Abstract
Biomarkers have an important influence on the clinical decision-making processes involved in diagnosis, assessment of disease activity, allocation of treatment, and determining prognosis. The clinical usefulness of a biomarker is dependant on demonstration of its validity. Ideally, biomarkers should provide information not available from currently available tests and should be tested as they would be used in clinical practice; however, potential biomarkers could be affected by many different clinical or patient variables-such as disease activity, therapeutic intervention, or the presence of comorbidities--and validation studies might not include all the design features that are required to ensure that the biomarker is a true measure of the clinical process it is intended to reflect. In this Review, we appraise studies that have been conducted to validate six promising new biomarkers for diagnosis, disease activity assessment, or prognosis in patients with systemic autoimmune diseases. We discuss the validity of these six biomarkers with particular reference to the features of the studies that lend weight to or distract from their findings. The intent of this discussion is to draw attention to elements of validation study design that should be considered when evaluating the robustness of a biomarker, which differ according to the marker's intended use.