Flexible Multiple Testing Procedures Based on Resampling Methods for Gatekeeping Applications

• Activity Number: 661
• Type: Contributed
• Date/Time: Thursday, August 2, 2012 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Kentaro Sakamaki*+ and Yutaka Matsuyama and Yasuo Ohashi
• Companies: University of Tokyo and University of Tokyo and University of Tokyo
• Keywords: multiple endpoints ; gatekeeping ; resampling methods

Abstract

In clinical trials with multiple primary and secondary endpoints, gatekeeping procedures are utilized to control type I family wise error rate since hypotheses are hierarchically ordered. Multiple endpoints are usually correlated and some endpoints may be discrete. To disregard the correlation and discreteness will decrease power. However, recently proposed gatekeeping procedures are difficult to apply resampling methods which regard them. In this talk, we propose simple and more powerful multiple testing procedures based on resampling methods for gatekeeping applications. Proposed procedures apply resampling methods to a sequence of subsets of null hypotheses, defined by gatekeeping manner. Procedures start with testing a null hypothesis of primary endpoints. In each subset, we reject one null hypothesis. If we fail to reject a null hypothesis, no further hypotheses are rejected. Another advantage of proposed procedures is flexibility to change weights assigned to each hypothesis. We confirmed through simulation studies that proposed procedures control type I family wise error rate and increase power compared with other gatekeeping procedures using Bonferroni test.