ICH E14/S7B问答:QT间期延长和致心律失常潜在作用综合风险评估的新策略及其挑战

New strategies and challenges raised by ICH E14/S7B Q&As:Integrated risk assessment of QT/QTc interval prolongation and proarrhythmic potential

随着致心律失常机制研究的深入、非临床研究试验技术的发展和临床回顾性分析数据的积累,采用经验证的非临床研究方法进行心血管安全药理学评价,并增加其在风险评估中的权重,减少低风险药物进行不必要的临床全面QT/QTc研究等整体研究策略逐渐成熟。本文主要介绍了国际人用药品注册技术协调会E14/S7B问答(Q&A)中新增或修订的内容,包括明确用于综合风险评估的试验要求和不同情况下低风险药物的定义,鼓励致心律失常模型的验证和应用等,并结合国内指导原则的实施现状,对整体试验策略带来的挑战进行了分析。

With the progressing research on the mechanism of arrhythmia,the continuous accumulation of nonclinical toxicity testing methods and clinical retrospective data,the overall cardiovascular system safety evaluation strategies become mature now.The main updated contents of International Council for Harmonisation of technical requirements for pharmaceuticals for human use(ICH)E14/S7 B Q&A intended to increase the weight of nonclinical data in proarrhythmic evaluation,to reduce the unnecessary thorough QT research.This article firstly introduced the contents of ICH E14/S7 B Q&A,including testing requirements for integrated risk assessment and the definition of low risk drugs in different situations,encouraged qualification and application of proarrhythmia models,discussed the challenges from integrated risk assessment or the overall cardiovascular system safety evaluation strategies based on the domestic research status.