Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993-0002, USA.
Am Heart J. 2012 Jun;163(6):912-30. doi: 10.1016/j.ahj.2012.02.023. Epub 2012 May 4.
This White Paper, written collaboratively by members of the Cardiac Safety Research Consortium from academia, industry, and regulatory agencies, discusses different methods to characterize the QT effects for drugs that have a substantial direct or indirect effect on heart rate. Descriptions and applications are provided for individualized QT-R-R correction, Holter bin, dynamic QT beat-to-beat, pharmacokinetic-pharmacodynamic modeling, and QT assessment at constant heart rate. Most of these techniques are optimally performed using continuous electrocardiogram data obtained in clinical studies designed to characterize a drug's effect on the QT interval. An important study design element is the collection of drug-free data over a range of heart rates seen on treatment. The range of heart rates is increased at baseline by using ambulatory electrocardiogram recordings in addition to those collected under semisupine, resting conditions. Discussions in this study summarize areas of emerging consensus and other areas in which consensus remains elusive and provide suggestions for additional research to further increase our knowledge and understanding of this topic.
本白皮书由来自学术界、工业界和监管机构的心脏安全研究联盟成员共同撰写，讨论了不同方法来描述对心率有显著直接或间接影响的药物的 QT 效应。为个体 QT-R-R 校正、动态 Holter -bin、动态 QT 逐拍、药代动力学-药效学建模和恒速心率下的 QT 评估提供了描述和应用。这些技术中的大多数都需要使用在设计用于描述药物对 QT 间期影响的临床研究中获得的连续心电图数据来进行最佳操作。一个重要的研究设计元素是在治疗期间收集在药物作用下观察到的一系列心率范围内的无药物数据。通过在半卧位休息条件下收集心电图数据之外，还使用动态心电图记录来增加基线时的心率范围。本研究中的讨论总结了一些领域已经达成共识，而在其他领域仍未达成共识，并提出了进一步研究的建议，以进一步增加我们对这一主题的知识和理解。
