Real-World Evidence in Pharmaceutical Regulation: Administrative and Policy Challenges in Post-Market Drug Safety Surveillance

Background: Pharmaceutical regulators in the United States, Canada, and the European Union have moved real-world evidence (RWE) drawn from electronic health records, administrative claims, and patient registries from a peripheral analytical tool to a structural feature of postmarket drug safety surveillance. Foundational guidance issued by the FDA, Health Canada, and the European Medicines Agency between 2019 and 2025 has established RWE as a settled regulatory expectation. Yet implementation across health systems remains uneven, and the burden of integration falls on healthcare administrators who lack a consolidated framework for thinking through what that integration requires.Argument: This paper offers an original four-challenges analytical framework for healthcare administrators navigating regulatory RWE integration: data governance fragmentation across jurisdictions, gaps in health information technology infrastructure required for regulatory-grade analytics, workforce capacity deficits in pharmacoepidemiology and health informatics, and the layered privacy compliance burden created by HIPAA, U.S. state-level statutes, provincial Canadian frameworks, the General Data Protection Regulation, and the European Health Data Space Regulation. Drawing on cross-jurisdictional regulatory synthesis spanning the FDA Sentinel System, the OMOP Common Data Model, the joint CADTH and Health Canada Guidance for Reporting Real-World Evidence, and the EMA RWE framework, the paper argues that successful RWE integration is not primarily a technical problem but a leadership and governance problem.Implications: Healthcare administrators must address all four challenges simultaneously rather than sequentially. Practical responses include embedding biostatisticians and health informatics specialists within regulatory affairs teams, partnering with academic pharmacoepidemiology programs, aligning institutional data practices with national reporting frameworks, investing in interoperability infrastructure that meets ASTP/ONC certification standards, and designing governance mechanisms that reconcile layered privacy obligations while preserving the data access that pharmacovigilance research requires. Health systems that adopt these practices position themselves to participate in federally coordinated drug safety surveillance; those that do not risk operational marginalization within an increasingly evidence-driven regulatory environment