Statistical assessment of QT/QTc prolongation based on maximum of correlated normal random variables.

To establish noninferiority in QT/QTc prolongation of a test drug with respect to either a placebo or an active control, a thorough QT/QTc study is recommended by ICH (ICH E14, ICH 2005) which concerns statistical inference on the maximal time-matched drug effect. The existing statistical methods for assessing such effects suffer either power loss or parameter restriction. In this paper, we propose a new asymptotic test with small sample correction based on distribution of maximum of correlated random variables under both a parallel-group design and a crossover design. Simulations indicate that our proposed test has adequate powers.

Duke Scholars

Author Shein-Chung Chow Biostatistics & Bioinformatics, Division of Biostatistics