title: Sample size calculation for thorough QT/QTc study considering various factors related to multiple time points.
abstract: 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.
authors.affiliation: Biostatistics and Programming, Sanofi-Aventis, Bridgewater, New Jersey, USA. zhaoling.meng@sanofi-aventis.com
authors.forename: Zhaoling
authors.initials: Z
authors.lastname: Meng
authors.forename: Robert
authors.initials: R
authors.lastname: Kringle
authors.forename: Xun
authors.initials: X
authors.lastname: Chen
authors.forename: Peng-Liang
authors.initials: PL
authors.lastname: Zhao
mesh_terms: 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