FDA is prioritizing the utilization of real-world evidence (RWE), and seems to recognize the importance of allowing sponsors to leverage data from electronic health records, medical claims, disease registries, and digital drug development tools, which we previously discussed online here.

Toward this end, FDA announced the Advancing RWE Program, which aims to improve the quality and acceptability of RWE-based approaches that can meet regulatory requirements in support of labeling for effectiveness such as new indications, populations, dosing information),or for meeting post-approval study requirements. The Advancing RWE Program is among FDA’s commitments under the Prescription Drug User Fee Amendments for fiscal years 2023 through 2027, included as part of the FDA User Fee Reauthorization Act of 2022.  The program will allow selected product sponsors the opportunity to work closely with FDA staff in the Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research on protocol development and planning for RWE studies to support regulatory decision-making and medical product development. In addition, Oncology applications also will include Oncology Center of Excellence participation.

FDA said the Advancing RWE Program is designed to:

• identify approaches for generating RWE that meet regulatory requirements in support of labeling for effectiveness (e.g., new indications, populations, dosing information) or for meeting post-approval study requirements;

• develop agency processes that promote consistent decision-making and shared learning regarding RWE; and

• promote awareness of characteristics of RWE that can support regulatory decisions by allowing FDA to discuss study designs considered in the Advancing RWE Program in a public forum.

FDA welcomes submissions related to any eligible RWE proposal, when deciding on acceptance into the program, the agency indicated that it will select requests based on the potential for generating fit for purpose data, diversity of data sources, study designs, analytical methodologies, regulatory indications, and diversity of diseases.

The Advancing RWE Program is an optional pathway for sponsors submitting RWE proposals; established procedures to engage the agency will continue to be available. Sponsors who are a part of the program must agree to make their study public, and the disclosure requirement allows the agency to include ideas on new regulatory uses for RWE in guidance or to speak publicly about the study designs to promote awareness of RWE characteristics that can support regulatory decisions.

What information should a meeting request include?

FDA’s Advancing RWE Program webpage lists the information that should be included in the initial request for a meeting. Among other elements, the request should include the following information:

1. Attributes of study design: objectives; design architecture (e.g., randomized trial with pragmatic elements, externally controlled trial, observational cohort study) with a schematic representation; eligibility criteria; covariates of interest; primary and key secondary endpoints; treatment of interest, comparator, and concomitant therapies

2. Potential data sources: category (e.g., electronic health records, medical claims, registries, and/or other) and description; data reliability and relevance; validation, timing, and completeness of key data elements; linkage to other data sources; additional data collection.

3. Anticipated analysis plan: approximate sample size; analytic plan for primary and key secondary endpoints; approach to confounding factors; definition of follow-up period; handling of intercurrent events, missing or misclassified data, and multiplicity.

4. Miscellaneous considerations: pre-specification of study design and conduct; availability and FDA access to patient-level data; approach to human subject protection.

The semi-annual submission deadlines for initial meeting requests to the Advancing RWE Program are March 31 and September 30. FDA will review all meeting requests received in the preceding 6 months after each submission deadline.   FDA provided the following infographic depicting the pertinent timelines in the application process:

Discussions at Advancing RWE program-related meetings will focus seeking general agreement on key design elements and the potential to generate RWE in support of a proposed regulatory decision. The acceptability of evidence generated from any completed study is a subsequent review issue.

Next steps

FDA’s Advancing RWE Program underscores how drug and biologic sponsors should prepare protocols and statistical analysis plans ahead of FDA submissions and meetings to explain the reliability, relevance, and comprehensiveness of their data sources, as well as the methodologies used to validate key design elements and maintain quality during data accrual, curation, and transformation to the final data set. Drug and biological product sponsors should also consider the potential impact of linking one or more registries or data systems on the overall integrity of the data used in the clinical trial.

If you have any questions on apply for this program, or on utilizing RWD/RWE in drug or biologics applications or clinical study design more generally, please contact any of the authors of this alert or the Hogan Lovells attorney with whom you regularly work.

Authored by Heidi Gertner, Lowell Zeta, Lynn Mehler, and Sally Gu