Imperfect gold standards for biomarker evaluation

BACKGROUND: Serum creatinine has been used as the diagnostic test for acute kidney injury (AKI) for decades despite having imperfect sensitivity and specificity. Novel tubular injury biomarkers may revolutionize the diagnosis of AKI; however, even if a novel tubular injury biomarker is 100% sensitive and 100% specific, it may appear inaccurate when using serum creatinine as the gold standard. CONCLUSIONS: In general, the apparent diagnostic performance of a biomarker depends not only on its ability to detect injury but also on disease prevalence and the sensitivity and specificity of the imperfect gold standard. Apparent errors in diagnosis using a new biomarker may be a reflection of errors in the imperfect gold standard itself rather than poor performance of the biomarker.