Early-Phase Studies of Biomarkers: What Target Sensitivity and Specificity Values Might Confer Clinical Utility?

Background: Many cancer biomarker research studies seek to develop markers that can accurately detect or predict future onset of disease. To design and evaluate these studies, one must specify the levels of accuracy sought. However, justified target levels are rarely available.

Methods: We describe a way to calculate target levels of sensitivity and specificity for a biomarker intended to be applied in a defined clinical context. The calculation requires knowledge of the prevalence or incidence of cases in the clinical population and the ratio of benefit associated with the clinical consequences of a positive biomarker test in cases (true positive) to cost associated with a positive biomarker test in controls (false positive). Guidance is offered on soliciting the cost/benefit ratio. The calculations are based on the longstanding decision theory concept of providing a net benefit on average in the population, and they rely on some assumptions about uniformity of costs and benefits to those tested.

Results: Calculations are illustrated with 3 applications: predicting colon cancer recurrence in stage 1 patients; predicting interval breast cancer (between mammography screenings); and screening for ovarian cancer.

Conclusions: It is feasible to specify target levels of biomarker performance that enable evaluation of the potential clinical impact of biomarkers in early-phase studies. Nevertheless, biomarkers meeting the criteria should still be tested rigorously in studies that measure the actual impact on patient outcomes of using the biomarker to make clinical decisions.