Strategic Considerations for Externally Controlled Trials

This white paper presents strategic considerations for planning externally controlled single-arm trials, particularly in the context of drug development. It outlines the FDA's recommendations for designing and analyzing these trials, emphasizing the importance of addressing potential biases that may affect the validity of results. The document discusses the role of real-world data (RWD) in supporting external control arms and highlights the challenges associated with single-arm trials, including the need for careful selection of patient eligibility criteria and the handling of intercurrent events. It details the estimand framework, which defines treatment effects and includes attributes such as population and endpoints of interest. The paper also addresses the significance of comparability between trial arms and the necessity of a robust statistical analysis plan to manage missing data and other biases. Overall, the document serves as a comprehensive guide for researchers and sponsors involved in the design and execution of externally controlled trials.