A novel Bayesian approach to analyzing ‘Thorough QT/QTc Study’

The ICH E14 guidelines recommend performing a ‘thorough QT/QTc study’ to support the safety profile of a drug. The standard way of analyzing a ‘thorough QT/QTc study’ to assess a drug for its potential for QT prolongation is to construct a 90% two-sided (or a 95% one-sided) confidence interval (CI), for the difference in baseline corrected mean QTc (heart-rate corrected version of QT) between drug and placebo at each time-point, and to conclude non-inferiority if the upper limit for each CI is less than 10 ms. The intent of the ICH E14 guidelines is to establish that the mean effect of the drug is less than 5 ms and the standard approach may not be well suited to achieve this goal. In this paper, we propose a novel Bayesian approach to address this problem directly keeping in line with the intent of the ICH E14 guidelines. We assess the performance of our proposed approach using simulated data, discuss its advantages over the standard approach, and illustrate the method by applying it to a real data set obtained from a GlaxoSmithKline (GSK) conducted thorough QT study.