Hosmane Balakrishna, Locke Charles, Chiu Yi-Lin
Northern Illinois University, DeKalb, Illinois, USA.
J Biopharm Stat. 2010 May;20(3):615-31. doi: 10.1080/10543400903582026.
We assess the QT effect using an exposure-response model in a "thorough QT/QTc study" with a four-period crossover design in which the treatments are placebo, positive control, higher dose of investigational drug, and therapeutic dose of investigational drug. In the study, QTc interval values and the drug concentrations are obtained for several specified times during treatment. This approach to the assessment of non-inferiority of the higher dose to placebo is an alternative strategy suggested in ICH-E14 guideline (Section 2.2.5) to the intersection-union test.
我们在一项采用四周期交叉设计的“全面QT/QTc研究”中，使用暴露-反应模型评估QT效应，该研究中的治疗药物分别为安慰剂、阳性对照、高剂量研究药物和治疗剂量研究药物。在研究中，在治疗期间的几个特定时间点获取QTc间期值和药物浓度。这种评估高剂量药物相对于安慰剂非劣效性的方法是ICH-E14指南（第2.2.5节）中建议的一种替代策略，用于替代交叉联合检验。
