Using real world data to support regulatory approval of drugs in rare diseases: A review of opportunities, limitations & a case example.

Conducting clinical research in patients with rare diseases presents a variety of challenges. At the same time, rare diseases represent a large area of unmet medical need with a significant burden of morbidity throughout the world. One of the most common issues with designing clinical trials for rare disease populations is that the gold-standard randomized controlled trial design is often not feasible in these small and usually geographically dispersed populations. Real world data therefore has particular relevance in the rare disease setting, where it may be used as a comparator for single-arm treatment trials and in support of submissions to regulatory agencies for drugs to treat these conditions. In this report, we review the potential utility and limitations of external controls for regulatory approval of drugs in rare diseases and present a recent case example of the successful utilization of external controls in the Neurofibromatosis type 1 (NF1) population.