Superchain procedures in clinical trials with multiple objectives.
This paper introduces a new class of multiple testing procedures for addressing multiplicity problems arising in clinical trials with multiple objectives grouped into families. The families may correspond to equally important sets of objectives (co-primary endpoints) or ordered sets of objectives (primary and secondary endpoints). The procedures, termed superchain procedures, serve as an extension of several classes of other multiple testing procedures, including chain procedures and parallel gatekeeping procedures. Superchain procedures exhibit several desirable features, including flexible decision rules that can be tailored to a broad class of win criteria in confirmatory clinical trials. Additionally, superchain procedures enable the trial's sponsor to efficiently incorporate available distributional information to improve overall power. Finally, superchain procedures rely on straightforward testing algorithms, which facilitates their development. We illustrate the new methodology by using clinical trial examples with two and three families of objectives.
U.S. Food and Drug Administration, Silver Spring, MD, U.S.A. george.kordzakhia@fda.hhs.gov
George
G
Kordzakhia
Alex
A
Dmitrienko
D000465:Algorithms; D002986:Clinical Trials as Topic / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination / Q000706:statistics & numerical data; D006801:Humans; D015233:Models, Statistical