FDA finalizes guidance on submitting RWD and RWE in application letters for product regulation decision-making

The FDA asks for RWD/RWE submission to support regulatory decision-making to be detailed in drug and biological product application cover letters

The US Food and Drug Administration (FDA) has published its definitive guidance for drug and biological product applications to highlight the inclusion of real-world data (RWD) and real-world evidence (RWE) to inform regulatory decision-making by specifically detailing this in covering letters. This will facilitate the FDA’s tracking and appraisal of the growing role of RWD and RWE in medical product regulation.

Ongoing evaluation of the scope and use of RWD/RWE in regulatory decision-making is one facet of the FDA’s 2018 RWE Program, a framework mandated from its 2016 21^st Century Cures Act. On Sept 8 2022, the FDA published its definitive guidance on submitting RWD/RWE in drug and biological product applications that supersedes prior draft guidance issued in 2019 and 2021.

The new guidance to summarize RWD/RWE in application cover letters applies to submissions for new drug applications, investigational new drug applications, and biological product license applications. This only applies where RWD/RWE is intended to support a regulatory decision regarding product safety and/or effectiveness, and will be included in product labelling. Applications that include RWD for other purposes, such as clinical trial planning or hypothesis generation, should not detail the RWD/RWE in the cover letter.

The agency intends to track submissions featuring RWD/RWE from an array of study designs. These include: randomized clinical trials that use RWD to determine clinical outcomes related to safety or effectiveness; single-arm studies that use RWD in an external control arm; observational studies, such as cohort and case-control studies, that generate RWE intended to help support additional efficacy indication; and clinical trials or observational studies that use RWD or RWE to fulfil a post-marketing requirement or commitment.

The FDA guidelines feature a check-box form as an appendix specifying all the information required, which is subdivided into three categories. The first covers the purposes of using RWD/RWE, e.g. to support labelling changes for an already approved product. The second is the study design deployed to use RWD to generate RWE, and the third covers the sources of RWD employed, such as electronic health record or medical claims data.

The forthcoming analyses from this extensive data capture and collation will be invaluable in the progression of unlocking the potential of RWD and RWE.