On December 15, 2025, the U.S. Food and Drug Administration (FDA) announced a significant update to its regulatory approach regarding the use of real-world evidence (RWE) in drug and medical device application reviews. Under new guidance for certain categories of medical device submissions, the FDA will no longer require that identifiable individual patient-level data from real-world data sources always be included in marketing submissions.
The agency also indicated that it intends to consider similar updates to existing guidance for drugs and biologics.
Background: Real-World Evidence in FDA Submissions
Real-world evidence refers to clinical evidence derived from the analysis of real-world data, such as patient registries, electronic health records, insurance claims, and other large healthcare databases. Although RWE has been highlighted in recent years as a potential tool to complement traditional clinical trial data, its regulatory use has remained limited.
Historically, FDA expectations required that RWE submissions include private and identifiable patient-level information. This requirement restricted the use of many large-scale databases that contain aggregated or de-identified data, despite their potential to provide meaningful insights at a population level.
Previous Use of RWE in Regulatory Decisions
Since 2016, RWE has been included in applications for 35 drugs, biologics, or vaccines submitted to the FDA. In comparison, the use of RWE in medical device applications has been more frequent, with more than 250 premarket authorizations incorporating such data during the same period. However, even within device approvals, the growth in RWE-based authorizations has slowed in recent years.
The new guidance seeks to address these limitations by allowing greater flexibility in how evidence from real-world data sources is evaluated.
Key Changes in FDA Review Approach
Under the updated framework, FDA reviewers will assess the adequacy and reliability of submitted RWE on a case-by-case basis rather than applying a uniform requirement for identifiable patient-level data. This shift reflects the agency’s recognition that robust and meaningful evidence can be generated from certain large datasets without direct access to individual identifiers.
According to the FDA, this change is intended to remove procedural barriers rather than alter evidentiary standards, with the strength and relevance of RWE continuing to be evaluated during regulatory review.
Implications for Data Sources and Research Use
The policy change expands the potential use of de-identified, large-scale databases that include millions of patient records. These may include national cancer registries, hospital system databases, insurance claims data, and electronic health record networks. Such resources can capture treatment patterns and outcomes across diverse populations and care settings, providing perspectives that may not be fully represented in traditional clinical trials.
By allowing broader consideration of these data sources, the FDA may enable more comprehensive assessments of product performance in real-world settings.
FDA’s Role and Ongoing Responsibilities
The FDA, an agency within the U.S. Department of Health and Human Services, is responsible for protecting public health by ensuring the safety, effectiveness, and security of drugs, biologics, and medical devices. The agency also oversees food safety, cosmetics, dietary supplements, radiation-emitting products, and tobacco regulation.
Written by Nare Hovhannisyan, MD