Exploring the use of Real-World Evidence in Regulatory Decision Making Under PDUFA VII

The PDUFA VII Commitment Letter builds on the programs supporting the use of Real-World Evidence (RWE) in regulatory decision-making begun under PDUFA VI. Specifically, the following initiatives incorporating RWE have been incorporated into PDUFA VII:

  • Pilot Advancing RWE Program 
  • Use of RWE negative controls
  • Use of RWE for capturing post-approval safety and efficacy data for cell and gene therapy (CGT) products

Pilot Advancing RWE Program  

In a Federal Register notice released on October 20, 2022, the FDA has announced that it is committed to establishing an “Advancing RWE Program.”

Per FDA, the purpose of this program is to “seek to improve the quality and acceptability of RWE-based approaches in support of new intended labeling claims, including approval of new indications of approved medical products or to satisfy post-approval study requirements.”

Given the high cost and administrative burden of randomized clinical trials (the current standard for regulatory decision-making), this announcement has garnered much interest.  

 In the PDUFA Commitment letter, FDA commits to running this pilot intended to identify and characterize and build consistent RWE approaches that could potentially support labeling claims for the efficacy of the drug or that could be used to meet further study requirements implemented at the time of marketing approval, such as PMRs.

To do this, FDA intends to discuss study designs under consideration in public forums. These discussions will focus on data, design, and regulatory issues for studies that have the potential to generate RWE in support of a proposed regulatory decision.

FDA has committed to report “aggregate and anonymized information” on the RWE submissions at least annually starting in June of 2024, if not earlier.

Subsequently, a discussion will be held in a public forum to discuss RWE case studies, and the focus will be on RWE approaches to support regulatory decision-making.

Finally, RWE-related guidance documents will be updated or drafted to contain FDA recommendations built on the experience gained from this pilot.  

Use of RWE Negative Controls 

As part of PDUFA VII, FDA has committed to the optimization of the Sentinel Initiative and has stated that one of their goals is to build a methodology to allow for causal inference in Sentinel/BEST that may allow for product safety questions to be addressed and thus further advance FDA’s understanding of using RWE for determining effectiveness.

First, the FDA is planning to hold a public workshop and then intends to kick off two projects to develop methods to automate the process and build negative controls. FDA plans to release a report of their findings in 2027. 

CGT and RWE 

FDA has also committed to continuing to work on novel approaches to development, specifically within the field of cell and gene therapy.

This innovative field has been at the forefront of ground-breaking approvals in recent years, including those for rare diseases, so, understandably, FDA will continue to develop its capabilities to make recommendations and understand the complexities unique to these programs.

Under this initiative, FDA has committed to convening a public meeting on complex CGT products by the end of the fiscal year 2024 and has indicated that the use of RWE and registries for capturing post-approval safety and efficacy data will be discussed. Updated or new guidance on this topic will subsequently be issued. 

If you have questions about RWE or any other PDUFA VII Updates, email info@mmsholdings.com to speak to a regulatory or RWE expert.

By: Supriya Perambakam, Global Regulatory Affairs Manager


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