06/2005BrightWire IIRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved05/2002Market Spotlight Coronary Artery Disease1409 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateWaveWireRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved08/1997Endeavor Zotarolimus-Eluting Coronary Stent SystemMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved02/2008ComboMap Pressure and Flow SystemRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved06/2004ComboWire XTRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved11/2004RAPIDO Guiding CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved08/2002ExpressBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved09/2002TAXUS Libert Coronary Stent SystemBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved10/2008NIRxcell Coronary StentMedinol Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved04/2012Venture CathetersTeleflex IncorporatedCoronary Artery DiseaseDevice MiscellaneousApproved08/2004GuideLiner CatheterTeleflex IncorporatedCoronary Artery DiseaseDevice MiscellaneousApproved11/2009XIENCE VBoston Scientific CorporationAbbott(ABT)Coronary Artery DiseaseDevice MiscellaneousApproved07/2008CronusStereotaxis,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved02/2005Titan GuidewireStereotaxis,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved03/2006AssertStereotaxis,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved02/2004Coda Balloon CatheterCook Group,Inc.Coronary Artery DiseaseDevice MiscellaneousApprovedMarket Spotlight Coronary Artery Disease1509 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateTwin-Pass Dual Access CatheterTeleflex IncorporatedCoronary Artery DiseaseDevice MiscellaneousApproved11/2005iSight CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved03/2006ION Coronary Stent SystemBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved04/2011TAXUS Express2 Paclitaxel-Eluting Coronary Stent System(Monorail and Over-the-Wire)Boston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved03/2004CVX-300 Excimer Laser SystemRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved02/1993Emerge PTCA Dilatation CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved03/2012IQCathTeleflex IncorporatedCoronary Artery DiseaseDevice MiscellaneousApproved07/2010XIENCE PRIMEAbbottCoronary Artery DiseaseDevice MiscellaneousApproved11/2011SuperCross MicrocatheterTeleflex IncorporatedCoronary Artery DiseaseDevice MiscellaneousApproved12/2010XareltoJohnson&JohnsonBayer AG(BAYN)Coronary Artery DiseaseCoagulation Factor XApproved10/2018Verrata Pressure Guide WireRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved06/2013OptiCrossBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved04/2013AlbuteinGrifols,S.A.Coronary Artery DiseaseAmyloid Beta/Amyloid PlaquesApproved08/1978BrilintaAstraZeneca PLCThe Medicines CompanyCoronary Artery DiseaseAdenosine Diphosphate P2Y12 ReceptorApproved05/2020Market Spotlight Coronary Artery Disease1609 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateREBEL Platinum Chromium Coronary Stent SystemBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved06/2014Multi-Link VISION Coronary Stent SystemAbbottCoronary Artery DiseaseDevice MiscellaneousApproved07/2003POWERSAIL Coronary Dilatation CathetersAbbottCoronary Artery DiseaseDevice MiscellaneousApproved03/2001PrimeWire PRESTIGERoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved04/2010SyncVisionRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved12/2013NC Euphora Noncompliant Balloon Dilatation CatheterMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved08/2014AngioSculpt PTCA Scoring Balloon CatheterRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved01/2007Agent Drug-Coated Balloon CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved03/2024Resolute Integrity Coronary Stent SystemMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved02/2012PROMUS Element PlusBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved11/2011Diamondback 360 Coronary OAS Micro CrownAbbottCoronary Artery DiseaseDevice MiscellaneousApproved03/2017Turnpike CatheterTeleflex IncorporatedCoronary Artery DiseaseDevice MiscellaneousApproved11/2014OrsiroBIOTRONIK AGCoronary Artery DiseaseDevice MiscellaneousApproved02/2019Euphora Semicompliant Balloon Dilatation CatheterMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved04/2015Resolute Onyx Drug Eluting StentMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved04/2017Market Spotlight Coronary Artery Disease1709 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateNanoCross EliteMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved09/2013XIENCE AlpineAbbottCoronary Artery DiseaseDevice MiscellaneousApproved09/2014Promus PREMIERBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved11/2013ENROUTE Transcarotid Stent SystemBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved05/2015CorPath Vascular Robotic SystemSiemens AGCoronary Artery DiseaseDevice MiscellaneousApproved07/2012Corsair ProAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved02/2009HeartFlow FFRHeartFlow,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved11/2014Chocolate PTCA Balloon CatheterTeleflex IncorporatedCoronary Artery DiseaseDevice MiscellaneousApproved06/2014Glider PTCA Balloon CatheterTeleflex IncorporatedCoronary Artery DiseaseDevice MiscellaneousApproved03/2012ULTRASKIN Hydrophilic Guide WireLepu Medical Technology(Beijing)Co.,Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved01/2015Galeo Guide WireBIOTRONIK AGCoronary Artery DiseaseDevice MiscellaneousApproved01/1999Acarix CADScor SystemAcarix ABCoronary Artery DiseaseDevice MiscellaneousApprovedR350 GuidewireTeleflex IncorporatedCoronary Artery DiseaseDevice MiscellaneousApproved11/2015FOXTROT NC PTCA Balloon CatheterMicroPort Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved03/2014SapphireOrbusNeich Medical Group Holdings Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved08/2011CTMarket Spotlight Coronary Artery Disease1809 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DatePalmaz-Schatz Balloon Expandable StentCardinal Health,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved08/1994TREK Coronary Dilatation CathetersAbbottCoronary Artery DiseaseDevice MiscellaneousApproved01/2011RXi Rapid Exchange FFR SystemBracco S.p.A.Coronary Artery DiseaseDevice MiscellaneousApproved01/2014Kodama HD IVUS CatheterBracco S.p.A.Coronary Artery DiseaseDevice MiscellaneousApproved06/2012EMPIRA Balloon CatheterTE Connectivity Ltd.Cardinal Health,Inc.(CAH)Coronary Artery DiseaseDevice MiscellaneousApproved06/2011Pro-Flo Angiographic CatheterMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved10/1996Launcher Coronary Guide CatheterMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved05/2002Sherpa NX Active Coronary Guide CatheterMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved06/1992Sherpa NX Balance Coronary Guide CatheterMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved06/1992ADROIT Guiding CathetersCardinal Health,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved05/2013NC Sprinter RX Balloon Dilation CatheterMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved10/2008NC Stormer OTW Noncompliant Balloon Dilation CatheterMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved03/2003Comet FFRBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved10/2015Guidezilla Guide Extension CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved03/2013INFINITI Diagnostic CatheterCardinal Health,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved04/1996Market Spotlight Coronary Artery Disease1909 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateSUPER TORQUE Diagnostic CatheterCardinal Health,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved10/1991Angiodyn Angiographic CatheterB.Braun Melsungen AGCoronary Artery DiseaseDevice MiscellaneousApproved08/1995AcuNav Ultrasound CatheterSiemens AGCoronary Artery DiseaseDevice MiscellaneousApproved12/1999Radifocus Optitorque Angiographic CatheterTerumo CorporationCoronary Artery DiseaseDevice MiscellaneousApproved10/1986ExpoBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved04/1995VeriFLEXBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved04/2005Encore 26Boston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved04/2012PTBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved05/2003Reprocessed SOUNDSTAR 3D Diagnostic Ultrasound CatheterStryker CorporationCoronary Artery DiseaseDevice MiscellaneousApproved10/2009Platinum Plus Guide WireBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved06/1994Mailman Guide WireBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved01/2015Fort Floppy Guidewire and Marker WireBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved03/1998RunWay Guide CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved11/2003Mach1 Guide CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved06/20012Market Spotlight Coronary Artery Disease2009 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateConvey Guiding CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved08/2012Ultra ICE PlusBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved02/2016Quantum Maverick Balloon CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved10/2002Impulse Diagnostic CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved02/1997Crosser CatheterBecton,Dickinson and CompanyCoronary Artery DiseaseDevice MiscellaneousApproved01/2007Magellan Robotic Catheter 10FrJohnson&JohnsonCoronary Artery DiseaseDevice MiscellaneousApproved07/2015Valet Micro CatheterRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved01/2012SION PTCA Guide WireAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved09/2010SION blue PTCA Guide WireAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved03/2013Confianza Pro PTCA Guide WireAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved08/2004Fielder PTCA Guide WireAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved08/2005Fielder XT PTCA Guide WireAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved09/2007Tornus Support CathetersAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved09/2005Precious Guide CatheterAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved11/2006Stride MicrocatheterAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved06/2007Market Spotlight Coronary Artery Disease2109 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateSUOH PTCA Guide WireAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved01/2009Zenyte EX PTCA Guide CatheterAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved02/2010ULTIMATEbros 3 PTCA Guide WireAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved09/2011SheathLess Eaucath Coronary Guide CatheterAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved10/2013Gaia PTCA Guide WireAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved03/2014RG3 PTCA Guide WireAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved10/2014ASAHI Caravel MicrocatheterAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved01/2016EluNIR Drug Eluting Coronary Stent SystemMedinol Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved11/2017CORE SystemRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved11/2013XIENCE nanoAbbottCoronary Artery DiseaseDevice MiscellaneousApproved05/2010XIENCE XpeditionAbbottCoronary Artery DiseaseDevice MiscellaneousApproved12/2012SLENDER IDSSvelte Medical Systems,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved12/2021DIRECT RX Drug-Eluting StentSvelte Medical Systems,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved12/2021C-Port Distal Anastomosis SystemB.Braun Melsungen AGCoronary Artery DiseaseDevice MiscellaneousApproved11/2005Alviguide Blue Guiding CatheterAlvimedicaCoronary Artery DiseaseDevice MiscellaneousApprovedMarket Spotlight Coronary Artery Disease2209 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateSapphire NCOrbusNeich Medical Group Holdings Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved09/2011FLASH Ostial SystemOstial CorporationCardinal Health,Inc.(CAH)Coronary Artery DiseaseDevice MiscellaneousApproved08/2011Shockwave Lithoplasty SystemJohnson&JohnsonCoronary Artery DiseaseDevice MiscellaneousApproved02/2021FuStar Steerable IntroducerLifetech Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved02/2011ConcierGE Guiding CatheterMerit Medical Systems Inc.Coronary Artery DiseaseDevice MiscellaneousApproved02/2004Tryton Side Branch Stent SystemTryton Medical,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved02/2017CROSSWIRETerumo CorporationCoronary Artery DiseaseDevice MiscellaneousApproved10/1995Eliminate Aspiration CatheterTerumo CorporationCoronary Artery DiseaseDevice MiscellaneousApproved12/2011MEGA IAB CatheterGetinge ABCoronary Artery DiseaseDevice MiscellaneousApproved04/2012AXIUS Coronary ShuntGetinge ABCoronary Artery DiseaseDevice MiscellaneousApproved04/2001SwiftNINJAMerit Medical Systems Inc.Coronary Artery DiseaseDevice MiscellaneousApproved11/2016biofluxBiotricity Inc.Coronary Artery DiseaseDevice MiscellaneousApproved10/2016ENZO Steerable MicrocatheterJohnson&JohnsonCoronary Artery DiseaseDevice MiscellaneousApproved05/2007Pivot Steerable MicrocatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved01/2004Excelsior 1018 MicrocatheterStryker CorporationCoronary Artery DiseaseDevice MiscellaneousApproved10/2004Market Spotlight Coronary Artery Disease2309 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DatePROWLER Plus MicrocathetersJohnson&JohnsonCoronary Artery DiseaseDevice MiscellaneousApprovedMozecMeril Life Sciences Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved12/2013Mozec NCMeril Life Sciences Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved07/2016COBRA PzF NanoCoated Coronary StentCeloNova Biosciences Inc.Coronary Artery DiseaseDevice MiscellaneousApproved02/2017PRO-Kinetic Energy StentBIOTRONIK AGCoronary Artery DiseaseDevice MiscellaneousApproved02/2017Firefighter PTCA Balloon Dilatation CatheterMicroPort Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved07/2023XIENCE SierraAbbottCoronary Artery DiseaseDevice MiscellaneousApproved05/2018MultiCross Support CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved11/2012MicroCross CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved04/2015CenterCross CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved11/2014CenterCross Ultra CatheterBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved01/2016CrossBoss Catheter SystemBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved05/2009Wingman Crossing CatheterReFlow Medical IncCoronary Artery DiseaseDevice MiscellaneousApproved06/2017Telemark Support MicrocatheterSurmodics,Inc.Coronary Artery DiseaseDevice MiscellaneousApproved01/2018Pursue MicrocatheterMerit Medical Systems Inc.Coronary Artery DiseaseDevice MiscellaneousApproved03/2018Market Spotlight Coronary Artery Disease2409 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateYOGA MicrocatheterJohnson&JohnsonCoronary Artery DiseaseDevice MiscellaneousApproved01/2017NovaCross Micro-CatheterMicrobot Medical Inc.Nitiloop Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved05/2015NovaCross ExtremeMicrobot Medical Inc.Nitiloop Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved10/2017RX TakeruKaneka CorporationCoronary Artery DiseaseDevice MiscellaneousApproved04/2017Refinity Rotational IVUS Imaging CatheterRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved10/2016Prowater PTCA GuidewireAsahi Intecc CO.,LTD.Coronary Artery DiseaseApproved11/2005GrandSlam PTCA CatheterAsahi Intecc CO.,LTD.Coronary Artery DiseaseDevice MiscellaneousApproved05/2003Artimes Semi-Compliant Coronary Balloon CatheterBrosMed Medical Co,Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved09/2014Apollo Non-Compliant Coronary Balloon CatheterBrosMed Medical Co,Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved09/2014SeQuent NeoB.Braun Melsungen AGCoronary Artery DiseaseDevice MiscellaneousApproved06/2017OPN NC Super High Pressure PTCA BalloonSIS Medical AGCoronary Artery DiseaseDevice MiscellaneousApproved03/2022Promus ELITE Drug Eluting StentBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved09/2018Teleport MicrocatheterOrbusNeich Medical Group Holdings Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved11/2018KaterziaAzurity Pharmaceuticals,Inc.Coronary Artery DiseaseCalcium ChannelApproved07/2019OmniWireRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApprovedMarket Spotlight Coronary Artery Disease2509 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateXIENCE SkypointAbbottCoronary Artery DiseaseDevice MiscellaneousApproved05/2021XO Cross MicrocatheterTransit ScientificCoronary Artery DiseaseDevice MiscellaneousApproved04/2022Onyx Frontier DESMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved05/2022NorliqvaCMP Pharma,Inc.Coronary Artery DiseaseCalcium ChannelApproved02/2022POT PTCA Balloon Dilatation CatheterBrosMed Medical Co,Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved04/2023Ringer Perfusion Balloon CatheterTeleflex IncorporatedCoronary Artery DiseaseDevice MiscellaneousApproved05/2024XO Cath MicrocatheterTransit ScientificCoronary Artery DiseaseDevice MiscellaneousApproved11/2023Gusta PTCA Balloon Dilatation CatheterBeijing Demax Medical Technology co.,Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeVIVO ISARTranslumina GmbHCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeWedge NC Scoring Balloon Dilatation CatheterBrosMed Medical Co,Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeAlveo HP Balloon Dilatation CatheterBrosMed Medical Co,Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeMaRVis Golden WireMaRVis Interventional GmbHCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeNavitianiVascular S.L.UCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeEasyT High Performance PTCA Dilatation CatheterSIS Medical AGCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeWedge Semi-Compliant Scoring PTCA Balloon CatheterBrosMed Medical Co,Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeMarket Spotlight Coronary Artery Disease2609 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateITRIX Rapamycin Eluting Coronary Stent Implantation SystemQ3 Medical Devices LimitedCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeARTHOS Pico Cobalt Chromium StentQ3 Medical Devices LimitedCoronary Artery DiseaseDevice MiscellaneousApproved in EuropePacSol Drug Eluting BalloonQ3 Medical Devices LimitedCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeISTAR PTCA Semi-Compliant BalloonQ3 Medical Devices LimitedCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeSerpentisSTENTYS SACoronary Artery DiseaseDevice MiscellaneousApproved in EuropeXLIMUS Sirolimus Eluting Coronary Stent SystemCardionovum GmbHCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeFantom Encore Bioresorbable ScaffoldREVA Medical Inc.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeBeGraft Aortic Stent SystemBentley Innomed GmbHCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeBeGraft Coronary Stent Graft SystemBentley Innomed GmbHCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeDevoir DEBSTENTYS SACoronary Artery DiseaseDevice MiscellaneousApproved in EuropeAmazonia SIRSTENTYS SACoronary Artery DiseaseDevice MiscellaneousApproved in EuropeYangtze PTCA BalloonsSTENTYS SACoronary Artery DiseaseDevice MiscellaneousApproved in EuropeTREATPurple Medical Solutions Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeBRAVO NC Balloon Dilatation CatheterSino Medical Sciences Technology Inc.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeSLEEK Prime PTCA Balloon CatheterSino Medical Sciences Technology Inc.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeMarket Spotlight Coronary Artery Disease2709 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateFlexinniumSahajanand Medical Technologies Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeGenXsyncPurple Medical Solutions Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeProteaPurple Medical Solutions Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeCoroflex ISAR NEO Sirolimus Eluting Polymer-Free Coronary Stent SystemB.Braun Melsungen AGCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeXperience Coronary Dilatation CatheteriVascular S.L.UCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeOceanus PTA Dilatation CatheteriVascular S.L.UCoronary Artery DiseaseDevice MiscellaneousApproved in EuropePantera ProBIOTRONIK AGCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeSolarFlex Coronary Artery StentDISA Vascular Pty LtdCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeCape Cross PTCA Balloon CatheterDISA Vascular Pty LtdSurmodics,Inc.(SRDX)Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeEscape Aspiration CatheterDISA Vascular Pty LtdCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeVactaFlexSahajanand Medical Technologies Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeAneugraftDxAmnis Therapeutics Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeIndolimusSahajanand Medical Technologies Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeMarket Spotlight Coronary Artery Disease2809 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateDESolve Cx Scaffold SystemElixir Medical CorpCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeSupport C Paclitaxel Coated Coronary Balloon Cathetereucatech AGCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeAngioliteiVascular S.L.UCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeeucaLimuseucatech AGCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeIkazuchi ZeroKaneka CorporationCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeBioMime Sirolimus Eluting Coronary Stent SystemMeril Life Sciences Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeCre8 Amphilimus Eluting StentAlvimedicaCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeNIC Nano 0.85 CTO BalloonSIS Medical AGCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeNIC 1.1 ULP CTOSIS Medical AGCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeSupralimus-CoreSahajanand Medical Technologies Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeWilma SCSahajanand Medical Technologies Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in Europe11/2014SupraflexSahajanand Medical Technologies Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeGenous CoCrOrbusNeich Medical Group Holdings Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeLunawave Coronary Imaging ConsoleTerumo CorporationCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeMarket Spotlight Coronary Artery Disease2909 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateFastview Coronary Imaging CatheterTerumo CorporationCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeFOXTROT PRO PTCA Balloon CatheterMicroPort Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeBioMatrix AlphaBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeCHROMA Coronary Stent SystemBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeGazelle Rapid Exchange Coronary Stent SystemBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeBioStream Paclitaxel Eluting PTCA Balloon CatheterBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeWALTZ CoCr Coronary Stent SystemMicroPort Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeFirehawkMicroPort Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeChocolate HeartTeleflex IncorporatedCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeUltimaster Drug Eluting StentTerumo CorporationCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeXposition S Sirolimus-Eluting Self Apposing Coronary Stent SystemSTENTYS SACoronary Artery DiseaseDevice MiscellaneousApproved in EuropeDriver Sprint RX Coronary Stent SystemMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeART Pure Bioresorbable ScaffoldArterial Remodeling Technologies S.A.Terumo Corporation(4543)Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeFreesolveBIOTRONIK AGCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeMarket Spotlight Coronary Artery Disease3009 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateFantom Bioresorbable ScaffoldREVA Medical Inc.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeNobori DESTerumo CorporationBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeDESyne Novolimus Eluting Coronary Stent SystemElixir Medical CorpCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeDESolve Scaffold System Elixir Medical CorpCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeDESyne BD Novolimus Eluting Coronary Stent SystemElixir Medical CorpCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeYukon Choice 4Translumina GmbHCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeAngioSculptX Drug-Coated PTCA Scoring Balloon CatheterRoyal PhilipsCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeIN.PACT FalconMedtronic plcCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeSeQuent PleaseB.Braun Melsungen AGCoronary Artery DiseaseDevice MiscellaneousApproved in EuropePantera LuxBIOTRONIK AGCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeBiomatrix NeoFlexBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeDexamet Dexamethasone-Eluting Coronary StentAbbottCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeBioMatrix FlexBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropePowerline PTCA Balloon CathetersBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeMarket Spotlight Coronary Artery Disease3109 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateAxxessBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeValecor Coronary Stent SystemAdvanSource Biomaterials CorporationCoronary Artery DiseaseDevice MiscellaneousApproved in EuropeSparrow StentBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in EuropeNeoVas Bioresorbable Coronary ScaffoldLepu Medical Technology(Beijing)Co.,Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in other than U.S./E.U.Partner DESLepu Medical Technology(Beijing)Co.,Ltd.Coronary Artery DiseaseDevice MiscellaneousApproved in other than U.S./E.U.Cobal C Cobalt Chromium Coronary Stent SystemRelisys Medical Devices LimitedCoronary Artery DiseaseDevice MiscellaneousApproved in other than U.S./E.U.Cobal CE Cobalt Chromium Coronary Stent SystemRelisys Medical Devices LimitedCoronary Artery DiseaseDevice MiscellaneousApproved in other than U.S./E.U.Legend-V Stainless Steel Coronary Stent SystemRelisys Medical Devices LimitedCoronary Artery DiseaseDevice MiscellaneousApproved in other than U.S./E.U.Release-R Sirolimus Eluting Coronary Stent SystemRelisys Medical Devices LimitedCoronary Artery DiseaseDevice MiscellaneousApproved in other than U.S./E.U.Release-T Paclitaxel Eluting Coronary Stent SystemRelisys Medical Devices LimitedCoronary Artery DiseaseDevice MiscellaneousApproved in other than U.S./E.U.Veda R PTCA CatheterRelisys Medical Devices LimitedCoronary Artery DiseaseDevice MiscellaneousApproved in other than U.S./E.U.Veda PTCA CatheterRelisys Medical Devices LimitedCoronary Artery DiseaseDevice MiscellaneousApproved in other than U.S./E.U.Ananth Radial Angiographic CatheterRelisys Medical Devices LimitedCoronary Artery DiseaseDevice MiscellaneousApproved in other than U.S./E.U.Inspiron DESScitech Produtos Medicos S/ACoronary Artery DiseaseDevice MiscellaneousApproved in other than U.S./E.U.OPTIMUS NCScitech Produtos Medicos S/ACoronary Artery DiseaseDevice MiscellaneousApproved in other than U.S./E.U.Market Spotlight Coronary Artery Disease3209 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateASA/Pravastatin(Endo)Endo,Inc.Coronary Artery DiseaseCyclooxygenase 1(COX1)/Prostaglandin-Endoperoxide Synthase 1(PTGS1)HMG CoA Reductase(HMGR)Withdrawn from MarketCypher StentCardinal Health,Inc.Coronary Artery DiseaseDevice MiscellaneousWithdrawn from Market04/2003ABSORB BVSAbbottCoronary Artery DiseaseDevice MiscellaneousWithdrawn from Market07/2016Obicetrapib/Ezetimibe FDCNewAmsterdam Pharma BVCoronary Artery DiseaseCholesteryl Ester Transfer Protein(CETP)LipoproteinsNiemann-Pick C1-Like 1(NPC1L1)proteinIIIRUC-4CeleCor Therapeutics,Inc.Coronary Artery DiseaseAlpha 2 Adrenergic ReceptorIIbMAS-825Novartis AGCoronary Artery DiseaseTIM3(T-cell Immunoglobulin and Mucin domain 3)IIDFV-890Novartis AGCoronary Artery DiseaseNLRP3/InflammasomeIIVascu-GrowVenturis Therapeutics,IncCoronary Artery DiseaseFibroblast Growth Factor Receptor(FGFR)IIREG-101Regio BiosciencesAstraZeneca PLC(AZN)Shionogi&Co.Ltd.(4507)Coronary Artery DiseaseEndothelial lipaseReverse Cholesterol Transport(RCT)IIALD-201Nuo Therapeutics,Inc.Coronary Artery DiseaseStem Cells/Other Cell TherapiesIMarket Spotlight Coronary Artery Disease3309 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateKP-001Kaken Pharmaceutical Company,LtdCoronary Artery DiseasePI3K/AKT pathwayUnknownIPrevail DCBMedtronic plcCoronary Artery DiseaseDevice MiscellaneousIDESELUTIONCordis Corp.Coronary Artery DiseaseDevice MiscellaneousIDESoundBite Crossing SystemSoundBite Medical Solutions IncVFLO MedicalCoronary Artery DiseaseDevice MiscellaneousIDEVirtue Sirolimus AngioInfusion BalloonOrchestra BioMed Holdings,Inc.Terumo Corporation(4543)Coronary Artery DiseaseDevice MiscellaneousIDEMGuard PrimeInspireMD,Inc.Coronary Artery DiseaseDevice MiscellaneousIDEMagicTouch Sirolimus DCBConcept Medical Inc.Coronary Artery DiseaseDevice MiscellaneousIDEImpella ECPJohnson&JohnsonCoronary Artery DiseaseDevice MiscellaneousIDEBuMA Biodegradable Drug Coating Coronary Stent SystemSino Medical Sciences Technology Inc.Coronary Artery DiseaseDevice MiscellaneousIDEMiStentMicell Technologies,Inc.STENTYS SA(STNT)Coronary Artery DiseaseDevice MiscellaneousIDEOMEGA Stent SystemBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousIDECOMBOOrbusNeich Medical Group Holdings Ltd.Coronary Artery DiseaseDevice MiscellaneousIDEASD-002Ascendia PharmaceuticalsCoronary Artery DiseaseAdenosine Diphosphate P2Y12 ReceptorINDBiosensors MicrocatheterBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Market Spotlight Coronary Artery Disease3409 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateYN001Beijing Inno Medicine Co.,Ltd.Coronary Artery DiseaseUnknownDevelopment Outside U.S.DESyne BDS Plus StentElixir Medical CorpCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.LithiX Hertz Contact Lithotripsy CatheterElixir Medical CorpCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Venus-NeoVenus MedTech,Inc.