title: Comparison of statistical models adjusting for baseline in the analysis of parallel-group thorough QT/QTc studies.
abstract: The ICH E14 guidance recommends the use of a time-matched baseline, while others recommend alternative baseline definitions including a day-averaged baseline. In this article we consider six models adjusting for baselines. We derive the explicit covariances and compare their power under various conditions. Simulation results are provided. We conclude that type I error rates are controlled. However, one model outperforms the others on statistical power under certain conditions. In general, the analysis of covariance (ANCOVA) model using a day-averaged baseline is preferred. If the time-matched baseline has to be used as per requests from regulatory agencies, the analysis by time point using ANCOVA model should be recommended.
authors.affiliation: Biostatistics and Programming, Celgene Corporation, Summit, NJ, USA. gsun@celgene.com
authors.forename: Guowen Gordon
authors.initials: GG
authors.lastname: Sun
authors.forename: Hui
authors.initials: H
authors.lastname: Quan
authors.forename: Robert
authors.initials: R
authors.lastname: Kringle
authors.forename: Zhaoling
authors.initials: Z
authors.lastname: Meng
mesh_terms: D000704:Analysis of Variance; D017408:Guidelines as Topic; D006801:Humans; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*