FDA’s new real-world evidence program offers early agency feedback

Regulatory NewsRegulatory News | 21 December 2022 |  By 

The US Food and Drug Administration is aiming to improve the quality of real-world evidence (RWE) used in regulatory submissions through a new program offering early agency meetings – before full protocol development or study initiation – for sponsors using RWE in medical product development.
The Advancing RWE Program, first announced in October 2022, will provide a small number of sponsors with early, iterative feedback on RWE-based proposals that are intended to support new labeling claims or to satisfy postapproval study requirements, according to the FDA (RELATED: FDA starts PDUFDA VII programs for real-world evidence, innovative trial designs, Regulatory Focus 19 October 2022).
The optional program is similar in approach to the Complex Innovative Design (CID) and Model-Informed Drug Development (MIDD) programs, an FDA spokesperson told Focus. Those programs both offer a mechanism for in-depth discussion between the agency and the sponsor on a particular aspect of drug development. The Advancing RWE Program currently is slated to run during fiscal years 2023-2027, with meeting request submission deadlines on 31 March and 30 September of each year.
What you need to know
“The Agency’s standard for substantial evidence has not changed,” the FDA spokesperson said. “The intent of the Advancing RWE Program is to explore how and when an RWE-based approach could meet the approval standard and support regulatory decision-making. Sponsors should also understand that many worthy ideas may not ultimately be accepted into the program given program limits. In such cases, existing meeting pathways remain available.”
The agency will accept one to two primary meeting requests and up to two alternates for each submission cycle in FY 2023-2024. In FY 2025-2027, the program will expand to accept up to four primary meeting requests and up to four alternates per submission cycle. For each accepted meeting request, FDA will conduct an initial meeting and up to three follow-up meetings with sponsors.
Sponsors are eligible if they have an Investigational New Drug (IND) or pre-IND number for the medical product in development and the proposed RWE is intended to meet regulatory requirements in support of labeling for effectiveness or for meeting postapproval study requirements.
Before applying, FDA advises sponsors to consider the regulatory question and then determine whether fit-for-purpose real-world data are available; whether potential study designs are likely to adequately address the regulatory question; and whether they can conduct and submit the results to the agency in accordance with regulatory requirements. When it comes to determining if real-world data is fit-for-purpose, FDA emphasizes the need for data reliability and relevance, as well as study designs that follow epidemiologic principles. The agency has address its current thinking on fit-for-purpose data in a series of guidance documents on the use of RWE.
The Advancing RWE Program will be focused on novel methods more than any one disease area, according to the FDA spokesperson. The selection process for participation in the program will consider the diversity of regulatory indications, diseases under study, data sources, design types, and other factors. The agency is looking for “novel and creative uses of RWE in drug development that are likely to meet regulatory requirements,” the spokesperson said.
Sharing lessons
FDA plans to extend the benefit of the program more broadly by sharing lessons learned from participants. Sponsors who participate in the program must sign a disclosure agreement allowing FDA to share learnings from the program that promote awareness of characteristics of RWE that can be used to support regulatory decisions. The agency also may share key design elements in public workshops or in guidance. However, FDA will not share specifics on the sponsor’s name, treatment of interest, or full description of study eligibility criteria or patient-level data.
Additionally, as part of the PDUFA VII commitments, FDA plans to report information on RWE submissions annually starting in 2024, convene a public meeting on RWE case studies in 2025, and update existing RWE guidance documents or issue new draft guidance by the end of 2026.
Sponsor reaction
Drugmakers who are already working with RWE in drug development praised the launch of the program. Seema Betigeri, PhD, Executive Director of Oncology Global Regulatory Affairs at Merck, said the discussions enabled by the program could provide insights across therapeutic areas. She noted that the agency had clearly spelled out the content, format and timeline expectations for the meeting requests and follow-up meetings under the program. However, she suggested that the agency consider increasing the number of meeting request accepted per submission cycle, depending on sponsor response to the program.
“Pilot programs such as these represent a collaborative partnership between industry and FDA and will help enable the development of rigorous real-world data/noninterventional studies for regulatory purposes to help advance drug development,” Betigeri said.
Bristol Myers Squibb (BMS) also praised the program, calling it an “exciting pilot” with the potential to create a “thoughtful body of experience” around RWE for regulatory purposes. BMS noted that it would be especially helpful if the workshops and learnings from the program shared insights about how FDA assessed the proposed data sources, including what evidence provided confidence in the data source’s relevance and reliability and what did not.
Advancing RWE Program


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