A Multiplicity Strategy Incorporating Fixed Sequential, Hochberg, and Fallback Procedures

• Activity Number: 409
• Type: Contributed
• Date/Time: Tuesday, August 3, 2010 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Duane Snavely*+ and Kenneth Liu
• Companies: Merck & Co., Inc. and Merck & Co., Inc.
• Keywords: Multiplicity ; Hochberg ; Fallback

Abstract

A new drug may be simultaneously developed for two different indications within a patient population. Two sets of hypotheses (one for each indication) within a single study may include evaluation of multiple variables, time points or doses which contribute to the desired claim structure(s) for the new product. If strong type I error control is desired across these indications and factors, a number of multiplicity strategies may be conceived. We consider a combination of Bonferroni, Fixed Sequential, and Hochberg procedures with incorporation of a Fallback procedure to increase the power for the second set of hypotheses that may be related to the indication of less importance or lower power. Simulations are used to demonstrate the type I error control and power implications of such a strategy compared to other viable alternatives.