title: Assessing treatment efficacy in noninferiority trials.
abstract: Often one of the primary objectives of an active-controlled noninferiority trial without a placebo arm is to assert that an experimental treatment would have been more effective than a putative placebo had the placebo been included in the trial. This may be an important consideration for regulatory applications. To achieve this objective, such a noninferiority analysis entails cross-trial statistical inference. Because of the uncertainty and difficulty surrounding cross-trial inference, the noninferiority analysis often aims to demonstrate that the experimental treatment preserves a specified fraction of the effect of the active control. The rationale is that by demonstrating the percent effect retention, the efficacy of the experimental treatment can be established with a great level of confidence. The confidence interval approach and synthesized test approach have been used for inferring the percent effect preservation. In this work we evaluate the type I error rates of these approaches to the cross-trial statistical inference for establishing treatment efficacy. The evaluation provides guidance as to what percentage of the control effect needs to be preserved so that through noninferiority testing of effect retention one can assert the treatment efficacy within a desired level of the error rate.
authors.affiliation: Division of Biometrics II, Office of Biostatistics, CDER, FDA, Rockville, MD 20857, USA. wangs@cder.fda.gov
authors.forename: Sue-Jane
authors.initials: SJ
authors.lastname: Wang
authors.forename: H M James
authors.initials: HM
authors.lastname: Hung
mesh_terms: D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D016001:Confidence Intervals; D003627:Data Interpretation, Statistical; D006801:Humans; D012306:Risk