Designing Rigorous and Efficient Clinical Utility Studies for Early Detection Biomarkers

Area of Science:

• Biomedical research
• Clinical trial design
• Biomarker development

Background:

• Clinical utility of biomarkers requires demonstrating positive patient outcomes through actionable clinical decisions.
• Early detection utility trials, particularly those focused on mortality, face significant cost and time challenges.
• Specialized design considerations are essential for accurately assessing early detection assays.

Purpose of the Study:

• To outline a recommended process for conducting single-organ biomarker-driven clinical utility studies.
• To present early detection utility studies within a phased biomarker development framework.
• To discuss design aspects including biomarker test features, clinical endpoints, performance criteria, and sample size.

Main Methods:

• Review and discussion among National Cancer Institute's Early Detection Research Network investigators.
• Exploration of novel adaptive design approaches for enhanced trial efficiency and practicality.
• Integration of real-world evidence, emulated trials, and mathematical modeling.

Main Results:

• A framework for phased biomarker development and clinical utility assessment is presented.
• Key study design elements for biomarker utility trials are detailed.
• Adaptive designs and alternative evidence sources are proposed to overcome trial challenges.

Conclusions:

• Establishing biomarker clinical utility necessitates rigorous study designs that address practical challenges.
• Novel adaptive designs and the integration of real-world evidence can improve the efficiency of clinical utility trials.
• A multi-strategy approach is recommended for successful early detection utility studies.