Adaptive platform trials: definition, design, conduct and reporting considerations
Angus, Derek C.; Alexander, Brian M.; Berry, Scott; Buxton, Meredith; Lewis, Roger; Paoloni, Melissa; Webb, Steven A. R.; Arnold, Steven; Barker, Anna; Berry, Donald A.; Bonten, Marc J. M.; Brophy, Mary; Butler, Christopher; Cloughesy, Timothy F.; Derde, Lennie P. G.; Esserman, Laura J.; Ferguson, Ryan; Fiore, Louis; Gaffey, Sarah C.; Gaziano, J. Michael; Giusti, Kathy; Goossens, Herman; Heritier, Stephane; Hyman, Bradley; Krams, Michael; Larholt, Kay; LaVange, Lisa M.; Lavori, Philip; Lo, Andrew W.; London, Alex John; Manax, Victoria; McArthur, Colin; O'Neill, Genevieve; Parmigiani, Giovanni; Perlmutter, Jane; Petzold, Elizabeth A.; Ritchie, Craig; Rowan, Kathryn M.; Seymour, Christopher W.; Shapiro, Nathan, I; Simeone, Diane M.; Smith, Bradley; Spellberg, Bradley; Stern, Ariel Dora; Trippa, Lorenzo; Trusheim, Mark; Viele, Kert; Wen, Patrick Y.; Woodcock, Janet
(2019) Nature Reviews Drug Discovery, volume 18, issue 10, pp. 797 - 807
(Article)
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
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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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Keywords: Pharmacology, Drug Discovery
ISSN: 1474-1776
Publisher: Nature Publishing Group
Note: Funding Information: APTs do not lend themselves to traditional funding models. National Institutes of Health grants, for example, typically require known trial sizes and timelines to calculate and distribute budgets. A trial design intended to enrol perpetually, with an unclear — and theoretically unbounded — number of enrollees, does not fit this paradigm. Similarly, APTs that test multiple experimental interventions must overcome the financial and legal hurdles that arise when approaching multiple pharmaceutical companies to participate in a single trial. In this scenario, the APT sponsor would interact with industry by offering various financial terms to participate in the trial. For smaller trials without registration potential, this might take the form of investigator-initiated studies through the usual channels. For larger trials with potential for registration, more significant financing is required. This may take the form of a fee-for-service arrangement whereby industry partners pay a per-patient or per-arm cost to participate (a form of ‘pay-to-play’). I-SPY 2 was initially funded through federal support and donations, but has now evolved to a pay-to-play model. REMAP-CAP has thus far focused on comparative effectiveness questions and is funded by government grants from multiple countries. GBM AGILE is funded via donations and a pay-to-play model. Publisher Copyright: © 2019, Springer Nature Limited.
(Peer reviewed)