Defining Biomarker Performance and Clinical Validity

In the evaluation of biomarkers three questions can be answered: what is the analytical validity of the marker, what is its clinical validity, and does the marker have clinical utility? In most cases, clinical validity will be expressed in terms of the marker's accuracy: the degree to which it can be used to correctly identify diseased patients or, more generally, patients with the target condition. Diagnostic accuracy is evaluated in studies in which the biomarker values are compared to the outcome of the clinical reference standard in the same patients. There are several ways in which the results of diagnostic accuracy studies can be summarized, reported, and interpreted. In this paper we summarize and present the available measures. We classify these as error-based measures, information-based measures, and measures of the strength of the association. Clinical validity is linked to clinical utility. If the target condition is well defined and associated with unequivocal downstream management decisions, clinical validity, when defined in comparative terms, may sometimes act as a surrogate outcome measure for clinical utility.