Clinical evaluation of QT/QTc prolongation and proarrhythmic potential for nonantiarrhythmic drugs: The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use E14 Guideline
Clinical evaluation of QT/QTc prolongation and proarrhythmic potential for nonantiarrhythmic drugs: The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use E14 Guideline
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DOI：
10.1177/0091270006286436
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发表时间：
2006-05-01
影响因子：
2.9
通讯作者：
T Sager, P
中科院分区：
文献类型：
--
作者：
Darpo, B;Nebout, T;T Sager, P
药物诱导的QT间期延长导致的心律失常是停药的第二大常见原因，并引起了越来越多的关注。两个新的人用药品注册技术要求国际协调会议（ICH）指南最近获得批准，其中讨论了非临床（S7B）和临床（E14）方法，并为行业提供指导。本评论描述了E14文件的关键组成部分、非临床试验对临床项目的影响、全面QT研究及其结果对后期开发的影响。S7B和E14中描述的研究将有助于更好地理解非临床试验与人体QT间期延长之间的联系。主要地区个别监管机构之间的解释差异。关于E14指南中提出的措施的问题可能会影响区域监管决定。这些差异包括非临床试验对后续临床试验的价值，以及阴性的全面QT研究结果对患者心律失常风险的预测性。
Proarrhythmias due to drug-induced QT prolongation are the second most common cause for drug withdrawal and have caused increasing concern. Two new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines were recently endorsed in which nonclinical (S7B) and clinical (E14) methodologies are discussed and guidance is given to the industry. This commentary describes the key components of the E14 document, the impact of nonclinical testing on the clinical program, the thorough QT study, and the impact of its result on latestage development. The studies described in S7B and E14 will contribute to a better understanding of the link between nonclinical assays and QT prolongation in humans. Differences in interpretation among individual regulators in the major regp. ons with respect to measures proposed in the E14 guideline might impact regional regulatory decisions. These differences include the value of nonclinical assays for the subsequent clinical testing and how predictive a negative thorough QT study result is for proorrhythinic risk in patients.