Adaptive trials in clinical research: scientific and ethical issues to consider.

INTEREST IN THE USE OF ADAPTIVE TRIAL DESIGN HAS INcreased among clinical investigators, pharmaceutical companies, and regulatory authorities. Adaptive trials are randomized clinical trials that allow for adaptations in the study design while the study is being conducted. Modifications as a study is being conducted can include changes in sample size, adjustments in medication dosage, or changes in the number of treatment groups. Adaptive trials can often decrease drug development time, which can have clinical and economic advantages. Adaptive trials also have certain ethical advantages because fewerparticipantsareassignedtotheinferiorprocedureordrug compared with trials with fixed designs. For instance, in the ASTIN trial, researchers conducted an adaptive phase 2 dose response trial to determine whether a neutrophil inhibitory factorimprovedrecoveryinpatientswithacuteischemicstroke; it did not. However, this trial needed to enroll 966 patients, compared with the need to enroll 1080 patients if a traditional designhadbeenused.Furthermore, theadaptivedesignmade it possible to stop the trial early for futility. However, certain features of adaptive trials may create some potential scientific and ethical challenges. This Viewpoint explores several ethical issues that researchers and participants in adaptive trials should consider.