Electrocardiography and repolarization abnormalities in cardiac safety: Benefits and limitations of fully automated methods for QT measurement

During early phase drug safety trials in humans, prolongation of the rate-corrected QT interval has become a surrogate marker for heterogeneity of ventricular repolarization that can cause potentially fatal arrhythmic events. “Thorough QT” studies have been designed to test for clinically significant QT prolongation by new drugs, with “positive controls” used to assess sensitivity of the method Measurement of the QT interval may be done manually, automatically, or by adjudication of selected automated samples. Automated measurement of QT is improving, but in the absence of a universally accepted ECG definition of the end of the T wave, QT measurements have become proprietary engineering solutions that differ among ECG core labs and among algorithm developers. Alternative measures of repolarization beyond QT interval alone might further increase the benefit of fully automated ECG algorithms in drug safety testing.