Three recommendations for generating regulatory-grade RWE: Considerations for the FDA on PDUFA VII
Jeremy Rassen, Sc.D.
Co-Founder, President, and Chief Science Officer, Aetion
With the passage of the 21st Century Cures Act and the sixth Prescription Drug User Fee Act (PDUFA), Congress created a mandate and funding for the use of real-world evidence (RWE) in decision-making by the U.S. Food and Drug Administration (FDA).
Since then, we’ve seen significant progress from the Agency as it has explored where RWE can support decisions—an effort that has intensified with the COVID-19 pandemic. Amy Abernethy, M.D., Ph.D., Principal Deputy Commissioner of the FDA, expressed that the Agency is “approaching the generation of RWE for COVID-19 with a sense of urgency” to advance its understanding of the disease, its impact on populations, and how available treatments are working in clinical practice.
As the FDA and its stakeholders assess considerations for the reauthorization of PDUFA, the Agency is presented with a key opportunity to build on its RWE momentum. In a comment letter to FDA Commissioner Stephen Hahn, M.D., and Lowell Schiller, J.D., the Agency’s Principal Associate Commissioner for Policy, Aetion shared three recommendations for using real-world data (RWD) to generate meaningful, valid, expedited, and transparent RWE to inform regulatory decision-making.
1. Establish additional demonstration projects to build empirical evidence and inform standards for the use of RWE in regulatory decision-making.
Through demonstration projects like RCT DUPLICATE, in which researchers from Brigham and Women’s Hospital are attempting to replicate 30 completed randomized controlled trials (RCTs) and predict the results of seven ongoing trials with RWE via the Aetion Evidence Platform, the Agency is building knowledge about when RWE can support its decisions (and when RWE is not appropriate). Investing in additional demonstration projects will allow the FDA to expand its knowledge of RWE’s potential applications; beneficial projects for stakeholders may include those that demonstrate how multiple types of RWD—such as administrative claims and electronic health record data—can be deployed in combination to address a research question, or a deep-dive into the use of RWD in specific therapeutic areas.
2. Issue guidance to clarify how the Agency may use the patient-level RWD that are submitted as part of an application.
When assessing a regulatory submission with RWD, FDA reviewers should be able to trace data provenance and to understand all data transformations. They may also wish to reproduce studies submitted and to perform sensitivity analyses on submitted data, which may necessitate access to patient-level data rather than just tabular results. Guidance around the FDA’s specific uses for patient-level data will help sponsors understand how best to choose data sources and to ultimately provide data. It may also spur further development of technology to support the presentation of patient-level data in a way that serves the Agency’s goals, while also protecting patients’ privacy and data providers’ proprietary information.
3. Issue review documents and metrics from RWE studies submitted as part of a regulatory submission.
In May 2019, the FDA released a draft guidance that encourages sponsors to include a uniform cover letter to identify RWE submitted as part of a regulatory submission, effectively allowing the Agency to track RWE submissions. The information held in these cover letters—for example, the study design or data sources drawn upon—are valuable for the community at large and, if released publicly, offer a broad learning opportunity for all stakeholders as they continue to learn from the successes and failures of RWE submitted for regulatory purposes. A similar model has proven helpful in the Breakthrough Therapy program, which makes salient data points publicly available for the purposes of shared learning.
Renewed commitment to RWE in the face of COVID-19
As stakeholders from across health care have mobilized to combat the COVID-19 pandemic and identify safe and effective treatments, diagnostics, and vaccines, we as an industry are faced with increased urgency around how we analyze patient experiences in clinical practice. In looking ahead to PDUFA VII, we recognize the importance of sustaining the momentum of PDUFA VI to allow for expanded uses of RWE to support regulatory decisions.
Aetion maintains our focus on using principled database epidemiology to generate scientifically valid RWE, and looks forward to continued collaboration with the FDA on the successful implementation and use of RWE in regulatory decision-making. By conducting RWE studies that apply the appropriate scientific standards, we can support the Agency’s mission to protect public health by ensuring the safety and efficacy of interventions—for COVID-19 and beyond.
The Evidence Digest
Subscribe to our newsletter for insights and updates on research and applications for real-world evidence.