title: An efficient analysis of covariance model for crossover thorough QT studies with period-specific baseline days.
abstract: Baseline adjustment is an important consideration in thorough QT studies for nonantiarrhythmic drugs. For crossover studies with period-specific baseline days, we propose an analysis of covariance model with change from time-matched baseline as response, time-matched baseline for the current treatment, day-averaged baseline for the current treatment, time-matched baseline averaged across treatments, and day-averaged baseline averaged across treatments as covariates. This model adjusts for within-subject diurnal effects for each treatment and is more efficient than commonly used models for treatment comparisons. We illustrate the benefit using real clinical trial data.
authors.affiliation: Biostatistics, Forest Laboratories, Inc., Jersey City, NJ, USA. kaifeng.lu@frx.com
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Lu
mesh_terms: D000704:Analysis of Variance; D002940:Circadian Rhythm; D002986:Clinical Trials as Topic / Q000379:methods*; D018592:Cross-Over Studies; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D015233:Models, Statistical; D013997:Time Factors
keywords: day-averaged baseline; diurnal effect; efficiency; time-matched baseline