Scientific Publications by FDA Staff

Ther Innov Regul Sci 2016 Mar;50(2):195-203

CBER's experience with adaptive design clinical trials.

Lin M, Lee S, Zhen BG, Scott J, Horne A, Solomon G, Russek-Cohen E

There is considerable interest among pharmaceutical and other medical product developers in adaptive clinical trials, in which knowledge learned during the course of a trial affects ongoing conduct or analysis of the trial. When the FDA released a draft Guidance document on adaptive design clinical trials in early 2010, expectations were high that it would lead to an increase in regulatory submissions involving adaptive design features, particularly for confirmatory trials. A 6-year (2008-2013) retrospective survey was performed within the Center for Biologics Evaluation and Research (CBER) at the FDA to gather information regarding the submission and evaluation of adaptive design trial proposals. We present an up-to-date summary of adaptive design proposals seen in CBER and provide an overview of our experiences. We share our concerns regarding the statistical issues and operational challenges raised during the review process for adaptive design trials. We also provide general recommendations for developing proposals for such trials. Our motivation in writing this paper was to encourage the best study design proposals to be submitted to CBER. Sometimes these can be adaptive, and sometimes a simpler design is most efficient.