Do Cost-Effectiveness Analyses Account for Drug Genericization? A Literature Review and Assessment of Implications

Published:November 12, 2021DOI:



      We investigated how health technology assessment (HTA) organizations around the world have handled drug genericization (an allowance for future generic drug entry and subsequent drug price declines) in their guidelines for cost-effectiveness analyses (CEAs). We also analyzed a large sample of published CEAs to examine prevailing practices in the field.


      We reviewed 43 HTA guidelines to determine whether and how they addressed drug genericization in their CEAs. We also selected a sample of 270 US-based CEAs from the Tufts Medical Center’s CEA Registry, restricting the sample to studies on pharmaceuticals published from 1991 to 2019 and to analyses taking a lifetime time horizon. We determined whether each CEA examined genericization (and if so, whether in base case or sensitivity analyses), and how inclusion of genericization influenced the estimated incremental cost-effectiveness ratios.


      Fourteen (33%) of the 43 HTA guidelines mention genericization for CEAs and 4 (9%) recommend that base case analyses include assumptions about future drug price changes due to genericization. Most published CEAs (95%) do not include assumptions about future generic prices for intervention drugs. Only 2% include such assumptions about comparator drugs. Most studies (72%) conduct sensitivity analyses on drug prices unrelated to genericization.


      The omission of assumptions about genericization means that CEAs may misrepresent the long run opportunity costs for drugs. The field needs clearer guidance for when CEAs should account for genericization, and for the inclusion of other price dynamics that might influence a drug’s cost-effectiveness.


