Regulatory Acceptable Real-World Effectiveness Endpoints: How Clarity Can Best be Achieved in the United States

Abstract

Background: The therapies many patients need do not exist today. Real-world evidence (RWE) can accelerate patient access to treatment. However, lack of clarity on regulatory acceptable realworld effectiveness endpoints can result in delayed or lost new therapy opportunities to bring new treatments to patients. Research question: How can clarity on regulatory acceptable real-world effectiveness endpoints in the United States best be achieved? Methods: A qualitative research study was conducted by interviewing expert informants from diverse stakeholder types to explore their perceptions of gaps, solutions, action needed, and determinants for achieving clarity. Themes were derived using an inductive coding approach, followed by an appraisal of the potential macro-level solutions using Bardach's criteria for policy analysis. Results: Four macro-level solutions were identified: Food and Drug Administration (FDA) Advancing RWE Program, FDA report or dashboard for stakeholders to more easily locate FDA reviews and decisions about RWE, a tool to help stakeholders apply existing related FDA guidance, and FDA guidance on real-world effectiveness endpoints. Plan for Change: Recommended actions for implementing the four solutions and potential evaluation measures were derived from interview themes and Expert Recommendations for Implementing Change. Of the four solutions, an immediate opportunity that FDA and non-FDA stakeholders could initiate is a tool to help stakeholders apply existing FDA guidance, precedent, and endpoint validation principles from the scientific literature. Conclusion: Two solutions are already in progress to increase stakeholders experiences with RWE for regulatory decision making (e.g., FDA Advancing RWE Program and FDA report on RWE submitted for regulatory review). Parallel implementation of other solutions is likely needed (e.g., developing a tool to help stakeholders navigate the existing guidance and precedents on real-world effectiveness endpoints), with regulatory guidance on real-world effectiveness endpoints to follow. Good engagement and transparency across the stakeholder communities are essential to make the most meaningful impact.