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 in sample selection, outcome ascertainment, or unblinded sample handling and assaying process. The principles of a prospective-specimen collection and retrospective-blinded-evaluation (PRoBE) design can be adapted to mitigate various sources of biases in discovery. We recommend establishing quality biospecimen repositories using matched two-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 se- lection to avoid biases. Consideration of clinical application and the corresponding biomarker performance characteristics in study designs will lead to a more fruitful discovery study.
Impact: Appropriate study designs will improve the quality and clinical rigor of biomarker discovery studies.
Keywords: bias; case-cohort study; discovery study; nested case-control study; sample size; specimen repository; two-phase designs.