Need for discriminating between diagnostic and screening efficacy to estimate a biomarker based on case control and cohort studies.

This study proposes the comprehensive index of biomarker (CIB), based on the consistency of a biomarker in case control (Youden index, J) and cohort studies (Crc), to evaluate biomarker efficacy. CIB was calculated as the mean of J and Crc. Analysis of the effect of sensitivity and specificity on CIB and ROC analysis of CIB were performed in simulated and actual datasets. J and CIB had similar values for high-probability events (say probability was 0.50), but there was a significant difference between J and CIB for low-probability events (say probability was 0.05). Therefore, as the subjects considered for diagnosis are usually symptomatic, the occurrence of a disease can be assumed to be a high-probability event. In contrast, as the subjects considered in screening for a disease are usually healthy and asymptomatic, the occurrence of a disease is assumed to be a low-probability event. Although J is the common index used to evaluate the diagnostic effectiveness, unfortunately, the J value is significantly larger than CIB value in a low-probability event, showing overestimation for screening purpose. CIB could have more potential than J for determining the screening efficacy of a biomarker. The efficacy of a biomarker could differ for diagnostic, screening, predictive, and prognostic purposes, and it would be better to evaluate the efficacy of biomarkers for specific systems or contexts.