This preprint presents a comparative policy analysis of real-world evidence (RWE) frameworks across major regulatory and health technology assessment (HTA) agencies, including the UK MHRA, European Medicines Agency (EMA), U.S. FDA, CADTH, and other international authorities. While consensus exists on the scientific value of real-world data (RWD), operational expectations for data quality, statistical methodology, and registry governance remain fragmented across jurisdictions. These inconsistencies generate duplication of effort, increased costs, and delays in patient access to innovation. Drawing on a narrative comparative review of twelve global agencies, this paper:• maps areas of convergence and divergence in RWE governance• analyses the operational consequences of fragmented frameworks• evaluates the UK’s evolving post-Brexit role• proposes six pragmatic strategies to accelerate international harmonisation The work aims to support regulators, HTA bodies, policymakers, and industry scientists seeking more efficient, transparent, and decision-ready evidence ecosystems. This manuscript is currently under peer review at a scientific journal. It is shared here as a preprint to facilitate early discussion, transparency, and timely knowledge exchange.