Project description:  

Cardiovascular safety events have become the second most common cause of post-market drug withdrawal.   QT-prolongation has been said to be the cause of cardiac adverse events in certain post-market scenarios after drugs have been through stringent clinical development.  As a result, regulatory bodies have mandated the inclusion of the thorough-QT (TQT) trial as part of the drug development process with strict trial setting criteria, analysis and interpretation guidelines. Currently, efforts are being made to develop a model-based framework for the evaluation of concentration – QTc prolongation relationship for novel compounds.  The framework includes the prediction of the probability for increased QTc-interval in humans under controlled clinical trials and in real-life scenarios. Furthermore, opportunities for study design optimisation are being explored using clinical trial simulations. Clinical data on reference compounds with known effect on QTc-interval (positive and negative controls) are available for this research.