Researchers, clinicians, policymakers and patients are increasingly interested in questions about therapeutic interventions that are difficult or costly to answer with traditional, free-standing, parallel-group randomized controlled trials (RCTs). Examples include scenarios in which there is a desire to compare multiple interventions, to generate separate effect estimates across subgroups of patients with distinct but related conditions or clinical features, or to minimize downtime between trials. In response, researchers have proposed new RCT designs such as adaptive platform trials (APTs), which are able to study multiple interventions in a disease or condition in a perpetual manner, with interventions entering and leaving the platform on the basis of a predefined decision algorithm. APTs offer innovations that could reshape clinical trials, and several APTs are now funded in various disease areas. With the aim of facilitating the use of APTs, here we review common features and issues that arise with such trials, and offer recommendations to promote best practices in their design, conduct, oversight and reporting.
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The authors are grateful to the Harvard/Massachusetts Institute of Technology (MIT) Center for Regulatory Science for hosting the meeting, and to the Harvard/MIT Center for Regulatory Science, the University of Pittsburgh, the PREPARE consortium, REMAP-CAP and Berry Consultants for financial support towards travel, lodging and expenses. They thank C. D’Avanzo, L. Dilworth, L. Maliszewski (Harvard University), R. Rice (University of Pittsburgh) and J. Clenell (Berry Consultants) for organizational and administrative support and J. Vates (University of Pittsburgh) for detailed review and editing.
B.M.A. reports employment at Foundation Medicine, Inc.; personal fees from Bristol-Myers Squibb, Schlesinger Associates and Precision Health Economics; and unpaid leadership as president and CEO of the Global Coalition for Adaptive Research, a non-profit research organization. S. Berry reports being a part owner of Berry Consultants, LLC (a company that designs and implements platform and adaptive clinical trials for pharmaceutical companies, medical device companies, National Institutes of Health cooperative groups, international consortia and non-profit organizations) and providing consulting for platform trials. M. Buxton, M. Paoloni and K. Viele are currently employees of Berry Consultants, LLC. R. Lewis is a senior medical scientist at Berry Consultants, LLC. D. A. Berry is a co-owner of Berry Consultants, LLC. B. Hyman has current research support from AbbVie, Amgen, Denali, Fidelity Biosciences, Eli Lilly, Merck and co. and Arvinas; serves as a consultant for Biogen, Ceregeen, Genentech, Roche, Eli Lilly, Neurophage, Novartis, Takeda and Sunovian; and owns stock in, as well as having a family member who works for, Novartis. M. Krams is an employee of Johnson & Johnson. A.W. Lo has personal investments in biotechnology companies, biotech venture capital funds and mutual funds; serves as an adviser to BridgeBio Capital; is director of Roivant Sciences Ltd. and chairman emeritus and senior adviser to AlphaSimplex Group; has during the past 6 years received speaking/consulting fees or honoraria from AIG, AlphaSimplex Group, BIS, BridgeBio Capital, Citigroup, Chicago Mercantile Exchange, Financial Times, Harvard University, IMF, National Bank of Belgium, Q Group, Roivant Sciences, Scotia Bank, State Street Bank, University of Chicago and Yale University; and is a director of the Massachusetts Institute of Technology Whitehead Institute for Biomedical Research and a member of the Board of Overseers of Beth Israel Deaconess Medical Center. C. Ritchie provides consultancy and/or receives grant funding from Actinogen, Allergan, Biogen, Eisai, Alector, Janssen, MSD, Lundbeck, Prana Biotechnology, AbbVie, Roche, Eli Lilly and Pfizer. B. Spellberg in the last 12 months consulted for Bayer, Forge, Shionogi, Alexion, Synthetic Biologics, Paratek, TheoremDx, Bioversys and Acurx; and owns equity in Motif, BioAIM, Synthetic Biologics, Mycomed and ExBaq. M. Trusheim is owner of Co-Bio Consulting LLC, which provides services to biomedical companies, and has received speaking fees over the past 6 years from Cowen Group, Merck & Co. and Shire. P. Y. Wen reports receiving research support from Eli Lilly, Puma and Celgene and serving on advisory boards for Eli Lilly and Puma. The remaining authors declare no competing interests.
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The Adaptive Platform Trials Coalition., Angus, D.C., Alexander, B.M. et al. Adaptive platform trials: definition, design, conduct and reporting considerations. Nat Rev Drug Discov 18, 797–807 (2019). https://doi.org/10.1038/s41573-019-0034-3
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