ABSTRACT
This chapter presents an overview of how to adopt external control using Real-world data and historical control in clinical development. External control using real-world evidence and historical data are playing an important role in the clinical development and drug evaluation. The chapter demonstrates the use of external control in clinical development and approval in two parts: single-arm trials using external control for the new drug application/biologic license application and comparison across trials with historical control for label expansion. It provides the important considerations when designing studies and analyzing data using external control in clinical development including study selection, comparability of the data, choice of propensity score model, baseline covariates selection and checking, sensitivity analysis and prospectively plan of study using external control. Without comparability between groups in terms of baseline covariates and outcome measurement, the estimation of treatment effect is biased, so the results cannot be used in the confirmatory trials.
