Series: Pragmatic trials and real world evidence: Paper 7. Safety, quality and monitoring.

Objective Pragmatic trials offer the opportunity to obtain real-life data on the relative effectiveness and safety of a treatment before or after market authorization. This is the penultimate paper in a series of eight, describing the impact of design choices on the practical implementation of pragmatic trials. Study Design and Setting This paper focuses on the practical challenges of collecting and reporting safety data and of monitoring trial conduct while maintaining routine clinical care practice. Conclusion Current ICH guidance recommends that all serious adverse events and all drug-related events must be reported in an interventional trial. In line with current guidance, we propose a risk-based approach to the collection of non–drug-related non–serious adverse events and even serious events not related to treatment based on the risk profile of the medicine/class in the patient population of interest. Different options available to support the collection and reporting of safety data while minimizing study-related follow-up visits are discussed. A risk-based approach to monitoring trial conduct is also discussed, highlighting the difference in the balance of risks likely to occur in a pragmatic trial compared to traditional clinical trials and the careful consideration that must be given to the mitigation and management of these risks to maintain routine care.