On December 15, 2025, the US Food and Drug Administration (FDA) issued a press release announcing that FDA eliminated a major barrier to the use of real-world evidence (RWE) in medical device regulatory submissions. Namely, for certain types of medical device submissions, sponsors may not need to provide individually identifiable source data when using RWE. FDA also indicated that it intends to consider making a similar change for drugs and biologics signaling that there could be a broader shift in FDA policy coming, meaning that medical product developers of all types should be paying attention to FDA developments in this area.
This policy shift opens the door for the use of large, de-identified healthcare datasets, such as registries and claims databases.
On December 16, 2025, FDA published a guidance titled Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices, which updates and supersedes the 2017 guidance of the same name, and outlines the agency’s current recommendations for the use of real-world data (RWD) and RWE in device submissions. However, whether this change around the use of de-identified data from large registries and healthcare databases for regulatory purposes will lead to greater openness at FDA to novel data sets for medical devices remains to be seen.
The detailed recommendations for thorough documentation that remain to assess whether RWD is fit-for-purpose to be used as RWE in a submission may be just another factor limiting how broadly RWE can be effectively deployed in medical device submissions and—if these trends can be extrapolated to drugs and biologics—to medical products generally.
A Sea Change?
FDA had previously insisted that sponsors submit individual patient-level data in every marketing application, making it impractical for sponsors to use large, existing databases in support of marketing applications and resulting in increased costs to sponsors that would need to conduct their own surveillance of post-market performance to collect patient-level information to replicate the data that may be otherwise available in these large datasets.
FDA’s revised policy will permit sponsors to take advantage of de-identified databases containing millions of patient records, including national cancer registries such as the National Cancer Institute’s Surveillance, Epidemiology, and End Results, hospital systems databases, insurance claims databases, and electronic health record networks. And while the expansion of these databases (further facilitated by the widespread use of digital health technology and wearables (a future As Prescribed post is forthcoming on recent developments on this) and the promise of AI-algorithms that can analyze large amounts of data and identify patterns) creates an aura of promise for the development of medical products, it is not without FDA guard rails that may significantly limit the impact of this development.
In short, despite FDA’s policy shift regarding de-identified databases, FDA has not completely released the dam when it comes to clinical studies. FDA continues to hold high standards for data collection and rigorous study design, recommending that sponsors include documentation as to how the RWE supports the purpose of the submission and the relevance and reliability assessment of the RWD to generate RWE.
A helpful summary of recommended relevance and reliability assessment elements that should be documented can be found in Appendix A of the recently published guidance, where FDA stresses the need for documentation containing, among other elements, the sponsor’s strategies to connect patients to their data, and to address redundant, inconsistent, or missing data when using de-identified data from large databases.
For example, sponsors will need to document how they would handle potential overcounting of a particular measure caused by multiple records for a single individual in de-identified data collected from sites in a geographical region. FDA also mentions that sponsors should attempt to obtain all information and associated documentation related to the processes, procedures, and methods around data collection and data quality and integrity, including recommending that sponsors identify who has access/permission to this information if the sponsor is unable to obtain access to this information.
FDA indicates that a failure to include this information may lead to uncertainty on FDA’s assessment of the underlying data, undermining FDA’s confidence in its ability to rely on the data in support of marketing approval.
Other Key Takeaways from the New Guidance
- FDA will assess the relevance and reliability of RWE submissions on a case-by-case basis considering the scientific strength and quality of the evidence.
- A central tenet of the new guidance is the rigorous assessment of RWD for relevance and reliability. (Relevance considers whether the data is sufficient in detail, representative of the target population, and appropriate for the regulatory question at hand. Reliability encompasses the integrity of data collection, quality assurance, completeness, and consistency.)
- FDA emphasizes comprehensive documentation of RWD sources, study protocols, definitions of all study elements, relevance, and reliability assessments, and makes specific methodological recommendations. Sponsors are expected to document data provenance, collection methods, and quality controls, adhering to good clinical practice (GCP) and data management standards.
- The guidance also clarifies when an investigational device exemption (IDE) is required for studies using RWD, providing hypothetical examples and noting that retrospective analyses typically do not require an IDE unless data collection affects patient care.
Impacts Across All Medical Products
Of course, the promise of RWD does not stop at CDRH’s doorway, and drug and device developers are just as eager to fully develop the utility of these data sources into new drug and biologic applications as well. FDA will need to separately consider if and how this approach will fit into the drug and biologic contexts, and FDA statements indicate that they expect that they will.
However, between the potential limitations of these developments in the device space, coupled with high degrees of case-by-case agency decision-making, the impact that this may ultimately have in medical device, drug, and biologic development remains to be seen, however welcome this development may otherwise be.