Table 2.

Considerations when moving to a biomarker-based screening paradigm for HCC.

Issue	Potential hazards	Solutions
Test performance for early-stage HCC detection	• Inferior sensitivity to imaging-based screening	• Non-inferiority design with acceptable margin • Pragmatic trial design to incorporate the impact of adherence
False positive management	• Lack of care pathways for false positives results • Implications of a false positive result on future cancer risk	• Longitudinal trial design to understand and delineate the optimal care pathway for false positives and the associated future cancer risk
Costs	• Lack of payor coverage • Low HCC incidence will result in high numbers needed to screen for cancer detection	• Rational price setting based on cost-effectiveness analyses with contemporary inputs • Calibrate intensity of screening based on patient risk
Blood processing	• For central processing, errors in local blood collection and shipping • Lack of standardisation of results across centres for markers that are processed onsite	• Quality control for central shipping of blood samples with adequate site training • Calibration of local labs to ensure consistency of results across centres
Test reporting	• Linkage of test result back to ordering provider/patient • Providing a dichotomous or continuous test result	• Develop reporting pathways for test results • Providing continuous test results depending on assay characteristics with interpretation (positive/negative)

HCC, hepatocellular carcinoma.