title: Group sequential test strategies for superiority and non-inferiority hypotheses in active controlled clinical trials.
abstract: In a group sequential active controlled clinical trial, the study hypothesis may be a superiority hypothesis that an experimental treatment is more effective than the active control therapy or a non-inferiority hypothesis that the treatment is no worse than the active control within some non-inferiority range. When it is necessary to plan for testing the superiority and the non-inferiority hypotheses, we propose an adaptive group sequential closed test strategy by which the sample size is planned for testing superiority and is to be increased for showing non-inferiority given that it is deemed more plausible than superiority based on the observed sample path during the course of the trial. The proposed adaptive test strategy is valid in terms of having the type I error probability maintained at the targeted alpha level for both superiority and non-inferiority. It has power advantage or sample size saving over the traditional group sequential test designed for testing either superiority only or non-inferiority only.
authors: Division of Biometrics II, OB/CDER, Food and Drug Administration, HFD-715, 5600 Fishers Lane, Rockville, MD 20857, USA. wangs@cder.fda.gov
authors: S J
authors: SJ
authors: Wang
authors: H M
authors: HM
authors: Hung
authors: Y
authors: Y
authors: Tsong
authors: L
authors: L
authors: Cui
mesh_terms: D018849:Controlled Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D004341:Drug Evaluation / Q000379:methods / Q000592:standards; D006801:Humans; D018401:Sample Size; D013223:Statistics as Topic / Q000379:methods*