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.BMS-986141Bristol Myers Squibb CompanyCoronary Artery DiseaseProtease Activated Receptor-4(PAR4)Development Outside U.S.RESTORE DEBCardionovum GmbHCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.IBS Sirolimus-Eluting Iron Absorbable Coronary Stent SystemLifetech Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.SEQUENCE Sirolimus Eluting Coronary StentENDOCOR Gmbh.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.CONSTELLATION Coronary Stent SystemENDOCOR Gmbh.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.CARDIOGLIDE HPENDOCOR Gmbh.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.CARDIOGLIDE CTOENDOCOR Gmbh.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.CARDIOGLIDEENDOCOR Gmbh.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.IKAZUCHI X Hyp PTCA Balloon CatheterKaneka CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Ryusei PTCA Balloon CatheterKaneka CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Thrombuster II 6Fr Thrombus Aspiration CatheterKaneka CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Market Spotlight Coronary Artery Disease3509 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateThrombuster II 8Fr Thrombus Aspiration CatheterKaneka CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Thrombuster III SL Thrombus Aspiration CatheterKaneka CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Thrombuster III GR Thrombus Aspiration CatheterKaneka CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.NEXGEN Cobalt Chromium Coronary Stent SystemMeril Life Sciences Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Crypton Stainless Steel Coronary Stent SystemMeril Life Sciences Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.BioMime Morph Sirolimus Eluting Coronary Stent SystemMeril Life Sciences Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Vesta CorPurple Medical Solutions Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.VestasyncPurple Medical Solutions Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.GenX CrCoPurple Medical Solutions Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.GenXPurple Medical Solutions Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.TetriniumSahajanand Medical Technologies Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Wilma CTOSahajanand Medical Technologies Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Wilma NCSahajanand Medical Technologies Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.TR BandTerumo CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Market Spotlight Coronary Artery Disease3609 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateCES-1 Stent SystemOtsuka Holdings Co.,Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.X-changePurple Medical Solutions Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.DirectXPurple Medical Solutions Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.FASTTECHPurple Medical Solutions Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.ZOOMEXPurple Medical Solutions Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Galaxy Rapamycin Drug-Eluting Bioresorbable Coronary Stent SystemShanghai Bio-heart Biological Technology Co.,Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Axetis Inert Coronary StentAxetis AGCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Supralimus Grace Drug Eluting Coronary StentSahajanand Medical Technologies Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.BIOTRONIK Anti-Proliferative Limus Coronary StentBIOTRONIK AGCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.FiresorbMicroPort Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.ABLUMINUS Sirolimus-Eluting Stent SystemEnvision Scientific Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.FOCUS np Stent SystemEnvision Scientific Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Coracto Sirolimus Eluting Coronary StentAlvimedicaCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.MGuard Drug ElutingInspireMD,Inc.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Market Spotlight Coronary Artery Disease3709 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateEssentialiVascular S.L.UCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Excel Drug Eluting StentBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Titan OptimaxHexacathCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Titan 2HexacathCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.HelixHexacathCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Mistral SCHexacathCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Mistral NCHexacathCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.ZondaHexacathCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.RecoverHexacathCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Amruth Femoral Angiographic CatheterRelisys Medical Devices LimitedCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Lotus II GuidewireRontis CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.EveroflexSahajanand Medical Technologies Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Abrax Sirolimus-Euting Stent SystemRontis CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.TetriFlexSahajanand Medical Technologies Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Market Spotlight Coronary Artery Disease3809 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateTetrilimus Everolimus-Eluting Cobalt Chromium Coronary Stent SystemSahajanand Medical Technologies Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.PICSO Impulse SystemMiracor Medical SACoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.TINSIS Medical AGCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.BEO NCSIS Medical AGCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Standard PTCA Guide WiresSIS Medical AGCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.CTO Guide WiresSIS Medical AGCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.PTA Guide WiresSIS Medical AGCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Ikazuchi-RevKaneka CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.RAIDEN3Kaneka CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.CCflexeucatech AGCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.eucaVIeucatech AGCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.ArchitectiVascular S.L.UCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.eucaACeucatech AGCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Inno-SpringSuzhou Innomed Medical Device Co.,Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.AMIMarket Spotlight Coronary Artery Disease3909 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateAMITYElixir Medical CorpCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.AMITY CxElixir Medical CorpCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.DESolve NXTElixir Medical CorpCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.DESolve NXT PLUSElixir Medical CorpCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.JACTAX StentBoston Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Corio Pimecrolimus-eluting StentJohnson&JohnsonCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.BMX-JBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Mustang Coronary Stent SystemMicroPort Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Tango Cobalt Chromium Coronary Stent SystemMicroPort Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Firebird2 Rapamycin-Eluting Coronary CoCr Stent SystemMicroPort Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.JIVE PTCA Balloon CatheterMicroPort Scientific CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.MeRes 100Meril Life Sciences Pvt.Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Drug-Filled Stent(DFS)Medtronic plcCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Coroflex DEBlueB.Braun Melsungen AGCoronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Igaki-Tamai Coronary StentKyoto Medical Planning Co.,Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopment Outside U.S.Market Spotlight Coronary Artery Disease4009 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateEngensisHelixmith Co.,Ltd.Beijing Northland Biotechnology Co.,LtdCoronary Artery DiseaseHepatocyte growth factor receptor(c-Met,HGFR)Development Outside U.S.IntelliWireMerit Medical Systems Inc.IntelliMedical TechnologiesCoronary Artery DiseaseDevice MiscellaneousPreclinicalArterioSorbArterius LimitedCoronary Artery DiseaseDevice MiscellaneousPreclinicalAGEX-VASC1AgeX Therapeutics,Inc.Coronary Artery DiseaseStem Cells/Other Cell TherapiesPreclinicalCYP-006TKCynata Therapeutics LimitedCoronary Artery DiseaseStem Cells/Other Cell TherapiesPreclinicalFluydo Non-Compliant Balloon CatheterAlvimedicaCoronary Artery DiseaseDevice MiscellaneousDevelopmentBiolimus A9 DCBBiosensors International Group Ltd.Coronary Artery DiseaseDevice MiscellaneousDevelopmentLacrosse NSE ALPHA Coronary Dilatation Balloon CatheterInfraReDx Inc.Coronary Artery DiseaseDevice MiscellaneousDevelopmentSirPlux Duo Drug-Coated BalloonAdvanced NanoTherapies,Inc.Coronary Artery DiseaseDevice MiscellaneousDevelopmentSoundBite Active Microcatheter SystemSoundBite Medical Solutions IncVFLO MedicalCoronary Artery DiseaseDevice MiscellaneousDevelopmentPropel Percutaneous Ventricular Assist DeviceAbbottCoronary Artery DiseaseDevice MiscellaneousDevelopmentBioresorbable Coronary StentKaneka CorporationCoronary Artery DiseaseDevice MiscellaneousDevelopmentPulsatile Intravascular Lithotripsy SystemAVSCoronary Artery DiseaseDevice MiscellaneousDevelopmentCreaValve TAVR systemOnecrea Medical,Inc.Coronary Artery DiseaseDevice MiscellaneousDevelopmentMarket Spotlight Coronary Artery Disease4109 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)DrugLead CompanyPartnerIndicationTargetPhaseApproval DateDynamX Drug-Eluting StentElixir Medical CorpCoronary Artery DiseaseDevice MiscellaneousDevelopmentCADence SystemAUM CardiovascularCoronary Artery DiseaseDevice MiscellaneousDevelopmentCORGUARD Coronary Stent SystemContego Medical,LLCCoronary Artery DiseaseDevice MiscellaneousDevelopmentReZolve ScaffoldREVA Medical Inc.Coronary Artery DiseaseDevice MiscellaneousDevelopmentSymBio Pimecrolimus/Paclitaxel-eluting stentJohnson&JohnsonCoronary Artery DiseaseDevice MiscellaneousDevelopmentMyoVista Wavelet ECGHeart Test Laboratories,Inc.Coronary Artery DiseaseDevice MiscellaneousDe Novo Market Spotlight Coronary Artery Disease4209 Jan,2025Copyright 2025 Citeline,a Norstella company(Unauthorized photocopying prohibited)Citeline powers a full suite of complementary business intelligence offerings to meet the evolving needs of life science professionals to accelerate the connection of treatments to patients and patients to treatments.These patient-focused solutions and services deliver and analyze data used to drive clinical,commercial and regulatory related-decisions and create real-world opportunities for growth.Our global teams of analysts,journalists and consultants keep their fingers on the pulse of the pharmaceutical,biomedical and medtech 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CRISPR:UPDATES ON THE GROWING IMPORTANCE OF THIS TECHNOLOGYCAS INSIGHTSCRISPR(clustered regularly interspaced short palindromic repeats)and CRISPR-associated proteins(Cas)are naturally occurring mechanisms in bacteria and archaea that work as a defense mechanism against viral infection that have since been harnessed to enable precise and efficient genome editing in a variety of organisms.16 This technology has revolutionized the field of genetic engineering and therapeutic development,1,79 offering unprecedented opportunities to advance our understanding of genetic diseases,develop novel therapies,and potentially cure previously intractable conditions.1 However,it is important to recognize its broader potential in medical diagnosis,synthetic biology,agriculture and food,and environmental bioremediation.For example,CRISPR/Cas has been harnessed for plant genome editing17,18 to develop crops that are high-yielding and resistant to abiotic and biotic stresses,and around 13%of CRISPR-related documents are associated with the application of CRISPR in plants and agricultural use-according to our search in the CAS Content CollectionTM.In this report,we examine data from the CAS Content Collection,the largest human-compiled multi-disciplinary database of published documents and substances,to highlight the latest advances and developments in CRISPR technology,with a focus on its potential in medicine.IntroductionCRISPR INSIGHT REPORT|3From nature to the lab:How does the CRISPR/Cas system work?In bacteria,the CRISPR/Cas system works by capturing snippets of DNA from invading viruses and storing them.When the same virus attacks again,the bacteria can quickly produce segments of a molecule called ribonucleic acid(RNA)to target the viral DNA.This RNA guides Cas proteins to the complementary viral DNA,where they can act like molecular scissors,cutting the DNA and neutralizing the threat.3,10This natural mechanism has been adapted for use in gene editing.1,11 The most commonly used system,CRISPR/Cas9,involves a guide RNA(gRNA)that matches the target DNA sequence and the Cas9 enzyme,which cuts the DNA at a specific desired location.This break in the DNA can then be repaired by the cells natural repair mechanisms,allowing for the insertion,deletion,or modification of genes.12,13 Figure 1 summarizes both the role of Cas9 in nature and its use as a genome-editing tool.Since its adaptation for gene editing,CRISPR/Cas technology has rapidly advanced,and researchers have developed various modifications of the original CRISPR/Cas9 system to improve specificity,efficiency,and versatility.The approval of the first CRISPR-Cas9-based gene editing therapy,Casgevy,approved by the U.S.Food and Drug Administration(FDA)for the treatment of patients with transfusion-dependent-thalassemia,marked a significant milestone in CRISPR technology development.The same therapy has also been approved in Europe and the U.K.with the additional indication of sickle cell disease.1416Figure 1.CRISPR/Cas9 system in nature(left)versus its adaptation for genome editing(right).S,Spacer;R,Repeats.OutcomeTarget DNA cutTarget searchCas9&gRNAproducedtracrRNAcas9RRSTargetPhage genomeDNA destroyedProkaryotic cell(immune system)Eukaryotic cell(genome editing)Custom sgRNAdesigned by scientistDelivery of genome editing toolsChromatinNucleusDNA editedAmong the key milestones for CRISPR(Figure 2),understanding of CRISPR-mediated mechanisms has significantly improved.Firstly,the natural CRISPR defense mechanism that protects bacteria was defined in three basic stages(Figure 3A):adaptation(spacer acquisition),CRISPR RNA(crRNA)maturation,and target interference.2830 Another breakthrough was the synthesis of single guide RNA(sgRNA)in the lab which combines the role of crRNA and trans-activating crRNA(tracrRNA)into a single molecule by fusing them together with a linker.26,31 The mechanism of CRISPR/Cas-9 genome editing contains three steps:recognition,cleavage,and repair,as depicted in Figure 3B.32 Figure 2.Timeline of significant events for CRISPR technology.The CRISPR timeline1987 Presence of CRISPR first reported in the Escherichia coli genome by Nakata et al.19Mid 2000s Functionality and importance of CRISPR first described in prokaryotes wherein the CRISPR system is a key component of their adaptive immunity.23252020 Doudna and Charpentier awarded the Nobel Prize in Chemistry.272002 Cas discovered by Jansen et al.20Further identification in both Gram-positive and Gram-negative bacteria,as well as archaea,led to the obvious questions regarding the relevance of CRISPR to these organisms.21,222012 Jennifer Doudna and EmmanuelleCharpentier propose that the bacterial CRISPR-Cas9 system could be used as a programmable toolkit for genome editing in humans and other animal species.262023 First CRISPR-Cas9-based gene editing therapy,Casgevy,approved by the FDA for the treatment of patients with transfusion-dependent-thalassemia.14-16 CRISPR INSIGHT REPORT|5Figure 3.Mechanisms of CRISPR/Cas9.(A)CRISPR/Cas9 adaptive immunity.The CRISPR/Cas systems are composed of a Cas operon and a CRISPR array,which comprises identical repeat sequences that are interspersed by phase-derived spacers.The CRISPR/Cas-mediated adaptive immunity consists of three stages:adaptation,maturation,and interference.(B)CRISPR/Cas9-mediated genome engineering.The synthetic sgRNA guides Cas9 in introducing a double-strand break in the target DNA.The double-strand break is repaired by DNA repair mechanisms.Figures were created with www.BioR and adapted from Jiang and Doudna(Jiang F,Doudna,2017.Annu.Rev.Biophys.46:50529).crRNA,CRISPR RNA;PAM,protospacer adjacent motif;sgRNA,single guide RNA;tracrRNA,trans-activating crRNA.sgRNACas9sgRNA(crRNA tracrRNA)Double stranded break(DSB)Endogenous DNA repairs at theDSB siteHomology directed repairKnocked-in DNAsequence of interest(Precise gene modification)InsertionDonor DNADeletionSubstitution(Random mutations causedisruption of gene function)Nonhomologous end joiningPAM5335353355Spacer acquisitioncrRNA biogenesisTarget interferenceLocusCas operonTranscriptionSpacersRepeatsPre-crRNAcrRNASite-specific cleavageCas9Cas9PAMcrRNAtracrRNAComplementary foreign DNAcrRNA maturation(RNase III processing)IntegrationInvasive viral DNAProtospacerCas1-Cas2CRISPR arrayPAMtracrRNAtracrRNACas9Cas1Cas2Csn2ABCRISPR/Cas systems have been divided largely into two classes,six types and 48 subtypes(Figure 4).33 Class 1 systems include Types I,III,and IV,which use multiprotein complexes to destroy nucleic acids,while class 2 systems include Types II,V,and VI,which use single proteins.34Below is a brief overview of natural Cas nucleases and engineered variants that have been adopted for use as therapeutics.Class 1 CRISPR/Cas systems Class 1 systems require multiple Cas proteins to come together in a complex to mediate interference against foreign genetic elements,limiting gene editing applications of class 1 systems.Class 1 systems are further divided into three CRISPR/Cas types based on the presence of a specific signature protein:Type I contains Cas3,Type III contains Cas10,and Type IV contains Csf1,a Cas8-like protein.35Class 2 CRISPR/Cas systems Unlike the Class 1 CRISPR/Cas system,the effector module of the Class 2 CRISPR/Cas system is only a single protein with multiple domains and functions.36 Class 2 CRISPR/Cas systems are further divided into three types:Type II,Type V,and Type VI.CRISPR classificationType IIType IIIType VsgRNAHNHTarget sequenceREC lobeCas9Linker loopsgRNA(crRNA tracrRNA)RuvCdsDNAPAM5335NUC lobe35Cas12asgRNATarget sequenceREC lobeLinker loopcrRNARuvCdsDNAPAM533355NUC lobessDNACollateral activity3ssDNACas12f/Cas14Target sequenceREC lobeLinker loopcrRNANUC lobessDNACollateral activitysgRNA553Type VIRNA3Cas13Target sequenceREC lobeLinker loopcrRNAPFSHEPNNUC lobessDNACollateral activitysgRNA553Class IIClass ICsf ComplexType IVcrRNAPAM533355Nuclease?CasDinGdsDNACas3Type IcrRNALinker loopPAMHDsgRNA533355dsDNAssDNACollateral activityTarget sequenceCascade ComplexCas10-Csm/Cmr ComplexcrRNACoding strandTemplate strandcrRNACas10RNAPTranscriptCsm3553DNA55Figure 4.Schematic depiction of various CRISPR/Cas system types and their cleavage characteristics.The CRISPR/Cas system is classified into two classes based on the effector molecules involved.Class I systems are characterized by multi-unit effectors,while Class II systems involve a single effector.Each class is further divided into three types,distinguished by their catalytic domain and target nucleotide specificity.The illustration was created using www.BioR.CRISPR INSIGHT REPORT|7Therapeutic possibilities with CRISPRThe concept of gene therapy was introduced by Friedmann and Roblin in 1972.37 Zinc finger nucleases(ZFN)and transcription activator-like effector nucleases(TALENs)were developed as mainstream tools to evaluate the possibility of targeting or editing genes to treat and cure diseases.However,both methods have unfavorable characteristics,making the development of effective gene therapy challenging.3841Since then,CRISPR/Cas has been defined and explored as a potential therapeutic approach for disorders previously believed to be incurable or difficult to treat.These include certain types of cancer,infectious diseases,and various genetic disorders,among others.CRISPR/Cas technology has various key applications in the field of therapeutics,the most prominent of which is the ability to correct or replace mutated or disease-causing gene(s).42 As of today,numerous CRISPR-based therapeutics are in the pre-clinical stage of development,and many are undergoing clinical trials to validate their safety and efficacy for diverse disease conditions,with one CRISPR therapeutic being U.S.FDA approved.CRISPR therapeutics publication landscape at a glanceA quantitative analysis of data from the CAS Content Collection(19952024)revealed 39,000 academic journal articles and over 14,000 patents on the application of CRISPR to therapeutics.Publications sharply rose in 2008 and have steadily increased ever since,with an average growth rate of 54%in the last decade.This total rise in publications is primarily led by academic journal articles;however,patents have shown a larger average yearly growth rate of 72%in the last decade,compared to 50%for journals,demonstrating an increase in commercial interest.Key commercial assignees of patents in the field of CRISPR therapeutics include Regeneron Pharmaceuticals in the U.S.,CRISPR Therapeutics in Switzerland,and Shandong Shunfeng Biotechnology in China,while non-commercial activity is led by the Chinese Academy of Sciences,a group of 124 individual research institutions(Figure 5).43CRISPR INSIGHT REPORT|7Figure 5.Leading commercial(A)and non-commercial(B)patent assignees in the field of CRISPR between 20042023.BANumber of patent publicationsChinese Academy of SciencesThe Broad InstituteUniversity of CaliforniaHarvard CollegeChinese Academy of Agricultural SciencesHuazhong Agricultural UniversityStanford UniversityZhejiang UniversityJiangnan UniversityChina Agricultural UniversityMassachusetts Institute of TechnologyAcademy of Military Medical Science Peoples Liberation Army of ChinaZhejiang UniversityYangzhou UniversityThe General Hospital Corporation020040015035010030050250450ChinaUnited StatesNumber of patent publicationsRegeneron Pharmaceuticals Inc.CRISPR Therapeutics AGShandong Shnufeng Biotechnology Co.,Ltd.Editas Medicine Inc.Emendo Bio Inc.Beam Therapeutics Inc.Shenzhen Biocan Technologies Co.,Ltd.Mammoth Biosciences Inc.Flagship Pioneering Inc.Arbor Biotechnologies Inc.Intellia Therapeutics Inc.Childrens Medical Center CorporationChina Tobacco Yunnan Industrial Co.,Ltd.Metagenomi Technologies LLCNanjing Superyears Gene Technology Co.,Ltd0408030702060105090ChinaSwitzerlandUnited StatesHot topics in the CRISPR publication landscape:therapeutics targeting diseasesAmong the various diseases or disorders currently being investigated,the majority of documents in the CRISPR therapeutics dataset focus on cancer and infectious diseases(Figure 6).The publication trend also shows a significant increase in the number of CRISPR articles focused on these two conditions.Other conditions investigated include blood disorders,genetic disorders,nervous system disorders,cardiovascular diseases,respiratory diseases,immune diseases,and metabolic disorders.35$%9%8%9%7%4%3%3%3%1%1%4%4%2%Infectious diseasesBlood disordersGenetic disordersNervous system disordersCardiovascular diseasesRespiratory diseasesImmune diseasesMetabolic disordersDigestive system disordersCancerJournal(outer donut),Patent(inner pie),ACRISPR INSIGHT REPORT|9CancerImmuneBloodMetabolicInfectiousRespiratoryGeneticCardiovascularNervous systemDigestive systemFigure 6.(A)Distribution and(B)time trends for CRISPR documents co-occurring with various disease conditions.Data includes journal and patent publications from the CAS Content Collection.B1,4001,2001,000800600200400Number of journal publicationsPublication year020112013201520172019202120234504003503002502001501005002011201520192013201720212023500400300200100Number of patent publicationsPublication year020112013201520172019202120232502001001505002011201520192013201720212023Figure 7A.Publication frequencies of potential gene targets occurring in the CRISPR dataset retrieved from the CAS Content Collection.Data includes patent and journal publications for the period 19952024 and is based on CAS indexing.Note that data for 2024 is incomplete due to the time of data extraction and encompasses data for January to June.Figure 7B.Time trends of some of the most highly occurring potential gene targets in the CRISPR dataset retrieved from the CAS Content Collection.Data includes patent and journal publications for the period 2014-2023 and is based on CAS indexing.Regarding target genes,TP53,c-myc,the hemoglobin beta subunit(HBB)and c-Ki-Ras are most commonly associated with CRISPR publications.In particular,TP53 has seen a rapid increase over the last few years(Figure 7).GenesYear50040030020010009075604530150Number of publicationsNumber of publicationsTP53c-mycHBBc-Ki-RasBRCA1DMDBcl-2ERBB1ERBB2CDKN2ACCL2CFTRAPCTGFB1TRPAX6ICAM1N-rasHPRTHLA-ACXCL1RB1NF1HLA-BIL-6COL1A1 SOD1CXCL10LDLRRAG1APOEHLA-CIL1BFasMDM22014201520172016201920182021202020232022TP53c-mycBRCA1ERBB1c-Ki-RasHBBCCL2ERBB2Bcl-2DMDCDKN2ACRISPR INSIGHT REPORT|11Figure 8.Co-occurrence of cancer subtypes with genes in the CRISPR dataset retrieved from the CAS Content Collection.Data includes patent and journal publications for the period 19952024.CancerFundamentally,cancer originates from activating and inactivating mutations or from the dysregulation of the epigenome.At the cellular level,altered metabolism,cell structure,and migration facilitate the expansion of cancer cells.Eventually,cancer cells circumvent the immune defense mechanism of the host and co-exist with normal cells.Understanding the complex genomic,cellular,and tissue level changes is crucial for the developing more effective treatment options and improving outcomes.CRISPR has had a significant impact on our understanding of cancer biology and is continuously driving new discoveries in the field.44Multiple gene candidates are being studied in cancer in the context of CRISPR.Figure 8 below shows the co-occurrence of cancer types and genes found in the CRISPR dataset retrieved from the CAS Content Collection,and Table 1 shows the variety of applications of CRISPR to cancer therapy.Table 1.Approaches to using CRISPR/Cas technology in cancer.Therapeutic Correcting driver mutations in oncogenes or tumor suppressor genes4554 Modifying or silencing epigenetic markers5559 Supporting immunotherapy6064 Targeting mutations that determine drug response or susceptibility6571 Inactivating carcinogenic viral infections7276Disease pathology Creating tumor models and organoids195197 Creating high-throughput genetic screens198200Breast cancerAcute myeloid leukemiaLiver cancerLung cancerRectal cancerMelanomaGlioblastomaKidney cancerProstate cancerTP53:120BRCA1:32ERCC1:18c-Ki-Ras:50c-myc:36ERCC2:16APC:26ERBB2:15ERBB1:33XRCC1:13ERCC3:12N-ras:12Bcl-2:12NF1:10c-Ki-Ras2:9CDKN2A:8ERCC6:8RB1:6MGMT:5HBB:4VHL:4ICAM1:4LPL:4CCL2:4JUN:4CXCL1:4fos:4Cancer subtypeGeneInfectious diseases Infectious diseases represent the second largest subset of CRISPR-related documents in the CAS Content Collection.Of the journal and patent publications mentioning human diseases,infectious diseases account for 25%and 22%,respectively.Over the past few years,there has been a significant increase in the number of documents on infectious diseases and CRISPR/Cas technology.The majority of these documents focus on anti-viral studies.CRISPR/Cas technology has emerged as a promising alternative to develop therapeutics against various pathogens via the following methods:7779 Targeting the pathogen genes required for replication,or entering or infecting the host cells Altering the host genes required by the pathogen to cause infection Modifying the genes responsible for drug resistance or susceptibilityBlood disorders CRISPR/Cas technology possesses an interesting possibility of providing a cure for patients with inherited monogenic blood diseases like sickle cell anemia and-thalassemia.As previously highlighted,Casgevy was the first U.S.FDA-approved CRISPR therapeutic and is an autologous gene therapy that targets the BCL11A gene,preventing red blood cells from adopting the sickle shape.80 Other gene-targeting therapies for the treatment of sickle cell anemia and-thalassemia are currently in clinical trials.81 Genetic disorders Among the many promising possibilities of using CRISPR-based therapeutics,their translational use in monogenic human genetic diseases has the potential to provide long-term therapy with a single treatment.Genetic disorders can be treated with the help of CRISPR by editing the defective(disease-causing)gene or by editing the enhancer or regulator of the defective gene.Numerous studies have shown promising results by using these two approaches.Genetic disorders for which CRISPR-based therapeutics have been investigated include Duchenne muscular dystrophy(Dystrophin DMD gene),Huntingtons disease(Huntingtin HTT gene),and glaucoma(MYOC).8284Nervous system disorders The publication rate of CRISPR-related documents on Alzheimers and Parkinsons diseases has increased in recent years.CRISPR/Cas9 technology has gained popularity in the field of neurodegenerative diseases due to its short experimental duration and easy molecular engineering requirements.It is currently being extensively utilized for building disease models,identifying pathogenic genes through screening,and for targeted therapy.8591 CRISPR in practiceClinical developmentOver the last decade,CRISPR has advanced significantly in clinical research,with numerous trials launched to explore its potential in therapeutics,and the first CRISPR-based medicine was approved in just 11 years.1416Figure 9A shows the steady increase in the number of CRISPR-based therapeutics in development over the past decade.There are currently 142 CRISPR therapeutics in different stages of development.Of these,10%are in Phase I,11%in Phase II,and 1%in Phase III clinical trials.The majority(77%)are in the pre-clinical stage(Figure 9B).CRISPR INSIGHT REPORT|13CRISPR pre-clinical research and clinical trials are targeting a wide range of diseases,from rare genetic disorders and blood diseases to various forms of cancer and infectious diseases such as human immunodeficiency virus(HIV),tuberculosis,and COVID-19(Figure 10).Figure 9.