A Brief Report on Proposed Areas of International Harmonization of Real-World Evidence Relevance, Reliability and Quality Standards Among Medical Product Regulators

Background: International harmonization of real-world data and evidence (RWD/E) standards is a goal among real-world data/real-world evidence (RWD/E) policy stakeholders. The Duke-Robert J. Margolis Institute for Health Policy developed an online 'International Harmonization of RWE Standards Dashboard' to provide timely updates around these goals.

Methods: Guidance for industry (draft and final) and related literature available online by medical product regulators globally was sought and, where needed, translated into English language using a certified translator. Consultations were then held with practicing experts to identify, collate, and interpret documents. An online Tableau tool was assembled to collate guidance documents and regulatory definitions of the following key terms used among the community to describe fit-for-use RWE in regulatory submissions: relevance, reliability, and quality.

Results: As of February 2025, the United States Food and Drug Administration (FDA) has released the most RWE guidance documents to date (n = 13; 4 draft, 9 final). Four (4) regulators globally (US FDA, EMA, Taiwan FDA, Brazil ANVISA) have directly defined at least two (2) out of the three key terms (reliability, relevance, quality), indicating alignment around the importance of these terms used in the context of RWD/E. Across these terms, we propose areas of definitional alignment: data representativeness and research and regulatory concern (relevance), accuracy in data interpretation and quality and integrity during data accrual (reliability), and data quality assurance across sites and time (quality). We propose areas of definitional misalignment regarding clinical context, data availability and representativeness, and ensuring study sample sizes and/or datasets are adequate to address a given study question.

Conclusions: Our assessment of definitions provided among these four regulators lends us to propose distinct areas for harmonization based on our assessment of where regulators appear to align and highlight opportunities to address misalignment.