Adaptive Clinical Trials in Stroke.

Designing a clinical trial to evaluate the efficacy of an intervention is often complicated by uncertainty over aspects of the study population, potential treatment effects, most relevant outcomes, dropouts, and other factors. However, once participants begin to be enrolled and partial trial data become available, this level of uncertainty is reduced. Adaptive clinical trials are designed to take advantage of the accumulating data during the conduct of a trial to make changes according to prespecified decision rules to increase the likelihood of success or statistical efficiency. Common adaptive rules address early stopping for benefit or futility, sample size reestimation, adding or dropping treatment arms or altering randomization ratios, and changing the eligibility criteria to focus on responder patient subgroups. Adaptive clinical trials are gaining popularity for clinical stroke research. We provide an overview of the methods, practical considerations, challenges and limitations, and potential future role of adaptive clinical trials in advancing knowledge and practice in stroke.
Competing Interests: Drs Crawford, Lorenzi, and Lewis report employment by Berry Consultants LLC. Dr Saville was previously employed by Berry Consultants LLC and is now the owner of Adaptix Trials LLC. Drs Crawford, Lorenzi, Saville, and Lewis and other staff of Berry Consultants LLC were involved in the design and operation of several of the clinical trials referenced in this review. Dr Lewis also reports funding from the National Institutes of Health; compensation from the National Academies of Sciences, Engineering, and Medicine for other services; and employment of the American Medical Association. Dr Anderson reports research grants from the National Health and Medical Research Council of Australia, the Medical Research Council and Medical Research Foundation of the United Kingdom, and Takeda and Penumbra. He has received consulting fees for being an Advisor to AstraZeneca Australia.