In December 2025, the FDA issued a news release and finalized a revision to its 2017 guidance document on the use of real-world evidence (RWE) in medical device submissions¹. The revised guidance document expands and clarifies how FDA staff and sponsors may use real-world data (RWD) to support regulatory decisions, with a key update: FDA will accept RWE without always requiring submission or availability of identifiable individual participant-level data derived from RWD².

This update builds on how RWE has already shaped regulatory decisions. Since 2016, RWE has supported more than 250 medical device authorizations and over 35 drug and biologic applications¹. The new guidance document does not lower scientific standards for use of RWE in medical device submissions; rather, it recognizes aggregate-only and privacy-preserving data access models as acceptable, with appropriate justification. By doing so, the guidance document reinforces the importance of rigorous data quality and traceability while acknowledging the practical realities of modern evidence generation.

What Changed in the 2025 Guidance?
Participant-Level Data Is Not Always Required

In the 2017 guidance document Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices, FDA described the need to verify individual source data with the expectation that sponsors be able to provide identifiable participant-level data upon request³. This expectation created a significant barrier to the use of large databases restricted to deidentified or aggregate analyses. The 2025 update lifts that barrier by removing the expectation that sponsors secure access to identifiable individual-level data as a condition for using a given RWD source. RWE will be evaluated on a case-by-case basis, with a focus on whether the evidence is scientifically sound and whether the data are fit for their intended purpose.

Sponsor Responsibilities and FDA Oversight

This flexibility comes with explicit expectations. While de-identified participant-level data enables FDA to replicate primary analyses or perform additional sensitivity analyses to assess robustness, identifiable patient-level data enables assessment of data provenance and traceability. If a sponsor can reasonably obtain participant-level data from a data source they do not own, they should attempt to do so. When that is not possible, for example when a registry or health system only allows aggregate or controlled-access analyses, sponsors must document:

• Who retains control of the underlying data
• How data quality, validation, and traceability were ensured
• How the absence of participant-level data affects (or does not affect) interpretability

FDA retains discretion to request additional verification, audits, or source-data access if concerns arise. In practice, this means flexibility in data accessibility, not in the rigor of evidentiary standards².

The updated guidance document provides detailed instructions on documentation and reporting of both the relevance and reliability of RWD used for regulatory submissions including a comprehensive checklist of items to document and provide to the FDA. It is critical that sponsors review this guidance and address these requirements for all real-world regulatory submissions.

Use of Global RWD for U.S. FDA Submissions

RWD— data collected during routine health care — can come from sources both in the U.S. and ex-U.S. FDA recognizes that privacy rules and other legal requirements may limit a sponsor’s ability to access or share participant-level data. In the new guidance document, FDA notes that some RWD sources provide only aggregate results or restrict sponsor access to participant-level records². FDA does not discourage use of these sources, and a sponsor’s inability to obtain participant-level data does not automatically prevent FDA from evaluating the evidence so long as the sponsor clearly explains what data are available, who has access, and how any limitations could affect the results. The guidance document also emphasizes that it does not override applicable U.S. or foreign laws, including requirements for human subject protections and patient privacy. Taken together, these updates support the idea that high-quality data from both U.S. and ex-U.S. sources can be used in FDA decision-making when they are relevant and reliable—and when sponsors are transparent about data access constraints and their impact.

Reinforced Emphasis on Data Quality and Transparency

While the updated guidance document introduces procedural flexibility, it reinforces expectations for data quality. FDA places strong emphasis on relevance (whether the data reflect the population, exposure, and outcomes of interest) and reliability (how the data were generated, curated, processed and validated). The guidance document includes detailed considerations to help sponsors systematically assess their RWD sources².

For sponsors, this means data feasibility and assessment of fit-for-purpose remain essential. Key data elements must be validated, missing or inconsistent data addressed, and data provenance clearly documented. When FDA cannot directly inspect raw participant-level data, the burden shifts to the submission to demonstrate trustworthiness through documentation, validation studies, sensitivity analyses, and transparent analytic assumptions.

No Change Yet for Drugs and Biologics

The December 2025 update applies to medical devices only. FDA has indicated that it intends to consider updating parallel RWE guidance for drugs and biologics in the future. Until then, drug sponsors should continue engaging FDA early and on a case-by-case basis when proposing RWE approaches that may not include full participant-level data.

What This Means for Sponsors

The updated guidance document creates meaningful opportunities while reinforcing sponsor responsibilities:

• Greater flexibility in data sources: De-identified, aggregate, and international datasets may now be more viable for regulatory use so long as data relevance, reliability, and traceability are demonstrated. Sponsors should identify whether datasets include the clinical or physiological measures needed to demonstrate safety and/or effectiveness, and assess whether device exposure is directly captured (e.g. via universal device identifiers [UDIs]) or requires alternative approaches (e.g., data linkage or mining of unstructured data). Limitations and applicability of data to U.S. clinical practice should be documented.
• Scientific rigor remains essential: FDA continues to require valid scientific evidence; limited data access may invite greater scrutiny, not less. The guidance document emphasizes the importance of prespecified protocols, transparent endpoint definitions (including justification for surrogate endpoints), assessment of bias and confounding, and well-defined standards for validation, auditability, and documentation, particularly when participant-level data are not available.
• More efficient evidence generation approaches: Tokenization, privacy-preserving techniques and multi-source RWE architectures can help address data access and privacy constraints and, when executed rigorously, accelerate timelines. When primary endpoints are not directly observable, sponsors should clearly justify any derived endpoints and, where appropriate, supplementation with linked data sources.
• Importance of early FDA engagement: Given the case-specific nature of RWE acceptability, pre-submission discussions with regulators remain essential to align data sources, endpoint strategy, validation plans, and evidentiary standards. Proactive FDA interaction can help de-risk novel RWE approaches.

FDA’s 2025 RWE guidance document reflects a pragmatic evolution in regulatory science: greater flexibility in how evidence is accessed and analyzed, paired with continued insistence on scientific rigor and transparency. For sponsors willing to invest in high-quality data, robust validation, and proactive regulatory engagement, RWE can play an increasingly central role in regulatory decision-making, without compromising confidence in safety or effectiveness.

How IQVIA Can Help

IQVIA has extensive experience generating regulatory-grade RWE under global privacy and data-access safeguards and standards. Our integrated capabilities— spanning global de-identified data assets, tokenization and federated analytics, epidemiology and biostatistics, and regulatory strategy— enable sponsors to design, validate, and communicate RWE that aligns with FDA’s updated expectations. IQVIA has a dedicated team focused on RWE for medical devices and diagnostics including experts with experience at relevant FDA offices and expertise in using medical technology RWD leveraging IQVIA’s vast capabilities. We support sponsors end-to-end, from feasibility and study design through FDA engagement and submission, across the medical device total product lifecycle.

References

¹FDA Eliminates Major Barrier to Using Real-World Evidence in Drug and Device Application Reviews. U.S. Food and Drug Administration. Published 2025.

²Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices; 2025. https://www.fda.gov/media/190201/download

³Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices; 2017. https://www.fda.gov/media/99447/download