Khawaja A, Petrovic R, Safer A, Baas T, Dössel O, Fischer R
Biosigna GmbH, Munich, Germany.
Comput Cardiol (2010). 2010;37:349-352.
Following the ICH E14 clinical evaluation guideline [1], the measurement of QT/QTc interval prolongation has become the standard surrogate biomarker for cardiac drug safety assessment and the faith of a drug development. In Thorough QT (TQT) study, a so-called positive control is employed to assess the ability of this study to detect the endpoint of interest, i.e. the QT prolongation by about five milliseconds. In other words the lower bound of the one-sided 95% confidence interval (CI) must be above 0 [ms]. Fully automated detection of ECG fiducial points and measurement of the corresponding intervals including QT intervals and RR intervals vary between different computerized algorithms. In this work we demonstrate the ability and reliability of Hannover ECG System (HES(®)) to assess drug effects by detecting QT/QTc prolongation effects that meet the threshold of regulatory concern as mentioned by using THEW database studies namely TQT studies one and two.
根据国际人用药品注册技术协调会（ICH）E14临床评价指南[1]，QT/QTc间期延长的测量已成为心脏药物安全性评估的标准替代生物标志物以及药物研发的关键所在。在全面QT（TQT）研究中，采用所谓的阳性对照来评估该研究检测感兴趣终点的能力，即QT延长约5毫秒。换句话说，单侧95%置信区间（CI）的下限必须高于0[毫秒]。不同的计算机算法对心电图基准点的全自动检测以及包括QT间期和RR间期在内的相应间期的测量存在差异。在这项工作中，我们通过使用THEW数据库研究（即TQT研究一和研究二）来检测达到监管关注阈值的QT/QTc延长效应，从而证明了汉诺威心电图系统（HES(®)）评估药物效应的能力和可靠性。
