Use of the average baseline versus the time-matched baseline in parallel group thorough QT/QTc studies.
Using historical studies, we compared the impact of using the average baseline or time-matched baseline on diurnal effect correction, treatment effect estimation, and analysis of variance/covariance (ANOVA/ANCOVA) efficiency in a parallel thorough QT/QTc (TQT) study. Under a multivariate normal distribution assumption, we derived conditions for achieving unbiasness and better efficiency when using the average baseline, and confirmed these conditions using historical TQT studies. Furthermore, simulations were conducted under the randomized trial with and without observed imbalanced baseline settings. We conclude that the analyses using average baseline yield better efficiency and unbiased or less biased results under our TQT study conditions.
Meng
Zhaoling
Z
Biostatistics and Programming, Sanofi-Aventis, Bridgewater, New Jersey, USA. zhaoling.meng@sanofiaventis.com
Quan
Hui
H
Fan
Li
L
Kringle
Robert
R
Sun
Gordon
G
D000704:Analysis of Variance; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D015982:Bias; D002940:Circadian Rhythm; D003198:Computer Simulation; 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; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D013997:Time Factors