External control arms in oncology: current use and future directions

Highlights

• Considerations for the use of external controls in oncology clinical trials are multifaceted and depend on the intended use.

• Review of recent research and some marketing applications describe current usage of external control data in oncology.

• Including external controls for primary evidence of efficacy requires careful pre-specification of study design elements.

Although randomized control trials allow for a comparison of treatment arms with minimal concern for confounding by known and unknown factors, a randomized study is not feasible in certain disease settings. When a randomized design is not possible, incorporating external control data into the study design can be an effective way to expand the interpretability of the results of an experimental arm by introducing the ability to carry out a formal or an informal comparative analysis. This paper provides an introduction to the concepts of external controls in oncology trials, followed by a review of relevant and current research on this topic. The paper also focuses on general considerations for designing a trial that may incorporate external control data, followed by case studies of the marketing applications submitted to the Food and Drug Administration that included external control data.