title: Testing superiority and non-inferiority hypotheses in active controlled clinical trials.
abstract: Switching between testing for superiority and non-inferiority has been an important statistical issue in the design and analysis of active controlled clinical trial. In practice, it is often conducted with a two-stage testing procedure. It has been assumed that there is no type I error rate adjustment required when either switching to test for non-inferiority once the data fail to support the superiority claim or switching to test for superiority once the null hypothesis of non-inferiority is rejected with a pre-specified non-inferiority margin in a generalized historical control approach. However, when using a cross-trial comparison approach for non-inferiority testing, controlling the type I error rate sometimes becomes an issue with the conventional two-stage procedure. We propose to adopt a single-stage simultaneous testing concept as proposed by Ng (2003) to test both non-inferiority and superiority hypotheses simultaneously. The proposed procedure is based on Fieller's confidence interval procedure as proposed by Hauschke et al. (1999).
authors.affiliation: Quantitative Methods Research Staff, Office of Biostatistics, OPaSS, CDER, U.S. FDA, USA. Tsong@cder.fda.gov
authors.forename: Yi
authors.initials: Y
authors.lastname: Tsong
authors.forename: Juan Joanne
authors.initials: JJ
authors.lastname: Zhang
mesh_terms: D001702:Biopharmaceutics / Q000379:methods*; D016001:Confidence Intervals; D018849:Controlled Clinical Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D003627:Data Interpretation, Statistical; D004341:Drug Evaluation; D004358:Drug Therapy; D017408:Guidelines as Topic; D012106:Research; D013810:Therapeutic Equivalency