药物临床试验中QT/QTc间期的医学判断、安全认定与风险管理OA

Objective To summarize practical points for medical judgment,safety assessment and risk management of QT interval/corrected QT interval(QT/QTc)abnormalities in drug clinical trials,and to provide a reference for phase Ⅰ wards and clinical trial centers.Methods Based on the Questions & Answers:Clinical and Nonclinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential(ICH E14/S7B Q&As),electrocardiographic interpretation recomme-ndations,expert consensus on monitoring and risk assessment of QT prolongation,the Common Terminology Criteria for Adverse Events version 5.0(CTCAE v5.0),recent advances in concentration-QTc(C-QTc)analysis and the experience of our clinical trial center,key steps were summarized in terms of value verification,threshold interpretation,causality assessment,dosing decision-making and safety reporting.Results QT/QTc abnormalities should first be confirmed by reviewing acquisition quality,measurement method and protocol-specified correction formula,and by distinguishing automated readings from medically adjudicated values used for eligibility and safety evaluation.Safety assessment should then integrate baseline change,symptoms,arrhythmia,drug exposure,concomitant medications,electrolytes and central ECG reading.QTc＞500 ms,ΔQTc＞60 ms,torsade de pointes or sustained ventricular tachycardia should trigger repeat ECG,dose interruption or delay,medical intervention,AE/SAE evaluation and follow-up documentation.Conclusion Transforming QT/QTc evaluation from isolated threshold interpretation into a closed-loop process of confirmation,risk stratification,causality assessment and management can improve participant protection and the quality of cardiac safety data in clinical trials.