Interval and point estimation in adaptive Phase II trials with binary endpoint

Abstract

Phase II clinical trials are concerned with making decision of whether a treatment is sufficiently efficacious to be worth further investigations in late large scale Phase III trials. In oncology Phase II trials, frequentist single-arm two-stage group-sequential designs with a binary endpoint are commonly used. To allow for more flexibility, adaptive versions of these designs have been proposed. In this paper, we propose point and interval estimation for adaptive designs in which the second stage sample size is a pre-specified function of first stage’s number of responses. Our approach is based on sample space orderings, from which we derive p-values, and point and interval estimates. Simulation studies show that our proposed methods perform better, in terms of bias and root mean square error, than the fixed-sample maximum likelihood estimator.