FDA finalizes real-world evidence guidance for device sponsors, may consider more RWE in product reviews

On December 17, FDA published the final guidance “Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices.” Compared to the draft guidance of the same name, which was published in December 2023, the final version adds discussion on its recommended methodologies for collection and analysis of RWD, provides updated examples on previously used and accepted methodologies, and expounds on its guidance for the use of clinical data collected from the use of a medical device authorized under an Emergency Use Authorization (EUA), describing the type of information that could be applicable to support a determination under the Clinical Laboratory Improvement Amendments (CLIA). Specifically, we have observed the following changes:

• “Relevance and reliability.” The final version of the guidance replaces its emphasis on assessment of whether RWD are “fit-for purpose” for a particular regulatory decision relating to the device; instead focusing on inclusion of a specific assessment of how the data meets FDA’s factors for “relevance and reliability.”
• Importance of data segregation. The final guidance places a greater focus on protocol development, adding the warning that while “the protocol is being developed, sponsors should not have access to the outcome measure results.” FDA further stress that sponsors should “consider when individuals should not have access outcomes within the dataset(s) used for the study,” adding into the final version of the guidance the examples of “generating summary scores, propensity score modeling, [and] determining level of data missingness.” FDA advises: “Sponsors should implement the relevance and reliability concepts in this guidance when developing their study protocol.”
• RWD accrual process information. While recognizing that documentation and information about the methods used to obtain RWD (that is used in a marketing application) may not always be available to a device sponsor, FDA warns in the final guidance that “uncertainty may arise if FDA does not have access to all of the necessary processes, procedures, and methods.” Accordingly, FDA recommends that a sponsor conduct a reliability assessment when such information may be unavailable, “and provide a rationale for why the RWD is reliable for the regulatory purpose.” FDA encourages sponsors to not only attempt to obtain this information themselves, but to also connect FDA with the third-party RWD source when a sponsor cannot acquire the requested documentation on their own.
• Focus on privacy. The guidance recommends RWD elements that device sponsors should consider when assessing the relevance of data and directs sponsors to demonstrate that “appropriate patient privacy protections are applied…with linked data,” such as the Privacy-Preserving Record Linkage (PPRL). They also should implement and document strategies for avoiding redundancies, inconsistencies and gaps in data.
• Lengthier example analyses. Appendix B of the guidance contains examples of how FDA may consider RWE in regulatory decision-making, and was expanded in the final version to include more detailed examples for RWE use to support a new PMA approval, expanded indications for use, 522 responses, and a de novo grant, among other uses. In particular, the final version of the guidance expounds on FDA’s clarification of how device sponsors using RWE should account for potential differences from control groups.

FDA writes that it does not expect industry to start “operationalizing” the recommendations in this guidance until February 16, 2026; however, the agency also says it will be able to “review any such information if submitted at any time,” meaning that medical device sponsors may start incorporating any new recommendations regarding RWE into product applications today.

FDA mulls guidance on RWE for drug & biologic reviews

In addition to its new guidance on RWE for device reviews, FDA had publicly indicated the agency’s intent to consider updating its guidance for use of RWE to support decision-making also for drugs and biologics. On December 15, FDA issued a press release – which applies to drugs and biologics as well as medical devices – stating that the agency will accept RWE without requiring that identifiable individual patient data collected from RWD sources always be submitted in a marketing submission. Instead of requiring private, confidential information at the individual patient level, FDA said its reviewers will now consider the strength of submitted RWE on an application-by-application basis.

FDA pointed out in its press release that this policy change opens the door to using de-identified databases containing millions of patient records, “including national cancer registries like the National Cancer Institute’s Surveillance, Epidemiology, and End Results, hospital systems databases, insurance claims databases, and electronic health record networks.”

The press release indicates that FDA “intends to consider” updating its guidance on how FDA may use RWE to support regulatory decision-making for drug and biologics; the agency’s most recent guidance document on this topic was issued in August 2023. We will continue to monitor whether FDA updates its guidance and whether the updated guidance tracks the significant flexibility forecasted in the press release.

Next steps

Although the press release announcing this guidance seems to present a shift in the FDA’s willingness to review and accept RWE, taking into account the minimal changes in the finalized device guidance, it remains to be seen whether there will in fact be a broader willingness to utilize such datasets for regulatory decision-making by FDA’s device center.

Nevertheless, developing a shared understanding of the collection of RWD and use of RWE to inform regulatory decision-making has been an agency-wide strategic priority since the RWE Program was initiated in 2018. Given their expanding efforts to provide clarity in this arena, we see the agency as further acknowledging the impact that data from electronic health records (EHRs), medical claims, disease registries, and digital drug development tools can have on approval decisions.

Consistent with other agency guidance, when seeking to use RWD to support regulatory decisions for medical product development, sponsors should consult with FDA early in the planning of a study, including considering sharing protocols for data collection with FDA. We recommend trying to reach as much agreement as possible with FDA, as early in the product development timeline as possible, as to the specific data and evidence that will be needed to support product approval or licensure. If you have any questions on utilizing real-world data in medical device, drug, or biologics applications, or on clinical study design more generally, feel free to contact any of the authors of this alert or the Hogan Lovells attorney with whom you regularly work.

Authored by Melissa Bianchi, Lina Kontos, Kristin Zielinski Duggan, Robert Church, Melissa Levine, Heidi Gertner, Elizabeth Jungman, and Randy Prebula