OBJECTIVES : The United States Food and Drug Administration’s (FDA) real-world evidence (RWE) framework outlines the agency’s perspective for potential uses of RWE as supported by the 21^st Centuries Cures Act. Historically, the use of RWE to support product approval has been limited. However, given increased opportunities for manufacturers to utilize RWE under the FDA framework, there is a need to characterize these instances to inform planning for future regulatory submissions. This review aims to identify and describe RWE use in previous FDA regulatory submissions.

METHODS : The Drugs@FDA database and the Center for Biologics Evaluation and Research’s (CBER) list of biologic approvals were queried for regulatory submissions from January through July 2019. Results were restricted to original therapeutic approval, efficacy, supplement, new molecular entity, and new active ingredient submissions. Supporting documents, including the most recent prescribing information, medical or multi-disciplinary review for drugs, and summary basis for regulatory action for biologics, were searched using key terms to identify RWE. Because supplements were included in the submissions reviewed, the date of original product approval ranged from 1979-2019.

RESULTS : 267 regulatory submissions were identified from Drugs@FDA and CBER biologic approvals. Key word search identified 20% (N=54) of these submissions as having an RWE component. The most common therapeutic areas included autoimmune disorders (24%, n=13), oncology (22%, n=12), and hematology (13%, n=7); 11% (n=6) of these drugs were biosimilars. A minority (33%, n=18) received expedited review by the FDA. The most common RWE submitted were observational studies (54%, n=29) and registry data (30%, n=16).

CONCLUSIONS : RWE has been used in regulatory submissions prior to the 21^st Century Cures Act; however, identifying these submissions required a detailed review of a variety of supporting documents, as there is no resource that describes these submissions in aggregate. This review highlights a need for a standardized reporting structure to document RWE submissions.