• Yi Tsong and Juan Joanne Zhang.
• Quantitative Methods Research Staff, Office of Biostatistics, OPaSS, CDER, U.S. FDA, USA. Tsong@cder.fda.gov
• Biom J. 2005 Feb 1; 47 (1): 62-74; discussion 99-107.

AbstractSwitching 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).

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