ABSTRACT
Data from randomized controlled trials (RCTs) have traditionally played a primary role in regulatory decision-making. However, the increasing cost of clinical development coupled with challenges in studying hard-to-reach populations, rare diseases, and rare endpoints (such as for safety outcomes), along with a general lack of understanding as to how medical products are used in practice, has motivated regulators and pharmaceutical industry sponsors to explore the utility of other sources of data. The 21st Century Cures Act passed by the US Congress in 2016 empowers the US Food and Drug Administration to allow evidence from real-world data (RWD) sources to support new indications for approved drugs or to support or satisfy post-approval regulatory requirements. In this chapter, we provide an overview of RWD, discuss methods to account for confounding in observational studies, describe ways to utilize evidence from RWD alone or in conjunction with data from RCTs to answer important safety questions, and discuss the challenges and benefits of their inclusion into an analysis to support the regulatory decision-making process on product safety.
