Sample size calculation for thorough QT/QTc study considering various factors related to multiple time points.
The sample size requirement in a thorough QT/QTc study is discussed under a balanced parallel or crossover study design. First, we explore the impacts of various factors on the study power, including the mean effect profile across time and correlation among time points. Then we estimate the variability parameters needed based on multiple historical studies. Different baseline usage is illustrated to have a significant impact on the analysis variability in the parallel studies. Finally, the sample size calculations and recommendations are given for demonstrating a "negative" drug effect and the study assay sensitivity, respectively.
Meng
Zhaoling
Z
Biostatistics and Programming, Sanofi-Aventis, Bridgewater, New Jersey, USA. zhaoling.meng@sanofi-aventis.com
Kringle
Robert
R
Chen
Xun
X
Zhao
Peng-Liang
PL
D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D002940:Circadian Rhythm; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D004562:Electrocardiography / Q000706:statistics & numerical data; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D015233:Models, Statistical; D018401:Sample Size; D013997:Time Factors