Baseline Adjustment in Thorough QT Studies

• Activity Number: 67
• Type: Topic Contributed
• Date/Time: Sunday, August 4, 2013 : 4:00 PM to 5:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Kaifeng Lu*+
• Companies: Forest Laboratories
• Keywords: Time-matched baseline ; Day-averaged baseline ; Pre-dose baseline ; Efficiency

Abstract

Baseline adjustment is an important consideration in thorough QT (TQT) studies for non-antiarrhythmic drugs. For parallel-group TQT studies, we recommend an analysis of covariance (ANCOVA) model with change from time-matched baseline as response, time-matched baseline and day-averaged baseline as covariates. For crossover TQT studies with period-specific baseline days, we recommend an ANCOVA model with change from time-matched baseline as response, time-matched baseline for the current period, day-averaged baseline for the current period, time-matched baseline averaged across periods, and day-averaged baseline averaged across periods as covariates. For crossover TQT studies with period-specific pre-dose baselines, we recommend an ANCOVA model with change from pre-dose baseline as response, pre-dose baseline for the current period, and pre-dose baseline averaged across periods as covariates. These models are more efficient than commonly used models.