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        • Neumann P.J.
        • Sanders G.D.
        • Russell L.B.
        • Siegel J.E.
        • Ganiats T.G.
        Cost-Effectiveness in Health and Medicine.
        2nd ed. Oxford University Press, Oxford, United Kingdom2017
        • Institute for Clinical and Economic Review
        ICER’s reference case for economic evaluations: principles and rationale.
        • Garrison L.P.
        • Mansley E.C.
        • Abbott T.A.
        • Bresnahan B.W.
        • Hay J.W.
        • Smeeding J.
        Good research practices for measuring drug costs in cost-effectiveness analyses: a societal perspective: the ISPOR drug cost task force report - part II.
        Value Health. 2010; 13: 8-13
        • Shih Y.-C.T.
        • Han S.
        • Cantor S.B.
        Impact of generic drug entry on cost-effectiveness analysis.
        Med Decis Making. 2005; 25: 71-80
        • Mycka J.M.
        • Dellamano R.
        • Kolassa E.M.
        • et al.
        Good research practices for measuring drug costs in cost effectiveness analyses: an industry perspective: the ISPOR drug cost task force report--part V.
        Value Health. 2010; 13: 25-27
        • Gandhi S.K.
        • Jensen M.M.
        • Fox K.M.
        • Smolen L.
        • Olsson A.G.
        • Paulsson T.
        Cost-effectiveness of rosuvastatin in comparison with generic atorvastatin and simvastatin in a Swedish population at high risk of cardiovascular events.
        Clinicoecon Outcomes Res. 2012; 4: 1-11
        • Guertin J.R.
        • Mitchell D.
        • Ali F.
        • LeLorier J.
        Bias within economic evaluations – the impact of considering the future entry of lower-cost generics on currently estimated incremental cost-effectiveness ratios of a new drug.
        Clinicoecon Outcomes Res. 2015; 7: 497-503
        • Hua L.H.
        • Hersh C.M.
        • Morten P.
        • et al.
        The impact of price reductions after loss of exclusivity in a cost-effectiveness analysis: fingolimod versus interferon beta-1a for the treatment of relapsing-remitting multiple sclerosis.
        J Manag Care Spec Pharm. 2019; 25: 490-498
        • Hoyle M.
        Future drug prices and cost-effectiveness analysis.
        Pharmacoeconomics. 2008; 26: 589-602
        • Institute for Clinical and Economic Review
        Cystic Fibrosis response to public comments on draft evidence report.
        • Association for Accessible Medicines
        2019 generic drug & biosimilars access & savings in the U.S.
        • US Food and Drug Administration
        Generic drug facts.
        • Kolchinsky P.
        The Great American Drug Deal: A New Prescription for Innovative and Affordable Medicines.
        Evelexa Press, Boston, MA2020
        • Merlin T.
        • Tamblyn D.
        • Schubert C.
        • Salisbury J.
        • Irish J.
        Guidelines for preparing a submission to the Pharmaceutical Benefits Advisory Committee.
        • Walter E.
        • Zehetmatyr S.
        Guidelines on health economic evaluation: consensus paper.
        • Behmane D.
        • Lambot K.
        • Irs A.
        • Steikunas N.
        Baltic guideline for economic evaluation of pharmaceuticals (pharmacoeconomic analysis).
        • Cleemput I.
        • Neyt M.
        • Van de Sande S.
        • Thiry N.
        Belgian guidelines for economic evaluations and budget impact analyses.
        • Lee K.M.
        • McCarron C.E.
        • Bryan S.
        • Coyle D.
        • Krahn M.
        • McCabe C.
        Guidelines for the economic evaluation of health technologies: Canada.
        • Riquelme M.C.
        • Laborde C.C.
        • Saldivia S.L.
        • Pastén M.A.
        Guía metodológica para la evaluación económica de intervenciones en salud en Chile. Departamento de Economía de la Salud SdSP.
        • Moreno Viscaya M.
        • Mejía Mejía A.
        • Castro Jaramillo H.E.
        Manual para la elaboración de evaluaciones económicas en salud.
        • Gálvez González A.M.
        Guía metodológica para la evaluación económica en salud. Cuba, 2003.
        Rev Cuba Salud Publ. 2004; 30
        • Agency for Quality and Accreditation in Health Care
        The Croatian guideline for health technology assessment process and reporting. Department for Development Research and HTA.