(A)Year-wise distribution of CRISPR-based therapeutics in pre-clinical and clinical trials.(B)Current status of CRISPR-based therapeutics in various stages of development.Data taken from Pharmaproject Citeline Clinical Intelligence.Note that data for 2024 is incomplete due to time of data extraction and encompasses data for January to June.Figure 10.Distribution of CRISPR-based therapeutics under development among different disease groups.The stacked bar shows the split of therapeutics among various stages of development for each disease group.The percentage distribution among disease groups has been mentioned in parentheses.Data from Pharmaproject Citeline Clinical Intelligence.Note that data for 2024 is incomplete due to time of data extraction and encompasses data for January to June.ABNumber of CRISPR-based therapeutics in development16014012010080604020020152016201720182019Year2020 2021 2022 2023 2024Pre-clinical110Phase l14Phase II15Phase III 2Registered 1Disease groupNumber of CRISPR-based therapeuticsAnticancerBlood and clottingSensoryMusculoskeletalAlimentary/metabolicNeurologicalCardiovascularAnti-infectiveImmunologicalRespiratoryDermatological010203040Pre-clinicalPhase IPhase IIPhase III Registered (12%)(9%)(7%)(12%)(9%)(4%)(10%)(8%)(3%)(1%)(25%)The distribution of CRISPR-based therapeutics in pre-clinical development and clinical trials is shown in Figures 11A and 11B,respectively.Most pre-clinical research and clinical trials are focused on using CRISPR-related therapies as anticancer treatments,with solid cancers being the primary target.Figure 11A.Distribution of CRISPR-based therapeutics in the pre-clinical stage of development across disease groups,individual diseases,and their biological targets.Data retrieved from Pharmaproject Citeline Clinical Intelligence in June 2024.NOS,not specified;NA,not available.Disease groupDisease nameTarget nameNOS:55NA:16Dystrophin:3DDR1:1PTK7:1SLC39A6:1DNA pol:1CD70:1NFE2L2:1GPC3:1CD83:1PRPF31:1OTOF:1TGFBI:1VEGF-A:1DUX4L1:1LAMA1:1HAO1:1GAA:1C9orf72-SMCR8:1STMN2:1SOD1:1UBE3A:1TRR:1PMP22:1SCN9A:1Factor VIII:1Factor IX:1ALAS:1PCSK9:1AGT:1CFTR:1SERPINA1:1PRE-CLINICALAnticancer:22Sensory:14Solid cancer:12NOS cancer:12HM:2NSCLC:1NCC:1BCL:1BC:1ALM:1ODs:1RP:1CRD:1CD:1AMD:1DMD:7CMD:1DM:2HD:3UC:1PH:1IBD:3AS:1CMT:1HA:2HeFH:2DCM:1HTN:1HSV:1NOS BI:1CF:1RTI:1NOS ROs:1CIPN:1SCD:1HCM:1FH:1HIV:1HBV:1JCV:1AAT:1hATTR:1Neutropenia:1Thalassaemia:1AD:1RIGI:1T1D:2ALS:5HB:3EB:1ATTRv amyloidosis:2Pompes disease:1Porphyria:1NOS HLD:2CDs,MDD,GAD:1Staph bacteria:1FSHD:2MD:1Retinoschisis:1NOS MD:1Hearing loss:1Alimentary/metabolic:12Neurological:11Blood and clotting:9Cardiovascular:8Anti-infective:7Unspecified:6Respiratory:4Dermatological:1Musculoskeletal:12CRISPR INSIGHT REPORT|15Figure 11B.Distribution of CRISPR-based therapeutics in the clinical stages(Phase I,II and III)of development across disease groups,individual diseases,and their biological targets.Data retrieved from Pharmaproject Citeline Clinical Intelligence in June 2024.NOS,not specified;NA,not available.Disease groupClinical trial phaseDisease nameTarget namePhase I:14VEGF-A:2TNFRSF17:2IL3RA:1PIk4:1USP1:2CD19:3PD-1:1SOCS1:1ANGPTL3:1HBB:1NA:8CD70:1Lp(a):1NOS:3HBG1:1KLKB1 gene:1TTR:1Phase II:15Phase III:2Sensory:2Retinopathy:1BC,OC,PC,BPC cancer:1Solid cancer:2SCC,NSCLC:1HeFH/HoFH:1GI,NSCLC:1Thalassaemia:3AMD:1AML:1NHL:2SCD:4FH:1UTI:1HIV/AIDS:1T1D:1HAE:1hATTR:1BCL/TCL:1CVD NOS:1ALL:1BCL:1MM:2Anticancer:13Cardiovascular:3E.coli prophylaxis:1Blood and clotting:7Anti-infective:3Alimentary/Metabolic:1Immunological:1Neurological:1Disease names:AML:Acute myeloid leukemia,NHL:non-Hodgkins lymphoma,MM:multiple myeloma,NOS:unspecified,SCD:sickle cell disease,FH:familial hypercholesterolemia,HeFH/HoFH:heterozygous/homozygous familial hypercholesterolaemia,CVD:cardiovascular disease,AMD:wet age-related macular degeneration,BC:breast cancer,OC:ovarian cancer,PC:pancreatic cancer,BPH:benign prostatic hyperplasia,GI:gastrointestinal cancer,NSCLC:non-small cell lung cancer,SCC:squamous cell carcinoma,ALL:acute lymphocytic leukemia,BCL:B-cell lymphoma,TCL:T-cell lymphomas,HAE:hereditary angioedema,HIV/AIDS:human immunodeficiency virus/acquired immunodeficiency syndrome,T1D:type 1 diabetes,UTI:urinary tract Infection,hATTR:hereditary transthyretin amyloidosis,HD:hereditary disease of metabolism,UC:ulcerative colitis,HD:Hepatic dysfunction,PH:primary hyperoxaluria,IBD:Inflammatory bowel disease,RIGI:Radiation-induced gastric injury,HM:Hematological Malignancies,HCC:hepatocellular carcinoma,NOS BI:unspecified bacterial Infection,HBV:hepatitis-B virus,HSV:herpes simplex virus,JCV:John Cunningham virus,RTI:respiratory tract Infection,Staph:staphylococcal,HA:haemophilia A,HB:haemophilia B,DCM:dilated cardiomyopathy,HCM:hypertrophic cardiomyopathy,HLD:Hyperlipidaemia,HTN:hypertension,EB:epidermolysis bullosa,NOS AD:unspecified autoimmune disease,CMD:congenital muscular dystrophy,DMD:Duchennes muscular Dystrophy,FSHD:facioscapulohumeral muscular dystrophy,NOS MD:unspecified muscular dystrophy,MD:myotonic muscular dystrophy,AD:Alzheimers disease,ALS:amyotrophic lateral sclerosis,AS:angelman syndrome,CDs:Cognitive disorders,MDD:major depressive disorder,GAD:generalized anxiety disorder,CMT:CharcotMarietooth disease,CIPN:chemotherapy-induced peripheral neuropathy,CF:cystic fibrosis,AAT:alpha-1 antitrypsin deficiency,NOS RDs:unspecified respiratory diseases,ODs:ocular disorders,CRD:cone-rod dystrophy,MD:macular dystrophy,RP:retinitis pigmentosa,CD:corneal dystrophy.Target names:IL3RA:Interleukin 3 receptor alpha,CD19:CD19 molecule,TNFRSF17:TNF receptor superfamily member 17,Plk4:polo-like kinase 4,USP1:ubiquitination-specific proteases,NA:not applicable,NOS:unspecified,ANGPTL3:Angiopoietin-like protein 3,VEGF-A:vascular endothelial growth factor A,Lp(a):lipoprotein(a),SOCS1:suppressor of cytokine signaling 1,CD19:CD19 molecule,PD-1:programmed cell death 1,CD70:CD70 molecule,KLKB1:kallikrein B1,HBB:hemoglobin subunit beta,HBG1:hemoglobin subunit gamma 1,TTR:transthyretin,HAO1:hydroxyacid oxidase 1,GAA:glucosidase alpha,GPC3:glypican 3,NFE2L2:nuclear factor,erythroid 2 like 2,DDR1:discoidin domain receptor tyrosine kinase 1,PTK7:protein tyrosine kinase 7(inactive),SLC39A6:solute carrier family 39 member 6,DNA pol:DNA polymerase theta,Factor VIII:coagulation factor VIII,Factor IX:coagulation factor IX,ALAS:5-aminolevulinate synthase 1,PCSK9:proprotein convertase subtilisin/kexin type 9,AGT:angiotensinogen,LAMA1:laminin subunit alpha 1,DUX4L1:double homeobox 4 like 1(pseudogene),C9orf72-SMCR8:C9orf72-SMCR8 complex subunit,STMN2:stathmin 2,SOD1:superoxide dismutase 1,UBE3A:ubiquitin protein ligase E3A,PMP22:peripheral myelin protein 22,SCN9A:sodium voltage-gated channel alpha subunit 9,CFTR:CF transmembrane conductance regulator,SERPINA1:serpin family A member 1,PRPF31:pre-mRNA processing factor 31,OTOF:otoferlin,TGFBI:transforming growth factor beta induced.Delivery systems:The portal for therapeutic useDespite the potential of CRISPR,its therapeutic application faces some challenges,particularly in the area of cellular delivery systems.Effective and safe delivery of CRISPR components such as the Cas9 nuclease and gRNA to target cells and tissues is paramount for achieving the desired therapeutic outcomes while minimizing off-target effects and immune responses.9294The choice of delivery method can significantly influence the efficiency,specificity,and safety of CRISPR-mediated gene editing.Carriers currently used for delivery fall into three general groups:viral vectors,non-viral vectors,and physical delivery methods(Figure 12).9599 Viral vectors dominate the publication landscape,with adeno-associated vectors(AAVs)being the most commonly represented.Electroporation and microinjection are the most widely used physical delivery methods.ADelivery systemsCRISPR/Cas9 systemsGene editingViral vectorsNon-viral vectorsPhysicaldeliveryAdeno-associatedvirusMicroinjectionLipid nanoparticleAdenovirusElectroporationPolymer nanoparticleLentivirusPlasmid DNASonoproationHydrodynamicinjectionCas9 RNPGold nanoparticleCell penetration peptideCas9 mRNA sgRNACRISPR INSIGHT REPORT|17Table 2.Attributes of molecular diagnostic methods NGS,PCR,and CRISPR/Cas.138148cDNA,complimentary deoxyribonucleic acid;CRISPR/Cas,clustered regularly interspaced short palindromic repeats/CRISPR associated proteins;DNA,deoxyribonucleic acid;PCR,polymerase chain reaction;RNA,ribonucleic acid.The utility of CRISPR/Cas technology is not limited to disease modification and has rapidly evolved into a powerful tool for disease diagnosis.138140 Its ability to detect specific genetic sequences is invaluable for identifying infectious diseases,genetic disorders,and even cancers.Quantitative polymerase chain reaction(qPCR),isothermal amplification,and next-generation sequencing(NGS)are currently used in routine clinical diagnostics,141144 but all have pitfalls.144146 Therefore,the CRISPR/Cas system can open a new window of possibilities for genetic diagnostics that integrates the ease of use and cost efficiency of isothermal amplification with the diagnostic accuracy of qPCR.Moreover,the CRISPR/Cas system can fulfill the ASSURED criteria(affordable,sensitive,specific,user-friendly,rapid,equipment-free,delivered)set by the World Health Organization147 for infectious disease diagnostics.Table 2 compares the three molecular detection methods.CRISPR diagnosticsMethodTime required Response proceduresAdvantagesDisadvantagesNGS20 hoursLibrary preparation,NGS sequencing,bioinformatics analysisComprehensive analysis of all nucleic acids,rapid and preliminary identification of new pathogensExpensive equipment,complex operation,and not all genomes are availableqPCR1.5 hoursReverse transcription,RNA-cDNA hybridization denaturation,PCR amplification Gold standard,currently the most common detection methodRequires complex laboratory infrastructure and specialized technical personnelCRISPR/Cas0.6 hoursDNA amplification,Cas reactionLow cost,high sensitivity,no need for complex instruments and equipment,fast and convenient for field testingNot widely used in clinical trials,pending clinical validationFigure 12.(A)Schematic representation of CRISPR/Cas9 delivery systems.(B)Distribution of documents related to CRISPR delivery systems.Data includes journal and patent publications from the CAS Content Collection from 19952024.100137Physical delivery 36%Viral vectors 42%Non-viral vectors 22eno-associated 22%Hydrodynamic injection 2%Sonoporation 2%Electroporation 17%Microinjection 15%CPP 2%Gold NP 5%Polymer NP 4enovirus 6%Lentivirus 14%Lipid NP 11ata from the CAS Content Collection shows more than 6,500 journal articles and nearly 3,000 patent publications on the application of CRISPR technology in disease diagnosis from 2004 to 2023 which is 17%and 21%of total journal articles and patent publications,respectively,related to CRISPR therapeutics(Figure 13).The publication trend of CRISPR in disease diagnosis has shown a significant increase in recent years,reflecting its growing importance as a diagnostic tool in molecular biology and medical research.Since the discovery of CRISPRs potential in 2012,there has been an exponential rise in journal and patent publications,especially after 2015.A notable increase in publications(44%)between 2020 and 2022 is observable and coincides with the COVID-19 pandemic.Patent publications on CRISPR-based disease diagnostics have also surged in recent years,paralleling the technologys rapid adoption in both research and clinical applications.Figure 13.Journal and patent publications trends on CRISPR-based disease diagnostics from the CAS Content Collection from 2004 to 2023.1,6001,4001,2001,0008006004002000YearNumber of publications20042005200620072008200920102011201220132014201520162017201820192020202120222023JournalsPatentsJournals6,668Patents2,933CRISPR INSIGHT REPORT|19Figure 14.Time trends of publications related to artificial intelligence(AI)in the CRISPR dataset.Data includes journal and patent publications from the CAS Content Collection for the period 20102024.Note that data for 2024 is incomplete due to the time of data extraction and encompasses data for January to June.With the rise of artificial intelligence(AI),interest in its application to CRISPR/Cas technology has increased,as reflected by the growth of publications over the last decade.The incorporation of AI into CRISPR-mediated gene editing promises to improve both the precision and efficiency of the process.AI also possesses the ability to decipher complex genetic information,facilitate disease diagnosis,and inform on prognosis,going hand-in-hand with CRISPR capabilities.149AI may be used to design novel Cas proteins,aid in high-throughput screening of sgRNAs,and predict on-and off-target efficacy of particular CRISPR/Cas models.150170 CRISPR and artificial intelligenceTo read more about the application of AI to CRISPR/Cas technology,refer to the following review articles:Dixit,S,et al.Advancing genome editing with artificial intelligence:opportunities,challenges,and future directions.Front Bioeng Biotechnol 2023,11,1335901.DOI:10.3389/fbioe.2023.1335901.Lee,M.Deep learning in CRISPR-Cas systems:a review of recent studies.Front Bioeng Biotechnol 2023,11,1226182.DOI:10.3389/fbioe.2023.1226182.6005004003002001000YearNumber of publications201020112012201320142015201620172018201920202021202220232024JournalsPatentsIn the past decade,capital investment in CRISPR/Cas technology has seen a remarkable increase,with a sharp increase starting in 2018 and persisting until 2021,with investments exceeding a staggering$11 billion USD in 2021(Figure 15A).An overwhelming majority of these investments involved companies originating in the U.S.(96%).Other key players in terms of geographical distribution,though of much smaller magnitude,included Switzerland,China,and Japan(Figure 15B).Biotechnology,pharmaceuticals,and drug discovery together account for almost 90%of the capital invested(Figure 15C).Other industries with smaller contributions include agricultural chemicals,diagnostic equipment,and laboratory services,among others(Figure 15C).The largest influx of capital in the biotechnology industry occurred with two major spikes in 2019 and 2021.A record number of deals were made in 2021,with some of the largest involving Century Therapeutics and Mammoth Biosciences($150 million),and Caribou Biosciences and AgBiome($100 million).The most consistent influx in capital appears to be in drug discovery until 2021,with a plunge in 2022 and an uptick after 2022 (Figure 15D).Commercial interest in CRISPR technologyABCCapital invested(USD)Number of dealsYear14B12B10B8B6B4B2B080706050403020100201320142015201620172019202220232024201820202021China(1%)Switzerland(2%)Japan(0.4%)Others(1%)U.S.(96%)Laboratory services(0.4%)Diagnostic equipment(1%)Drug delivery(0.1%)Biotechnology(52%)Decision/risk analysis(1%)Agricultural chemicals(1%)Discovery tools(healthcare)(2%)Specialty chemicals(7%)Drug discovery(9%)Pharmaceuticals(27%)Primary industry codesCRISPR INSIGHT REPORT|21Figure 15.Commercial interest in CRISPR/Cas technology.(A)Capital invested in and number of deals in CRISPR.(B)Geographical distribution of capital invested in CRISPR.(C)Breakdown of capital invested as per primary industry codes and(D)their time trends over the last decade(20132024).Data from PitchBook Data,Inc.Data has not been reviewed by PitchBook analysts.DBiotechnologyDrug discoveryAgricultural chemicalsDrug delivery12B10B8B6B2B4BCapital invested(USD)Year0201320142015201620172018201920202021202220232024900M750M600M450M300M150M0201320172020 20212014 2015 20162018 2019202220242023Diagnostic equipmentDespite the widespread acceptance of CRISPR/Cas technology in gene editing,owing to its versatility and ease of use,several challenges remain.These include the ethical implications of genetic tampering,171175 potential for off-target effects,176183 packaging and delivery,184186 DNA damage and toxicity,187189 and regulatory hurdles.EthicsGenetic manipulation of eukaryotic organisms raises several ethical dilemmas.Jennifer Doudna,one of the pioneers behind CRISPR/Cas technology,expressed her concern at the 2016 American Association for the Advancement of Science Annual Meeting,stating that one of her biggest fears is“waking up one morning and reading about the first CRISPR baby,”which would undoubtedly create public backlash and regulatory uproar.171 In 2018,her fears were realized when Chinese researcher He Jiankui claimed that he used CRISPR to alter the DNA of seven embryos of couples,where the males were HIV carriers,to immunize the babies against HIV.This resulted in the birth of two twin girls,the first CRISPR babies.172,173In 1979,Beauchamp and Childress proposed the four principles of biomedical ethics:beneficence,nonmaleficence,respect for autonomy,and justice.174 In summary,the proposed“treatment”should result in a positive outcome/benefit(beneficence),avoid or minimize harm as much as possible(nonmaleficence),require informed consent from patients(autonomy),and ensure equitable access to treatment(justice).When looking at applications and study of CRISPR/Cas genome editing,researchers should take these principles into consideration.175Other ethical concerns are legal regulations,the use of the technology at home by communities without medical supervision(biohackers),175 and the use of CRISPR/Cas for non-therapeutic purposes like enhancements and eugenics.Off-target effectsIn the natural setting,CRISPR/Cas systems have evolved to tolerate mismatches between the gRNA and the target DNA to a certain extent.However,this property is not applied to genome engineering applications in the laboratory,as it may result in the alteration of off-target sites.Numerous studies have reported off-target activity at sites,ranging from a single base mismatch,to sites containing multiple consecutive mismatches or even nucleotide insertions or deletions.176179 High-throughput profiling studies exploring off-target effects have shown that their frequency is consistently lower in vivo as compared with isolated genomic DNA.182183Packaging and delivery In vivo delivery of CRISPR/Cas9 into mammalian cells is generally accomplished using viral vectors.AAVs remain the preferred choice due to their low immunogenicity and high transduction efficiency.However,AAVs have limited packaging capacity,making it difficult to package all of the components required for successful application.184,185Another limiting factor for most gene editing components is their safe,efficient,and targeted delivery to the specific organ or tissue.If CRISPR/Cas9 components are delivered via a systemic approach,they may get destroyed and cleared by the body before reaching their target site.186DNA-damage toxicity and immunotoxicityCRISPR-based gene editing involves cutting DNA,which can inadvertently trigger cell death and growth inhibition rather than the intended genetic edit.187 Multiple simultaneous off-target edits can ultimately result in genomic rearrangements such as inversions,deletions,and chromosomal translocations and trigger DNA damage and stress response pathways.188190Immunogenic toxicity is another known limitation of any gene editing technology,including CRISPR/Cas.Pre-existing antibodies against Cas9 and reactive T cells have been identified in humans,and Cas9 immunity has been associated with compromised therapeutic outcomes in various disease models.191194Regulatory hurdlesThe regulation of CRISPR-based gene editing varies between countries,and guidelines are still under development in some areas.In some countries,one regulatory agency oversees gene therapy,while other agencies regulate genetically modified organisms,creating a complex regulatory landscape for CRISPR-based therapeutics.Additionally,the long-term effects and safety of CRISPR-based therapeutics are not yet fully understood,which may contribute to lengthy and complex approval processes for these novel therapies.CRISPR:What challenges remain?CRISPR INSIGHT REPORT|23Concluding remarksSince the first use of CRISPR-based gene editing,the field has evolved at an exceptional pace,resulting in a plethora of publications exploring applications in disease management and diagnostics,as well as the identification of genes underlying various disorders.A considerable number of CRISPR-related publications appear to be connected to cancer and infectious diseases,while other diseases such as blood,genetic and nervous system disorders are also explored in the context of CRISPR/Cas technology.The use of CRISPR/Cas systems in disease diagnostics has also seen a surge,most notably after 2019.All of the research and development in the field has translated to a considerable increase in commercial interest in CRISPR-based diagnostics and therapeutics over the last few years.Currently,more than 140 CRISPR-based therapeutics are in various stages of clinical trials,with approximately a quarter of them targeting a range of cancer subtypes.Despite the great strides and widespread acceptance of CRISPR/Cas technology in gene editing,a few challenges remain in applying it for therapeutic purposes.The ongoing refinement of existing CRISPR components continues to improve the efficiency and specificity of CRISPR-based therapeutics.Expanding the targeting capabilities and optimizing delivery systems continue to aid in significant improvements in clinical outcomes.Ultimately,in the future,CRISPR-based therapeutics are likely to be developed successfully for myriads of diseases beyond cancer.CRISPR INSIGHT REPORT|231.Asmamaw,M.;Zawdie,B.Mechanism and Applications of CRISPR/Cas-9-Mediated Genome Editing.Biologics 2021,15,353361.DOI:10.2147/btt.S326422.2.Redman,M.;King,A.;Watson,C.;King,D.What is CRISPR/Cas9?Arch Dis Child Educ Pract Ed 2016,101(4),213215.DOI:10.1136/archdischild-2016-310459.3.Loureiro,A.;da Silva,G.J.CRISPR/Cas:Converting A Bacterial Defence 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Advancing Health Through Innovation:New Drug Therapy Approvals 2024CENTER FOR DRUG EVALUATION AND RESEARCHINNOVATION|PREDICTABILITY|ACCESSJanuary 2025Table of ContentsDirectors Message 1Executive Summary 2Innovation Across Medical Conditions 2New Drugs for Patients with Rare Diseases3Efficiencies in Bringing Therapies to Market 4CDERs Novel Drug Approvals of 2024 5First-in-Class Drugs 6Drugs for Rare Diseases 7Other Novel Drug Approvals 9Innovation:Use of Expedited Development and Review Pathways 11Fast Track 11Breakthrough Therapy 12Priority Review12Accelerated Approval12Overall Use of Expedited Development and Review Methods 13Predictability:Meeting PDUFA Goals 14Access:First Cycle Approvals and First in US Approvals 15New Uses of Approved Drugs 17Approved Drugs Expanded for New Pediatric Populations 19Biosimilar Approvals 21Other Important Approvals 23Conclusion 25Appendix A:CDERs Novel Approvals 26Appendix B:Novel Drug Designations 30 iiAdvancing Health Through Innovation:New Drug Therapy Approvals 2024Directors MessageWelcome to FDAs Center for Drug Evaluation and Researchs(CDER)14th annual report,Advancing Health Through Innovation:New Drug Therapy Approvals.The 2024 New Drug Therapy Approvals report is designed to showcase CDERs role in bringing safe and effective drugs to market for patients and consumers.This report describes CDERs 2024 notable drug approvals,which are actions we consider likely to have a significant impact on patient care and public health.These include novel drug approvals that contain a new active ingredient not previously approved by FDA.Also included are previously approved active ingredients that were also approved in 2024 to treat a different condition or new patient population.Throughout the report,we describe new therapies CDER approved in 2024 for safety and efficacy,as well as the regulatory tools used to streamline the review and approval of these applications.We approved most of these new treatments on or before their goal dates as defined by congressionally authorized agreements with industry(referred to as user fee programs).More than half of these drugs were approved in the U.S.before our regulatory counterparts in other countries did so.CDERs work on biosimilar biological products(biosimilars)reached several major milestones in 2024.CDER approved a record total of 18 biosimilars for 8 reference products in 2024,more than any previous year.We also surpassed our 60th biosimi-lar approval since 2015 when the first biosimilar was approved.In addition,this year 9 biosimilars,including those approved in 2024 and in previous years,were approved as interchangeable biosimilars,which means that they may be substituted for their reference product at the pharmacy without the intervention of the prescriber,subject to state law,similar to how generic drugs are substituted for brand name drugs.Our 2024 drug approvals include therapies for a variety of diseases and conditions,including rare diseases.FDA approved a significant number of rare disease therapies with orphan drug designation for patients with few to no treatment options.Therapies with orphan drug designations accounted for over 50%of our novel drug approvals,highlighting our steadfast commitment to address the huge unmet medical need in rare diseases.This year,we approved 26 novel therapies with this designation,including two of which treat conditions with no previously approved treatment such as Neimann-Pick disease type C and WHIM syndrome(warts,hypogammaglobulinemia,infections and myelokathexis).This report is intended to feature CDERs 2024 notable approvals.FDAs Center for Biologics Evaluation and Research(CBER)also approves novel biologics and there are times when CDER and CBER may collaborate on certain approval actions.For more information on CBERs 2024 product approvals,please visit CBERs webpage for 2024 Biological ApprovalsWe hope this report illustrates CDERs hard work and unwavering commitment to advance patient care through the timely and thorough review and approval of safe and effective treatments.Patrizia Cavazzoni,M.D.Director,Center for Drug Evaluation and ResearchPatrizia Cavazzoni,M.D.Director,Center for Drug Evaluation and Research 1Advancing Health Through Innovation:New Drug Therapy Approvals 2024Executive Summary CDER approved many safe and effective drug therapies in 2024.These approvals,spanning a broad scope of diseases and conditions,aim to help many people live better and potentially longer lives Innovation Across Medical Conditions In 2024,we approved 50 new drugs never before approved or marketed in the U.S.,known as“novel”drugs.We also made other important approval decisions,such as approving previously approved drugs for new uses and broader patient populations.The 2024 actions,both novel and other important drug approvals,focus on prevention,diagnosis,and treatment of diseases and conditions such as:Infectious diseases and associated conditions,including COVID-19,bloodstream infections,bacterial skin and associated tissue infections,community-acquired bacterial pneumonia,and urinary tract infections.Neurological conditions,such as Alzheimers disease and multiple sclerosis.Opioid use,misuse,and abuse.Heart,blood,and kidney diseases,including hypertension(high blood pressure);types of hemophilia(a blood clotting disorder);and major adverse cardiovascular events in adults at high risk.Lung diseases,such as chronic obstructive pulmonary disease.Different types of cancer,such as biliary,bladder,blood,breast,esophageal,lung,and low-grade gliomas(tumors that start in the brain).2Advancing Health Through Innovation:New Drug Therapy Approvals 2024New Drugs for Patients with Rare DiseasesPatients with rare diseases are often in critical need of new therapies,as these individuals generally have few or no existing treatment options.In 2024,26 of 50,or 52%of our novel drug approvals were approved for rare diseases,including:*Neimann-Pick disease type C,a genetic disease that results in progressive neurological symptoms and organ dysfunction.Duchenne muscular dystrophy,a severe,inherited disease that causes progressive muscle weakness and muscle wasting.Primary biliary cholangitis,a chronic autoimmune disease that damages the bile ducts in the liver Familial chylomicronemia syndrome,a life-threatening disease that prevents the body from digesting fats.Classic congenital adrenal hyperplasia,a group of genetic disorders that affect the adrenal glands and cause a deficiency in cortisol and/or aldosterone.In 2024,CDER also approved many therapies for rare cancers or tumors,including:HER2-positive(IHC3 )tumors,which have higher levels of the human epidermal growth factor receptor 2(HER2)protein that enables faster growth and spread.Grade 2 astrocytoma,a slow-growing brain tumor that can become more aggressive over time.Gastroesophageal junction adenocarcinoma,a rare type of cancer that starts in the gastroesophageal junction.Small cell lung cancer.