The U.S. Food and Drug Administration (FDA) continues to advance its Real-World Evidence (RWE) Program, designed to help sponsors use real-world data (RWD) to support regulatory decisions. However, recent updates from FDA health science policy advisor Kristen Miller highlight an important reality: most applications to join the program are rejected.
So, what can life sciences companies learn from FDA’s feedback—and how can organizations strengthen their strategies for using RWE?
Why the Program Matters
The Advancing RWE Program, launched under PDUFA VII, offers sponsors a chance to collaborate directly with FDA on how to design and use RWD studies. These interactions are intended to identify approaches that meet regulatory requirements and advance the use of RWE in drug development and approval.
Since its start, the program has received 26 submissions—but only five have been accepted, with two sponsors already completing the process. This shows both the promise of the program and the steep standards that FDA expects.
Common Reasons for Rejection
According to FDA, three major issues frequently lead to rejections:
- Study Interpretability Concerns: Proposals using highly heterogeneous patient populations, evolving treatment regimens, or those prone to large placebo effects or channeling bias often lack the clarity FDA needs to make regulatory decisions.
- Supportive vs. Primary Evidence: FDA wants RWE studies that provide primary evidence, not just supportive data. Proposals limited to endpoint validation or exploratory analyses are outside the program’s scope.
- Alternative Engagement Pathways: If sponsors are already receiving adequate feedback through their review divisions or other mechanisms, FDA may direct them elsewhere.
Tips for Sponsors
At EMMA International, we help clients anticipate these challenges and design stronger RWE strategies. Based on FDA’s feedback, here are three tips:
- Prioritize Robust Study Design
Ensure that your RWD study design can generate interpretable, high-quality data that answers regulatory questions. Define eligibility, endpoints, and comparators with precision to minimize bias. - Focus on Primary Evidence
Position your RWE study as a source of decision-driving evidence, not just supporting background. Be clear about how your study will contribute directly to safety, efficacy, or labeling decisions. - Engage Early and Strategically
Sponsors must have an active IND or pre-IND number to participate. Use early discussions with FDA and external advisors to align your RWE strategy before submission.
Looking Ahead
FDA has committed to building on lessons from this program. By December 2025, the agency will hold a public workshop to discuss RWE case studies, and by December 2026, FDA will update or create new guidance based on program findings.
This evolving landscape shows that RWE is no longer an optional tool—it’s becoming a core part of the regulatory decision-making process. Companies that can design rigorous, regulator-ready RWE studies will have a competitive edge.
EMMA International’s Perspective
At EMMA International, we help sponsors harness the potential of RWE by developing compliant, high-quality study designs that meet FDA expectations. From protocol development to evidence strategy, our team ensures that your RWE program is built for both regulatory success and scientific credibility.
For more information on how EMMA International can assist, visit www.emmainternational.com. Contact EMMA International at (248) 987-4497 or by email at info@emmainternational.com to learn more.
