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Tree‐structured gatekeeping tests in clinical trials with hierarchically ordered multiple objectives
Author(s) -
Dmitrienko Alex,
Wiens Brian L.,
Tamhane Ajit C.,
Wang Xin
Publication year - 2007
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.2716
Subject(s) - gatekeeping , context (archaeology) , computer science , multiple comparisons problem , class (philosophy) , tree (set theory) , clinical trial , clinical endpoint , medicine , medical physics , statistics , mathematics , artificial intelligence , combinatorics , paleontology , political science , law , biology
This paper discusses a new class of multiple testing procedures, tree‐structured gatekeeping procedures, with clinical trial applications. These procedures arise in clinical trials with hierarchically ordered multiple objectives, for example, in the context of multiple dose–control tests with logical restrictions or analysis of multiple endpoints. The proposed approach is based on the principle of closed testing and generalizes the serial and parallel gatekeeping approaches developed by Westfall and Krishen ( J. Statist. Planning Infer . 2001; 99 :25–41) and Dmitrienko et al . ( Statist. Med. 2003; 22 :2387–2400). The proposed testing methodology is illustrated using a clinical trial with multiple endpoints (primary, secondary and tertiary) and multiple objectives (superiority and non‐inferiority testing) as well as a dose‐finding trial with multiple endpoints. Copyright © 2006 John Wiley & Sons, Ltd.