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Updated: May 18, 2026

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
Published on: February 11, 2019
An efficient and robust analysis of covariance model for baseline adjustment in parallel-group thorough QT/QTc
1Forest Laboratories, Harborside Financial Center Plaza V, Jersey City, NJ 07311, USA. kaifeng.lu@frx.com
Abstract:
Baseline adjustment is an important consideration in thorough QT/QTc studies for non-antiarrhythmic drugs. The time-matched baseline is often used in practice to adjust for the within-subject diurnal effects. More recently, the day-averaged baseline has been proposed in the literature to improve the efficiency of treatment comparisons for the primary and assay sensitivity hypotheses. We recommend an analysis of covariance (ANCOVA) model with change from the time-matched baseline as the response and both the time-matched baseline and the day-averaged baseline as the covariates. This model adjusts for the within-subject diurnal effects and at the same time is more efficient and robust than the ANCOVA models based on either the time-matched baseline alone or the day-averaged baseline alone.
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