Optimal Sample Size Allocation in a Thorough QTc Study

Abstract

It is important to calculate the proper sample size for a thorough QTc study to ensure adequate study power without enrolling unnecessary subjects. In current practice, at least two tasks need to be performed to rule out clinically relevant QT liability of the study drug: (a) demonstrate that the largest 90% two-sided upper confidence bound for the baseline-adjusted mean differences between the study drug and the placebo is less than 10 ms; and (b) establish assay sensitivity of the study. Traditionally, the sample size is determined by the primary task (a), and then subjects are equally assigned into each treatment arm. This practice might not be the most appropriate method. In this article, an optimal sample size allocation scheme is introduced and discussed.