Keywords: Adaptive design, simulation, type I error
FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) published an adaptive design guidance in 2010, and the Center for Devices and Radiological Health (CDRH) published a final guidance on the same topic in 2016. The CDER/CBER guidance uses the terms well-understood and less well-understood to characterize various types of adaptive designs that may be used in both confirmative and exploratory studies. Even though the guidance generally encourages the use of adaptive designs in drug development programs, some aspects of the guidance have been criticized as being ambiguous, especially with respect to whether less well-understood designs are acceptable to the agency. In addition, further details on the use of simulations to determine Type I error probabilities are lacking. As a result, CDER and CBER plan to issue a revised draft guidance on adaptive designs that addresses some of the shortcomings in the 2010 guidance, clarifies some of the questions raised, and is also more consistent with the CDRH guidance on points for which drug vs device differences are not of consequence. In this talk, we will provide the rationale for revising the draft guidance rather than issuing a final version and describe some general and also give an update on recent experience with adaptive trials in oncology/hematology.