Causality Assessment of Adverse Events in paediatric trials

The PedCRIN tool on causality assessment of adverse events provides practical guidance to support consistent and informed evaluation of safety events in paediatric clinical trials. The tool addresses the challenges associated with determining whether an adverse event is caused by the investigational medicinal product, the underlying disease, concomitant treatments or other clinical factors. It aims to improve the quality and consistency of safety assessments by supporting investigators and trial teams in applying structured approaches to causality evaluation.

Causality assessment is particularly challenging in paediatric research because children differ from adults in disease presentation, physiology, treatment response and patterns of adverse events. The interpretation of safety signals requires consideration of developmental stage, age-related risks and background disease characteristics. The tool helps researchers account for these factors when evaluating adverse events and making decisions related to safety reporting and risk management.

This resource is especially relevant for rare disease clinical trials, where safety evaluation is often affected by small sample sizes, limited prior exposure to treatments, heterogeneous clinical presentations and uncertainty regarding the expected course of the disease. In many rare diseases, symptoms of disease progression may overlap with potential adverse reactions, making accurate attribution of events essential for reliable benefit–risk assessment. Consistent causality assessment approaches can therefore improve the quality of safety data generated during trials and support regulatory decision-making.

Although developed within the European PedCRIN framework, the principles described are broadly applicable internationally to paediatric and rare disease clinical trials. The tool provides practical support for investigators, sponsors and safety monitoring teams seeking to improve the reliability and interpretation of safety information in vulnerable and data-limited populations.