        • Státní Ústav pro Kontrolu Léçiv
        Postup posuzování analýzy nákladové efektivity 2017.
        Date accessed: January 21, 2021
        • Kristensen F.B.
        • Sigmund H.
        Health technology assessment handbook.
        • Elsisi G.H.
        • Kaló Z.
        • Eldessouki R.
        • et al.
        Recommendations for reporting pharmacoeconomic evaluations in Egypt.
        Value Health Reg Issues. 2013; 2: 319-327
        • National Institute for Health and Care Excellence
        Guide to the methods of technology appraisal 2013.
        • Pharmaceuticals Pricing Board
        Preparing a health economic evaluation to be attached to the application for reimbursement status and wholesale price for a medicinal product. Application instructions.
        • Haute Autorité de santé
        Choix méthodologiques pour l’évaluation économique à la HAS.
        • Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen
        Allgemeine Methoden.
        • Dóczy V.
        • Dózsa C.
        • Dudás D.
        • et al.
        Professional healthcare guideline on the methodology of health technology assessment.
        Gyógyszereink. 2017; 67
        • Indonesian Health Technology Assessment Committee
        Health technology assessment (HTA) guideline.
        • Health Information and Quality Authority
        Guidelines for the economic evaluation of health technologies in Ireland.
        • Ministry of Health Pharmaceutical Administration
        Guidelines for the submission of a request to include a pharmaceutical product in the national list of health services.
        • Capri S.
        • Ceci A.
        • Terranova L.
        • Merlo F.
        • Mantovani L.
        The Members of the Italian group for pharmacoeconomic studies. Guidelines for economic evaluations in Italy: recommendations from the Italian group of pharmacoeconomic studies.
        Ther Innov Regul Sci. 2001; 35: 189-201
        • Fukuda T.
        Guideline for preparing cost-effectiveness evaluation to the Central Social Insurance Medical Council.
        • Pharmacy Practice & Development Division
        Pharmacoeconomic guidelines for Malaysia.
        • Grupo Mercado Común
        Guía para estudios de evaluación económica de tecnologías sanitarias.
        • Comisión Interinstitucional del Cuadro Básico y Catálogo de Insumos del Sector Salud
        Guía para la conducción de estudios de evaluación económica para la actualización del cuadro básico y catálogo de insumos del sector salud en México.
        • Zorginstituut Nederland
        Guideline for economic evaluations in healthcare 2016.
        • Pharmaceutical Management Agency
        Prescription for pharmacoeconomic analysis. Methods for cost-utility analysis.
        • Statens legemiddelverk
        Guidelines for the submission of documentation for single technology assessment (STA) of pharmaceuticals.
        • Agencja Oceny Technologii Medycznych i Taryfikacji
        Wytyczne oceny technologii medycznych.
        • Conselho Diretivo do INFARMED
        Orientações metodológicas para estudos e avaliação económica de tecnologias de saúde.
        Rev Port Farmacoter. 2020; 11: 225-230
        • Scottish Medicines Consortium
        Guidance to submitting companies for completion of New Product Assessment Form (NPAF).
        • Agency for Care Effectiveness
        Drug evaluation methods and process guide.
        • Ministerstvo Zdravotníctva Slovenskej Republiky
        Metodická pomôcka pre vykonávanie farmako-ekonomického rozboru lieku, medicínsko-ekonomického rozboru zdravotníckej pomôcky a medicínsko-ekonomického rozboru dietetickej potraviny.
        • Zavod za zdravstveno zavarovanje Slovenije
        Pravilnik o razvrščanju zdravil na list.
        • Republic of South Africa Department of Health
        Publication of the guidelines for pharmacoeconomic submissions.
        • Health Insurance Review and Assessment Service
        의약품경제성평가 지침 및 자료작성요령.
        • López-Bastida J.
        • Oliva J.
        • Antoñanzas F.
        • et al.
        Spanish recommendations on economic evaluation of health technologies.
        Eur J Health Econ. 2010; 11: 513-520
      1. Tandvårds- och läkemedelsförmånsverket (TLV). Tandvårds- och läkemedelsförmånsverkets allmänna råd. 2017;2017. Accessed January 21, 2021.

