Review and Extension for the O’Brien Fleming Multiple Testing procedure

Abstract

Review and Extension for the O’Brien Fleming Multiple Testing procedure by Hanan Hammouri, MS. Advisor: Dr. Roy Sabo O'Brien and Fleming (1979) proposed a straightforward and useful multiple testing procedure (group sequential testing procedure) for comparing two treatments in clinical trials where subject responses are dichotomous (e.g. success and failure). O'Brien and Fleming stated that their group sequential testing procedure has the same Type I error rate and power as that of a fixed one-stage chi-square test, but gives the opportunity to terminate the trial early when one treatment is clearly performing better than the other. We studied and tested the O'Brien and Fleming procedure specifically by correcting the originally proposed critical values. Furthermore, we updated the O’Brien Fleming Group Sequential Testing procedure to make it more flexible via three extensions. The first extension is combining the O’Brien Fleming Group Sequential Testing procedure with the Optimal allocation, where the idea is to allocate more patients to the better treatment after each interim analysis. The second extension is combining the O’Brien Fleming Group Sequential Testing procedure with the Neyman allocation which aims to minimize the variance of the difference in sample proportions. The last extension is that we can allow for different sample weights for different stages, as opposed to equal allocation for different stages. Simulation studies showed that the O’Brien Fleming Group Sequential Testing procedure is relatively robust to the added features.