Real-world evidence and the regulators

Regulators in Europe and the United States have come to weigh real-world evidence in their decisions, and a study built on data from routine care serves such a decision only when it is presented so that a regulator can judge it. This branch covers that meeting point, and its parts divide by whose side of it the work stands on: the European Medicines Agency's programme, the FDA's programme, and the sponsor's presentation of a real-world study to a regulator. It leaves what real-world evidence is, where its data come from, and how it is analysed and written up for other readers to the rest of real-world evidence; real-world elements inside an interventional trial to clinical trial design; and the European regulatory network and its strategies as a whole to the regulatory framework for medicines.

• Real-world evidence at the European Medicines Agency — why the agency took up real-world evidence, the three pillars of the OPTIMAL framework and the pathways for generating evidence, the Big Data Task Force and the Big Data Steering Group with its workplans, DARWIN EU and its data partners, the catalogues of real-world data sources and studies, guidance, scientific advice and analysis, where the evidence has been used, international collaboration, and the obstacles of harmonisation, privacy and heterogeneity with the directions set for the work ahead
• Real-world evidence at the FDA — its origins in post-market safety monitoring with PDUFA III and Sentinel, the 21st Century Cures Act and the move to effectiveness, the guidance documents by what each covers, the Center for Real-World Evidence Innovation, and the labelling and approval decisions on methotrexate, the fluoroquinolones, Ibrance and Prograf that rested on real-world evidence
• Communicating real-world evidence to a regulator — why regulators began accepting evidence from routine practice, framing the case against the substantial evidence of effectiveness an approval needs, what the objectives and the study design have to say, knowing the data source behind the study, and the RIGOR checklist for showing the data are fit for purpose