Multiplicity Adjustment Methods Based on Structured Hypotheses (Graphical Approach, Fixed Sequence Procedure, Fallback Procedure)

Abstract

Multiple test procedures are often used in the analysis of clinical trials including multiple objectives. To control the familywise error rate in the strong sense, various powerful procedures for structured hypotheses have been developed. In this paper, we introduce the graphical approach based on Bonferroni-based closed test procedures. Using the graphical approach, one can discuss different test strategies with the clinical team and build the appropriate multiple test procedure for the given study objectives. We illustrate not only the property of the graphical approach but also how to perform it by using SAS or R. Moreover, fixed sequence procedure and fallback procedure are presented within the framework of the graphical approach.