Less than 15 years ago the CPMP released a points-to-consider memorandum describing steps to be taken to study the ventricular repolarization liability on the 12-lead ECG. Since that time, many steps have been undertaken by regulatory bodies and the industry (ICH S7A, S7B, and ICHE14 Guidance) as a whole to ensure that drugs that make it to market are safe and without ventricular repolarization liabilities as seen on the surface ECG, as evidenced by a prolongation of the QT interval. Despite these key steps on assessment of the risk of cardiac arrhythmias, drugs such as Vioxx and Avandia have shown a propensity for cardiac toxicity outside the risk of torsades de pointes. It is now realized that cardiac safety involves more than just measuring the QT interval on the surface ECG. This article reviews, briefly, the current state of affairs in the area of cardiac safety in the world of drug development.
Applied Clinical Trials, Oct 1, 2011