Adaptive Patient Population Selection Design in Clinical Trials
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Philip He, Sanofi-Aventis  Pierre Mancini, Sanofi-Aventis  *Hui Quan, Sanofi-Aventis  Dongli Zhou, Sanofi-Aventis 

Keywords: conditional power, sample size re-estimation, closed testing procedure, weighted combination test, trial simulation.

For the success of a new drug development, it is crucial to select the sensitive patient populations. To potentially reduce timeline and cost, we may apply an adaptive patient population selection design to a therapeutic trial. In such a design, based on early results of the trial, patient population(s) will be selected/determined for the final stage and analysis. Because of this adaptive nature and the multiple between-treatment comparisons for multiple populations, alpha adjustment must be performed. In this paper, we propose a closed testing procedure for assessing treatment effects for multiple populations and a weighted combination test for sample size and population adaptations. Computation/simulation is used to compare the performances of the proposed method and other multiplicity adjustment methods. A trial example is presented to illustrate the applications of the methods.