• Mark A Gamalo, Rui Wu, and Ram C Tiwari.
• Office of Biostatistics, Food and Drug Administration, Silver Spring 20993-0002, USA. Mark.Gamalo@fda.hhs.gov
• J Biopharm Stat. 2011 Sep 1; 21 (5): 902-19.

AbstractNoninferiority trials are unique because they are dependent upon historical information in order to make meaningful interpretation of their results. Hence, a direct application of the Bayesian paradigm in sequential learning becomes apparently useful in the analysis. This paper describes a Bayesian procedure for testing noninferiority in two-arm studies with a binary primary endpoint that allows the incorporation of historical data on an active control via the use of informative priors. In particular, the posteriors of the response in historical trials are assumed as priors for its corresponding parameters in the current trial, where that treatment serves as the active control. The Bayesian procedure includes a fully Bayesian method and two normal approximation methods on the prior and/or on the posterior distributions. Then a common Bayesian decision criterion is used but with two prespecified cutoff levels, one for the approximation methods and the other for the fully Bayesian method, to determine whether the experimental treatment is noninferior to the active control. This criterion is evaluated and compared with the frequentist method using simulation studies in keeping with regulatory framework that new methods must protect type I error and arrive at a similar conclusion with existing standard strategies. Results show that both methods arrive at comparable conclusions of noninferiority when applied to a modified real data set. The advantage of the proposed Bayesian approach lies in its ability to provide posterior probabilities for effect sizes of the experimental treatment over the active control.

26 keywords...

hide…