BACKGROUND: A core evaluation framework that captures the health care and societal benefits of value added medicines (VAMs, also often called repurposed medicines) was proposed in Report 1, aiming to reduce the heterogeneity in value assessment processes across countries and to create incentives for manufacturers to invest into incremental innovation. However, this can be impactful only if the framework can be adapted to heterogeneous health care financing systems in different jurisdictions, and the cost of evidence generation necessitated by the framework takes into account the anticipated benefits for the health care system and rewards for the developers. AREAS COVERED: The framework could potentially improve the pricing and reimbursement decisions of VAMs by adapting it to different country specific decision-contexts such as deliberative processes, augmented cost-effectiveness frameworks or formal multi-criteria decision analysis (MCDA); alternatively, some of its domains may be added to current general evaluation frameworks of medicines. The proposed evaluation framework may provide a starting point for practices based on which VAMs can be exempted from generic pricing mechanisms or can be integrated into the reimbursement and procurement system, allowing for price differentiation according to their added value. Besides evidence from RCTs, pricing and reimbursement decision processes of VAMs should allow for ex-ante non-RCT evidence for certain domains. Alternatively, relying on ex-post evidence agreements-such as outcome guarantee or coverage with evidence development-can also reduce decision uncertainty. CONCLUSIONS: The core evaluation framework for VAMs could trigger changes in the existing pricing, reimbursement and procurement practices by improving the appraisal of the added value created by incremental innovation.

Andalusian School of Public Health Granada Spain

Association of Health Insurance Companies Prague Czech Republic

Center for Health Technology Assessment Semmelweis University Üllői rd 25 1085 Budapest Hungary

Department of Organisation and Management of Pharmacy Faculty of Pharmacy Comenius University in Bratislava Bratislava Slovakia

Department of Public Health Policies Sector of Health Systems and Policy School of Public Health University of West Attica Athens Greece

Pharmaceutical Policy Research Syreon Research Institute Mexikói str 65 A 1142 Budapest Hungary

Technische Hochschule Nürnberg Nürnberg Germany

Zobrazit více v PubMed

Wouters OJ, McKee M, Luyten J. Estimated research and development investment needed to bring a new medicine to market, 2009–2018. JAMA. 2020;323:844–53. PubMed PMC

Attwood MM, Rask-Andersen M, Schiöth HB. Orphan drugs and their impact on pharmaceutical development. Trends Pharmacol Sci. 2018;39:525–35. PubMed

Hughes DA, Poletti-Hughes J. Profitability and market value of orphan drug companies: a retrospective, propensity-matched case–control study. PLoS One. 2016;11:e0164681. PubMed PMC

European Medicines Agency-EMA. 2021. https://www.ema.europa.eu/en/glossary/well-established-use. Accessed 18 June 2021.

Toumi M, Rémuzat C. Value added medicines: what value repurposed medicines might bring to society? J Mark Access Health Policy. 2017;5:1264717. PubMed PMC

Lin S, Chan G, Palczewski K, Lewis K. Drug Repurposing: The New R&D. 2017. https://www.researchgate.net/publication/320877009_Drug_Repurposing_The_New_RD. Accessed 18 Mar 2021.

Petykó ZI, Inotai A, Holtorf AP, Brixner D, Kaló Z. Barriers and facilitators of exploiting the potential of value-added medicines. Expert Rev Pharmacoecon Outcomes Res. 2020;20:229–36. PubMed

Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2019;18:41–58. PubMed

Petykó ZI, Kaló Z, Espin J, Podrazilová K, Tesar T, Maniadakis N, et al. Development of a core evaluation framework of value-added medicines: report 1 on methodology and findings. Cost Eff Resour Alloc. 2021 (manuscript under review). PubMed PMC

Phelps CE, Lakdawalla DN, Basu A, Drummond MF, Towse A, Danzon PM. Approaches to aggregation and decision making-a health economics approach: an ISPOR special task force report [5] Value Health. 2018;21:146–54. PubMed PMC

Kolasa K, Zwolinski KM, Zah V, Kaló Z, Lewandowski T. Revealed preferences towards the appraisal of orphan drugs in Poland—multi criteria decision analysis. Orphanet J Rare Dis. 2018;13:67. PubMed PMC

Iskrov G, Miteva-Katrandzhieva T, Stefanov R. Multi-criteria decision analysis for assessment and appraisal of orphan drugs. Front Public Health. 2016;4:214. PubMed PMC

Schey C, Krabbe PFM, Postma MJ, Connolly MP. Multi-criteria decision analysis (MCDA): testing a proposed MCDA framework for orphan drugs. Orphanet J Rare Dis. 2017;12:10. PubMed PMC

Gilabert-Perramon A, Torrent-Farnell J, Catalan A, Prat A, Fontanet M, Puig-Peiró R, et al. Drug evaluation and decision making in Catalonia: development and validation of a methodological framework based on multi-criteria decision analysis (MCDA) for orphan drugs. Int J Technol Assess Health Care. 2017;33:111. PubMed

Inotai A, Brixner D, Maniadakis N, Dwiprahasto I, Kristin E, Prabowo A, et al. Development of multi-criteria decision analysis (MCDA) framework for off-patent pharmaceuticals—an application on improving tender decision making in Indonesia. BMC Health Serv Res. 2018;18:1003. PubMed PMC

Endrei D, Molics B, Agoston I. Multicriteria decision analysis in the reimbursement of new medical technologies: real-world experiences from Hungary. Value Health. 2014;17:487–9. PubMed

