Group Sequential Test for Two-Sample Ordinal Outcome Measures.

Abstract

Group sequential trials include interim monitoring points to potentially reach futility or efficacy decisions early. This approach to trial design can safeguard patients, provide efficacious treatments for patients early, and save money and time. Group sequential methods are well developed for bell-shaped continuous, binary, and time-to-event outcomes. In this paper, we propose a group sequential design using the Mann-Whitney-Wilcoxon test for general two-sample ordinal data. We establish that the proposed test statistic has asymptotic normality and that sequential statistics satisfy the assumptions of Brownian motion. We also include results of finite sample simulation studies that show our proposed approach has the advantage over existing methods for controlling Type I errors while maintaining power for small sample sizes. A real data set is used to illustrate the proposed method and a sample size calculation approach is proposed for designing new studies.