Dose selection in seamless phase II/III clinical trials based on efficacy and safety

Seamless phase II/III clinical trials are attractive in development of new drugs because they accelerate the drug development process. Seamless phase II/III trials are carried out in two stages. After stage I (phase II stage), an interim analysis is performed and a decision is made on whether to proceed to stage 2 (phase III stage). If the decision is to continue with further testing, some dose-selection procedure is used to determine the set of doses to be tested in stage 2. In this paper, we propose a dose-selection procedure for binary outcomes in adaptive seamless phase II/III clinical trials that incorporates the dose-response relationship when the experimental treatments are different dose levels of the same drug, and explicitly incorporates both efficacy and safety. The choice of the doses to continue to stage 2 is made by comparing the predictive power of the potential sets of doses, which might continue. Copyright (C) 2009 John Wiley & Sons, Ltd.