Last month, the U.S. Food and Drug Administration (FDA) issued a final guidance on drug and biologic submissions to the agency that include real-world data (RWD) and real-world evidence (RWE). The procedural guidance aims to facilitate the FDA's internal tracking of RWD/RWE to help the agency evaluate its potential use in regulatory decision-making and inform future policy. The guidance does not address the FDA's substantive review of the RWD/RWE submitted as part of the agency's standard review process.
RWD is data relating to patient health status and/or the delivery of healthcare that are routinely collected from a variety of sources, including but not limited to:
- data obtained from electronic health records,
- medical claims,
- product or disease registry,
- digital health technologies, or
- other sources that can inform on health status, such as questionnaires.
RWE is narrower than RWD and considered to be clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of RWD. RWE can be generated from RWD using many different study designs, including but not limited to interventional studies (clinical trials) or non-interventional studies (observational).
RWD/RWE represents a regulatory paradigm that can yield efficient regulatory decision-making, including in the context of how sponsors and applicants: i) support safety and/or effectiveness for a product not previously approved by the FDA; ii) support or satisfy a post-marketing requirement or commitment; or iii) support labeling changes for an FDA-approved product. Labeling changes can include, for example, adding or modifying an indication; changing the dose, dose regimen, or route of administration; expanding the labeled indication of the product to a new population; or adding comparative effectiveness information.
The availability of RWD, evolving analytic techniques to generate RWE, and growing RWD/RWE regulatory policies have created interest within research and medical communities. RWD/RWE holds great promise and can be used to enhance clinical research, support regulatory decision-making, and promote regulatory efficiency.
This data source has also been the focus of congressional legislation. In 2016, the 21st Century Cures Act (Cures Act) was enacted to accelerate medical product development and bring innovations faster and more efficiently to the patients who need them. Section 505F of the Cures Act requires that an RWE program be established and that a framework be created to implement the program. The RWE framework for drug and biological products was created in 2018. The FDA hopes that its recent guidance will provide insight into RWD/RWE scope and use that will inform future development of the RWE program.
To help the FDA gather data about its growing use, sponsors and applicants are asked to identify certain RWD/RWE tracking data attributes in their submission cover letters. Applicable submissions include initial IND applications, meeting requests, study protocols, and final study reports submitted to INDs, BLAs, or NDAs.
The FDA asks that sponsors include the following information in their cover letter to facilitate agency tracking of RWD/RWE in submissions:
- The purpose of using RWD/RWE (e.g., supporting labeling changes)
- Study designs using RWD to generate RWE (e.g., observational studies)
- RWD sources used to generate RWE (e.g., medical claims or registry data)
Although the guidance provides sample presentations of how applicants can identify a submission containing RWD or RWE as part of their cover letters, any format may be used to provide the requested information. Before using RWE/RWD in regulatory submissions to the FDA, sponsors should review the 2021 FDA guidance documents that address regulatory considerations for using RWE/RWD to support a marketing application and1 data standards for submissions that contain RWD.2
These data, in turn, are expected to help the agency develop more informed and robust drug and biologic RWD/RWE policy. Although medical devices are not within the scope of the guidance, it is foreseeable that the lessons learned from drug and biologic submissions will influence device RWE policy as well. Last year, the FDA's Center for Devices and Radiological Health issued a nearly 200-page document outlining examples of RWE used in medical device regulatory submissions.
[1] https://www.fda.gov/media/154714/download.
[2] https://www.fda.gov/media/153341/download.
