Why RWE programs fail under regulatory scrutiny — and what leaders can do about it

FDA has made its expectations for RWE clearer and more structured through recent guidance and program activity. For sponsors, that changes the risk profile: evidence that is fast to generate but weak on data quality, provenance and reproducibility is more likely to break under review. FDA’s RWE guidance for drugs and biologics puts the focus on whether EHR and claims data are fit for regulatory decision-making, including documentation and assessment of data quality and relevance.¹

In oncology, FDA’s Oncology Center of Excellence has also emphasized “rigorous methodological use” of real-world data and fit-for-purpose application to support regulatory decision-making, reinforcing that the bar is not just results, but defensibility of the underlying data and methods.²

The executive problem behind most RWE failures

Most RWE programs do not fail because the analytics are wrong. They fail because teams cannot defend the data under review.

Three blind spots show up as:

• Fragmented datasets: Teams cannot defend a patient journey built from sources that do not stay consistent over time.
  
  
• Weak clinical grounding at scale: If the data does not reflect how care is delivered in the real world, results will not hold up when reviewers interrogate definitions, endpoints or missingness.
  
  
• Data strategies that fail auditability: If teams cannot explain provenance, permissions and reproducibility, assembly, validation, curation/transformation/or normalization they do not have regulatory-grade evidence.

HealthVerity is built to reduce RWE program risk. We resolve patient identity across the nation’s largest healthcare and consumer data ecosystem with 10x higher accuracy, then pair that identity layer with governed usage rights and privacy controls.

In many real-world data environments, datasets can change over time due to vendor turnover, market shifts or contractual changes that alter what data remains available. HealthVerity Marketplace is designed with the flexibility to address this volatility. Sources remain available and refresh cadence stays consistent so cohorts and endpoint results remain reproducible even as the broader data market evolves.

What leaders should do now

To reduce regulatory risk, leaders need to shift how they evaluate their real-world data foundation. The question is no longer how quickly evidence can be generated. It is whether that evidence can be defended under regulatory scrutiny months or years later.

Executives should ask:

• Will we be able to show where the data came from and why it is fit for purpose?
  
  
• Can we reproduce the cohort, endpoints and outputs on demand?
  
  
• Is our data supply stable enough that conclusions will not shift as sources change or can we defend that shifts are accurate reflections of patient behavior vs artifacts of poor quality data?
  
  
• If this is challenged in 12 months, or if priorities change, new mandates are introduced, or further research is requested, does our data assembly support this and build in this flexibility?

HealthVerity reduces RWE program risk by aligning the data foundation to what FDA guidance is already emphasizing: fit-for-purpose real-world data, documented assessment of data quality, traceable provenance and the ability to apply that data in a transparent, reproducible research framework.^1,2

• Identity: 10x higher-accuracy patient resolution (HVID) so cohorts stay accurate across sources and over time, with defensible patient-level provenance.
  
  
• Privacy and governance: Built-in privacy controls plus governed usage rights so teams can show what data was used, under what permissions and how it was managed.
  
  
• Exchange: Transparent sourcing and operational delivery through Marketplace so teams can access, refresh and reproduce the same data inputs over time without rebuilding the program.
  
  

This maps to FDA’s direction in oncology to advance fit-for-purpose use of real-world data with rigor, transparency and methodological discipline for regulatory purposes. Learn more about how HealthVerity set the government standard for secure data linkage here.

References

1. FDA. Real-world data: assessing electronic health records and medical claims data to support regulatory decision-making for drug and biological products. February 3, 2025. Accessed March 4, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/real-world-data-assessing-electronic-health-records-and-medical-claims-data-support-regulatory
2. FDA Oncology real world evidence program. FDA. Published online August 22, 2025. Accessed March 4, 2026. https://www.fda.gov/about-fda/oncology-center-excellence/oncology-real-world-evidence-program