Optimization of Mixture Gatekeeping Multiple Testing Procedures with Serial Logical Restrictions

• Activity Number: 459
• Type: Contributed
• Date/Time: Wednesday, August 6, 2014 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): George Kordzakhia *+
• Companies: FDA
• Keywords: multiplicity ; gatekeeping procedures ; closed testing

Abstract

The general mixture gatekeeping method applies to a very broad class of logical relationships among the null hypotheses of interest, including combinations of the so-called serial and parallel restrictions, and, thus, it is based on a more conservative approach in order to accommodate for these restrictions.

We show that for the multiplicity problems that include only serial logical restrictions, the power of the general mixture gatekeeping procedure may be uniformly enhanced. Mixture gatekeeping procedures are closed testing procedures, and hence they require to perform local tests for all intersection hypotheses. For some intersections, the local tests can be made more powerful(by making them alpha-exhaustive) which would lead to the overall power improvement. In addition, the mixture procedure is optimized by introducing an additional condition (transitivity) on the set of logical relations among the null hypotheses.