OBJECTIVES: The U.S. Food and Drug Administration (FDA) and other regulatory agencies are committed to advancing real-world data (RWD) and real-world evidence (RWE) use in regulatory decisions. The purpose of this review was to assess the current applications of RWD/RWE to clinical research, including novel methodology and study design, then determine the potential for using RWD/RWE to streamline pre-market regulatory approvals for biosimilars and interchangeable biologics.

METHODS: Articles indexed in PubMed, EMBASE, CINAHL, Scopus, Web of Science, and the grey literature were identified using the following keywords: real-world data, real-world evidence, regulatory, FDA or Food and Drug Administration, EMA or European Medicines Association. There were no date restrictions or countries where studies were conducted. Included articles were published in English and assessed RWD/RWE to address a regulatory need.

RESULTS: 7,938 unique records were identified for screening. After title and abstract review, 606 were included for full-text review, including 478 that were provisionally excluded but retained to evaluate reference lists, resulting in 24 additional articles for the analysis. RWD/RWE had been clearly documented in regulatory applications for at least 18 new drugs, most commonly as external controls for single-arm trials for rare diseases, or to assess the natural history of disease as a comparator for efficacy. Pragmatic designs where the intervention was tested in a real-world treatment setting have also been used to meet clinical trial requirements. Additionally, several methods and algorithms can be applied in a regulatory context: efficacy-to-effectiveness trials to capture a real-world patient population and narrowing inclusion criteria to focus on the patient population most likely to benefit from the treatment.

CONCLUSIONS: RWD/RWE have been used rarely in regulatory decisions for new drug products. While biosimilar applications have not included RWD/RWE to date, inclusion can improve the efficiency of regulatory approval, especially for demonstrating interchangeability for FDA decisions.