External control arms in oncology: current use and future directions

Area of Science:

• Oncology Clinical Trials
• Biostatistics
• Regulatory Science

Background:

• Randomized controlled trials (RCTs) are the gold standard but not always feasible in certain oncology settings.
• Confounding factors can limit the interpretability of non-randomized study designs.
• External control data offers a solution to compare experimental treatments when RCTs are not possible.

Purpose of the Study:

• To introduce the concept of external controls in oncology clinical trials.
• To review current research and general considerations for designing trials with external controls.
• To examine Food and Drug Administration (FDA) marketing applications that utilized external control data.

Main Methods:

• Literature review of external control concepts and applications in oncology.
• Analysis of general design considerations for incorporating external data.
• Case study review of FDA submissions featuring external control data.

Main Results:

• External controls can expand the interpretability of experimental arms by enabling comparative analysis.
• Successful FDA marketing applications demonstrate the utility of external control data.
• Key considerations for trial design include data quality, statistical methods, and regulatory acceptance.

Conclusions:

• External control data is a valuable tool for oncology trials where randomization is not feasible.
• Careful trial design and statistical methodology are crucial for valid comparative analyses.
• The use of external controls is supported by regulatory precedent in successful marketing applications.