title: Simultaneous test for superiority and noninferiority hypotheses in active-controlled clinical trials.
abstract: Two stage switching between testing for superiority (SUP) and noninferiority (NI) has been an important statistical issue in the design and analysis of the active-controlled clinical trials. Tsong and Zhang (2005) has shown that the Type I error rates do not change when switching between SUP and NI with the traditional generalized historical control (GHC) approach, however, they may change when switching with the cross-trial comparison (X-trial) approach. Tsong and Zhang (2005) further proposed a simultaneous test for both hypotheses to avoid the problem. The procedure was based on Fieller's confidence interval proposed by Hauschke et al. (1999). Since with the X-trial approach, using the simultaneous test, superiority is tested using all four treatment arms (current test and active control arms, active control and placebo arms in historical trials), the Type I error rate and power are expected to be somewhat different from the conventional superiority test (using the current test and active control arms only). Through a simulation study, we demonstrate that the Type I error rate and power between simultaneous test and the conventional superiority test are compatible. We also examine the impact of the assumption of equal variances of the current trial and the historical trial.
authors: Division of Biometrics VI, Office of Biostatistics, CDER, FDA, Silver Spring, MD 20993-0002 USA. yi.tong@cder.hhs.gov
authors: Yi
authors: Y
authors: Tsong
authors: Joanne
authors: J
authors: Zhang
mesh_terms: D016001:Confidence Intervals; D018849:Controlled Clinical Trials as Topic / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D006801:Humans; D015233:Models, Statistical; D012107:Research Design / Q000592:standards / Q000706:statistics & numerical data*