Comparison of Gatekeeping and Other Testing Methods for Identifying Superior Drug Combinations in Bi-Factorial Designs with Isotonic Parameters

• Activity Number: 132
• Type: Contributed
• Date/Time: Monday, August 1, 2011 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Julia Soulakova*+
• Companies: University of Nebraska at Lincoln
• Keywords: closure principle ; family-wise error rate ; maximum test ; multiple testing

Abstract

Several multiple testing procedures are discussed with respect to the problem of detecting combination drug superiority for a bi-factorial design with monotone gains. The testing methods include the generalized maximum test procedure (GMAXP) proposed by Soulakova (2009), and several gatekeeping strategies: the general multistage gatekeeping method (GMGP) proposed by Dmitrienko, Tamhane and Wiens (2008), and the serial Bonferroni gatekeeping method (TREE), proposed by Dmitrienko, Wiens, Tamhane and Wang (2007). The GMGP with the truncated Holm and Hochberg components is discussed. In addition, the truncated Sidak-Holm component is proposed.It is shown by simulations that the GMAXP achieves higher power if there are relatively many superior combinations, while the gatekeeping methods perform better if there is a single or just a few superior combinations. While in some cases the GMGP with the truncated Sidak-Holm component outperforms the GMGP with the truncated Hochberg component, the observed power advantages are not substantial. Thus, the GMGP with the truncated Hochberg component is recommended as it can dominate the other methods when the Min test statistics are independent.