Gatekeeping procedures with clinical trial applications

Abstract

The objective of this paper is to give an overview of a relatively new area of multiplicity research that deals with the analysis of hierarchically ordered multiple objectives. Testing procedures for this problem are known as gatekeeping procedures and have found a variety of applications in clinical trials. This paper reviews main classes of these procedures, including serial and parallel gatekeeping procedures, and tree gatekeeping procedures that account for logical restrictions among multiple objectives. We focus on procedures based on marginal p-values; extensions to procedures that exploit the joint distribution of the p-values are also noted. Clinical trial examples are used to illustrate the procedures and their important properties.