Methods for external control groups for single arm trials or long‐term uncontrolled extensions to randomized clinical trials Seeger et al.

Abstract

1. External controls may be needed to provide context to efficacy and/or safety in a trial that is single-arm or becomes single-arm (through a long-term extension). 2. Selection of an appropriate, fit-for-purpose data source is important. 3. Both selection bias and information bias need to be addressed in the design and analysis. 4. Historical examples are illustrative for key concepts and not exhaustive. 5. Until guidance is codified in the countries of interest, health authority input in advance is useful. 1## BACKGROUND Patient clinical experiences and outcomes are enormously complex and va