FDA Guidance: FDA Removes a Key Barrier to Using Real-World Evidence (RWE) in Drug and Device Application Reviews

Regulator: FDA (US Food and Drug Administration)

Region: United States

Area: Real-World Evidence (RWE) / Medical Devices / Regulatory Submissions

Published: 15th December 2025

Source: View here

 

Key Takeaway:

The FDA has confirmed it will accept real-world evidence (RWE) in certain medical device submissions without always requiring identifiable individual patient-level data to be submitted as part of the evidence package. This is a practical shift that may make it easier for sponsors to use high-value, de-identified data sources to support regulatory decision-making.

 

What’s Changed?

In its latest announcement, the FDA states that:

• For certain types of medical device submissions, it will accept RWE without requiring that identifiable individual patient data must always be submitted
• RWE will be reviewed case-by-case, based on the strength and suitability of the evidence
• The FDA also signals it intends to consider updates for drugs and biologics in the future

 

Why This Matters for Sponsors

Real-world evidence is often discussed as a way to strengthen submissions and better reflect real-life patient outcomes – but in practice, sponsors have faced genuine barriers in using RWE at scale.

Historically, expectations around submitting private, identifiable patient-level data have made many large datasets difficult (or impossible) to use in a regulatory context, even where those sources contain valuable insights.

This update helps open the door to using de-identified, large-scale datasets, including:

• National disease registries
• Hospital system databases
• Insurance claims databases
• Electronic health record (EHR) networks

 

The FDA also notes that while RWE has been included in submissions since 2016, uptake has remained limited:

• 35 drugs, biologics, or vaccines have included RWE in applications
• 250+ medical device premarket authorisations have included RWE
• and device authorisations involving RWE have plateaued in recent years

 

What Reviewers Will Still Expect

Whilst the barrier is lower, the quality threshold has not changed.

In our experience, RWE is most likely to be questioned (or discounted) when key foundations are not clear. Sponsors should still be prepared to demonstrate:

• Data governance and provenance (where the data came from, how it was collected, and how it has been managed)
• Data quality and completeness, including limitations and variability
• Methodology and transparency, with clear assumptions and reproducible approaches
• Bias and confounding controls, particularly with observational datasets
• Submission defensibility, including documentation that stands up under challenge

This is where teams often underestimate the work required – not in producing an RWE output, but in producing an evidence package that is genuinely submission-ready.

 

What You Should Do Now

If your programme includes RWE – either for development strategy, submission support, or lifecycle work – this update is a good prompt to review readiness.

• Reassess whether de-identified data sources could now support your submission strategy
• Confirm the regulatory question your RWE is intended to answer
• Strengthen governance and documentation early (before it becomes a last-minute scramble)
• Align across functions (Regulatory, PV, Clinical, Data Science, Quality)
• Plan for challenge: build your RWE narrative so it can hold up under review

 

PharSafer Perspective

This is a sensible and overdue move from the FDA. However, sponsors should be cautious about viewing it as a shortcut.

The differentiator will not be who has access to large datasets – it will be who can convert those datasets into regulatory-grade evidence that is well-governed, clearly explained, and defensible.

 

Need Support Assessing RWE Strategy or Submission Readiness?

If you would like to discuss what this FDA change means for your programme, PharSafer’s regulatory and safety teams can help you review evidence strategy, governance expectations, and submission defensibility.

 

PharSafer is committed to supporting our clients as regulatory expectations evolve.

If you have any questions or would like guidance on what this update could mean for your programme, please contact us directly at: enquiries@pharsafer.com 📧

 

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