title: Stepwise gatekeeping procedures in clinical trial applications.
abstract: This paper discusses multiple testing problems in which families of null hypotheses are tested in a sequential manner and each family serves as a gatekeeper for the subsequent families. Gatekeeping testing strategies of this type arise frequently in clinical trials with multiple objectives, e.g., multiple endpoints and/or multiple dose-control comparisons. It is demonstrated in this paper that the parallel gatekeeping procedure of Dmitrienko, Offen and Westfall (2003) admits a simple stepwise representation (n null hypotheses can be tested in n steps rather than 2n steps required in the closed procedure). The stepwise representation considerably simplifies the implementation of gatekeeping procedures in practice and provides an important insight into the nature of gatekeeping inferences. The derived stepwise gatekeeping procedure is illustrated using clinical trial examples.
authors.affiliation: Eli Lilly and Company, Indianapolis, IN 46285, USA. dmitrienko_alex@lilly.com
authors.forename: Alex
authors.initials: A
authors.lastname: Dmitrienko
authors.forename: Ajit C
authors.initials: AC
authors.lastname: Tamhane
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Xun
authors.initials: X
authors.lastname: Chen
mesh_terms: D000465:Algorithms; D001699:Biometry / Q000379:methods*; D003198:Computer Simulation; D018849:Controlled Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D016015:Logistic Models; D015233:Models, Statistical; D017063:Outcome Assessment, Health Care / Q000379:methods*; D018401:Sample Size; D016896:Treatment Outcome