Use of External Controls in Regulatory Decision-Making.

The expanded use of electronic data retrieval systems has greatly expanded the potential sources of real-world data and presents new opportunities for evidence generation outside of the traditional research trial. These data may be used to inform trial design and interpretation as well. Externally controlled trials, such as single-arm and noninferiority designs, have long been used in regulatory decision-making despite the potential flaws based on assumptions of assay sensitivity and constancy.