A recently published report by the Duke-Margolis Institute, titled “Applying Real-World Data and Real-World Evidence for Accelerated Approvals and Coverage Decisions,” delves into the intricate landscape of the Food and Drug Administration’s (FDA) accelerated approval process, emphasizing the pivotal role of real-world data (RWD) in both initial and confirmatory evidence generation. The FDA’s accelerated approval pathway, designed to expedite access to critical medical treatments for patients with unmet medical needs, has been controversial due to concerns about balancing rapid access with the assurance of safety and effectiveness.
The report underscores the need to swiftly deliver effective medical products while ensuring their safety and efficacy. Federal agencies are concurrently developing guidelines on leveraging real-world data to support these objectives. By exploring the FDA’s decisions on accelerated approvals, the report offers insights into the integration of RWD as part of a comprehensive evidence package that informs both regulatory bodies and payers.
The selection of endpoints in accelerated approval and payment decisions is highly context-dependent, necessitating careful consideration of reliability, validity, and sensitivity to treatment effects. The report highlights the need for endpoints that align with data quality specifications and reflect real-world outcomes. Generalizability and representativeness are crucial when assessing the clinical benefit and value of medical products. The report suggests that larger real-world data sources can enhance the totality of evidence for products granted accelerated approval, ensuring broader acceptance.
Report Highlights Value of Registries and Point-of-Care Trials for Real-World Evidence
Registries are identified as valuable sources of real-world data, supporting clinical trials and generating confirmatory real-world evidence (RWE). The report advocates for the development of fit-for-purpose registries that are complete, reflective of the patient journey, and capable of providing reliable data for both initial and confirmatory evidence generation. While external control arms offer promise, the report acknowledges challenges in matching heterogeneous patient populations across trial treatment arms. Future efforts should focus on developing methods to leverage historical or concurrent external control data from RWD sources, even when assessment timelines may not align.
Point-of-care trials are highlighted as a means to efficiently generate practical evidence in postmarket settings, confirming the benefits and risks of products granted accelerated approval. The report suggests that under favorable conditions, RWE-based approaches can address the limitations of traditional confirmatory trials. Additionally, the report emphasizes the critical role of private payers in evidence generation. As concerns about the affordability of new and expensive products rise, payer involvement in postmarket evidence generation is deemed essential to ensure improved patient care and effective utilization of medical products.
Report Highlights Real-World Data in Accelerated Approvals of Elevidys, Vijoice, and Keytruda
The report includes detailed case studies on three medical products—Elevidys, Vijoice, and Keytruda—to illustrate the practical application of real-world data in the accelerated approval process. Elevidys, gene therapy for Duchenne Muscular Dystrophy, had its approval based on a randomized study, with external control data deemed not helpful due to disease heterogeneity. The report discusses the challenges of endpoint subjectivity and the small treatment effect size.
Vijoice, approved for treating PIK3CA-related overgrowth spectrum, had its accelerated approval based on data from a retrospective chart review. The report highlights the importance of data quality and the use of real-world endpoints to support regulatory decisions. Keytruda, while not directly leveraging RWD/E in current applications, serves as an example of how RWD could be used to generate confirmatory evidence in postmarketing settings, particularly for its Merkel cell carcinoma indication.
The report concludes that while the potential of RWD for evidence generation remains relatively untapped, it holds significant promise for supporting both initial and confirmatory evidence cases within the FDA’s accelerated approval pathway. Aligning evidence-generation efforts to address the shared needs of regulators, payers, healthcare providers, and patients is essential. By leveraging real-world data effectively, stakeholders can enhance the robustness of evidence, ensuring timely access to innovative medical products without compromising on safety and effectiveness. The report provides comprehensive considerations to inform future efforts and chart potential paths for increased use of RWD in evidence generation.
Resource: Duke-Margolis Institute, July 25, 2024
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