A Practical Approach to ISO 15189 and Measurement Uncertainty in Clinical Chemistry: Analytic Bias is Still an Important Challenge

Abstract

Measurement uncertainty is an important issue in metrology and is increasingly applied in clinical chemistry, as a requirement of the ISO 15189:2012 standard. In this work, Calcium blood testing results are considered, with reference to CLIA 88 Clinical Laboratory Amendments, for precision and accuracy levels, by combining the uncertainties associated with within-day and between-day measurements with the performance relative to the peer group of an external quality assessment using Excel tools (ANOVA). Clinical laboratory results over a 4 months period are then discussed in terms of total error for acceptable performance and medical decision levels and medical allowable errors. Repeatability and day-today variations are reduced by highly automated measurements, but bias has not been decreased to the same extent. Calibration errors in clinical tests have been related to the false diagnosis of hypercalcemia as the calcium level was overestimated. Top-down and down-top approaches were employed in comparing the clinical decisions and yielded prevalence of disease values of 6.3% and 1.4% respectively. Therefore, laboratory's decision for estimating the uncertainty in clinical measurements must be top-down approach. The method used here can similarly be extended to other blood parameters such as glucose, total cholesterol, triglycerides, etc. © 2019 Elsevier B.V., All rights reserved.