Clinical validity: defining biomarker performance.

Abstract

A central phase in the evaluation of a biomarker is the assessment of its clinical validity. In most cases, clinical validity will be expressed in terms of the marker's diagnostic accuracy: the degree to which it can be used to identify diseased patients or, more generally, patients with the target condition. Diagnostic accuracy is evaluated in diagnostic accuracy 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. We present an overview and a critical commentary of the available measures. We classify them as error-based measures, information-based measures, and measures of the strength of the association.The diagnostic accuracy is not a fixed property of a marker. All accuracy measures may vary between studies, not just through chance, but also with changes in the definition of the target condition, the spectrum of disease, the setting, and the amount of prior testing. We discuss the relativity of the claim that likelihood ratios are a superior way of expressing the accuracy of biomarkers, and defend the use of the sometimes downgraded statistics sensitivity and specificity.