        • Taiwan Society for Pharmacoeconomics and Outcomes Research
        Guidelines of methodological standards for pharmacoeconomic evaluations in Taiwan.
        • Chaikledkaew U.
        • Teerawattananon Y.
        คู่มือการประเมินเทคโนโลยีด้านสุขภาพสําหรับประเทศไทย ฉบับที่2.
        Date accessed: January 21, 2021
        • Hay J.W.
        • Smeeding J.
        • Carroll N.V.
        • et al.
        Good research practices for measuring drug costs in cost effectiveness analyses: issues and recommendations: the ISPOR drug cost task force report—part I.
        Value Health. 2010; 13: 3-7
        • Kim D.D.
        • Silver M.
        • Kunst N.
        • Cohen J.T.
        • Ollendorf D.A.
        • Neumann P.J.
        Perspective and costing in cost-effectiveness analysis, 1974-2018 [published correction appears in Pharmacoeconomics. 2020;38(12):1377].
        Pharmacoeconomics. 2020; 38: 1135-1145
        • The International Society for Pharmacoeconomics and Outcomes Research
        Pharmacoeconomic guidelines around the world. The International Society for Pharmacoeconomics and Outcomes Research.
        Date accessed: January 21, 2021
        • The International Society for Pharmacoeconomics and Outcomes Research
        Pharmacoeconomic guidelines around the world: country/region: MERCOSUR (Argentina, Brazil, Paraguay, Uruguay).
        • The International Society for Pharmacoeconomics and Outcomes Research
        Pharmacoeconomic guidelines around the world: country/region: Baltic (Latvia, Lithuania, Estonia).
        • The International Society for Pharmacoeconomics and Outcomes Research
        Pharmacoeconomic guidelines around the world: country/region: England & Wales.
        • Center for the Evaluation of Value and Risk in Health
        The cost-effectiveness analysis registry. Institute for Clinical Research and Health Policy Studies, Tufts Medical Center.
        (Accessed January 21, 2021)
        • Association for Accessible Medicines
        2020 generic drug & biosimilars access & savings in the U.S. report.
        • Hoyle M.
        Accounting for the drug life cycle and future drug prices in cost-effectiveness analysis.
        Pharmacoeconomics. 2011; 29: 1-15
        • Neumann P.J.
        • Cohen J.
        • Ollendorf D.
        The Right Price: A Value-Based Prescription for Drug Costs.
        Oxford University Press, Oxford, United Kingdom2021
        • Neumann P.J.
        • Cohen J.T.
        • Kim D.D.
        • Ollendorf D.A.
        Consideration of value-based pricing for treatments and vaccines is important, even in the COVID-19 pandemic.
        Health Aff. 2021; 40: 53-61
        • Vondeling G.T.
        • Cao Q.
        • Postma M.J.
        • Rozenbaum M.H.
        The impact of patent expiry on drug prices: a systematic literature review.
        Appl Health Econ Health Policy. 2018; 16: 653-660
        • Kesselheim A.S.
        • Avorn J.
        • Sarpatwari A.
        The high cost of prescription drugs in the United States: origins and prospects for reform.
        JAMA. 2016; 316: 858-871
        • Dave C.V.
        • Sinha M.S.
        • Beall R.F.
        • Kesselheim A.S.
        Estimating the cost of delayed generic drug entry to Medicaid.
        Health Aff. 2020; 39: 1011-1017
        • US Food and Drug Administration
        Generic competition and drug prices. U.S. Food and Drug Administration.
        • Wineinger N.E.
        • Zhang Y.
        • Topol E.J.
        Trends in prices of popular brand-name prescription drugs in the United States.
        JAMA Netw Open. 2019; 2e194791
        • Bennette C.S.
        • Richards C.
        • Sullivan S.D.
        • Ramsey S.D.
        Steady increase in prices for oral anticancer drugs after market launch suggests a lack of competitive pressure.
        Health Aff. 2016; 35: 805-812
        • Collins S.M.
        • McCaskill C.
        Sudden price spikes in off-patent prescription drugs: the monopoly business model that harms patients, taxpayers, and the U.S. health care system.
        (Accessed January 21, 2021)
        • Hernandez I.
        • San-Juan-Rodriguez A.
        • Good C.B.
        Changes in list prices, net prices, and discounts for branded drugs in the U.S., 2007-2018.
        JAMA. 2020; 323: 854-862
        • National Academies of Sciences, Engineering, and Medicine
        Making Medicines Affordable: A National Imperative.
        The National Academies Press, Washington, DC2018
        • Khullar D.
        • Ohn J.A.
        • Trusheim M.
        • Bach P.D.
        Understanding the rewards of successful drug development - thinking inside the box.
        N Engl J Med. 2020; 382: 473-480
        • Crismaru I.
        • Stoian A.P.
        • Bratu O.G.
        • et al.
        Low-density lipoprotein cholesterol lowering treatment: the current approach.
        Lipids Health Dis. 2020; 19: 85
        • Horby P.
        • Lim W.S.
        • et al.
        • RECOVERY Collaborative Group
        Dexamethasone in hospitalized patients with Covid-19.
        N Engl J Med. 2021; 384: 693-704
        • Levy J.
        • Rosenberg M.
        • Vanness D.
        A transparent and consistent approach to assess U.S. outpatient drug costs for use in cost-effectiveness analyses.
        Value Health. 2018; 21: 677-684
        • Mattingly T.J.
        • Levy J.F.
        • Slejko J.F.
        • Onwudiwe N.C.
        • Perfetto E.M.
        Estimating drug costs: how do manufacturer net prices compare with other common U.S. price references?.
        Pharmacoeconomics. 2018; 36: 1093-1099