Suwantika AA, Purwadi FV, Zakiyah N, Puspitasari IM, Abdulah R, Diantini A, et al. Multi-criteria decision analysis to prioritize the introduction of new vaccines in Indonesia by using the framework of the strategic multi-attribute ranking tool for vaccines (SMART Vaccines). Expert Rev Vaccines. 2021. PubMed

Botwright S, Kahn AL, Hutubessy R, Lydon P, Biey J, Sidibe AK, et al. How can we evaluate the potential of innovative vaccine products and technologies in resource constrained settings? A total systems effectiveness (TSE) approach to decision-making. Vaccine. 2020;6:100078. PubMed PMC

De Nardo P, Gentilotti E, Mazzaferri F, Cremonini E, Hansen P, Goossens H, et al. Multi-criteria decision analysis to prioritize hospital admission of patients affected by COVID-19 in low-resource settings with hospital-bed shortage. Int J Infect Dis. 2020;98:494–500. PubMed PMC

Keeney RL, Raiffa H. Decisions with multiple objectives: preferences and value trade-offs. Cambridge: Cambridge University Press; 1993.

Belton V, Stewart TJ. Multiple criteria decision analysis: an integrated approach. Massachusetts: Kluwer Academic Publishers; 2002.

Inotai A, Nguyen HT, Hidayat B, Nurgozhin T, Kiet PHT, Campbell JD, et al. Guidance toward the implementation of multicriteria decision analysis framework in developing countries. Expert Rev Pharmacoecon Outcomes Res. 2018;18:585–92. PubMed

Wolf JA, Niederhauser V, Marshburn D, LaVela SL. Defining patient experience. Patient Exp. 2014;1:3.

Pontes C, Fontanet JM, Vives R, Sancho A, Gómez-Valent M, Ríos J, et al. Evidence supporting regulatory-decision making on orphan medicinal products authorisation in Europe: methodological uncertainties. Orphanet J Rare Dis. 2018;13:206. PubMed PMC

Drummond M, Griffin A, Tarricone R. Economic evaluation for devices and drugs—same or different? Value Health. 2009;12:402–4. PubMed

Frieden TR. Evidence for health decision making—beyond randomized, controlled trials. N Engl J Med. 2017;377:465–75. PubMed

Murray E, Hekler EB, Andersson G, Collins LM, Doherty A, Hollis C, et al. Evaluating digital health interventions: key questions and approaches. Am J Prev Med. 2016;51:843–51. PubMed PMC

Németh B, Kaló Z. European cooperation in health technology assessment implementation: the perspective of Central and Eastern European countries. Future Med. 2020;9:599–602. PubMed

Kristensen FB, Lampe K, Wild C, Cerbo M, Goettsch W, Becla L. The HTA Core Model®—10 years of developing an international framework to share multidimensional value assessment. Value Health. 2017;20:244–50. PubMed

EUnetHTA Joint Action 2, Work Package 8. HTA Core Model Version 3.0. 2016. http://www.corehta.info/model/HTACoreModel3.0.pdf. Accessed 18 Mar 2021.

Bodrogi J, Kaló Z. Principles of pharmacoeconomics and their impact on strategic imperatives of pharmaceutical research and development. Br J Pharmacol. 2010;159:1367–73. PubMed PMC

Garrison LP, Jr, Towse A, Briggs A, de Pouvourville G, Grueger J, Mohr PE, et al. Performance-based risk-sharing arrangements-good practices for design, implementation, and evaluation: report of the ISPOR good practices for performance-based risk-sharing arrangements task force. Value Health. 2013;16:703–19. PubMed

Kaló Z, Annemans L, Garrison LP. Differential pricing of new pharmaceuticals in lower income European countries. Expert Rev Pharmacoecon Outcomes Res. 2013;13:735–41. PubMed

Horizon Europe Programme (HORIZON)-Work Programme for Health 2021–2022. 2020. https://efmc.eu/wp-content/uploads/2021/02/Horizon-Europe-Programme-HORIZON-Work-Programme-2021-2022-for-Health-1.pdf. Accessed 18 June 2021.

Torjesen I. Covid-19: Hydroxychloroquine does not benefit hospitalised patients, UK trial finds. BMJ Online. 2020;369:m2263. PubMed

Mahase E. Hydroxychloroquine for covid-19: the end of the line? BMJ. 2020;369:m2378. PubMed

World Health Organization (WHO). Newsroom. 2020. https://www.who.int/news/item/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-treatment-arms-for-covid-19. Accessed 18 Mar 2021.

STAMP Working Group. Draft—proposal for a framework to support not-for-profit organisations in drug repurposing. 2019. https://ec.europa.eu/health/sites/health/files/files/committee/stamp/stamp_11_47_2_en.pdf. Accessed 18 Mar 2021.

Conti RM, Athey S, Frank RG, Gruber J. Generic drug repurposing for public health and national security: COVID-19 and beyond. Health Affairs Blog. 2020. https://www.healthaffairs.org/do/10.1377/hblog20201204.541050/full/. Accessed 18 June 2021. DOI

Godman B, McCabe H, Leong D. Fixed dose drug combinations—are they pharmacoeconomically sound? Findings and implications especially for lower- and middle-income countries. Expert Rev Pharmacoecon Outcomes Res. 2020;20:1–26. PubMed

Development of a core evaluation framework of value-added medicines: report 1 on methodology and findings