Self-designing trial combined with classical group sequential monitoring

Abstract

At the interim analyses of a clinical trial, it is appealing to modify the originally planned sample size in order to achieve an adequate power to detect a meaningful treatment effect. We propose a flexible sequential monitoring scheme through combining the self-designing and classical group sequential methods. The maximum sample size does not have to be specified in advance and one efficacy interim analysis is conducted for the purpose of possible early termination after the first block of data is observed. At the interim analysis for efficacy, the usual sufficient test statistic is used and the type I error rate is adjusted to maintain the overall nominal level. At the final analysis, the test is constructed from a weighted average of the blockwise test statistics based on the sequentially collected data. The weight function at each stage is determined by the observed data prior to that stage. The futility stopping rule allows the trial to be terminated when there is no beneficial treatment effect. We conduct simulation studies to evaluate the performance of the proposed design. Copyright © Taylor & Francis, Inc.