RWE Submission for European Regulators and Payers: Challenges, Uncertainties, and Opportunities

The new European Union Joint Clinical Assessment (JCA) process, effective January 2025, requires pharmaceutical companies to submit evidence within 100 days of notification. Key challenges include uncertainty about PICO (Population, Intervention, Comparator, Outcomes) parameters prior to PICO notification, limited timeframe for evidence generation, and need to reconcile differences between regulatory versus health technology assessment (HTA) evidence standards. Uncertainties involve predicting PICOs accurately and determining real-world evidence's (RWE) appropriate role. However, opportunities exist for integrated evidence planning across clinical development, regulatory, and health economics and outcomes research (HEOR) teams, leveraging real-world data to inform or address PICOs as well as support regulatory evidence requirements. Early alignment between key functional teams, combined with proactive RWE use, is essential for generating fit-for-purpose evidence that satisfies the dual scrutiny of regulatory approval and HTA relative effectiveness assessment.