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Adaptive platform trials: definition, design, conduct and reporting considerations

Nature Reviews Drug Discovery volume 18, pages 797–807 (2019)Cite this article

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An Author Correction to this article was published on 10 September 2019

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Abstract

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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Fig. 1: General operational flow of an adaptive platform trial.

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  • 10 September 2019

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Acknowledgements

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.

Author information

Authors and Affiliations

  1. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Derek C. Angus & Christopher W. Seymour

  2. Harvard Medical School, Boston, MA, USA

    Brian M. Alexander

  3. Berry Consultants, Austin, TX, USA

    Scott Berry & Kert Viele

  4. Berry Consultants, San Francisco, CA, USA

    Meredith Buxton & Melissa Paoloni

  5. University of California Los Angeles, Los Angeles, CA, USA

    Roger Lewis & Timothy F. Cloughesy

  6. Monash University, Melbourne, Australia

    Steven A. R. Webb, Stephane Heritier & Genevieve O’Neill

  7. Massachusetts General Hospital, Boston, MA, USA

    Steven Arnold & Bradley Hyman

  8. Arizona State University, Tempe, AZ, USA

    Anna Barker

  9. Anderson Cancer Center, Houston, TX, USA

    Donald A. Berry

  10. University Medical Center of Utrecht, Utrecht, Netherlands

    Marc J. M. Bonten & Lennie P. G. Derde

  11. Veterans’ Affairs Boston Healthcare System, Boston, MA, USA

    Mary Brophy & Ryan Ferguson

  12. University of Oxford, Oxford, UK

    Christopher Butler

  13. University of California San Francisco, San Francisco, CA, USA

    Laura J. Esserman

  14. Boston University, Boston, MA, USA

    Louis Fiore

  15. Dana-Farber Cancer Institute, Boston, MA, USA

    Sarah C. Gaffey & Patrick Y. Wen

  16. Harvard University, Cambridge, MA, USA

    J. Michael Gaziano & Nathan I. Shapiro

  17. Multiple Myeloma Research Foundation, Harvard Business School, Cambridge, MA, USA

    Kathy Giusti

  18. University of Antwerp, Antwerp, Belgium

    Herman Goossens

  19. Johnson and Johnson Pharmaceuticals, New Brunswick, NJ, USA

    Michael Krams

  20. Massachusetts Institute of Technology, Cambridge, MA, USA

    Kay Larholt, Andrew W. Lo & Mark Trusheim

  21. The US Food and Drug Administration, Washington, USA

    Lisa M. LaVange & Janet Woodcock

  22. Stanford University, Palo Alto, CA, USA

    Philip Lavori

  23. Carnegie Mellon University, Pittsburgh, PA, USA

    Alex John London

  24. Pancreatic Cancer Action Network, Dallas, TX, USA

    Victoria Manax

  25. Auckland District Health Board, Auckland, New Zealand

    Colin McArthur

  26. Harvard School of Public Health, Boston, MA, USA

    Giovanni Parmigiani & Lorenzo Trippa

  27. Gemini Group, Ann Arbor, MI, USA

    Jane Perlmutter

  28. Duke University, Durham, NC, USA

    Elizabeth A. Petzold

  29. University of Edinburgh, Edinburgh, UK

    Craig Ritchie

  30. ICNARC, London, UK

    Kathryn M. Rowan

  31. New York University, New York, NY, USA

    Diane M. Simeone

  32. IQVIA, Durham, NC, USA

    Bradley Smith

  33. University of Southern California, Los Angeles, CA, USA

    Bradley Spellberg

  34. Harvard Business School, Cambridge, MA, USA

    Ariel Dora Stern

Consortia

The Adaptive Platform Trials Coalition

  • Derek C. Angus
  • , Brian M. Alexander
  • , Scott Berry
  • , Meredith Buxton
  • , Roger Lewis
  • , Melissa Paoloni
  • , Steven A. R. Webb
  • , Steven Arnold
  • , Anna Barker
  • , Donald A. Berry
  • , Marc J. M. Bonten
  • , Mary Brophy
  • , Christopher Butler
  • , Timothy F. Cloughesy
  • , Lennie P. G. Derde
  • , Laura J. Esserman
  • , Ryan Ferguson
  • , Louis Fiore
  • , Sarah C. Gaffey
  • , J. Michael Gaziano
  • , Kathy Giusti
  • , Herman Goossens
  • , Stephane Heritier
  • , Bradley Hyman
  • , Michael Krams
  • , Kay Larholt
  • , Lisa M. LaVange
  • , Philip Lavori
  • , Andrew W. Lo
  • , Alex John London
  • , Victoria Manax
  • , Colin McArthur
  • , Genevieve O’Neill
  • , Giovanni Parmigiani
  • , Jane Perlmutter
  • , Elizabeth A. Petzold
  • , Craig Ritchie
  • , Kathryn M. Rowan
  • , Christopher W. Seymour
  • , Nathan I. Shapiro
  • , Diane M. Simeone
  • , Bradley Smith
  • , Bradley Spellberg
  • , Ariel Dora Stern
  • , Lorenzo Trippa
  • , Mark Trusheim
  • , Kert Viele
  • , Patrick Y. Wen
  •  & Janet Woodcock

Corresponding authors

Correspondence to Derek C. Angus or Brian M. Alexander.

Ethics declarations

Competing interests

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. 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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