Recently, the U.S. Food and Drug Administration (FDA) issued a guidance document entitled Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices. The guidance outlines the FDA’s current thinking on how real-world evidence (RWE) and real-world data (RWD) may be used to support regulatory decisions across the medical device total-product life cycle, as well as provides important considerations for manufacturers seeking to rely on RWE and RWD in regulatory submissions.
The guidance defines RWD as data relating to patient health status and/or healthcare delivery that are routinely collected outside traditional clinical trials. RWD is collected from sources such as electronic health records, medical device registries, and administrative claims data. It may potentially be applicable to premarket submissions, including 510(k)s, De Novo requests, and Premarket Approval applications. It may also facilitate the timely completion of postmarket requirements, post-approval studies, and labeling changes.
The guidance does not impose binding requirements but reflects the FDA’s current, nonbinding recommendations.
Key Principles for Use of RWE
The FDA emphasizes that RWE may be appropriate to support regulatory decision-making when the underlying RWD is both relevant and reliable for the particular study question and regulatory purpose. Relevance requires that the data appropriately address the intended regulatory purpose, while reliability depends on data quality, completeness, consistency, traceability, and the robustness of data collection and analytical methods. Sponsors are expected to demonstrate how these criteria are met in their submissions.
According to the guidance, RWE may be used to supplement or, in certain circumstances, partially replace traditional clinical evidence when adequately justified. The FDA identifies multiple potential applications for use of RWD in regulatory submissions, including, to generate hypotheses to be tested in a clinical study, as a historical control, as a concurrent control group or as a mechanism for collecting data to support marketing authorization when a registry, EHR, claims data, or some other systematic data collection mechanism exists, to generate (primary) clinical evidence to support marketing authorization, to generate evidence for postmarket surveillance activities, and to conduct post-approval studies that are imposed as a condition of device approval, among others.
Benefits and Limitations
FDA acknowledges that RWE can offer advantages over traditional clinical trials by capturing broader clinical experiences than are usually represented in traditional clinical studies, and reducing time and cost burdens associated with evidence generation. However, the FDA also cautions that RWD sources may vary significantly in quality and may be subject to bias, missing data, and confounding, particularly in nonrandomized settings. Robust study design and analytical rigor are therefore critical to the acceptability of RWE.
Key Takeaways
The guidance encourages early engagement with the FDA to discuss proposed RWD sources, study designs, and analytical plans. Manufacturers should develop clear protocols describing data collection, management, and analysis, and should thoroughly document assessment of data relevance and reliability. Attention to data governance, privacy, and security is also essential when using patient-level information.
The guidance underscores the FDA’s increasing openness to the use of RWE, while reaffirming the FDA’s expectation that such evidence meet appropriate scientific and methodological standards. Manufacturers should consider integrating RWD and RWE strategies early in product development and regulatory planning to take advantage of the flexibility described in the guidance.