*Not all drugs for rare diseases receive orphan drug designation.3Advancing Health Through Innovation:New Drug Therapy Approvals 2024Efficiencies in Bringing Therapies to MarketOur 2024 approvals demonstrate efficiencies in our review process,as shown by the following:User Fee Goals Performance:Of the 50 new drugs approved in 2024,CDER met or exceeded its Prescription Drug User Fee Act(PDUFA)goal dates for 47 of these approvals(94%).First Cycle Approvals:In 2024,CDER approved 37 of the 50 novel approvals(74%)on the first cycle.This differs from when CDER initially is unable to approve a drug because information in the application does not support approval.Subsequently,the sponsor resubmits the application with additional information,starting another review cycle that may lead to drug approval.Approvals in U.S.Before Other Countries:34 of the 50 novel drugs approved in 2024(68%)were first approved in the U.S.Expedited Programs for Serious Conditions:CDER has four broadly applicable programs to facilitate and expedite development and review of drugs for serious or life-threatening conditions:fast track designation,breakthrough therapy designation,priority review designation,and accelerated approval.In 2024,33 of the 50 of CDERs novel drug approvals(66%)used one or more of these expedited programs,which helped bring new therapies to the market sooner.4Advancing Health Through Innovation:New Drug Therapy Approvals 2024CDERs Novel Drug Approvals of 2024In 2024,CDER approved 50 novel drugs,either as new molecular entities(NMEs)under New Drug Applications(NDAs),or as new therapeutic biologics under Biologics License Applications(BLAs).The active ingredient(s)in a novel drug have not been approved in the U.S.CDERs novel drug approvals for 2024 are listed alphabetically below by proprietary name.*See Appendix B for a summary chart of designations for CDERs novel approvals.Proprietary Name Active Ingredient(s)Alhemo concizumab-mtci Alyftrekvanzacaftor,tezacaftor,deutivacaftor Anktivanogapendekin alfa inbakicept-pmlnAqneursalevacetylleucineAttrubyacoramidis Bizengrizenocutuzumab-zbcoCobenfyxanomeline,trospium chlorideCrenessitycrinecerfontDuvyzatgivinostatEbglysslebrikizumab-lbkzEnsacoveensartinib Exblifepcefepime,enmetazobactamFlyrcadoflurpiridaz F 18Hympavzimarstacimab-hncqImdelltratarlatamab-dlleIomervuiomeprolIqirvoelafibranorItovebiinavolisibKisunladonanemab-azbtLazcluzelazertinibLeqselvideuruxolitinibLetyboletibotulinumtoxinA-wlbgLivdelziseladelparLumisightpegulicianineMiplyffaarimoclomolNemluvionemolizumab-iltoNiktimvoaxatilimab-csfrOhtuvayreensifentrineProprietary Name Active Ingredient(s)OjemdatovorafenibOrlynvahsulopenem etzadroxil,probenecid Piaskycrovalimab-akkzRapiblyklandiololRevuforjrevumenibRezdiffraresmetiromRyteloimetelstatSofdrasofpironiumTevimbratislelizumab-jsgrTryngolzaolezarsen TryvioaprocitentanUnloxcytcosibelimab-ipdlVafseovadadustatVoranigovorasidenibVoydeyadanicopanVyloyzolbetuximab-clzbWinrevairsotatercept-csrkXolremdimavorixaforYorvipathpalopegteriparatideZelsuvmiberdazimerZevteraceftobiprole medocaril sodiumZiiherazanidatamab-hrii*This information is accurate as of December 31,2024.In rare instances,CDER may need to change a drugs NME designation or the status of its application as a novel BLA.For instance,new information may become available that could lead to a reconsideration of the original designation or status.If CDER makes these types of changes,the agency intends to communicate the nature of,and the reason for,any revisions as appropriate.5Advancing Health Through Innovation:New Drug Therapy Approvals 2024See Appendix B for a summary chart of designations for CDERs novel approvals.CDERs Annual Novel Drug Approvals:2015 2024The 10-year graph below shows that from 2015 through 2024,CDER has averaged about 47 novel drug approvals per year.First-in-Class DrugsCDER identified 24 of the 50 novel drugs approved(48%)in 2024 as first-in-class.These drugs produce a novel pharmacologic effect,the impact or influence that a drug has on the body or a specific biological target,in a disease.Novel drugs approved in 2024 that CDER identified as first-in-class were:Anktiva,Aqneursa,Bizengri,Cobenfy,Crenessity,Duvyzat,Hympavzi,Imdelltra,Iqirvo,Lumisight,Miplyffa,Nemluvio,Niktimvo,Revuforj,Rezdiffra,Rytelo,Tryngolza,Tryvio,Voydeya,Vyloy,Winrevair,Xolremdi,Zelsuvmi,Ziihera Notable examples of novel first-in-class approvals include:Anktiva(nogapendekin alfa inbakicept-pmln)intravesical solution(medications placed directly in the bladder through a catheter)to treat nonmuscle invasive bladder cancer with carcinoma in situ with or without papillary tumors that is unresponsive to prior therapy with Bacillus Calmette-Gurin.Cobenfy(xanomeline and trospium chloride)capsules are the first muscarinic-acting(mimics acetylcholines action on muscarinic receptors)drug to treat schizophrenia in adults.Lumisight(pegulicianine)intravenous injection for fluorescence imaging in adults with breast cancer as an adjunct for the intraoperative detection of cancerous tissue within the resection cavity following removal of the primary specimen during lumpectomy surgery.Nemluvio(nemolizumab-ilto)for injection to treat adults with prurigo nodularis,a chronic skin disorder characterized by multiple,firm,flesh-to-pink colored pruritic papules,plaques,and nodules.First-in-Class Drugs48ER identified 24 out of the 50 novel drugs(48%)approved in 2024 as first-in-class.6Advancing Health Through Innovation:New Drug Therapy Approvals 2024CDERs Novel Drug Approvals By Year010203040506020152016201720182019202020212022202320244522465953485055375070 Revuforj(revumenib)tablets and oral solution to treat relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene(KMT2A)translocation in patients 1 year and older Rezdiffra(resmetirom)tablets to treat adults with noncirrhotic MASH(metabol-ic-dysfunction associated steatohepatitis)with moderate-to-advanced liver fibrosis(consistent with stages F2 to F3 fibrosis).MASH is liver inflammation caused by excess fat cells.Rezdiffra was approved through the Accelerated Approval pathway.Tryvio(aprocitentan)tablets to treat hypertension(high blood pressure)in combination with other antihypertensive medications,to lower blood pressure in adults who are not adequately controlled on other medications.Drugs for Rare DiseasesIn 2024,26 of CDERs 50 novel drug approvals(52%),were approved to treat rare or“orphan”diseases(diseases that affect fewer than 200,000 people in the U.S.).Patients with rare diseases often have few or no drugs available to treat their conditions.Novel drugs approved in 2024 with the orphan drug designation were:*Alhemo,Alyftrek,Aqneursa,Attruby,Bizengri,Crenessity,Duvyzat,Hympavzi,Imdelltra,Iqirvo,Livdelzi,Miplyffa,Niktimvo,Ojemda,Piasky,Revuforj,Rytelo,Tevimbra,Tryngolza,Voranigo,Voydeya,Vyloy,Winrevair,Xolremdi,Yorvipath,ZiiheraExamples of novel approvals of 2024 for rare diseases include:Aqneursa(levacetylleucine)oral suspension to treat neurological manifestations of Niemann-Pick disease type C in adults and pediatric patients weighing at least 15 kg.Niemann-Pick disease type C is a genetic disorder caused by variants in either the NPC1 or NPC2 gene,resulting in impaired intracellular transport of cholesterol and other lipids.The disease affects the nervous system and other organs and systems.Crenessity(crinecerfont)capsules and oral solution to treat classic congenital adrenal hyperplasia,a genetic disorder affecting the adrenal glands that causes a deficiency in certain hormones(cortisol and sometimes aldosterone)and excess of other hormones(androgens).Duvyzat(givinostat)oral suspension to treat Duchenne muscular dystrophy in patients 6 years of age and older.Duchenne muscular dystrophy is a genetic disorder characterized by progressive muscle degeneration and weakness.Hympavzi(marstacimab-hncq)subcutaneous injection to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A(congenital factor VIII deficiency)without factor VIII inhibitors,or hemophilia B(congenital factor IX deficiency)without factor IX inhibitors.Hemophilia is a disorder that prevents blood from clotting properly.Imdelltra(tarlatamab-dlle)for intravenous injection to treat adults with extensive stage small cell lung cancer with disease progression on or after platinum-based chemotherapy.Imdelltra was approved through the Accelerated Approval pathway.Drugs for Rare Diseases52%Over half(52%)of the drugs CDER approved in 2024 received orphan drug designation.7Advancing Health Through Innovation:New Drug Therapy Approvals 2024 Iqirvo(elafibranor)tablets to treat primary biliary cholangitis in combination with ursodeoxycholic acid in adults who have an inadequate response to ursodeoxycholic acid,or as monotherapy in patients unable to tolerate ursodeoxycholic acid.Primary biliary cholangitis is a chronic autoimmune disease in which the livers bile ducts become inflamed and slowly destroyed.Iqirvo was approved through the Accelerated Approval pathway.Livdelzi(seladelpar)capsules for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults who have an inadequate response to ursodeoxycholic acid,or as monotherapy in patients unable to tolerate ursodeoxycholic acid Miplyffa(arimoclomol)capsules as the first treatment for the neurological manifestations of Niemann-Pick disease type C,in combination with miglustat,in patients 2 years of age and older.Ojemda(tovorafenib)oral suspension to treat patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma harboring a BRAF fusion or rearrangement,or BRAF V600 mutation.A glioma is a tumor that originates in the brain or spinal cord from glial cells,which support and protect nerve cells.Ojemda was approved through the Accelerated Approval pathway.Tryngolza(olezarsen)injection to treat adults with familial chylomicronemia syndrome,a rare disease that prevents the body from digesting fats.Voranigo(vorasidenib)tablets for the treatment of patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation following surgery including biopsy,sub-total resection,or gross total resection.An astrocytoma is a type of brain tumor that originates from star-shaped glial cells in the brain or spinal cord called astrocytes.An oligodendroglioma is a type of brain or spinal cord tumor that originates in glial cells called oligodendrocytes.Voydeya(danicopan)tablets as add-on therapy to ravulizumab or eculizumab for the treatment of extravascular hemolysis in adults with paroxysmal nocturnal hemoglobinuria.Paroxysmal nocturnal hemoglobinuria causes destruction of red blood cells(hemolysis)by the complement system(part of the immune system)and some hemolysis may be extravascular(outside of blood vessels,such as in the spleen,liver,bone marrow,and lymph nodes).Vyloy(zolbetuximab-clzb)intravenous injection in combination with fluoropyrimidine-and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are claudin 18.2 positive as determined by an FDA-approved test.Adenocarcinoma develops in glandular tissue.Winrevair(sotatercept-csrk)subcutaneous injection to treat adults with pulmonary arterial hypertension(WHO Group 1)to increase exercise capacity,improve WHO functional class,and reduce the risk of clinical worsening events.Pulmonary arterial hypertension is a chronic condition that causes high blood pressure in the arteries of the lungs Xolremdi(mavorixafor)capsules for the treatment of WHIM syndrome(warts,hypogammaglobulinemia,infections and myelokathexis)in patients 12 years of age and older to increase the number of circulating mature neutrophils and lymphocytes.WHIM syndrome is a rare genetic disease that causes the bodys immune system to not function properly,predisposing it to infections.8Advancing Health Through Innovation:New Drug Therapy Approvals 2024 Yorvipath(palopegteriparatide)subcutaneous injection to treat hypoparathyroidism in adults.Patients with hypoparathyroidism have abnormally low levels of parathyroid hormone,which leads to low levels of calcium in the blood and symptoms such as muscle cramping and spasms,nerve tingling,and fatigue.Ziihera(zanidatamab-hrii)intravenous injection for the treatment of adults with previously treated,unresectable or metastatic HER2-positive(IHC 3 )biliary tract cancer,a rare and aggressive type of cancer that affects the organs of the biliary system,which includes the gallbladder and bile ducts.Ziihera was approved through the Accelerated Approval pathway.*Not all drugs for rare diseases necessarily receive orphan designation.Other Novel Drug Approvals In addition to the first-in-class and drugs for rare diseases,CDER approved these notable approvals in 2024:Exblifep(cefepime and enmetazobactam)for intravenous injection to treat patients 18 years and older with complicated urinary tract infections,including pyelonephri-tis caused by the following susceptible microorganisms:Escherichia coli,Klebsiella pneumoniae,Pseudomonas aeruginosa,Proteus mirabilis,and Enterobacter cloacae complex.A complicated urinary tract infection occurs in patients with structural or functional abnormalities in the urinary tract,or certain signs or symptoms.Flyrcado(flurpiridaz F 18)intravenous injection for positron emission tomography(PET)myocardial perfusion imaging(MPI)in adults with known or suspected coronary artery disease to evaluate for myocardial ischemia and infarction.Myocardial ischemia occurs when the heart muscle does not receive enough blood flow and an infarction is tissue death that occurs when an area of the body doesnt receive enough blood flow.Kisunla(donanemab-azbt)intravenous injection to treat Alzheimers disease,a brain disorder that gradually destroys memory and thinking skills and eventually the ability to perform everyday tasks.It is the most common cause of dementia in older adults,accounting for 60-70%of cases.Lazcluze(lazertinib)tablets,in combination with amivantamab,for the first-line treatment of adults with locally advanced or metastatic non-small cell lung cancer(NSCLC)with epidermal growth factor receptor(EGFR)exon 19 deletions or exon 21 L858R substitution mutations,as detected by an FDA-approved test.NSCLC is a type of cancer that forms in the lung tissues.Orlynvah(sulopenem etzadroxil and probenecid)tablets for the treatment of uncomplicated urinary tract infections caused by the designated microorganisms Escherichia coli,Klebsiella pneumoniae,or Proteus mirabilis in adult women who have limited or no alternative oral antibacterial treatment options.An uncomplicated urinary tract infection is a bacterial infection of the bladder that occurs in females without structural abnormalities of the urinary tract or other health conditions.CDER approved a new amyloid beta-directed antibody to treat Alzheimers disease in 2024.9Advancing Health Through Innovation:New Drug Therapy Approvals 2024 Vafseo(vadadustat)tablets for the treatment of anemia due to chronic kidney disease in adults who have been receiving dialysis for at least 3 months.Anemia (an insufficient number of red blood cells to carry oxygen throughout the body)is a common complication of chronic kidney disease,a long-term condition that occurs when the kidneys are damaged.Zevtera(ceftobiprole medocaril sodium)for intravenous injection for the treatment of adults with Staphylococcus aureus bloodstream infections(bacteremia),adults with acute bacterial skin and skin structure infections,and adults and children(3 months to less than 18 years old)with community-acquired bacterial pneumonia.10Advancing Health Through Innovation:New Drug Therapy Approvals 2024Innovation:Use of Expedited Development and Review PathwaysCDER used diverse regulatory approaches to enhance and expedite drug review in 2024.These approaches enable increased flexibility,efficiency,and interactions between CDER staff and drug developers.They often also allow shorter review times to speed the availability of new therapies to patients with serious conditions,especially in cases where there are no satisfactory alternatives,while preserving FDAs rigorous standards for safety and effectiveness Fast TrackCDER granted fast track status to 22 of the 50 novel drugs(44%)in 2024.Fast track speeds development and review of new drugs and biologics by increasing the level of communication between FDA and drug developers and by enabling CDER to review portions of a drug application on a rolling basis.Drugs granted Fast Track status were:Anktiva,Aqneursa,Bizengri,Crenessity,Duvyzat,Ebglyss,Exblifep,Kisunla,Leqselvi,Lumisight,Miplyffa,Niktimvo,Orlynvah,Revuforj,Rezdiffra,Rytelo,Tryngolza,Voranigo,Vyloy,Xolremdi,Zevtera,Ziihera Fast Track 44ER designated 22 of the 50 novel drugs(44%)as fast track.11Advancing Health Through Innovation:New Drug Therapy Approvals 2024Breakthrough TherapyCDER designated 18 of the 50 novel drugs(36%)in 2024 as breakthrough therapies.A breakthrough therapy designation includes all the fast track program features and offers intensive FDA guidance during drug development,including involvement from senior managers.Drugs designated with breakthrough therapy status were:Anktiva,Bizengri,Crenessity,Imdelltra,Iqirvo,Itovebi,Kisunla,Livdelzi,Miplyffa,Nemluvio,Ojemda,Revuforj,Rezdiffra,Tryngolza,Voranigo,Voydeya,Winrevair,ZiiheraPriority ReviewIn 2024,28 of the 50 novel drugs approved(56%)were designated priority review.A drug receives a priority review if CDER determines that the drug treats a serious condition and,if approved,would provide a significant improvement in safety or effectiveness of the treatment,diagnosis,or prevention of serious conditions.Generally speaking,a priority review application is one on which CDER sets a goal to take action within 6 months of filing(compared to a target date of 10 months under standard review).(In some instances,sponsors may redeem a priority review voucher under CDERs priority review voucher program.Such drugs are not included in the list below,and do not meet priority review criteria.)Drugs designated Priority Review were:Alhemo,Aqneursa,Bizengri,Crenessity,Duvyzat,Exblifep,Imdelltra,Iqirvo,Itovebi,Kisunla,Lazcluze,Livdelzi,Lumisight,Miplyffa,Nemluvio,Niktimvo,Ojemda,Orlynvah,Revuforj,Rezdiffra,Tryngolza,Voranigo,Vyloy,Winrevair,Xolremdi,Yorvipath,Zevtera,Ziihera Accelerated ApprovalCDER approved 7 of the 50 novel drugs(14%)in 2024 under the accelerated approval pathway.This program works to bring certain drugs for unmet medical needs to market on a faster timeline than would be possible following the traditional approval pathway.Accelerated approval may be an option for a new drug intended to treat a serious condition that offers a meaningful advantage over available therapies.For drugs eligible to follow the accelerated approval pathway,a determination of safety and effectiveness will be made based not on measures of direct clinical benefit,but rather on one of two alternative endpoints:(1)a surrogate endpoint that is reasonably likely to predict clinical benefit;or(2)an intermediate clinical endpoint that is reasonably likely to predict clinical benefit.Use of such endpoints may enable the drug to be studied for a shorter duration than would be typical for a traditional approval,and to receive accelerated approval based on these findings.Importantly,however,for products approved under the accelerated approval pathway,FDA requires post-approval studies designed to confirm clinical benefit,and,among other things,may withdraw,using expedited procedures,an accelerated approval product from the market for failure to confirm clinical benefit.Accelerated Approval14ER identified 7 of the 50 novel drugs(14%)as accelerated approvals.Priority Review 56( of the 50 drugs (56%)approved in 2024 were designated as priority review.Breakthrough Therapy36ER identified 18 of the 50 novel drugs(36%)approved in 2024 as breakthrough therapies.12Advancing Health Through Innovation:New Drug Therapy Approvals 2024The novel drugs approved via Accelerated Approval were:Bizengri,Imdelltra,Iqirvo,Livdelzi,Ojemda,Rezdiffra,ZiiheraOverall Use of Expedited Development and Review Methods33 of the 50 novel drug approvals of 2024(66%)used one or more expedited programs,specifically fast track designation,breakthrough therapy designation,priority review designation,or accelerated approval.Novel drugs approved in 2024 that used at least one expedited program were:Alhemo,Anktiva,Aqneursa,Bizengri,Crenessity,Duvyzat,Ebglyss,Exblifep,Imdelltra,Iqirvo,Itovebi,Kisunla,Lazcluze,Leqselvi,Livdelzi,Lumisight,Miplyffa,Nemluvio,Niktimvo,Ojemda,Orlynvah,Revuforj,Rezdiffra,Rytelo,Tryngolza,Voranigo,Voydeya,Vyloy,Winrevair,Xolremdi,Yorvipath,Zevtera,Ziihera CDER used at least one expedited program to speed approval of 66%of all novel drugs approved in 2024.13Advancing Health Through Innovation:New Drug Therapy Approvals 2024Predictability:Meeting PDUFA GoalsUnder PDUFA,industry is assessed user fees that provide resources to CDER to expand capabilities for review activities.With PDUFA,applications are reviewed targeting specific timeframes.Throughout 2024,CDER met or exceeded the PDUFA goal date for taking action on 94%(47 of 50)of the novel drugs approved.Novel drugs approved in 2024 on or before their PDUFA goal dates were:Alhemo,Alyftrek,Anktiva,Aqneursa,Attruby,Bizengri,Cobenfy,Crenessity,Duvyzat,Ebglyss,Ensacove,Exblifep,Flyrcado,Hympavzi,Imdelltra,Iomervu,Iqirvo,Itovebi,Lazcluze,Leqselvi,Letybo,Livdelzi,Miplyffa,Nemluvio,Niktimvo,Ohtuvayre,Ojemda,Orlynvah,Piasky,Rapiblyk,Revuforj,Rezdiffra,Rytelo,Sofdra,Tryngolza,Tryvio,Unloxcyt,Vafseo,Voranigo,Voydeya,Vyloy,Winrevair,Xolremdi,Yorvipath,Zelsuvmi,Zevtera,ZiiheraMeeting PDUFA Goals94%In 2024,47 out of the 50 novel drugs(94%)were approved on or before their PDUFA goal date.14Advancing Health Through Innovation:New Drug Therapy Approvals 2024Access:First Cycle Approvals and First in U.S.ApprovalsCDER approved 37 of the 50 novel drugs of 2024(74%)on the“first cycle”of review.This high percentage is in part reflective of the extent to which CDER staff provide clarity to drug developers on the necessary study design elements and other data needed in the drug application to support a full and comprehensive drug assessment.Novel drugs approved in 2024 on the first cycle were:Alyftrek,Aqneursa,Attruby,Bizengri,Cobenfy,Crenessity,Duvyzat,Ensacove,Exblifep,Flyrcado,Hympavzi,Imdelltra,Iomervu,Iqirvo,Itovebi,Lazcluze,Leqselvi,Livdelzi,Lumisight,Nemluvio,Niktimvo,Ohtuvayre,Ojemda,Piasky,Revuforj,Rezdiffra,Rytelo,Tevimbra,Tryngolza,Tryvio,Voranigo,Voydeya,Winrevair,Xolremdi,Zelsuvmi,Zevtera,ZiiheraFirst Cycle Approvals74%In 2024,CDER approved 37 of the 50 novel drugs(74%)on the first cycle.15Advancing Health Through Innovation:New Drug Therapy Approvals 2024Approval in the U.S.Before Other Countries34 of the 50(68%)novel drugs approved in 2024 were approved in the U.S.before any other countryNovel drugs of 2024 approved first in the U.S.were:Alyftrek,Anktiva,Aqneursa,Attruby,Bizengri,Cobenfy,Crenessity,Duvyzat,Exblifep,Flyrcado,Hympavzi,Imdelltra,Iqirvo,Itovebi,Kisunla,Leqselvi,Livdelzi,Lumisight,Miplyffa,Niktimvo,Ohtuvayre,Ojemda,Orlynvah,Revuforj,Rezdiffra,Rytelo,Tryngolza,Tryvio,Unloxcyt,Voranigo,Winrevair,Xolremdi,Zelsuvmi,ZiiheraFirst in the U.S.684 of 50 novel drugs(68%)approved in 2024 were first approved in the U.S.16Advancing Health Through Innovation:New Drug Therapy Approvals 2024New Uses of Approved DrugsAfter CDER approves a new treatment,a drug sponsor may generate new data about the product that suggests an additional use.The drug sponsor may then submit an application to modify or expand the use of an approved drug based on this new data.The products below are some 2024 CDER approvals for new uses or indications of an approved drug:Alecensa(alectinib)capsules were first approved in 2015 to treat anaplastic lymphoma kinase(ALK)-positive,metastatic NSCLC in adults who have progressed on or are intolerant to crizotinib.Alecensa was approved in 2024 as an adjuvant treat-ment(a cancer treatment given after the primary treatment)in adults following tumor resection of ALK-NSCLC.ALK-NSCLC is caused by a gene fusion(joining of two genes together)that produces an abnormal ALK protein that causes cancer cells to grow and spread.Benlysta(belimumab)for intravenous injection was first approved in 2019 to treat pediatric patients 5 years of age and older with active,autoantibody-positive,systemic lupus erythematosus who are receiving standard therapy.In 2024,Benlysta was approved as a subcutaneous autoinjector formulation for pediatric patients 5 years and older,allowing children to receive treatment at home.Systemic lupus erythemato-sus is a chronic autoimmune disease that causes the bodys immune system to attack its tissues and organs Darzalex Faspro(daratumumab and hyaluronidase-fihj)subcutaneous injection was originally approved in 2020 to treat multiple myeloma.In 2024,CDER approved Darzalex Faspro,in combination with bortezomib,lenalidomide,and dexamethasone,for induction and consolidation in patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant.Multiple myeloma is a rare cancer that occurs when abnormal plasma cells build up in the bone marrow and form tumors in the bones.17Advancing Health Through Innovation:New Drug Therapy Approvals 2024 Enhertu(fam-trastuzumab deruxtecan-nxki)for intravenous injection was first approved in 2019 to treat unresectable or metastatic HER2-positive breast cancer.In 2024,CDER approved Enhertu to treat adults with unresectable or metastatic HER2-positive(IHC 3 )solid tumors who have received systemic treatment and have no satisfactory alternative treatment options.HER2-positive solid tumors have high levels of the HER2 protein.Epkinly(epcoritamab-bysp)subcutaneous injection was initially approved in 2023 to treat relapsed or refractory diffuse large B-cell lymphoma.In 2024,CDER approved Epkinly to treat adults with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.Follicular lymphoma is a slow-growing cancer that may appear in lymph nodes,bone marrow,and other organs.Fabhalta(iptacopan)capsules were first approved in 2023 to treat paroxysmal nocturnal hemoglobinuria.In 2024,CDER approved Fabhalta for lowering proteinuria(protein in the urine)in adults with primary immunoglobulin A(IgA)nephropathy at risk of rapid disease progression.Primary immunoglobulin A nephropathy,also known as Berger disease,is a chronic kidney disease that occurs when IgA builds up in the kidneys.Imfinzi(durvalumab)intravenous injection was initially approved in 2017 to treat locally advanced or metastatic urothelial carcinoma.In 2024,CDER approved Imfinzi to treat patients with resectable NSCLC and no known epidermal growth factor receptor mutations or anaplastic lymphoma kinase(ALK)rearrangements.Resectable NSCLC is a stage of lung cancer that can be treated with surgery.Livmarli(maralixibat)oral solution was first approved in 2021 to treat cholestatic pruritus in patients with Alagille syndrome.In 2024,CDER approved Livmarli to treat progressive familial intrahepatic cholestasis,a rare genetic disorder that prevents the liver from secreting bile properly,which leads to liver disease and eventually liver failure Otezla(apremilast)tablets were originally approved in 2014 to treat active psoriatic arthritis.In 2024,CDER approved Otezla to treat moderate-to-severe plaque psoriasis in adults.Plaque psoriasis is an autoimmune condition that causes thick skin patches(plaques).Rybrevant(amivantamab-vmjw)intravenous injection was first approved in 2021.In 2024,CDER approved Rybrevant as a first-line treatment for adults with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations,as detected by an FDA-approved test.EGFR exon 20 insertion mutations can cause uncontrolled cell growth and are a biomarker in lung cancer.Wegovy(semaglutide)subcutaneous injection was originally approved in 2021.In 2024,CDER approved Wegovy to reduce the risk of major adverse cardiovascular events(cardiovascular death,non-fatal heart attack,or non-fatal stroke)in adults with established cardiovascular disease and either obesity or overweight.Xolair(Omalizumab)subcutaneous injection was initially approved in 2003 to treat adults and adolescents(12 years of age and older)with moderate-to-severe persistent asthma.In 2024,CDER approved Xolair to treat IgE-mediated food allergy in adult and pediatric patients aged 1 year and older for the reduction of allergic reactions(Type I),including anaphylaxis,that may occur with accidental exposure to one or more foods(to be used in conjunction with food allergen avoidance).Zepbound(tirzepatide)subcutaneous injection was first approved in 2023 for chronic weight management.In 2024,CDER approved Zepbound to treat obstructive sleep apnea.Obstructive sleep apnea causes breathing to stop and start repeatedly during sleep.18Advancing Health Through Innovation:New Drug Therapy Approvals 2024Approved Drugs Expanded for New Pediatric PopulationsSection 505B of the Federal Food,Drug,and Cosmetic Act(FD&C Act)(often referred to by the legislation that originally created it,the Pediatric Research Equity Act,or PREA)and section 505A of the FD&C Act(often referred to by the legislation that originally created it,the Best Pharmaceuticals for Children Act,or BPCA)give CDER the authority to require(PREA)or request(BPCA)pediatric studies under certain circumstances.These two laws have been largely responsible for the inclusion of pediatric information in the labeling for many drugs.Upon drug approval,CDER may require pediatric studies of that drug under PREA.In response to that requirement,sponsors may submit new data to support the safe and effective use of the drug in the pediatric population studied.Sponsors submit this data in an application to expand the patient population.Under BPCA,sponsors may obtain additional marketing exclusivity for pediatric studies requested in a Pediatric Written Request.The products below are examples of 2024 approvals for drugs expanded to include new pediatric populations:Besponsa(inotuzumab ozogamicin)for intravenous injection was initially approved in 2017 to treat adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia.Besponsas patient population was expanded in 2024 to include pediatric patients 1 year and older.Acute lymphoblastic leukemia occurs when the bone marrow produces too many immature white blood cells called lymphocytes.Blincyto(blinatumomab)for intravenous injection was first approved in 2014 to treat CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblas-tic leukemia.In 2024,CDER expanded Blincytos patient population to include pediatric patients 1 month and older.19Advancing Health Through Innovation:New Drug Therapy Approvals 2024 Dovato(dolutegravir and lamivudine)tablets were originally approved in 2019 to treat human immunodeficiency virus type 1(HIV-1)infection in adults.Dovatos patient population was expanded in 2024 to include adolescents 12 years of age and over.Dupixent(dupilumab)subcutaneous injection was initially approved in 2017 for the treatment of adults with moderate-to-severe atopic dermatitis and was approved in 2022 for the treatment eosinophilic esophagitis in adults and pediatric patients 12 years of age and older.In 2024,CDER expanded the patient population for Dupixent to include pediatric patients aged 1 year and older who weigh at least 15 kg and have eosinophilic esophagitis.Eosinophilic esophagitis is a chronic allergic condition that causes inflammation in the esophagus.Farxiga(dapagliflozin)tablets and Xigduo XR(dapagliflozin and metformin hydrochloride)extended-release tablets were originally approved in 2014 to improve glucose control in adults with type 2 diabetes mellitus.In 2024,CDER expanded the patient populations to include pediatric patients aged 10 years and older with type 2 diabetes mellitus.Lutathera(lutetium Lu 177 dotatate)intravenous injection was originally approved in 2018 to treat somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors,including foregut,midgut,and hindgut neuroendocrine tumors in adults.In 2024,CDER expanded the patient population to include patients 12 years and older.Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors are rare tumors that overexpress somatostatin receptors.Veklury(remdesivir)for intravenous injection was first approved in 2020 to treat coronavirus disease 2019(COVID-19)requiring hospitalization in adults and pediatric patients 12 years of age and older.CDER expanded the patient population to include pediatric patients 1 month and older in 2022.In 2024,CDER expanded Veklurys patient population again to include patients from birth weighing at least 1.5 kg.20Advancing Health Through Innovation:New Drug Therapy Approvals 2024In 2024,CDER approved 18 biosimilars for 8 reference products.Biosimilar ApprovalsThe biosimilar pathway is an abbreviated approval pathway for biological products that are highly similar to and have no clinically meaningful differences in terms of safety,purity,and potency(safety and effectiveness)from an FDA-approved biological product,called a reference product.This pathway helps provide more treatment options,increase patient access,and potentially reduce the cost of therapies through competition.In 2024,CDER approved a total of 18 new biosimilars,including 8 for 3 reference products for which there were no previously approved biosimilars.Several of these biosimilars were approved as interchangeable biosimilars,which means that they may be substituted for the reference product at the pharmacy without the intervention of the prescriber,subject to state law Bkemv(eculizumab-aeeb)intravenous injection is the first interchangeable biosimilar to the reference product Soliris(eculizumab),for the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.Atypical hemolytic uremic syndrome is a rare,progressive,and potentially life-threatening disease that causes abnormal blood clots in small blood vessels,primarily in the kidneys.Jubbonti and Wyost(denosumab-bbdz)subcutaneous injections are the first interchangeable biosimilars for reference products Prolia and Xgeva(denosumab),to treat osteoporosis and prevent bone events in cancer.Osteoporosis causes bones to become weak and more likely to break.Opuviz(aflibercept-yszy)and Yesafili(aflibercept-jbvf)intravitreal(in the eye)injections were approved as the first interchangeable biosimilars for the reference product Eylea(aflibercept),to treat macular degeneration and other eye conditions.Macular degeneration causes gradual vision loss in the center of the visual field.21Advancing Health Through Innovation:New Drug Therapy Approvals 2024In 2024,CDER also approved the notable changes to the following biosimilars:Amjevita(adalimumab-atto)subcutaneous injection was originally approved in 2016 to treat several inflammatory conditions,such as rheumatoid arthritis.In 2024,CDER approved it as an interchangeable biosimilar(reference product:Humira).Rheumatoid arthritis is a chronic autoimmune disease that causes joint pain,swelling,and stiffness.Bkemv(eculizumab-aeeb)intravenous injection was initially approved in 2024 to treat paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.Later in 2024,CDER approved it to treat generalized myasthenia gravis(reference product:Soliris).Generalized myasthenia gravis is a chronic autoimmune disease that causes muscle weakness that can affect the entire body.Epysqli(eculizumab-aagh)intravenous injection was originally approved in 2024 to treat paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.Later in 2024,CDER approved it to treat generalized myasthenia gravis(reference product:Soliris).Eticovo(etanercept-ykro)subcutaneous injection was first approved in 2019 to treat several inflammatory conditions,including psoriatic arthritis.In 2024,CDER approved it as an interchangeable biosimilar(reference product:Enbrel).Psoriatic arthritis is a chronic inflammatory disease that affects the joints and entheses,where tendons and ligaments attach to bones.Hadlima(adalimumab-bwwd)subcutaneous injection was initially approved in 2019 to treat inflammatory conditions such as juvenile idiopathic arthritis.In 2024,CDER approved it as an interchangeable biosimilar(reference product:Humira).Juvenile idiopathic arthritis is a chronic inflammatory disease that causes joint pain,swelling,and stiffness in children Hyrimoz(adalimumab-adaz)subcutaneous injection was originally approved in 2018 to treat inflammatory conditions that included ulcerative colitis and ankylosing spondylitis.In 2024,CDER approved it as an interchangeable biosimilar(reference product:Humira).Ulcerative colitis is a chronic inflammatory bowel disease that causes inflammation and ulcers in the colon and rectum.Ankylosing spondylitis is a chronic inflammatory disease that causes inflammation in the joints and ligaments of the spine.Tofidence(tocilizumab-bavi)for intravenous injection was originally approved in 2023 to treat moderate-to-severe active rheumatoid arthritis in pediatrics and adults.In 2024,CDER approved it to treat hospitalized adults with COVID-19 who are receiving systemic corticosteroids and require supplemental oxygen,noninvasive or invasive mechanical ventilation,or extracorporeal membrane oxygenation(reference product:Actemra).CDER has approved a total of 63 biosimilars for 17 different reference products since 2015.This includes at least 1 biosimilar for each of these top selling biologics in the U.S.:10 biosimilars to Humira;7 biosimilars to Stelara,6 biosimilars to Herceptin and Neulasta;5 biosimilars to Avastin and Eylea;4 biosimilars to Neupogen and Remicade;3 biosimilars to Rituxan;2 biosimilars to Actemra,Enbrel,Lantus,Lucentis,and Soliris;and 1 biosimilar to Epogen/Procrit,Prolia/Xgeva,and Tysabri.Approval of multiple biosimilars for an approved reference product can enhance competition,which may lead to reduced costs for both patients and our health care system.22Advancing Health Through Innovation:New Drug Therapy Approvals 2024Other Important ApprovalsNew formulations of approved drugs can offer significant therapeutic advances.Similarly,new dosage forms(such as from a capsule to a chewable tablet for those unable to swallow pills)can help increase adherence,make sure patients take the proper dose,and improve quality of life for patients who must use the medication on a prolonged basis.Making a drug available as an over-the-counter product can also increase patient access to therapies.Below are examples of new formulations,new dosage forms,over-the-counter actions,and other notable approval actions of 2024:Aurlumyn(iloprost)intravenous injection is the first approved treatment for severe frostbite in adults to reduce the risk of digit(finger,toe)amputations.Iloprost,the active ingredient,had been previously approved to treat pulmonary arterial hypertension(high blood pressure in the arteries of the lungs,causing shortness of breath,dizziness,and tiredness).Eohilia(budesonide)oral suspension was approved as the first oral therapy to treat eosinophilic esophagitis in patients 11 years of age and older.Eohilia is approved as a 12-week course of treatment.Lumify Preservative Free(brimonidine tartrate)was approved as a new formulation to offer consumers the first preservative-free brimonidine-containing product to treat eye redness due to minor eye irritations.Neffy(epinephrine)nasal spray for emergency treatment of type I allergic reactions,including anaphylaxis,in patients who weigh 30 kg or greater.Neffy is the first non-in-jection epinephrine to treat anaphylaxis,a severe,life-threatening allergic reaction that can occur suddenly and rapidly.Ocrevus Zunovo(ocrelizumab and hyaluronidase-ocsq)subcutaneous injection was approved for the treatment of relapsing forms of multiple sclerosis(MS)and primary progressive MS in adults.Ocrevus Zunovo is a new dosage form of the 23Advancing Health Through Innovation:New Drug Therapy Approvals 2024previously approved,intravenously administered product Ocrevus(ocrelizumab).MS is a chronic autoimmune disease that damages the protective coating around nerve cells in the brain and spinal cord.Pivya(pivmecillinam)tablets to treat females 18 years of age and older with uncomplicated urinary tract infections caused by susceptible isolates of Escherichia coli,Proteus mirabilis and Staphylococcus saprophyticus.Pivmecillinam is a derivative of pivmecillinam hydrochloride,an active ingredient previously approved for use in the U.S.Prevymis(letermovir)oral pellets for the prophylaxis of cytomegalovirus(CMV)infection and disease.This is a new dosage form of Prevymis that was previously only available as tablets or intravenous injection.Pellets are a small,spherical-shaped units that may be used for patients who cannot swallow tablets.CMV is a virus related to the herpes virus group of infections that is an incurable life-time infection.Rezenopy(naloxone hydrochloride)nasal spray is for the emergency treatment of known or suspected opioid overdose.Naloxone hydrochloride,the active ingredient,was previously approved,but Rezenopy contains a higher strength per dose than the other naloxone products available in the U.S.Tecentriq Hybreza(atezolizumab and hyaluronidase-tqjs)subcutaneous injection to treat NSCLC,hepatocellular carcinoma,melanoma,and alveolar soft part sarcoma.Tecentriq Hybreza is the first anti-PD-L1 antibody administered subcutaneously.Voquezna(vonoprazan)tablets for relief of heartburn associated with non-erosive gastroesophageal reflux disease in adults.The active ingredient for Voquezna is in a class of medications called potassium-competitive acid blockers.Voquezna is the first drug approved to use this active ingredient for this indication.Gastroesophageal reflux disease is a chronic condition that occurs when stomach contents leak back into the esophagus.Zurnai(nalmefene)intramuscular or subcutaneous injection for the emergency treatment of known or suspected opioid overdose induced by natural or synthetic opioids in patients aged 12 years and older,as manifested by respiratory and/or central nervous system depression.Zurnai is the first approved nalmefene hydrochloride auto-injector.Please note that all drugs carry risks,and patients should review the drug labeling and consult with their health care professional to determine their preferred course of treatment.24Advancing Health Through Innovation:New Drug Therapy Approvals 2024ConclusionFrom the time we receive a drug application whether for a novel drug or a supplemental approval our review process is a collaborative effort that involves scientific,regulatory,and policy experts from throughout CDER and sometimes other parts of FDA.For each application,we complete a very thorough and timely analysis of safety and effectiveness data,including a benefit-risk analysis that factors in the severity of the disease or condition,the currently available treatment options,and the intended patient population.If the therapy meets the standard for approval,we must reach agreement on the indication,labeling,safety issues,and other considerations.We also gather external input from interested parties external to CDER and FDA.We often consult outside scientific experts,patients and patient advocates,industry representatives,academics,and other community members who are involved in drug development and review.Each of these parties has their unique expertise and perspective,and we consider their viewpoints.We take our regulatory decision-making seriously,because we know our decisions affect the health and well-being of patients and consumers nationwide.25Advancing Health Through Innovation:New Drug Therapy Approvals 2024Appendix A:CDERs Novel Approvals of 2024(in alphabetical order)For information about vaccines,allergenic products,blood and blood products,cellular and gene therapy products,go to the 2024 Biologics License Application Approvals.Approval DateProprietary NameActive Ingredient(s)Summary of FDA-approved use on approval date(see DrugsFDA for complete indication)Dosage Form12/20/2024 Alhemoconcizumab-mtciFor routine prophylaxis of bleeding in hemophilia A and B.Injection12/20/2024Alyftrekvanzacaftor,tezacaftor,deutivacaftorTo treat cystic fibrosis.Tablet4/22/2024Anktivanogapendekin alfa inbakicept-pmlnIn combination with Bacillus Calmette-Gurin(BCG)to treat BCG-unresponsive nonmuscle invasive bladder cancer.Intravesical solution9/24/2024AqneursalevacetylleucineTo treat neurological manifestations of Niemann-Pick disease type C.Granules for oral suspension11/29/2024 AttrubyacoramidisTo treat cardiomyopathy of wild-type or variant transthyretin-mediated amyloidosis.Tablet12/4/2024Bizengrizenocutuzumab-zbcoTo treat non-small cell lung cancer and pancreatic adenocarcinoma.Injection9/26/2024Cobenfyxanomeline,trospium chlorideTo treat schizophrenia.Capsule12/29/2024 CrenessitycrinecerfontTo treat classic congenital adrenal hyperplasia.Capsule,Oral solution3/21/2024DuvyzatgivinostatTo treat Duchenne muscular dystrophy.Oral suspension9/13/2024Ebglysslebrikizumab-lbkzTo treat moderate-to-severe atopic dermatitis.Injection12/28/2024 EnsacoveensartinibTo treat NSCLC.Capsule2/22/2024Exblifepcefepime,enmetazobactamTo treat complicated urinary tract infections.Injection9/27/2024Flyrcadoflurpiridaz F 18To use with positron emissiontomography(PET)myocardial perfusion imaging(MPI)to evaluate for myocardial ischemia and infarction.Injection10/11/2024Hympavzimarstacimab-hncqTo prevent or reduce the frequency of bleeding episodes with hemophilia A and B.Injection5/16/2024Imdelltratarlatamab-dlleTo treat extensive stage small cell lung cancer.Injection 26Advancing Health Through Innovation:New Drug Therapy Approvals 2024Approval DateProprietary NameActive Ingredient(s)Summary of FDA-approved use on approval date(see DrugsFDA for complete indication)Dosage Form11/30/2024 IomervuiomeprolTo use with intra-arterial and intravenous procedures for diagnostic radiographic imaging.Injection6/10/2024IqirvoelafibranorIn combination with ursodeoxycholic acid to treat primary biliary cholangitis.Tablet10/10/2024ItovebiinavolisibIn combination with palbociclib and fulvestrant to treat endocrine-resistant,PIK3CA-mutated,HR-positive,HER2-negative,locally advanced or metastatic breast cancer.Tablet7/2/2024Kisunladonanemab-azbtTo treat Alzheimers disease.Injection8/19/2024LazcluzelazertinibIn combination with amivantamab to treat locally advanced or metastatic NSCLC.Tablet7/25/2024LeqselvideuruxolitinibTo treat severe alopecia areata.Tablet2/29/2024LetyboletibotulinumtoxinA-wlbgTo improve the appearance of moderate-to-severe glabellar lines.Injection8/14/2024LivdelziseladelparIn combination with ursodeoxycholic acid to treat primary biliary cholangitis.Capsule4/17/2024LumisightpegulicianineTo use as an optical imaging agent for fluorescenceimaging of breast cancer.Injection9/20/2024MiplyffaarimoclomolIn combination with miglustat to treat the neurological manifestations of Niemann-Pick disease type C.Capsule8/12/2024Nemluvionemolizumab-iltoTo treat prurigo nodularis.Injection8/14/2024Niktimvoaxatilimab-csfrTo treat chronic graft-versus-host disease.Injection6/26/2024OhtuvayreensifentrineTo treat chronic obstructive pulmonary disease(COPD).Inhalation suspension4/23/2024OjemdatovorafenibTo treat pediatric low-grade glioma harboring an activating RAF alteration.Tablet and Powder for oral suspension10/25/2024Orlynvahsulopenem etzadroxil,probenecidTo treat uncomplicated urinary tract infections caused by the designated microorganisms Escherichia coli,Klebsiella pneumoniae,or Proteus mirabilis in adult women with limited or no alternative oral antibacterial treatment options.Tablet 27Advancing Health Through Innovation:New Drug Therapy Approvals 2024Appendix A(continued)Appendix A(continued)Approval DateProprietary NameActive Ingredient(s)Summary of FDA-approved use on approval date(see DrugsFDA for complete indication)Dosage Form6/20/2024Piaskycrovalimab-akkzTo treat paroxysmal nocturnal hemoglobinuria.Injection11/29/2024 Rapiblyk landiolol hydrochlorideTo treat supraventricular tachycardia.Injection12/26/2024 RevuforjrevumenibTo treat relapsed or refractory acute leukemia with a KMT2A translocation.Tablet3/14/2024RezdiffraresmetiromTo treat non-cirrhotic MASH(metabolic dysfunction-associated steatohepatitis)with moderate-to-advanced liver fibrosis(consistent with stages F2 to F3 fibrosis).Tablet6/6/2024RyteloimetelstatTo treat low-to-intermediate-1 risk myelodysplastic syndromes.Injection6/18/2024Sofdrasofpironium bromideTo treat primary axillary hyperhidrosis.Gel3/13/2024Tevimbratislelizumab-jsgrTo treat unresectable or metastatic esophageal squamous cell carcinoma.Injection12/19/2024 TryngolzaolezarsenTo treat familial chylomicronemia syndrome.Injection3/19/2024TryvioaprocitentanIn combination with other antihypertensive drugs to treat hypertension.Tablet12/28/2024 Unloxcytcosibelimab-ipdlTo treat metastatic or locally advanced cutaneous squamous cell carcinoma.Injection3/27/2024VafseovadadustatTo treat anemia due to chronic kidney disease.Tablet8/6/2024VoranigovorasidenibTo treat Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation.Tablet3/29/2024VoydeyadanicopanTo treat extravascular hemolysis associated with paroxysmal nocturnal hemoglobinuria.Tablet10/18/2024Vyloyzolbetuximab-clzbIn combination with fluoropyrimidine-and platinum-containing chemotherapy to treat locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors claudin 18.2-positive.Injection 28Advancing Health Through Innovation:New Drug Therapy Approvals 2024Appendix A(continued)Approval DateProprietary NameActive Ingredient(s)Summary of FDA-approved use on approval date(see DrugsFDA for complete indication)Dosage Form3/26/2024Winrevairsotatercept-csrkTo treat pulmonary arterial hypertension(World Health Organization WHO Group 1).Injection4/26/2024XolremdimavorixaforTo treat WHIM syndrome(warts,hypogammaglobulinemia,infections and myelokathexis).Capsule8/9/2024YorvipathpalopegteriparatideTo treat hypoparathyroidism.Injection1/5/2024ZelsuvmiberdazimerTo treat molluscum contagiosum.Gel4/3/2024Zevteraceftobiprole medocarilTo treat Staphylococcus aureus bloodstream infections(bacteremia),acute bacterial skin and skin structure infections,and community-acquired bacterial pneumonia.Injection11/20/2024 Ziiherazanidatamab-hriiTo treat unresectable or metastatic HER2-positive(IHC 3 )biliary tract cancer.InjectionAppendix A(continued)29Advancing Health Through Innovation:New Drug Therapy Approvals 2024Appendix B:Novel Drug Designations(in alphabetical order)30Advancing Health Through Innovation:New Drug Therapy Approvals 2024Proprietary NameAlhemoAlyftrekAnktivaAqneursaAttrubyBizengriCobenfyCrenessityDuvyzatEbglyssEnsacoveExblifepFlyrcadoHympavziImdelltraIomervuIqirvoItovebiKisunlaLazcluzeLeqselviLetyboLivdelziLumisightMiplyffaNemluvioNiktimvoFirst-in-ClassOrphanFast TrackBreakthrough TherapyPriority ReviewAccelerated ApprovalPDUFA Goal MetFirst in the United StatesFirst Cycle ApprovalAppendix B(continued)Proprietary NameOhtuvayreOjemdaOrlynvahPiaskyRapiblyk RevuforjRezdiffraRyteloSofdraTevimbraTryngolzaTryvioUnloxcytVafseoVoranigoVoydeyaVyloyWinrevairXolremdiYorvipathZelsuvmiZevteraZiiheraFirst-in-ClassOrphanFast TrackBreakthrough TherapyPriority ReviewAccelerated ApprovalPDUFA Goal MetFirst in the United StatesFirst Cycle Approval 31Advancing Health Through Innovation:New Drug Therapy Approvals 2024U.S.Food and Drug Administrationwww.fda.govCenter for Drug Evaluation and Research U.S.Food and Drug Administration 10903 New Hampshire AvenueSilver Spring,Maryland 20903Center for Drug Evaluation and Research U.S.Food and Drug Administration 10903 New Hampshire Avenue Silver Spring,Maryland 20903
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Ensuring Access,Affordability,and Quality in the Age of Healthcare Consolidation:Lessons Learned and Insights for the FutureThe report builds on a convening held in Washington,DC in May 2024 that brought together 17 health policy experts to consider the status of consolidation among healthcare providers,the challenges it poses to healthcare,and the legal,regulatory,and policy frameworks that can influence its impact.We had the privilege of serving as cochairs of that stellar,nonpartisan Working Group.The meeting was organized by the Health,Medicine,and Society program of the Aspen Institute,with the participation of KFF(formerly known as the Kaiser Family Foundation).Together,we identified a package of strategies that could reduce the ability of providers to dominate the healthcare landscape in ways that pose a broad threat to patient care.The Working Groups vigorous discussions were informed by two background papers,which are included as part of this report:“Policy Options to Address Consolidation in Healthcare Provider Markets,”prepared by Benedic Ippolito of the American Enterprise Institute,and“Ten Things to Know about Consolidation in Health Care Provider Markets,”prepared by KFFs Zachary Levinson,Jamie Godwin,Scott Hulver,and Tricia Neuman.Our most sincere thanks go to the Working Group members who offered their exceptional expertise and insights and gave so generously of their time,and to Arnold Ventures,whose support made this project possible.Alan Weil,editor-in-chief of Health Affairs,kept us focused with his remarkable abilities as convening facilitator,and HMS communications consultant Karyn Feiden masterfully synthesized the discussions and research into this report.We believe the ideas presented here,and especially the proposals for action,can point the way towards a more competitive healthcare system that honors the right of the American people to have equitable access to quality services at a price they can afford.This report is dedicated to that shared goal.We are pleased to present Ensuring Access,Affordability,and Quality in the Age of Healthcare Consolidation:Lessons Learned and Insights for the Future.This report looks at the increasing marketplace dominance of large health systems and explores options for safeguarding competition and protecting patient care.FEBRUARY 2025Holly VedovaCochairKathleen FooteCochair1|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONContentsReport.2Background PapersPolicy Options to Address Consolidation in Healthcare Provider Markets.26 Benedic Ippolito,PhD,MSTen Things to Know About Consolidation in Health Care Provider Markets.45 Zachary Levinson,PhD,MA,MPP,Jamie Godwin,PhD,Scott Hulver,PhD,and Tricia Neuman,DSc,MSAppendicesWorking Group Participants.58Special Guests.66Program Staff and Acknowledgment.67Program Conveners.692|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONThe potential for these developments to tamp down competition has fostered considerable debate.Two key questions frame the discussions:What is the impact of consolidation on cost,quality,equity,and access to services?And do existing legal frameworks and regulatory structures at the federal and state levels offer adequate safeguards against monopolistic practices?A careful analysis is essential to find the answers and inform proposals for policy change.To explore the ramifications of consolidation among healthcare providers,the Health,Medicine&Society(HMS)Program of the Aspen Institute,with the participation of KFF(formerly known as the Kaiser Family Foundation),convened a Working Group in May 2024.Funding for the conveningEnsuring Access,Affordability,and Quality in the Age of Healthcare Consolidation:Lessons Learned and Insights for the Futurewas provided by Arnold Ventures.The meeting was cochaired by Kathleen Foote,who recently retired as antitrust chief of the California Office of the Attorney General,and Holly Vedova,who recently retired as director of the Bureau of Competition at the Federal Trade Commission(FTC).Fifteen other participants with a broad range of health policy expertise in the public,private,nonprofit,and academic sectors joined the Working Group(see Appendix 1).Their charge was to consider the forces that are driving provider consolidation;the nature of existing regulations and their gaps;the consequences for market competition,price,and access to care;and the opportunities to curb further consolidation.Two background papers were circulated to the Working Group before the convening to ensure a baseline of knowledge as discussions began:ReportAmerican healthcare has become increasingly consolidated over the past few decades.Health systems*are acquiring hospitals,health systems and hospitals are both acquiring physician practices,and physician practices are pairing up.Some of these mergers and acquisitions occur within the same geographic area,but they are also taking place across different regions of the country.At the same time,private equity firms and corporations that have not traditionally provided healthcare services,such as Amazon,are entering the marketplace and aggressively purchasing clinical practices.1“What is the impact of consolidation on cost,quality,equity,and access to services?Are existing safeguards against monopolistic practices adequate?”*While definitions of health systems vary,they are often described as having at least one hospital plus other types of providers(e.g.,one or more physician groups)or as including multiple hospitals(see Agency for Healthcare Research and Quality,Defining health systems,at https:/www.ahrq.gov/chsp/defining-health-systems/index.html and American Hospital Association,Fast facts:U.S.health systems,at https:/www.aha.org/system/files/media/file/2022/06/Fast-Facts-US-Health-Systems-2022-with-FY20-Data.pdf).3|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATION“Policy Options to Address Consolidation in Healthcare Provider Markets,”prepared by Benedic Ippolito of the American Enterprise Institute,reviews potential federal and state strategies for increasing competition.These strategies include increasing transparency around consolidation,strengthening antitrust enforcement authority,tamping down on anticompetitive contract provisions,introducing premerger approval requirements,and repealing Certificate of Public Advantage(COPA)laws.2“Ten Things to Know About Consolidation in Health Care Provider Markets,”prepared by Zachary Levinson and colleagues at KFF,highlights consolidation trends,key findings from existing research,potential harms and benefits,and policy options that could promote more competition.3This report builds on those background papers and captures the vigorous conversations at the Working Group convening,supplementing them with additional research and further input from the participants.However,it is important to acknowledge it is by no means a comprehensive look at every factor fueling consolidation in healthcare markets nor all the potential remedies available for anticompetitive practices.Political shifts,the changing dynamics of regulatory authority,and structural changes to the healthcare system could all alter the landscape in ways that the Working Group could not predict and did not fully consider.Nor did it examine the increasing consolidation within the insurance industry,which has resulted in highly concentrated insurance markets in 95 percent of the nations metropolitan statistical areas and is a likely driver of further provider consolidation.4,5In focusing instead on the challenges that mergers and acquisitions among providers pose to the American healthcare system,a shared goal emerged:identifying ways to leverage the healthcare system so that it is competitive enough to provide quality,affordable,and accessible care.The State of Healthcare Consolidation TodayA widely accepted premise is that there are benefits to vigorous competition and the degree of patient choice that competition offers.