Gatekeeping Procedures in Complex Multiplicity Problems in Clinical Trials

• Activity Number: 556
• Type: Topic Contributed
• Date/Time: Wednesday, August 1, 2012 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Olga V Marchenko*+ and Alex Dmitrienko
• Companies: Quintiles, Inc. and Quintiles, Inc.
• Keywords: Clinical trials ; Multiple testing procedures ; Type I error rate ; Power ; Powerful gatekeeping procedures

Abstract

This presentation discusses solutions to complex multiplicity problems arising in confirmatory clinical trials with multiple families of objectives (for example, primary and secondary endpoints). The solutions are based on a class of multiple testing procedures known as gatekeeping procedures. Gatekeeping procedures have attracted much attention in clinical drug development due to the regulatory requirement to protect the Type I error rate across multiple families. The presentation provides an overview of regulatory requirements and introduces a general process for building gatekeeping procedures. The process utilizes logical relationships among the objectives and all available distributional information to build flexible and powerful gatekeeping procedures. Optimal gatekeeping procedures are selected from a set of candidate procedures based on application-specific criteria. The development process is illustrated using a clinical trial with a "three-dimensional" multiplicity problem based on multiple endpoints, dose-placebo comparisons and timepoints.