Draft ICH guideline S7B: Guideline on safety pharmacology studies for assessing the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals

Abstract

Nonclinical assessment of potential of QT interval prolongation caused by non-antiarrhythmic drugs has been an issue for drug development because QT interval prolongation increases the risk of ventricular tachyarrhythmia, including torsade de pointes when combined with other risk factors. However, there is no scientific consensus on approaches and no international consensus on regulatory recommendations. This guideline is being developed to provide the general nonclinical testing strategy for evaluating the potential risk of QT prolongation and presents some major principles for in vitro and in vivo electrophysiology studies. The basis of this guideline is the integrated risk assessment that provides overall evaluations based on nonclinical study results and chemical/pharmacological class information to predict the potential of a test substance to prolong QT interval in humans (i.e., evidence of risk) and that contributes clinical study design and interpretation of clinical results. Safety margins are also components of integrated risk assessment. Since this guideline addresses a field of research that is in a state of rapid evolution, the proposed concept for evidence of risk and safety margins needs to be further refined based on the data being collected by international initiatives. In this article, the draft S7B guideline is outlined.