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Paper No. 07-25

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PK Kimani, N Stallard and JL Hutton

Dose Selection in Seamless Phase II/III Clinical Trials based on Efficacy and Toxicity

Abstract: 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 1 (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 e±cacy and toxicity. 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 2007 John Wiley & Sons, Ltd.

Keywords: Seamless phase II/III clinical trials; Closure principle; Adaptive testing; Conditional power; Predictive power.