Noninferiority hypotheses and choice of noninferiority margin.
Ng (Drug Inf. J. 1993; 27:705-719; Drug Inf. J. 2001; 35:1517-1527) proposed that the noninferiority (NI) margin should be a small fraction of the therapeutic effect of the active control as compared with placebo in the setting of testing the NI hypothesis of the mean difference with a continuous outcome. For testing the NI hypothesis of the mean ratio with a continuous outcome, a similar NI margin on a log scale is proposed. This approach may also be applied in the setting of testing the NI hypotheses for survival data based on hazard ratios. Some pitfalls of testing the NI hypotheses with binary endpoints based on the difference or the ratio of proportions will be discussed. Testing the NI hypothesis with binary endpoints based on the odds ratio is proposed.
Ng
Tie-Hua
TH
US Food and Drug Administration, 1401 Rockville Pike, #200S, HFM-219, Rockville, MD 20852-1448, USA. tiehua.ng@fda.hhs.gov
D002986:Clinical Trials as Topic / Q000379:methods*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D023381:Endpoint Determination / Q000379:methods*; D006801:Humans; D016016:Proportional Hazards Models; D012107:Research Design