FDA expands real-world evidence examples used in regulatory decision-making

The US Food and Drug Administration (FDA) has updated its catalogue of real-world evidence (RWE) examples used in regulatory decision-making, adding new cases from across multiple product centers and providing additional insight into how RWE has informed regulatory actions over the past decade.

The Baseline

• The FDA has updated its catalogue of RWE examples, adding new cases and expanding information on how RWE has supported regulatory decision-making since 2011.
• The resource includes examples of RWE use across drug, biologic, and medical device approvals, labeling changes, and postmarketing safety assessments.
• The update highlights the growing role of diverse real-world data sources and study designs in supporting regulatory evaluations and reflects the FDA’s ongoing efforts to provide greater transparency around RWE use.

According to the agency, the resource brings together examples of regulatory decisions made since 2011 in which RWE contributed to product approvals and authorizations, labeling changes, postmarketing safety assessments, and evaluations that ultimately resulted in no regulatory action. The FDA notes that the compilation forms part of “a comprehensive landscape analysis to assess the scope and frequency of RWE use in regulatory determinations across the Agency.”

The latest update builds on the examples first published in September 2025. Alongside new entries from the Center for Devices and Radiological Health (CDRH), the FDA has added more recent examples and expanded information across sections covering Center for Drug Evaluation and Research (CDER) drug approvals and postmarketing studies, CDRH premarket authorizations, and Center for Biologics Evaluation and Research (CBER) biological product approvals and safety-related labeling changes, expanding the information available on how RWE has been used in regulatory decision-making across drugs, biologics, and medical devices.

Collectively, the entries illustrate the wide range of data sources and study designs used to generate RWE for regulatory purposes. Across the resource, the FDA highlights the use of medical records, disease registries, administrative healthcare claims databases, natural history studies, pregnancy registries, public health surveillance systems, and expanded access programs. The examples also span a variety of methodological approaches, including cohort studies, externally controlled trials, case-control studies, descriptive analyses, and randomized controlled trials.

Several examples in the updated resource show how RWE has complemented clinical trial data in regulatory decisions. One is Gamifant (emapalumab-lzsg), for which the FDA considered data from the retrospective AMETHYST cohort study alongside pooled data from two single-arm studies. According to the agency, the RWE provided important context on the disease's natural history and helped support evidence of effectiveness. Similarly, RWE from the Achondroplasia Natural History Study registry was used as an external control for BioMarin's Voxzogo (vosoritide) and combined with clinical trial data to provide confirmatory evidence for approval.

The resource also includes examples of RWE use in medical device evaluations. For example, the 23andMe Personal Genome Service relied on published studies using medical records, registries, and clinically annotated biobanks to demonstrate links between genetic variants and health conditions. Clearance of APPRAISE-HRI, a device designed to assess hemorrhage risk, was supported by a retrospective validation study using vital-sign and trauma registry data.

Beyond approvals and authorizations, the compilation includes postmarketing assessments involving products such as Avandia (rosiglitazone), clozapine, and vedolizumab, as well as broader safety evaluations using healthcare claims data, pregnancy registries, and the FDA's Sentinel System.

Commenting on the update, Marie Bradley wrote on LinkedIn:

"By documenting these examples, FDA aims to provide interested parties with greater insight into how and when RWE informs agency decision-making, both pre- and postmarket."

She added that the publication "updates the September 2025 posting with more recent examples, as well as newly added examples from CDRH."

The FDA also noted that participating centers collaborated to standardize the format of the examples and align definitions for study designs and data sources. The agency said it intends to continue updating the resource on a regular basis.