Advancing model-informed assessment of QT prolongation in drug development

How model-informed approaches are used to assess QT prolongation during medicine development matters. Published in the Journal of Pharmacokinetics and Pharmacodynamics, the article, “Model informed assessment of QT prolongation during drug development: a five-year retrospective analysis of EMA scientific advices”, reviews five years of European Medicines Agency (EMA) Scientific Advice to examine how concentration-QT (C-QT) modelling has been considered in regulatory discussions.

C-QT modelling has been recognised as an alternative to dedicated Thorough QT (TQT) studies, offering potential ethical and practical advantages in the assessment of cardiac safety. Its authors have reviewed EMA Scientific Advice documents issued between January 2020 and January 2025, examining discussions related to QT prolongation and the factors considered when assessing requests for TQT waivers. As a result, the analysis identifies 110 QT-related requests, 81% of which sought TQT waivers, most supported by C-QT modelling. While the majority of these requests received supportive feedback, the review also identifies recurring areas which require further attention, including exposure justification, study design, data availability, and methodological reporting. These results provide a practical perspective on the factors that can influence regulatory confidence in model-informed QT assessments.

For ERAMET, the study offers valuable insights into the role of innovative methodologies in regulatory science. By examining how C-QT modelling has been considered in regulatory practice over a five-year period, it identifies areas where greater methodological consistency and clearer reporting could support its broader and more reliable use. These findings reflect ERAMET’s commitment to promoting transparent and robust modelling practices that can improve the quality of evidence underpinning medicine development and build confidence in model-informed QT risk assessment.

Explore the full study and its insights here!