On December 8, 2021 and in response to the mandate under the 21st Century Cures Act to issue guidance on the use of real-world evidence (RWE) in regulatory decision-making, the U.S. Food and Drug Administration (FDA) released a draft guidance document: Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products(Draft Guidance). As part of the RWE program, FDA previously issued the following draft guidance documents:

• Real-World Data: Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products Guidance for Industry: Outlining FDA’s recommendations for sponsors proposing to design a registry or to use real-world data (RWD) from existing registries to support regulatory decision-making.

• Real-World Data: Assessing Electronic Health Records and Medical Claims Data to Support Regulatory Decision-Making for Drug and Biological Products: Providing FDA’s considerations on the use of RWD derived from electronic health records and medical claims data to support regulatory decision-making for drugs and biologics.

• Data Standards for Drug and Biological Product Submissions Containing Real World Data: Outlining FDA’s recommendations on how a sponsor should submit study data derived from RWD sources using data standards specified in the Data Standards Catalog.

In the Draft Guidance, FDA discusses the applicability of 21 C.F.R. Part 312 (Investigational New Drug Application) to studies that use RWD, and addresses FDA’s expectations related to studies using RWD in support of a regulatory decision for the safety and effectiveness of a drug. In the Draft Guidance, FDA defines RWE as “the clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of RWD” and RWD as “data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources.” Additionally, the focus of this guidance is primarily on non-interventional studies (i.e., observational studies). FDA defines an observational study as a “type of study in which patients received the marketed drug of interest during routine medical practice and are not assigned to an intervention according to a protocol.”

In the Draft Guidance, FDA discusses regulatory considerations for observational studies involving the use of RWD, including RWD access, study monitoring, safety reporting, and other sponsor responsibilities. With respect to RWD access, FDA advises that sponsors should confirm that they are able to submit patient-level data for any RWD used in studies in support of a marketing application required under a New Drug Application and Biologics License Application. Furthermore, FDA advises that sponsors should ensure that RWD, in addition to associated programming codes and algorithms, are documented and complete to allow FDA to replicate the study analysis.

With respect to safety reporting, FDA recommends that sponsors submit relevant adverse events to FDA in accordance with regulations pertaining to post-marketing safety reporting. For other sponsor responsibilities, FDA advises that sponsors should take responsibility for all activities related to the design, conduct, and oversight of the observational studies. This includes selecting researchers qualified by training and experience, maintaining and retaining study records, and ensuring that FDA can access and verify relevant records.

FDA recommends that stakeholders submit any comments on the Draft Guidance by March 8, 2022 through this docket.