Gatekeeping Strategies and Graphical Approaches in Clinical Trials with Hierarchically Structured Study Objectives: A Review

Abstract

In this paper, we give a review of recent development on gatekeeping strategies and graphical approaches. First, we give an overview of fundamental theories for multiple testing, such as partition testing and closed testing procedure. We then describe how gatekeeping strategies have been developed in the last decade to handle multiplicity issues that arise in clinical trials with hierarchically structured study objectives and how graphical approaches help to visualize such gatekeeping strategies and tailor a multiple testing procedure. Finally, we describe further availability of graphical approaches to more complex clinical trial designs such as group-sequential designs and adaptive designs.