External Comparator Groups Derived from Real-world Data Used in Support of Regulatory Decision Making: Use Cases and Challenges

Real-world data (RWD) from electronic health records (EHRs) and administrative claims databases are used increasingly to generate real-world evidence (RWE). RWE is used to support clinical evidence packages for medicines that inform decision-makers. In this review of current issues in the use of RWD-derived external comparator groups to support regulatory filings, we assess a series of topics that generally apply across many disease indications. However, most of the examples and illustrations focus on the oncology clinical research setting. The topics include an overview of current uses of RWD in drug development, a discussion of regulatory filings using RWD-derived external comparators, a brief overview of guidance documents and white papers pertaining to external comparators, a summary of some limitations and methodological issues in the use of external comparator groups and finally, a look at the future of this area and recommendations.