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.
Cheng
Bin
B
Department of Biostatistics, Columbia University, New York, New York 10032, USA. bc2159@columbia.edu
Chow
Shein-Chung
SC
Burt
David
D
Cosmatos
Dennis
D
D000704:Analysis of Variance; D018592:Cross-Over Studies; D015507:Drugs, Investigational / Q000009:adverse effects / Q000493:pharmacokinetics; D004562:Electrocardiography / Q000706:statistics & numerical data*; D017408:Guidelines as Topic; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology; D015233:Models, Statistical; D016011:Normal Distribution; D011897:Random Allocation; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012107:Research Design / Q000706:statistics & numerical data*; D018401:Sample Size
D015507:Drugs, Investigational