A landscape review of real-world data sources in the United States for healthcare decision-making

Abstract Objectives Following the FDA’s 2018 Real-World Evidence (RWE) framework, US real-world data (RWD) availability has surged. This landscape review systematically evaluates current US RWD sources and their utility for real-world evidence to support healthcare decision-making. Methods PubMed, Embase, and conference proceedings were searched (2019–2025) for studies utilizing US RWD. Data sources were evaluated for representation, relevance, longitudinality, and clinical depth. RESULTS 346 distinct RWDs met the inclusion criteria. Registry ( n = 125) was the most common source of RWD, followed by electronic medical records (+/- claims) ( n = 86), and claims only ( n = 66). Most registries were specific to cardiometabolic and oncology. EMRs were mostly disease-agnostic originating primarily in health systems and EMR providers. Claims primarily originated from the public or private single/multiple payers. Most RWDs had limited information on laboratory, genomic, patient-reported outcomes, imaging, and social determinants of health. Most had a data lag time of 3–6 months with varying acquisition costs and access logistic issues. Conclusions This review summarizes information on existing US RWDs, with their key features for selecting fit-for-purpose RWD to support regulatory and healthcare decision-making. Despite a vast RWD inventory, clinical richness and patient-centricity remain limited. The US ecosystem’s fragmentation necessitates enhanced data linkage and the leverage of AI/technology to unlock unstructured data.