“There is reasonably strong agreement across ideological bounds of the value of competitive marketplaces and the challenges that consolidation pose to having competitive marketplaces,”*observed one Working Group participant.“If youre a market kind of person,you want the markets to work and if youre a regulator,you want to use that regulatory lever as Report“A widely accepted premise is that there are benefits to vigorous competition and the degree of patient choice that competition offers.”*Quotes throughout the document are synthesized from Working Group comments at the convening.4|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReportlittle as possible.And so to the extent that you can rely on markets,thats a good thing.”Increasing consolidation clearly threatens the possibility of competitive healthcare markets.KFFs issue brief describes three broad forms of mergers,all of which are becoming more common:horizontal mergers of two entities providing similar services(e.g.,a health system acquiring a hospital);vertical mergers of different providers along the supply chain(e.g.,a health system acquiring a physician practice);and cross-market mergers,in which providers combine across geographic market boundaries.A recent example of a consequential cross-market deal was the merger of Advocate Aurora Health and Atrium Health in 2022,which created a health system that operates 67 hospitals and more than 1,000 other clinical sites in six states.6In 2005,slightly more than half of all hospitals were affiliated with a health system(53 percent);by 2022,that figure had jumped to more than two-thirds(68 percent).Likewise,in 2012,fewer than one-third(29 percent)of physicians either worked for hospitals or were in practices at least partially owned by a hospital or health system,according to survey data;by 2022,that figure had increased to 41 percent.7In an evolving landscape,there are also mergers that involve both vertical and horizontal consolidation,joint ventures,and various affiliation agreements that do not involve ownership changes but nonetheless increase market domination.As well,there are transactions that one Working Group participant described as“involving everything in healthcarepayer,provider,pharmaceutical benefit manager,pharmacy chain,data pipelines,and everything in the middle.”A large body of evidence indicates that consolidation has led to increases in the price of healthcare services as providers gain bargaining power.While this evidence is especially strong in analyses of hospital mergers,similar trends are suggested by research into mergers of hospitals and physicians and of physician practices.8Studies have likewise generally reported that consolidation is associated with a rise in overall spending as patient choice diminishes.This could reflect some combination of price increases,greater use and intensity of healthcare services,and a shift in care toward more expensive settings,such as a hospital outpatient department rather than a physicians office.For example,one study indicates that total spending on chemotherapy tends to increase after oncologists are integrated into a hospital system.9“A large body of evidence indicates that consolidation has led to increases in the price of healthcare services as providers gain bargaining power.”5|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReportWhile private payers are most affected by healthcare consolidation,the cost consequences are also felt in the federal budget.In testimony before the US House of Representatives Committee on the Budget,Chapin White,director of health analysis for the Congressional Budget Office,noted that the resulting price increases may affect tax revenue if employers shift labor costs from taxable wages to tax-free insurance benefits.Higher prices can also drive up the federal subsidies provided through the Affordable Care Acts health insurance marketplace.10Research on the impact of consolidation on quality of care is mixed.The majority of studies have found either no quality difference or a negative impact after horizontal hospital consolidation.Studies of vertical hospital or physician consolidation variously show negative,positive,or mixed effects or none that are statistically significant.11,12 In total,the research is limited,and the findings vary with the measures used.The lead time before the effects of consolidation become apparent,the potentially different effects across patient populations,and the differences in the nature of mergers also contribute to uncertain results.Another question about consolidation is how it relates to hospital closures or the availability of certain service lines.One Working Group participant called out evidence that consolidation can be a precursor to closure and said that is happening more quickly than in the past.“Even before the ink is dry in the transaction,the hospital is being parceled up and readied to shut down,”he said.Conversely,a merger can sometimes be the only option for a financially fragile hospital to survive.For example,one study found health system affiliation was associated with a reduced risk of closure among rural hospitals with weak finances.13 Overall,the evidence here,too,is mixed.Health inequities loom as another troubling risk of consolidation.“Whats happening in this market is that it has a different effect on different populations,”indicated one participant.In healthcare,he said,it is“creating a social disparity unlike what weve seen in any other industry.”The research on access to care is limited,and the findings are again mixed,but The Century Foundation,a progressive think tank,has called out longer travel times for those who can least afford them;the need to leave trusted communities to find care;decreased local employment opportunities;and the prospect of“care deserts,”including for maternal health and pediatric services,which are especially crucial for vulnerable populations.14Despite the many concerns,Working Group participants agreed that consolidation might offer benefits under certain limited circumstances.The potential advantages are particularly likely to enter conversations about financially vulnerable rural hospitals.In sparsely populated areaswhere“Health inequities loom as another troubling risk of consolidation.”6|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReportcompetition is limited,new entrants into the marketplace are unlikely,and the prospect of closure is a looming threatmerging with a larger health system could be an appropriate option to preserve hospital access and perhaps create a springboard for expanding services.15,16 However,these pluses must be weighed against the risk that such acquisitions could lead to higher prices and reduced services.The potential also exists for vertical integration to improve the coordination of clinical care,such as by easing provider-to-provider communication and ensuring readier clinician access to medical records.Furthermore,consolidation in any form could offer opportunities for economies of scale,reduced administrative burdens,lessened waste and service duplication,and other efficiencies.17Absent in these conversations are clear criteria for identifying potentially beneficial mergers,acquisitions,or affiliation agreements.The lack of adequate data or definitive standards for measuring the trade-offs inherent in consolidation make ambiguity and disagreement inevitable.Though it is difficult to draw,a road map would be useful to differentiate between transactions likely to raise costs,scale back services,or produce other negative outcomes and those with a reasonable prospect of yielding new healthcare investments or other benefits.Federal and State Authorities to Promote CompetitionA multitiered regulatory structure provides some leverage over healthcare consolidation.At the federal level,the FTC and the Department of Justice(DOJ)are empowered to enforce federal antitrust laws,challenge mergers and acquisitions perceived as threats to competition,and curtail the anticompetitive conduct of existing entities.18 In general,the FTC specializes in provider markets,while DOJ primarily oversees health insurance markets.The FTC can challenge mergers involving either nonprofit or for-profit entities but lacks the authority to challenge other anticompetitive practices among nonprofits.While it can refer those to the DOJ,the departments history of enforcement action against nonprofit health systems is limited.Additional capacity is lodged within the offices of state attorneys general,who are guided by both federal and state statutes and often work in partnership with federal regulators.19But the current structure was not built for overseeing or regulating the scale and stakes of the consolidation that is occurring in healthcare today.Indeed,one Working Group participant suggested that the legal framework had changed only modestly since Standard Oil was broken up more than a century ago.“The lack of adequate data or definitive standards for measuring the trade-offs inherent in consolidation make ambiguity and disagreement inevitable.”7|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReportOne example of the limits is that federal law currently requires that the FTC be notified before certain mergers or acquisitions valued at more than$119.5 million take place(the figure is adjusted annually).20 But a series of small acquisitions,each of which falls below this threshold,is commonplace in healthcare,allowing many of the cumulative effects to go forward without scrutiny.“The rollups and sequential mergers in which investors combine multiple small entities into a single larger one can have the same effect as two large entities merging,”one participant explained.“And whether thats done through private equity acquisitions or more traditional acquisitions,its very significant.The impacts really need to be looked at.”The rapid growth in cross-market mergers promises to have a particularly powerful impact on prices and access to care.21,22 From 2010 through 2019,more than half of completed mergers or acquisitions involved hospitals or health systems in different markets.23“Cross markets are the burning issue,”asserted one participant.“That is what is going to change the direction of healthcare consolidation.”While government antitrust agencies have intervened in few,if any,of these transactions,the FTC sees them as an important area of interest.24The Working Group agreed that identifying and potentially curtailing anticompetitive practices in healthcare is a shared responsibility likely to call for a combination of legislation,regulation,and litigation that engages federal agencies,state agencies,and private plaintiffs.Given the cost and complexity of legal action,the FTC and the DOJ are highly selective in the cases they pursue,generally choosing those most likely to have not only a substantial impact on the litigants involved but also a deterrent effect on other big health systems.In practice,said one participant,that means“carefully picking the right cases to get at the root causes of the problems and then pushing the law in the right direction.”While bigger agency budgets would likely improve the capacity to enforce or strengthen oversight,additional funds alone will not be a panacea.Limited authority,adverse court decisions,a rapidly shifting marketplace,and the risk of unintended consequences can all complicate health system antitrust efforts.The challenges of hiring and placing qualified personnel,establishing an evidence base that is persuasive to judges,and juggling demands to address mergers and acquisitions in other fields are further constraints.Nonetheless,regulatory responses to marketplace shifts in recent years suggest there may be new enforcement opportunities.For example,the FTC has indicated an interest in using Section 5 of the Federal Trade“The rapid growth in cross-market mergers promises to have a particularly powerful impact on prices and access to care.”8|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReportCommission Act more aggressively.25 Section 5 explicitly prohibits unfair methods of competition and can be used“for unusual cases that dont fall into the monopolization standard to get at something thats unfair and is going to lead to competitive harm,”explained one Working Group member.“Thats something unique that the FTC brings to the table.”In 2021,the FTC rescinded a statement it had issued in 2015,explaining that it“contravenes the text,structure,and history of Section 5 and largely writes the FTCs standalone authority out of existence.”26 The earlier statement,wrote the FTC,essentially abrogated“the Commissions congressionally mandated duty to use its expertise to identify and combat unfair methods of competition even if they do not violate a separate antitrust statue.”Another tool of interest is the 2023 Merger Guidelines,which were released jointly by the FTC and the DOJ following a two-year public engagement process.27 According to KFF,“the guidelines expand the definition of highly concentrated markets,rely on a lower threshold for identifying large changes in market concentration,consider the combined effect of a series of acquisitions(e.g.,of a health system acquiring several small physician practices over time),add an explicit discussion of the agencies views on how workers may be negatively impacted when their employers merge,and touch on cross-market mergers.”28Just how those guidelines,which are nonbinding,will be applied to antitrust actions remains to be seen.But Working Group participants suggested that they demonstrate the FTCs eagerness to identify new legal frameworks for challenging a wider variety of healthcare mergers that risk further concentrating the marketplace.Such actions will require in-depth investigation and involve a challenging journey through the courts,so the new guidelines will take some time to demonstrate impact.In a further signal that it intends to pursue more aggressive enforcement,the FTC issued a Request for Information(RFI)in February 2024,acknowledging concern about healthcare provider transactions that“may generate profits for those firms at the expense of patients health,workers safety,and affordable healthcare for patients and taxpayers.”The RFI called for public input about how these transactions could affect“patients,communities,payers,employers,providers,and other healthcare workers and businesses.”29 That request,said one Working Group member,is a strong indication that the FTC is eager to take action“with the right case,with the right facts,with a good story.”“The FTC seems eager to identify new legal frameworks for challenging a wider variety of healthcare mergers that risk further concentrating the marketplace,but such actions will involve a challenging journey through the courts.”9|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReportState-level engagement varies considerably,but the knowledge of local market conditions that rests with state officials can make them important partners to federal actors.State laws can limit anticompetitive contract clauses and define the authority that attorneys general have to oversee mergers and file lawsuits.They can also require mergers falling below the federal$119.5 million threshold to be reported to state authorities.Conversely,there are structures that allow states to shield mergers from federal antitrust laws or limit competition in other ways(see below for a discussion of COPA and Certificate of Need CON laws).Opportunities for ActionIn broad strokes,the Working Group agreed on the need to address the harms of consolidation.Although market power is not the only reason for high healthcare prices,it is a significant enough influence to warrant a nimble,multilevel policy response.“The question is not just how do we use the tools we already have,but how do we reshape them to meet the moment of where the market is actually going?”asked one member.The power of well-resourced health systems,which are often major employers in a community and wield significant local and national political influence,looms as a barrier.The extent to which advocates have the capacity and willingness to push forward actions opposed by hospitals is uncertain.“How much do we want to alienate or poke the tiger of the hospital lobby?”one Working Group participant asked.But,he warned,“That might be the first thing we have to do.It might be a necessary condition to anything else we do.”That could mean,for example,supporting punitive action or substantial financial penalties where clear antitrust violations are established.“Were never going to have enough enforcement resources for everything,”acknowledged a participant.“How can we start sending signals to actors in this field that its in their interest to be on the right side of this?”In addition to the appropriate mix of federal and state policy and regulation,important roles exist for private legal action and for the academics and advocates who can inform the conversation.“We need as much engagement as possible among the law enforcers,economists,academics,and policymakers to try to understand how todays more complex healthcare markets function,”urged a Working Group participant.“We need to figure out what the mechanisms are,tell a convincing story,and translate that into enforcement.”“Although market power is not the only reason for high healthcare prices,it is a significant enough influence to warrant a nimble,multilevel policy response.”10|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReportShared goals could also unite unlikely partners interested in bringing new providers into the marketplace.A potential alliance between insurers and patients,for example,is often overlooked.“There is a lot more alignment with the payers and consumers than what is visible publicly,”one participant pointed out.The shape of the response will depend in good measure on local conditions.In markets that are not yet heavily consolidated,the goal would be to reduce the likelihood that consolidation will take hold.Strategies here could include measures to encourage the entry of competitors,where feasible;enforce existing regulations more forcefully and expand their reach;and make consolidation less financially desirable from the provider perspective.Where options to foster competition are few,such as in rural areas and for highly specialized services,the emphasis could shift to constraining the market power of dominant providers,regulating prices,or regulating spending.Here,authorities could prohibit anticompetitive contract provisions and encourage service delivery innovations.It may also be possible to take affirmative action to retain or restore competition by unraveling previous mergers,although that could prove very challenging.The Working Group recognized that no single solution would be sufficient to curb healthcare consolidation.The multiple intersecting and overlapping strategies they explored at both the federal and state levels are presented below and organized as follows:Emphasizing transparency,value,stakeholder education,and analytic capacity.Strengthening federal and state regulations and enforcing them more vigorously.Reducing financial incentives for health systems to consolidate.Barring anticompetitive provisions in contracts between health systems and payers.Unwinding consolidation where it is already embedded.Considering innovative care delivery models in sparsely populated areas.Filling data and research gaps on quality,access to care,and the labor market.“No single solution would be sufficient to curb healthcare consolidation but multiple intersecting and overlapping strategies exist at both the federal and state levels.”11|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReportEmphasizing transparency,value,stakeholder education,and analytic capacity could alter the healthcare consolidation landscape.A number of cross-cutting strategies could help foster competition in diverse healthcare markets.Requiring more price,cost,and ownership transparency:The capacity to take preventive action or pursue antitrust cases to reduce consolidation is closely linked to the availability of information.In the current environment,informed policymaking is stymied by the lack of clear and comprehensive information about provider prices,cost inputs,and ownership.30(The absence of contract transparency,discussed below,is a related barrier.)Explicit reporting mandates could alter provider and patient behavior and influence public policy.Some states do require providers to feed data into all-payer claims databases,which provide key information about pricing,but self-insured employers are not obligated to report,and no federal database would allow data to be aggregated and analyzed.Federal regulations do require hospitals and payers to report prices for healthcare services,though using these data can be difficult.31“There is no transparency in everything in the supply chain that goes into the commercial price,from the provider all the way up to data about the purchase and ultimately to the consumer,”said one Working Group participant.Likewise,no single database documents who owns what.The complexity of affiliation agreements further clouds any attempt to figure out the locus of control.“To establish a case,you have to know who the owner of a physician practice is,and right now we cant tell,”said one participant.Elevating value:A number of proposals could clear certain barriers to competition by allowing more high-value caredefined as services that result in measurable health improvements at lower cost32to enter the marketplace and expand.For example,federal and state policies could direct more financial resources and administrative support to primary care physicians and their practices,which are a particular target of acquisitions.As well,some states are attempting to increase the clinician supply by broadening the scope of allowable practice for nurse practitioners,physician assistants,and other nonphysicians.Innovative structures that deliver healthcare in new waysfor example,through telehealth and in-home hospital modelscan also draw players into the market.“Informed policymaking is stymied by the lack of clear and comprehensive information about provider prices,cost inputs,and ownership.”12|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReport Educating stakeholders:Tamping down the power of dominant health systems requires a mix of sound public policy,enforced by regulation;effective litigation,confirmed by court decisions;and informed marketplace decisions.These approaches require federal and state elected officials to understand the justification for passing laws that promote competition,regulators and litigators to be cognizant of provider conduct that leads to monopoly behavior,judges to recognize the validity of claims made in antitrust cases,and purchasers and patients to be able to consider the relative value of healthcare as they make decisions.Educating each of these stakeholders requires advocates,user-friendly policy reports and recommendations,and narrative changes that highlight the perils of consolidation.“What has helped to turn the tide in terms of the political narrative at the national level has been amplifying the abuses and the harmful effects on affordability and access to quality care,”commented one Working Group participant.Boosting capacity for analysis,discovery,and action:Although the FTC and DOJ have had some success at challenging hospital mergers,the time and resources involved limit the scope of their activity.To curb further consolidation and address the conduct of already-consolidated health systems requires new resources,statutory changes,and successful sentinel litigation that serves as a warning to dominant providers.A platform for addressing market domination is also needed at the state level,where the existing tools available in the attorneys general office or elsewhere are sometimes insufficient.A 2024 Health,Medicine&Society Program/KFF report,“State Efforts to Control Healthcare Costs:Lessons Learned and Insights for the Future,”outlines a number of measures that could facilitate state action to lower healthcare costs.Among others,the report called for a supportive infrastructure to give each state“a platform to facilitate the effective use of data,accommodate appropriate oversight,allocate the necessary resources,and ensure that the expertise needed to bring stakeholders together and drive action is available.”33 Such a platform could also serve as the springboard for measures that promote competition.Strengthening federal and state laws and regulations and enforcing them more rigorously could slow consolidation.The Working Group considered the regulatory changes at both the federal and state levels that could limit consolidation.Some of these involve changes to the legal framework that are relevant to any antitrust action,while others are health specific.“Tamping down the power of dominant health systems requires a mix of sound public policy,enforced by regulation;effective litigation,confirmed by court decisions;and informed marketplace decisions.”13|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReport Expanding premerger reporting or review:At the federal level,new policies could prevent at least some mergers from falling under the regulatory radar screen.In addition to lowering the transaction threshold for premerger reporting,mandatory reporting could kick in when the total value of a new healthcare entity reaches a certain size.That would capture the multiple smaller transactions that together lead to greater consolidation.Policymakers could also collect more information from providers about ownership and market shares,as the FTCs Bureau of Economics has begun to do.34 Access to such data could improve the oversight capacity of antitrust agencies and has the potential to inform further action.States have separate authority to establish premerger reporting,such as by requiring disclosure at lower thresholds than the federal mandate.They can also establish their own review requirements,including mandating prior government approval for certain mergers,or all of them,and expanding the authority of attorneys general to challenge transactions.A number of states are already experimenting with broader reporting mandates.35 Some are also considering legislation designed to curb abuses among businesses that have a dominant market share within the state.36 Proposals define dominance in various waysfor example,by percentage of market share or volume of servicesbut generally have the stated aim of fostering a more competitive economy.New standards could subject more health systems to further regulatory requirements.Lowering burden-of-proof requirements in antitrust laws:Current federal regulations require evidence that a merger would“substantially”lessen competition before a challenge can go forward.The Working Group expressed interest in a proposal to alter the language so that mergers that“meaningfully”lessen competition come under greater scrutiny.“That seems like a fairly profound change,”said one member.“It would be quite helpful to have a better understanding of the potential pitfalls,trade-offs,and counterarguments.”Challenging anticompetitive practices among nonprofit hospitals:Beyond mergers,the FTC currently has limited authority to challenge anticompetitive practices of nonprofits,as noted previously.Legislation to amend the FTC Act to extend its authoritythe Stop Anticompetitive Healthcare Act of 2023has been introduced in Congress.37 Restricting COPA laws:Certificate of Public Advantage laws are statutes currently in place in 19 states38 that essentially shield mergers“States have separate authority to establish premerger reporting.They can mandate prior government approval for certain mergers,or all of them,and expand the authority of attorneys general to challenge transactions.”14|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReportfrom federal antitrust laws and replace them with state regulation.The theory is that under certain circumstances it is less harmful to allow a hospital merger than to deny one with the potential to improve healthcare quality,efficiency,or access.Financial distress,clinician shortages,and competitive impact are all factors that states may consider in approving a COPA.In exchange,state regulators can impose any number of new requirements to address potential harms,such as capping rates in some form,requiring public reports of quality metrics,requiring additional community services or more outreach to underserved populations,providing more charity care,or increasing research funding.39 The FTC has been explicit in its objection to COPAs.“Experience and research demonstrate that COPA oversight is an inadequate substitute for competition among hospitals and a burden on the states that must conduct it.Research demonstrates that COPAs have resulted in significant price increases and contributed to declines in quality of care.”40 Like the FTC,the Working Group was forceful in its concern about COPAs,suggesting that in the face of the immense political power hospitals often wield,states face substantial barriers to regulating prices,ensuring quality of care,and promoting innovation at merged hospitals.The effect of COPAs depends crucially on their design,enforcement,and duration,and even COPAs that are initially successful may fail over time as enforcement wanes or lapses.