An efficient analysis of covariance model for crossover thorough QT studies with period‐specific baseline days

Abstract

Listen

Translate article

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.