An efficient analysis of covariance model for crossover thorough QT studies with period‐specific pre‐dose baselines
An efficient analysis of covariance model for crossover thorough QT studies with period‐specific pre‐dose baselines
复制标题
对交叉彻底 QT 研究与特定时期给药前基线的协方差模型进行有效分析
作者：
K. Lu
基线调整是对非抗心律失常药物进行全面QT研究的重要考虑因素。对于具有阶段特异性给药前基线的交叉研究，我们提出了按时间点分析的协方差模型，其中较给药前基线的变化作为响应，治疗作为固定效应，当前治疗的给药前基线和治疗间平均给药前基线作为协变量，受试者作为随机效应。模型中应酌情纳入其他因素，如周期和性别。可对多个给药前测量值取平均值，以获得给药前平均基线并用于模型。我们提供的条件下，所提出的模型是比其他模型更有效。我们证明了所提出的模型的效率和鲁棒性分析，并通过仿真研究。所提出的模型的优点也说明了使用从一个真实的临床试验的数据。版权所有© 2014约翰威利父子有限公司.
Baseline adjustment is an important consideration in thorough QT studies for non‐antiarrhythmic drugs. For crossover studies with period‐specific pre‐dose baselines, we propose a by‐time‐point analysis of covariance model with change from pre‐dose baseline as response, treatment as a fixed effect, pre‐dose baseline for current treatment and pre‐dose baseline averaged across treatments as covariates, and subject as a random effect. Additional factors such as period and sex should be included in the model as appropriate. Multiple pre‐dose measurements can be averaged to obtain a pre‐dose‐averaged baseline and used in the model. We provide conditions under which the proposed model is more efficient than other models. We demonstrate the efficiency and robustness of the proposed model both analytically and through simulation studies. The advantage of the proposed model is also illustrated using the data from a real clinical trial. Copyright © 2014 John Wiley & Sons, Ltd.