“COPAs rarely work as promised,”asserted one participant.Indicating that the signal against COPAs is“flashing red,”members generally agreed that states without COPA laws should not enact them.They also expressed considerable support for repealing existing laws that would permit future harmful mergers while ensuring continuing state oversight of systems that had already merged under a COPA.Reconsidering Certificate of Need laws:Thirty-five states and Washington,DC,currently have some type of CON law(three others use similar processes).41 These laws vary considerably,but all require state approval before a health provider is permitted to undertake major capital expenditures or a new provider enters the market.Initially intended to reduce the costs and inefficiencies that can result from oversupply,critics argue that they have instead shielded existing providers from competition and contributed to higher costs.42 A number of states have repealed their CON laws,and Working Group participants agreed that they can be a barrier to competition that works to the advantage of dominant providers.But they also discussed the possibility of using the existing infrastructure and expertise of the“The Federal Trade Commission and this Working Group have been forceful in their concerns about Certificates of Public Advantage.”15|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReportCON mechanism to serve new purposes,possibly for planning or as a way to oversee proposed transactions,the availability of healthcare services,or access to care.In that context,an effective CON approach could work as both carrot and stick.In North Carolina,for example,the attorney general opposed a CON request from a dominant provider to increase beds,instead issuing the certificate to a different provider in order to foster competition.43 In another scenario,a state could consider past behavior in deploying its approval authority.One participant proposed this message:“You have to comply with the conditions that were placed on your transaction.And,oh,you didnt comply the last time?Then sorry,youre not going to be able to get the new CON to purchase the next round of physicians or to acquire the community hospital because you closed a key facility or a key service line when you promised you wouldnt.”Payment and pricing reforms and other policy changes could make healthcare market consolidation less financially rewarding to providers.If a key motivation for consolidation is to enhance revenue,measures could be put in place so it becomes less lucrative for health systems to pursue mergers.“Getting the payment incentives right means you dont have to tackle this tactic by tactic,transaction by transaction,”advised one Working Group participant.“You can get ahead of consolidation in a much more scalable way.”Requiring site-neutral payments:Under the current reimbursement structure,Medicare often pays more for identical procedures provided in hospital outpatient settings than in an unaffiliated physicians office,creating a clear incentive for physician practices to merge with hospitals.44 Changing this two-tiered system so that reimbursement is the same regardless of the service sitea move that sounds straightforward enough for one participant to call it“low-hanging fruit”has garnered a degree of bipartisan support.In a limited number of circumstances,Medicare has already imposed site-neutral payments,and there have been repeated attempts in Congress to legislate further mandates.45 These policies would reduce costs for both the Medicare program and for beneficiaries and could have spillover effects on commercial prices and spending(e.g.,by reducing consolidation incentives).However,opponents of site-neutral“If a key motivation for consolidation is to enhance revenue,measures could be put in place so it becomes less lucrative for health systems to pursue mergers.”16|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReportreforms argue that lower hospital revenues could reduce access to care and that higher payments are needed to support emergency care and certain other services.Regulating prices and spending in the private market:Working Group participants agreed that high commercial prices had to be part of any dialogue about market domination.Because the ability to negotiate prices is one reason that providers seek to merge,price and spending regulationsincluding capping prices at a percentage of Medicare reimbursement rates,limiting out-of-network charges,establishing global budgets,creating spending growth targets,or implementing state-level health coverage public options(in the absence of a federal option)could all reduce incentives for consolidation.The true impact deserves closer study,however,because regulating price and spending could,in theory,create an incentive for further consolidation as providers seek the efficiencies and scale that allow them to maintain profits.More broadly,price and spending constraints could improve affordability for patients and employers.However,major policy changes in this arena are vehemently opposed by the hospital industry,which claims that they can diminish access to care and harm quality.46 Beyond acknowledging their potentially critical role,the details of these strategies were not explored at the convening.Reforming the 340B program:The federal 340B program requires pharmaceutical manufacturers participating in Medicaid to offer significant purchase discounts to eligible nonprofit and government providers.The intent is to stretch federal resources while supporting entities that provide care to low-income and other underserved populations.47 The American Hospital Association is a vigorous defender of the program,claiming that it benefits both vulnerable populations and the capacity of hospitals to expand health services.48 Research suggests,however,that 340B hospitals prescribe more costly drugs and employ more physicians in specialties that use more expensive therapies49 but do not actually treat more underserved populations.50 One Working Group participant said,“340B creates huge incentives for becoming part of a qualified entity so you can get access to low-price drugs.It creates huge incentives for consolidation that have nothing to do with efficiency or equity.”Several reform proposals has been put forth to ensure that the program works as originally intended.One would shift program rules so that it no“Research suggests that 340B hospitals prescribe more costly drugs and employ more physicians in specialties that use more expensive therapies but do not actually treat more underserved populations.”17|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReportlonger provides blanket discounts to certain health providers but rather is available only for drugs provided to low-income patients.51Another proposes an enforceable standard that would ensure discounts are given only to outpatient facilities and pharmacies that serve vulnerable populations or are located in medically underserved areas.52 Strengthening bans on the corporate practice of medicine:Legislation in more than 30 states bars corporations,as nonlicensed providers,from controlling,employing,or owning physician practices.However,the contractual affiliations that many corporate entities have increasingly put in place,typically through management services organizations,arguably undermine this restriction.In effect,they can force physicians to cede control of billing and coding practices,personnel decisions,and payer contracts while imposing constraints on their freedom to speak out.Often positioned as a way to eliminate administrative burdens while protecting physician autonomy over clinical decision making,they instead can turn physicians“into cogs in a corporate wheel,”claimed one participant.The intent of a strengthened ban would not be to clamp down on contracting out back-office support but rather to prevent corporate owners from taking full charge of coding,billing,and personnel decisions or imposing noncompete and nondisclosure clauses.“It restores the principal-agent relationship where the practice will still be in charge,”said one participant.However,the effects of bans are not well studied,and another participant warned that they could,in principle,make it harder to develop a new physician practice.In any case,the scope of new provisions is unlikely to affect most vertical mergers,because many states exclude hospitals from restrictions against owning and controlling physician practices.Prohibiting anticompetitive contracting provisions could reduce the ability of health systems in consolidated markets to exert their market power.Consolidation can allow health systems to tamp down on competition and protect their dominant position by dictating contract terms with payers that enhance their control over the composition of provider networks,limit referral options,restrict patient choice,and reduce transparency.Yet those contract provisions are often labeled as proprietary,even to purchasers,making it almost impossible to identify and assess their anticompetitive impact or to respond with informed policy.While pushing for fully“Contract provisions are often labeled as proprietary,even to purchasers,making it almost impossible to identify and assess their anticompetitive impact or to respond with informed policy.”18|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReporttransparent contracts will engender significant pushback,advancing the position that purchasers with a fiduciary duty to health plan enrollees should know the contract terms seems easier.“It makes no sense that you can be legally responsible for doing the best thing for your employees and not actually have an ability to see what youre binding them to,”said one participant.One of the best-known attempts to challenge a package of anticompetitive contract clauses was a series of lawsuits filed against Sutter Health,a large nonprofit health system in California created through a number of mergers that took place over several decades.One Working Group participant said that Sutter had“the most sophisticated system of contracting terms anyplace in the country.”Navigating uncharted waters through a lengthy investigation,a consolidated state case culminated in a 2019 settlement requiring Sutter to halt some dozen different contracting practices and pay$575 million in damages.53Whether such cases ultimately have a broader deterrent effect is uncertain,especially since health systems have so many opportunities to pursue workarounds.Indeed,one participant paraphrased a hospital executive who had just learned about a successful legal challenge to another hospitals anticompetitive clause.The executive purportedly said,“We had better close our deal with the insurer we are negotiating with before they hear about this.We have this exact same provision,so lets speed things up.”Arguably,an alternative to after-the-fact litigation would be federal or state legislation that prohibits anticompetitive conduct.But here,too,powerful health systems may find ways to sidestep contractual restrictions,essentially insisting on the same provisions without actually putting them in writing.The result,suggested one participant,is that“at the end of the day,when were sitting at the negotiating table,they are still taking that anticompetitive stance,so its not actually changing the relative power.”Nonetheless,policymakers could consider prohibiting any combination of the following provisions(in some states,this has already occurred):54,55 All-or-nothing clauses require an insurer to contract with every provider in a given health system if it is going to contract with any of them.This makes it impossible for insurers to create more limited networks or to exclude higher-cost,lower-value providers.Any ban on such clauses could include carveouts for smaller physician practices where market power is not a concern to lessen their administrative burdens and help them remain competitive.“Powerful health systems may find ways to sidestep contractual restrictions,essentially insisting on the same provisions without actually putting them in writing.”19|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReport Antitiering and antisteering clauses prevent insurers from using mechanisms that encourage patients to seek higher-value care.Antitiering clauses bar insurers from sorting providers into preferred and nonpreferred slots,while antisteering clauses bar insurers from offering incentives,such as lower cost sharing,to influence the provider choices patients make.Exclusive contracting clauses prevent insurers from including competing providers as in-network providers.Similar clauses can limit a physicians ability or willingness to make referrals outside their own health system.Noncompete clauses prevent clinicians from taking jobs with other health systems or hospitals within a certain geographical distance or within a certain period of time.Gag clauses prohibit parties to a contract from disclosing its terms.That can undermine negotiations between health systems and insurers because the insurer does not know if a competitor is getting more favorable terms.Gag clauses can also be imposed on physicians once their practices have been incorporated into a larger system or used to prevent certain claims data from being shared.Most-favored-nation clauses require a provider to give an insurer the lowest price it negotiates with any competitor.Unlike the other provisions described here,this is primarily a benefit to insurers,not health systems,but it also affects pricing by discouraging competing providers from negotiating lower rates with one insurer that it would then have to match with others.Options for unraveling consolidated healthcare markets merit consideration.Given the degree of healthcare consolidation that has already taken place,Working Group participants did not dismiss the possibility that some kind of assertive action to break up consolidated entities could be warranted.While reversing“facts on the ground”introduces an additional layer of complexity to any policy response,the Working Group wanted the possibility of mandatory divestiture to remain an option,especially for physician practices.“It shouldnt be off the table by any means,”commented one participant.“Weve bought the argument that provider hospitals have madeonce weve integrated our electronic health records,you cant pull us apartbut thats just not true for other provider types.”“Working Group participants did not dismiss the possibility that some kind of assertive action to break up consolidated entities could be warranted.They wanted the possibility of mandatory divestiture to remain an option.”20|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReportSome policy advocates believe that it is,in fact,reasonable to target fully consolidated health systems.One analyst suggested giving health systems two choices:“remain consolidated but without monopoly pricing power”or“voluntarily divest some holdings to restore competition in a hospital market.”56 Members also suggested that an affirmative attempt to reverse mergers could be a potent deterrent to future ones.In sparsely populated areas unable to support competition,innovative approaches to delivering care could broaden access.In some regions,especially rural areas,the population may be too small to support high-quality care at multiple hospitals,so competition may not be a realistic goal.At the same time,the possible closure of a sole rural hospital raises concerns,given research that demonstrates negative health impacts,especially for patients with time-sensitive health conditions when there are no alternative providers nearby.57,58,59A regulatory approach may thus be needed both to address the harmful consequences of complete market dominance and to ensure ready access to at least some hospital services.Here,policymakers could think less about maintaining access to hospital care and more about maintaining appropriate access to healthcare.“When we think about the hospital as something thats irreplaceable,not only are we locking ourselves into a bad delivery system,but we are also precluding the possibility of valuable innovation,”said one Working Group participant.Alternative delivery systems in rural markets could involve more care provided by nurse practitioners,the use of telehealth,and limited-service hospitals with hub-and-spoke linkages to centers of excellence.More research is needed to understand the cumulative effects of consolidation on quality,access to care,and the labor market;the effects on price are well established.Marketplace changes spurred by a combination of horizontal and vertical mergers are likely to have a more potent effect than either of them alone.A deeper understanding of what happens when a single health system becomes the dominantor,in some cases,onlyplayer in a community,region,or state can inform both regulation and litigation.So,too,could a fuller understanding of cross-market mergers and their impact,an urgent need made more challenging because datasets across states are inconsistent and difficult to compare.While the research is clear on the impact of consolidation on pricing,more knowledge is needed to fully understand its effect on quality and access.The consequences for the labor force,where workforce shortages and“In sparsely populated areas,policymakers could think less about maintaining access to hospital care and more about maintaining appropriate access to healthcare.”21|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONReportincreased demand on providers are already stressing the system,is another realm that demands attention.Some research suggests that consolidation leads to lower wages and reduce staffing,but to the extent that it prevents hospital closuresan area of study with inconsistent resultsit could also preserve jobs.60Weak reporting mandates,data gaps,and a lack of transparency have limited the capacity to conduct much of that research.“We need a lot more research and investment of resources to document the effects in order to have a shot at change,”urged one Working Group participant.ConclusionIn an optimal policy environment,the structures to promote competition would already have been put in place before so many communities became dominated by so few health systems.Addressing consolidation today is something of a catch-up game,and any policy reforms are certain to face resistance and court challenges prior to implementation.“Change is going to be super slow,”acknowledged one participant.The narrative among many health providers has been that,like it or not,they have to become part of a consolidated entity to survive.But the evidence to support this claim is limited,and there are hints that public sentiment and political will are shifting as research documents the rising healthcare prices that accompany consolidation,without clear improvements in quality.A constituency may be emerging that is prepared to challenge assumptions about healthcare systems,promote policies designed to foster a more competitive healthcare marketplace,and better serve the public interest.“There are hints that public sentiment and political will are shifting as research documents the rising healthcare prices that accompany consolidation,without clear improvements in quality.”22|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATION1 Abdelhadi,O.,Fulton,B.D.,Alexander,L.,&Scheffler,R.M.(2024).Private equityacquired physician practices and market penetration increased substantially,20122021.Health 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brief.KFF.https:/www.kff.org/health-costs/issue-brief/ten-things-to-know-about-consolidation-in-health-care-provider-markets/12 Liu,J.L.,Levinson,Z.M.,Zhou,A.,Zhao,X.,Nguyen,P.,Qureshi,N.(2022).Environmental scan on consolidation trends and impacts in health care markets.RAND.https:/www.rand.org/pubs/research_reports/RRA1820-1.html13 Levinson,Z.,Godwin,J.,Hulver,S.,&Neuman,T.(2024).Ten things to know about consolidation in health care provider markets Issue brief.KFF.https:/www.kff.org/health-costs/issue-brief/ten-things-to-know-about-consolidation-in-health-care-provider-markets/14 Oakman,T.,Waldrop,T.,&Brierley,L.(2024,March 6).How states can advance equity when addressing health care consolidation.The Century Foundation.15 Carroll,C.,Euhus,R.,Beaulieu,N.,&Chernew,M.E.(2023).Hospital survival in rural markets:Closures,mergers and profitability.Health Affairs,42(4).https:/doi.org/10.1377/hlthaff.2022.0119116 Jian,H.J.,Fingar,K.R.,Liang,L.,Henke,R.M.,Gibson,T.P.(2021).Quality of care before and after mergers and acquisitions of rural hospitals.JAMA Network Open,4(9),e2124662.https:/ 17 Noether,M.,and May,S.(2017).Hospital merger benefits:Views from hospital leaders and econometric analysis.Charles River Associates.https:/www.aha.org/system/files/2018-04/Hospital-Merger-Full-Report-FINAL-1.pdf18 Federal Trade Commission.(n.d.).The enforcers.https:/www.ftc.gov/advice-guidance/competition-guidance/guide-antitrust-laws/enforcers19 Hulver,S.,&Levinson,Z.(2023).Understanding the role of the FTC,DOJ,and states in challenging anticompetitive practices of hospitals and other health care providers Issue brief.KFF.https:/www.kff.org/health-costs/issue-brief/understanding-the-role-of-the-ftc-doj-and-states-in-challenging-anticompetitive-practices-of-hospitals-and-other-health-care-providers/20 Federal Trade Commission.(2024,January 22).FTC announces 2024 update of size of transaction thresholds for premerger notification filings.https:/www.kff.org/health-costs/issue-brief/understanding-the-role-of-the-ftc-doj-and-states-in-challenging-anticompetitive-practices-of-hospitals-and-other-health-care-providers/21 Arnold,D.R.,King,J.S.,Fulton,B.D.,Montague,A.D.,Gudiksen,K.L.,Greaney,T.L.,&Scheffler,R.M.(2024).New evidence on the impacts of cross-market hospital mergers on commercial prices and measures of quality.Health Services Research.https:/doi.org/10.1111/1475-6773.1429122 Godwin,J.,Levinson,Z.,&Hulver,S.(2023,August 23).Understanding mergers between hospitals and health systems in different markets Issue brief.KFF.https:/www.kff.org/health-costs/issue-brief/understanding-mergers-between-hospitals-and-health-systems-in-different-markets/23 Godwin,J.,Levinson,Z.,&Hulver,S.(2023,August 23).Understanding mergers between hospitals and health systems in different markets Issue brief.KFF.https:/www.kff.org/health-costs/issue-brief/understanding-mergers-between-hospitals-and-health-systems-in-different-markets/Report References23|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATION24 Kacik,A.(2024,October 31).FTC drills down on cross-market hospital mergers.Modern Healthcare.https:/ Federal Trade Commission Act,15 U.S.C.45(a)(1).https:/www.govinfo.gov/app/details/USCODE-2011-title15/USCODE-2011-title15-chap2-subchapI-sec4526 Federal Trade Commission.(2021,July 9).Statement of the Commission on the withdrawal of the statement of enforcement principles regarding“unfair methods of competition”under Section 5 of the FTC Act Public statement.https:/www.ftc.gov/system/files/documents/public_statements/1591706/p210100commnstmtwithdrawalsec5enforcement.pdf27 Federal Trade Commission.(2023,December 18).Federal Trade Commission and Justice Department release 2023 Merger Guidelines Press release.https:/www.ftc.gov/news-events/news/press-releases/2023/12/federal-trade-commission-justice-department-release-2023-merger-guidelines28 Levinson,Z.,Godwin,J.,Hulver,S.,&Neuman,T.(2024).Ten things to know about consolidation in health care provider markets Issue brief.KFF.https:/www.kff.org/health-costs/issue-brief/ten-things-to-know-about-consolidation-in-health-care-provider-markets/29 Department of Justice,Department of Health and Human Services,&Federal Trade Commission.(2024).Request for information on consolidation in health care markets.https:/www.ftc.gov/system/files/ftc_gov/pdf/FTC-2024-0022-0001-Request-for-Information-on-Consolidation-in-health-care-markets.pdf30 Hulver,S.,Levinson,Z.,Godwin,J.,Claxton,G.,&Neuman,T.(2024,March 22).Gaps in data about hospital and health system finances limit transparency for policymakers and patients Issue brief.KFF.https:/www.kff.org/health-costs/issue-brief/gaps-in-data-about-hospital-and-health-system-finances-limit-transparency-for-policymakers-and-patients/31 Hulver,S.,Levinson,Z.,Godwin,J.,Claxton,G.,&Neuman,T.(2024,March 22).Gaps in data about hospital and health system finances limit transparency for policymakers and patients Issue brief.KFF.https:/www.kff.org/health-costs/issue-brief/gaps-in-data-about-hospital-and-health-system-finances-limit-transparency-for-policymakers-and-patients/32 Teisberg,E.,Wallace,S.,&OHara,S.(2020).Defining and implementing value-based health care:A strategic framework.Academic Medicine,95(5),682685.http:/doi.org/10.1097/ACM.000000000000312233 Health,Medicine&Society Program.(2024,May 29).State efforts to control healthcare costs:Lessons learned and insights for the future.Aspen Institute.https:/www.aspeninstitute.org/publications/state-efforts-to-control-healthcare-costs-lessons-learned-and-insights-for-the-future/34 Vita,M.G.(2021,April 14).Physician group and healthcare facility merger study.Federal Trade Commission.https:/www.ftc.gov/enforcement/competition-matters/2021/04/physician-group-healthcare-facility-merger-study35 Gordon,C.(2024,January 9).Starting this month,California health care entities will need to provide state notice of mergers set to close on or after April 1,2024.Squire Patton Boggs.https:/ Data Catalyst.(n.d.).Analysis of state-level“abuse of dominance”antitrust legislation and its relevance to small and midsize businesses.https:/datacatalyst.org/wp-content/uploads/2023/06/Analysis-of-State-Level-Abuse-of-Dominance-Antitrust-Legislation-and-its-Relevance-to-Small-and-Midsize-Businesses.pdf37 Stop Anticompetitive Healthcare Act of 2023,H.R.2890,118th Cong.(2023).https:/www.congress.gov/bill/118th-congress/house-bill/289038 Hulver,S.,&Levinson,Z.(2023,August 7).Understanding the role of the FTC,DOJ,and states in challenging anticompetitive practices of hospitals and other health care providers Issue brief.KFF.https:/www.kff.org/health-costs/issue-brief/understanding-the-role-of-the-ftc-doj-and-states-in-challenging-anticompetitive-practices-of-hospitals-and-other-health-care-providers/39 Berenson,R.A.,King,J.S.,Gudiksen,K.L.,Murray,R.,&Shartzer,A.(2020).Addressing health care market consolidation and high prices:The role of the states.Urban Institute&UC Hastings Law San Francisco.https:/www.urban.org/sites/default/files/publication/101508/addressing_health_care_market_consolidation_and_high_prices_1.pdf40 Federal Trade Commission.(2022).FTC policy perspectives on certificates of public advantage.https:/www.ftc.gov/system/files/ftc_gov/pdf/COPA_Policy_Paper.pdf41 National Conference of State Legislatures.(2024,February 26).Certificate of need state laws.https:/www.ncsl.org/health/certificate-of-need-state-laws 42 Hamilton,S.,&Kimbrell,T.(2024,June 14).Certificate of need laws con rural patients out of health care.STAT.https:/ Office of Attorney General Jeff Jackson.(2024,December 2).Attorney General Josh Stein statement on certificate of need for western North Carolina Press release.North Carolina Department of Justice.https:/ncdoj.gov/attorney-general-josh-stein-statement-on-certificate-of-need-for-western-north-carolina/Report 24|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATION44 Levinson,Z.,Neuman,T.,&Hulver,S.(2024).Five things to know about Medicare site-neutral payment reforms Issue brief.KFF.https:/www.kff.org/medicare/issue-brief/five-things-to-know-about-medicare-site-neutral-payment-reforms/45 Emerson,J.(2024,May 13).20 things to know about site-neutral payment policies.Beckers Hospital Review.https:/ Chernew,M.E.,Pany,M.J.,&Dafny,L.S.(2022,March 31).Two approaches to capping health care prices.Health Affairs Forefront.https:/www.healthaffairs.org/content/forefront/two-approaches-capping-health-care-prices47 Hulver,S.,Levinson,Z.,Godwin,J.,Claxton,G.,&Neuman,T.(2024,March 22).Gaps in data about hospital and health system finances limit transparency for policymakers and patients Issue brief.KFF.https:/www.kff.org/health-costs/issue-brief/gaps-in-data-about-hospital-and-health-system-finances-limit-transparency-for-policymakers-and-patients/48 American Hospital Association.(2023,March).Fact sheet:the 340b Drug Pricing Program.https:/www.aha.org/fact-sheets/fact-sheet-340b-drug-pricing-program49 Ippolito,B.(2025).Policy options to address consolidation in healthcare provider markets.Health,Medicine&Society Program.https:/www.aspeninstitute.org/wp-content/uploads/2025/01/HMS-HCC-AV-Report-Final.pdf50 Digiorgio,A.M.,Hammond,J.W.,&Lopez,N.(2024,January 9).Increasing transparency in the 340b and Medicaid drug rebate programs.Health Affairs Forefront.https:/www.healthaffairs.org/content/forefront/increasing-transparency-340b-and-medicaid-drug-rebate-programs51 Schatz,T.(2024,September 8).Reforming 340B vital for affordable medication for low-income patients.The Hill.https:/ Wofford,D.,&Kendall,D.(2024,September 23).One way to fix Americas broken hospitals:Reform 340B.Third Way.https:/www.thirdway.org/report/one-way-to-fix-americas-broken-hospitals-reform-340b53 Bird,D.G.,&Varanini,E.E.(2022,May 10).Deciphering Sutter Healths state-court settlement and federal-court win in parallel antitrust cases.Health Affairs Forefront.https:/www.healthaffairs.org/content/forefront/deciphering-sutter-health-s-state-court-settlement-and-federal-court-win-parallel54 National Academy for State Health Policy.