基于风险的C-QTc研究策略在药物心脏安全性评价中的应用

Risk-based C-QTc research strategy in drug cardiac safety evaluation

目的:探讨在早期药物心脏安全性评价中基于风险浓度-QTc(concentration-QTc,C-QTc)的研究策略。方法:参考ICH-E14全面QT研究(thorough QT study,TQT研究)指南和FDA'白皮书'指导原则,结合既往实际开展TQT研究及C-QTc研究经验,探讨应用C-QTc研究评估药物心脏安全性研究策略。结果:本文探讨了C-QTc研究代替TQT研究对候选药物进行心脏安全性评价的方法,并对C-QTc研究的适用范围、受试人群选择、样本量、剂量设计、组别设计、心电图数据采集、C-QTc模型建立及评价、结果判定及安全预案进行分析及阐述。结论:前期基于风险的充分设计考虑是成功开展以C-QTc模型评价新药心脏安全性的基础,对豁免开展TQT研究具有重要意义。

Objective:To explore the risk-based C-QTc research strategy in early drug cardiac safety evaluation.Methods:With reference to the ICH-E14 guidance of TQT research and FDA'white paper',as well as practical experience of TQT research and C-QTc research,the research strategy of applying C-QTc research to evaluate the cardiac safety of drugs was discussed.Results:The method of conducting a C-QTc study to evaluate the cardiac safety of candidate drugs in order to replace a TQT study was developed.And the application scope,target population,sample size,dosage,collection of ECG data,establishment and evaluation of C-QTc model,determination of the results and safety plan were analyzed and discussed.Conclusion:The Sufficient risk-based design in the early stage are the basis for the successful implementation of the C-QTc model to evaluate the cardiac safety of new drugs.It is great significance for the exemption from conducting a TQT study.