Optimal adaptive designs for binary response trials

Abstract

We derive the optimal allocation between two treatments in a clinical trial based on the following optimality criterion: for fixed variance of the test statistic, what allocation minimizes the expected number of treatment failures? A sequential design is described that leads asymptotically to the optimal allocation and is compared with the randomized play-the-winner rule, sequential Neyman allocation, and equal allocation at similar power levels. We find that the sequential procedure generally results in fewer treatment failures than the other procedures, particularly when the success probabilities of treatments are smaller.