Presentation (CTI)

OBJECTIVES: To examine the evolving role of real-world evidence (RWE) in the regulatory lifecycle of precision medicine and evaluate its utility in addressing gaps inherent in traditional randomized controlled trials (RCTs), particularly for rare genetic disorders and molecularly defined patient subgroups.
METHODS: A comprehensive review of U.S. Food and Drug Administration (FDA) guidance and recent regulatory milestones was conducted. We analyzed the systemic integration of real-world data (RWD) from diverse sources, including electronic health records (EHRs), insurance claims, and specialized disease registries, across the drug lifecycle. Key applications were assessed, including the use of external control arms for orphan drugs, tumor-agnostic approvals in the oncology field, and large-scale post-market surveillance systems, like the Sentinel Initiative.
RESULTS: RWE has become an essential bridge between experimental efficacy and real-world effectiveness. Analysis of landmark cases (e.g., pembrolizumab, carglumic acid, and ivacaftor) demonstrates that RWE can successfully support initial approvals and indication expansions where RCTs are impractical or unethical. Specifically, disease registries enabled the expansion of therapies to rare genetic disorders by providing longitudinal outcomes. Furthermore, distributed surveillance networks were found to increase the sensitivity of detecting subgroup-specific safety signals in populations typically excluded from clinical trials. However, our review identified critical hurdles in data interoperability, genomic nomenclature standardization, and the mitigation of observational bias that must be addressed to ensure “regulatory-grade” evidence.
CONCLUSIONS: RWE is no longer supplementary but foundational to precision medicine. Transitioning to a hybrid evidentiary standard of proof, wherein RCTs provide internal validity, and RWE provides external generalizability, accelerates patient access to targeted therapies. For Health Economics and Outcomes Research (HEOR) stakeholders, these findings emphasize the need for robust data governance and standardized analytical frameworks to realize the full potential of genetically guided healthcare.