Study Design Considerations for Cancer Biomarker Discoveries

Background Biomarker discovery studies have generated an array of omic data; however, few novel biomarkers have reached clinical use. Guidelines for rigorous study designs are needed. Content Biases frequently occur during sample selection, outcome ascertainment, or unblinded sample handling and the assaying process. The principles of a prospective specimen collection and retrospective blinded evaluation design can be adapted to mitigate various sources of biases in discovery. We recommend establishing quality biospecimen repositories using matched 2-phase designs to minimize biases and maximize efficiency. We also highlight the importance of taking the clinical context into consideration in both sample selection and power calculation for discovery studies. Summary Biomarker discovery research should follow rigorous design principles in sample selection to avoid biases. Consideration of clinical application and the corresponding biomarker performance characteristics in study designs will lead to a more fruitful discovery study.