(2021,April 12).A tool for states to address health care consolidation:Prohibiting anticompetitive health plan contracts.https:/nashp.org/a-tool-for-states-to-address-health-care-consolidation-prohibiting-anti-competitive-health-plan-contracts/55 Ippolito,B.(2025).Policy options to address consolidation in healthcare provider markets.Health,Medicine&Society Program.56 Roy,A.(2019,January 16).Improving hospital competition:A key to affordable health care White paper.FREEOPP.https:/freopp.org/whitepapers/improving-hospital-competition-a-key-to-affordable-medicine/57 Carroll,C.(2023,December).Impeding access or promoting efficiency?Effects of rural hospital closure on the cost and quality of care Working paper.https:/ Gujral,K.,&Basu,A.(2020,June).Impact of rural and urban hospital closures on inpatient mortality Working paper.National Bureau of Economic Research.https:/www.nber.org/papers/w2618259 Petek,N.(2022).The marginal benefit of hospitals:Evidence from the effect of entry and exit on utilization and mortality rates.Journal of Health Economics,86,102688.https:/doi.org/10.1016/j.jhealeco.2022.10268860 Levinson,Z.,Godwin,J.,Hulver,S.,&Neuman,T.(2024).Ten things to know about consolidation in health care provider markets Issue brief.KFF.https:/www.kff.org/health-costs/issue-brief/ten-things-to-know-about-consolidation-in-health-care-provider-markets/Report 25|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONBackground PapersBackground Papers Policy Options to Address Consolidation in Healthcare Provider Markets Benedic Ippolito,PhD,MS Ten Things to Know About Consolidation in Health Care Provider Markets Zachary Levinson,PhD,MA,MPP,Jamie Godwin,PhD,Scott Hulver,PhD,and Tricia Neuman,DSc,MS26|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONBackground PapersPolicy Options to Address Consolidation in Healthcare Provider MarketsBenedic Ippolito,PhD,MSIntroductionWell-functioning healthcare markets rely on competition among firms to lower costs and encourage high quality.However,many healthcare markets have high and rising levels of consolidation that can weaken these competitive dynamics.This paper briefly summarizes the state of consolidation in hospital and physician markets and outlines state and federal policy options that could increase competition in these markets.While similar competitive issues are relevant for other healthcare markets,including insurance and drug markets,they are beyond the scope of this paper.The last few decades have seen significant consolidation within hospital and physician markets(Fulton,2017;Gaynor,2020;Levinson et al.,2024).This includes both horizontal consolidation between potential competitors(e.g.,two hospitals merging)and vertical integration between different types of providers(e.g.,a hospital acquiring a physician practice).The effects of consolidation are theoretically ambiguous.On one hand,it can allow for efficiencies that come from a larger scale,reduce the need for duplication of certain services,or improve coordination across different entities.On the other,it can reduce competitive pressures among firms,leading to higher prices and depressed quality.The effect of consolidation within provider markets has been the subject of considerable research.In general,the accumulated evidence suggests that provider consolidation over the last few decades has increased prices with limited evidence of improvements to quality or access.A large body of research shows that hospital mergers within the same market tend to increase costs to varying degrees and may reduce the quality of care(e.g.,see Gaynor,2020;Liu et al.,2022,for reviews).A smaller body of research suggests this may also be true of mergers and acquisitions involving hospitals in different markets within the same state(Dafny et al.,2019;Lewis&Pflum,2017).Research suggests that consolidation within physician markets also leads to higher prices(e.g.,Austin&Baker,2015;Baker,Bundorf,Royalty,and Levin,2014;Dunn&Shapiro,2014;Koch&Ulrick,2021).Likewise,a growing body of evidence finds that vertical integration between hospitals and physicians within the same market tends to increase costs(Baker,Bundorf,&Kessler,2014;Capps et al.,2018;Godwin et al.,2021;Post et al.,2017;Saghafian et al.,2023),while research has not yet found clear evidence of quality improvements(Koch et al.,2021).Economic theory predicts that higher payments to healthcare providers will ultimately be passed on to consumers.Higher prices may be directly reflected in higher cost sharing for individuals receiving care.However,most individuals are heavily insured,meaning that their out-of-pocket payments account for a small share of total costs.As a result,individuals pay these costs through higher insurance premiums and other less-direct ways.Empirical research is consistent with these predictions.Increased healthcare costs have been shown to lower wages,reduce employment,and trigger changes in benefit design,such as greater cost sharing(Arnold&Whaley,2020;Baicker&Chandra,2006;Gruber,1994;Sommers,2005;Vistnes&Selden,2011).27|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONBackground PapersTogether,the evidence from recent decades suggests that consolidated healthcare markets have tended to raise costs.Efforts to increase competition,or dissuade further consolidation,have the potential to benefit consumers who ultimately bear the burden of higher healthcare costs.The remainder of this paper outlines federal and state options to dissuade further consolidation and encourage competition in hospital and physician markets.In doing so,it is worth noting the potential limits of procompetitive policies on markets.Notably,some healthcare markets are unlikely to sustain meaningful levels of competition even under an ideal policy environment.For example,less densely populated rural areas may not support more than one acute care hospital.Moreover,it may be difficult to generate competition within markets that are already heavily consolidated,at least in the near term.While there remain many opportunities to improve competition,these constraints are relevant as policymakers weigh their policy options.Federal Policy Options to Increase CompetitionThe federal government has several mechanisms through which it can affect competition in healthcare provider markets.Notably,the two federal antitrust agenciesthe Federal Trade Commission(FTC)and Department of Justice(DOJ)oversee mergers and acquisitions along with anticompetitive business practices.Congress can implement laws that would increase their awareness of potentially anticompetitive behavior and enhance their ability to impede it.Congress could also amend features of public programs,such as Medicare,that may incentivize consolidation.Finally,they can expand transparency efforts that may have procompetitive effects.Increasing the Transparency of Mergers and Acquisitions Existing law requires that antitrust authorities are notified of certain mergers or acquisitions with a value over$119.5 million(Federal Trade Commission FTC,2024)(adjusted annually).In practice,this excludes most transactions.Research shows that the average hospital merger between 2016 and 2020 and the vast majority of transactions involving physicians has fallen below this threshold(Capps et al.,2017;Fulton et al.,2021).Such mergers and acquisitions are much less likely to be challenged(Wollmann,2019).While larger mergers often raise the most pronounced competitive concerns,these smaller mergers can meaningfully increase consolidation.Notably,firms can acquire large cumulative market shares through a series of small or modestly sized transactions(Fuse Brown et al.,2021).Even modestly sized transactions may raise competitive concerns,particularly in markets with high existing levels of consolidation.Policymakers could increase the transparency of these transactions in a number of ways.First,Congress could pass legislation that lowers the threshold for reporting proposed transactions to federal antitrust agencies,allowing them to identify modestly sized mergers that raise antitrust concerns.Legislation could also require premerger notification if the accumulated value of transactions by a single parent company in a given market exceeds reporting thresholds,regardless of whether the marginal acquisition alone would exceed that threshold(Adler&Ippolito,2023).28|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONBackground PapersRelatedly,lawmakers could pass legislation that increases transparency of ownership structures and market shares.Doing so could make it easier for antitrust agencies to quickly assess the competitiveness of a healthcare market and distinguish innocuous transactions from more concerning ones.This could be particularly helpful in cases in which antitrust agencies are tasked with assessing more transactions,as many relevant policies envision.One antitrust scholar has suggested establishing a database that contains ownership and spending information for healthcare entities(Dafny,2021).Similar information could be generated by adding information on the volume of services to the Transparency in Coverage Rule,which currently requires insurers to release pricing data.There has been some recent legislative interest in increasing ownership transparency,but legislators have particularly focused on cases in which providers are controlled by private equity funds(e.g.,Healthcare Ownership Transparency Act,2022).Many of these policies come with similar tradeoffs.Devoting more resources to antitrust enforcement in healthcare may reduce the agencies enforcement ability in other areas.Some observers have argued that agency budgets have not increased appropriately over time,suggesting this may be a notable concern(Gaynor,2020).Congress could increase agency budgets;however,this has been the subject of some recent debate.The Merger Filing Fee Modernization Act of 2022 increased fees on merging parties,which functionally increased funding of antitrust agencies.On the other hand,recent proposals from the House and Senate Appropriations Committees would limit how much this could increase DOJ funding(Consolidated Appropriations Act,2024).These policies also often impose additional burdens on firms.Greater premerger notification,for example,increases costs on firms that previously did not need to notify regulators about transactions,including those that raise no competitive concerns.The size of these costs would depend on the specific policy.Requiring reporting of ownership structures or additional information also comes with administrative costs that should be weighed against potential benefits.Policies Affecting Antitrust Enforcement StandardsCongress could also make it easier for federal antitrust agencies to challenge transactions they view as problematic.First,while the FTC has broad authority to review proposed mergers,it is currently prohibited from investigating other anticompetitive conduct by nonprofit firms.This is a particularly notable omission in hospital markets in which nearly half of all hospitals are nonprofits(American Hospital Association,n.d.-b).Congress could expand the FTCs enforcement authority to include nonprofits.The Stop Anticompetitive Healthcare Act(2023)would amend the Federal Trade Commission Act in such a manner.More generally,policymakers could explicitly lower the required burden of proof for the agencies when challenging transactions.One antitrust scholar has suggested amending Section 7 of the Clayton Antitrust Act of 1914,which requires that agencies demonstrate that a transaction“substantially”lessens competition or“tends to create a monopoly”(Dafny,2021).Replacing“substantially”with“meaningfully”or“materially”could lower the burden of proof on agencies in these cases.Proposals to alter the Clayton Antitrust Act in this manner would likely trigger substantial debate about the appropriate burden of proof on antitrust agencies.Supporters of such a change are likely to 29|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONBackground Papersargue that current law imposes an unduly high bar and results in many anticompetitive transactions moving forward(either because the agencies lose their legal challenge or because they are dissuaded from challenging an action).Little evidence exists on how such a change would alter markets.The FTC conducted retrospective analyses of a few mergers that were consummated after the agency or state attorney general unsuccessfully attempted to block them.The agency found evidence of price increases in two cases(Haas-Wilson&Garmon,2009;Tenn,2011),no effect on prices in one(Haas-Wilson&Garmon,2009),and mixed results in one(Thompson,2011).Supporters of this policy are likely to note that a large share of consummated hospital mergers results in increased prices(Cooper et al.,2019).Opponents are likely to emphasize the potential costs from overly active enforcement.Targeting too many transactions could both impede otherwise innocuous market activity and impose significant costs on those that are challenged.Potential opposition is likely to be stronger if these changes applied to all markets regulated by the agencies,including those in which consolidation may be a less pronounced concern than in healthcare.Prohibiting Potentially Anticompetitive Contracting PracticesProviders with significant market power can require that insurers agree to contracting provisions that could limit competition.These include antitiering clauses,which require that the provider is not placed on a lower tier of coverage than any other.Similarly,antisteering provisions disallow the insurer from using financial incentives to encourage patients to see another provider.Finally,all-or-nothing contracts require that an insurer include either all providers affiliated with a dominant health system or none of them.By limiting insurers ability to incentivize enrollees,antitiering and antisteering clauses could make it more challenging for a lower-cost or higher-quality competitor to attract patients away from a dominant provider.All-or-nothing provisions could further allow a provider with a dominant position in one market segment(e.g.,acute care hospitals)to extend that market power to others.These types of clauses may make it difficult for existing competitors to gain market share and dissuade potential competitors from entering a market in which they may be disadvantaged.The effects of these contracting provisions are likely to be most noticeable in markets that have less competition.If a hospital in a competitive market demanded one of these provisions,insurers could omit that provider from their networks in favor of a competitor.In markets with few providers,however,insurers may not have a credible option to do so.These clauses may also be more powerful where network adequacy laws effectively require the inclusion of certain providers.That said,limited direct evidence exists on how these contracting practices affect healthcare costs.Restricting these types of contracting practices may have a small effect on healthcare costs because dominant providers would still have significant market power.As the Congressional Budget Office(CBO,2022)noted,it also may be difficult to enforce such a ban if providers and insurers implicitly agreed to similar terms without formalizing them in contracts.Providers,particularly those with significant market share,are likely to oppose policies that would impede the use of these contracting tools.They argue that prohibiting antitiering or antisteering 30|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONBackground Papersprovisions would reduce access by encouraging insurers to make it difficult for enrollees to seek care at their preferred provider(American Hospital Association,n.d.-a).Moreover,they argue that insurers have significant market power,suggesting this type of policy might increase their bargaining position too much.Finally,they are likely to argue that these contracting tools are not unusually anticompetitive but instead reflect negotiations in which a provider agrees to a lower rate in exchange for a larger volume of an insurers patients.Congress has considered multiple proposals that would restrict the use of these clauses.Examples include provisions in the Lower Health Care Costs Act(2019)and the Bipartisan Primary Care and Health Workforce Act(2023),which the CBO(2019,2024)projected would lower costs.The Addressing Anti-Competitive Health Care Contract Clauses Act,introduced in 2023,would require the US Government Accountability Office to study the effects of these clauses and assess the ability of antitrust agencies to take action in these cases.Site-Neutral PaymentsMedicare typically pays more for a service if it is delivered in a hospital outpatient department(HOPD)rather than in a physicians office or,to a lesser degree,an ambulatory surgery center.This payment differential is meant to reflect higher operating costs for hospitals.For example,hospitals maintain capabilities to treat a larger range of emergencies than a physicians office.However,current policy also provides an incentive for physicians offices to consolidate with hospitals and take advantage of the ability to charge higher rates(see Medicare Payment Advisory Commission MedPAC,2023,for a discussion of this issue).Many observers argue that this payment difference is not justified for services that rarely use those hospital-specific capabilities.Medicare could instead pay the lower physician fee schedule price regardless of where services were delivered.This site-neutral rate would lower Medicare spending and reduce the incentive for hospitals to consolidate with physicians.Sources have documented an increase in vertical integration between physicians and hospitals over time(Kane,2023).While direct evidence of the effect of Medicares policy on this trend is modest,MedPAC(2022)has highlighted consistent effects.For example,from 2015 to 2019,the volume of chemotherapy administration rose 27.8 percent in HOPDs,in which payments are higher,while falling 5.4 percent in clinician offices,in which payments are lower.One paper showed that integrating with a hospital would increase Medicare payments per physician per year by 78 percent for primary care doctors,74 percent for medical specialists,and 224 percent for surgeons(Post et al.,2021),suggesting that financial incentives are substantial.The paper finds evidence that larger payment differences are associated with greater hospital-physician integration.Recently,Medicare adopted site-neutral payments in a small number of casesnamely for clinic visits at off-campus HOPDs and any visit at off-campus HOPDs established after November 2,2015(note that such entities can expand over time)(for a discussion,see Adler et al.,2018).Policymakers could expand this policy to include nonclinic visits at off-campus HOPDs built before 2015 and certain services at on-campus HOPDs to reduce incentives to vertically integrate.The CBO(2022)has argued that if site-neutral payments were expanded in this way,“consolidation would become less financially appealing.”31|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONBackground PapersThe Transparency of Hospital Billing Act(2022)would require Medicare to adopt site-neutral payments based on the physician fee schedule for all off-campus HOPD services.Because these services are already being delivered away from the hospital,proponents argue that they are unlikely to use hospital-specific resources.MedPAC(2023)has also suggested adopting site-neutral payments in all HOPDs(including on campus)for services that can be safely delivered outside a hospital.One approach identified services based on whether they were most commonly delivered outside an HOPD(e.g.,in a freestanding physicians office or ambulatory surgery center).The House of Representatives recently passed the Lower Costs,More Transparency Act(2023),which would impose site-neutral payments in a small number of casessuch as drug administration services in off-campus facilities.The CBO(2023)estimated that this would reduce federal spending by roughly$3.7 billion over 10 years and would likely have a small effect on consolidation incentives.A related policy would require that hospitals use separate billing codes for off-campus facilities.This would allow commercial insurers to better identify where services are delivered and potentially allow them to adjust payments across sites of service.This proposal was included in the Lower Costs,More Transparency Act.It was also included in the SITE Act(2023),which has been introduced in the Senate.The CBO(2023)anticipated that this would slightly reduce healthcare costs.Relatively small savings likely reflect the fact that this additional transparency does not fundamentally alter the bargaining power of hospitals or insurers.Opponents of these types of policies often argue that lower hospital reimbursement could trigger hospital closures and reduced access(Pollack,2024).This possibility would be affected by the scale of the policy change and other design features.Meanwhile,proponents of the site-neutral policy typically argue that the financial vulnerability of some hospitals is not a sufficient justification to oppose site-neutral payments for all hospitals.Some policies attempt to address concerns about certain vulnerable hospitals.For example,MedPAC(2022)has modeled a stop-loss policy that would limit financial losses for hospitals with a large share of low-income patients(see Ippolito et al.,2023,for a discussion of related options).Policymakers could presumably target other types of hospitals where viability and access challenges are most pronounced(e.g.,rural areas).Such limits would reduce how much the policy dissuades consolidation but also attenuate potential financial challenges for hospitals.Alternatively,policymakers could apply site-neutral reforms to all providers and use a distinct mechanism to target additional assistance to financially vulnerable hospitals(Adler et al.,2023).This may attenuate consolidation incentives more fully while also addressing access and equity concerns.Another argument is that HOPDs treat sicker patients on average,which justifies higher payments(Pollack,2024).There is some disagreement about whether this is true.For example,MedPAC(2022)has argued that patient severity has minimal effects on HOPD costs when considering the specific services that are candidates for site-neutral payments.340B ReformThe 340B program requires that drugmakers give mandatory discounts on outpatient drugs to certain“qualified entities,”including disproportionate share hospitals and smaller provider groups,such as critical-access hospitals.By giving these hospitals an advantage on the acquisition costs of drugs,the 32|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONprogram provides an incentive to vertically integrate with physicians,particularly if they administer or prescribe large amounts of expensive outpatient medicines.Required 340B discounts are large,with recent data suggesting they are around 50 percent of the gross(or list)price of a drug(Fein,2023).These discounts are intended to support care for vulnerable populations and are not required to be passed along to public or private insurers,allowing qualified entities to earn significant profit margins.The resulting profit need not be used in any specific way,and there is limited oversight into its use(US Government Accountability Office,2011).This program has grown markedly over time.From 2015 to 2022,purchases by covered entities at discounted prices grew from$12.2 billion to$53.7 billion(the prediscount value of sales grew from$32.6 billion to$106.0 billion during this time)(Fein,2023).This growth is largely attributable to the Affordable Care Act,which allowed covered entities to contract with an unlimited number of pharmacies to dispense drugs.Because they can purchase drugs for lower prices than a standalone physicians office,340B entities have an incentive to integrate with physicians.One study found that qualifying for the 340B program led hospitals to employ more physicians in specialties that prescribe high numbers of infusion drugs,including hematologist-oncologists,ophthalmologists,and rheumatologists(Desai&McWilliams,2018).They did not observe evidence that these hospitals provided more care to low-income patients.The US Government Accountability Office(2015)has also noted that 340B hospitals prescribe more(or more expensive)drugs than non-340B hospitals.This is consistent with 340B encouraging the aforementioned integration but not proof of it.However,one other study found little evidence that 340B had encouraged vertical integration.A summary of the literature suggests that qualifying facilities respond to program incentives in margin-motivated ways(e.g.,strategic consolidation)in a number of cases,though some work has found positive effects in areas like providing safety net care(Levengood et al.,2024).Policymakers could alter the program so that discounts were based on patient eligibility rather than distinguishing at the provider level(e.g.,tying discounts to the number of low-income patients treated).The CBO(2022)has indicated that this change may attenuate consolidation incentives but that the magnitude of this effect is uncertain.Provider groups are generally opposed to reforms that might reduce eligibility for the 340B program and argue that the program is central to their provision of safety net care(Pollack,2024).Increasing Price TransparencySeveral mechanisms exist by which increasing price transparency might improve competition.In some cases,better information about prices may allow individuals to more effectively choose lower-cost providers in some cases.It may also allow employers to better assess the plans offered by insurers and be more informed purchasers(e.g.,by making the cost of including a dominant hospital more salient).Greater price transparency may also affect policymaking by informing legislative proposals and directing more attention to markets that are heavily consolidated.It is possible that price transparency may not spurn much additional competition but rather lead to a compression of prices.Public prices may make insurers less willing to accept higher prices once they know their competitors are getting lower ones.On the other hand,hospitals may be unwilling to offer Background Papers33|ENSURING ACCESS,AFFORDABILITY,AND QUALITY IN THE AGE OF HEALTHCARE CONSOLIDATIONBackground Paperscertain payers low prices if it will trigger other payers to demand similar rates.The net effect of these forces is unclear.It also may not reduce the market power held by dominant providers in already-consolidated markets.Certain features of healthcare markets may also attenuate the mechanisms through which transparency may increase competition.The vast majority of healthcare is purchased by consumers who are heavily insured,meaning they pay a small share of the marginal cost of care.In addition,they may face incentives that are independent of a specific providers price(e.g.,if they owe a flat copay).A large portion of healthcare is consumed in urgent situations in which price shopping may not be feasible.Finally,research shows that consumers use existing transparency tools infrequently(Mehrotra et al.,2017;Sinaiko&Rosenthal,2016).Two recent regulationsthe Hospital Price Transparency Rule(45 C.F.R 180)and the Transparency in Coverage Rule(85 C.F.R 72158)have meaningfully increased price transparency.The Transparency in Coverage rule requires commercial insurers to publish contracted rates for all health care services and some out-of-network payments.It also requires that plans create internet-based tools that allow enrollees to estimate their cost-sharing obligations.The Hospital Price Transparency Rule requires that hospitals post data files that include payer-specific and cash prices for services as well as provide prices of shoppable services in a consumer-friendly format.Some observers have highlighted potential challenges to using these data.For example,it can be difficult to forecast the price of an episode of care that involves many services.Moreover,commercial insurers can use different payment structures that may make it difficult to translate these prices into estimates for cost of care(Hulver et al.,2024).While these rules are already in effect,Congress could codify them as the Lower Cost,More Transparency Act would do.Doing so would ensure that a future administration does not repeal them.It would also give Congress an opportunity to make some improvements aimed at increasing compliance and expanding the information contained in them(e.g.,by including information about volume of services in the Transparency in Coverage rule).It would also provide an opportunity to reduce duplicate reporting across the two rules,which increases administrative costs on market actors(Adler et al.,2023).State Policy Options to Increase CompetitionStates can use a number of policy levers to increase competition within healthcare provider marketssome of which overlap with federal authority and some of which are distinct.First,lawmakers could give state attorneys general greater oversight of proposed mergers and acquisitions.Second,they could limit certain contracting practices that may impede competition.Third,they can seek to increase competition by expanding the supply of providers through policies like certificates of need or scope of practice regulation.Finally,they can increase price transparency in these markets.Increasing State Oversight of Mergers and AcquisitionWhile federal antitrust agencies play a central role in competition policy,state attorneys general can also do more to enforce antitrust laws at the state level.State policymakers could consider a number of policies that would give them(and potentially state hea
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