Intelligent ECG

Beginning in the late 1980s, a number of non-cardiac drugs have been linked to an increased risk of adverse cardiac events. Since late 2005, regulators require that all new drugs go through ECG-based cardiac safety testing (1). Prolongation of the QT interval on surface ECG is currently used as a surrogate marker of risk for the potentially lethal druginduced arrhythmia, torsades de pointes. The studies performed according to this guidance have been termed ‘Thorough QT’ (TQT) studies. A ‘positive TQT’ study means that the drug was found to prolong the QT interval in excess of the threshold for regulatory concern (upper 95 per cent confidence bound exceeding 10 msec).

Looking at the cardiac safety environment three years after the E14 guidance, it has become clear that, while some issues have been addressed, a new set of challenges has emerged. Greater focus from regulators and sponsors on cardiac safety is, undoubtedly, a good thing. The guidance has lead to the standardisation of ECG data collection and assessment in clinical trials, as well as to greater use of digital technologies. The FDA ECG warehouse now contains millions of ECGs collected from clinical development programmes, and it has become a foundation for ongoing FDA-academia-industry collaboration around advanced ECG analysis technology development and validation. Some breakthrough technologies have emerged from these efforts and are discussed in this article.