Harmonization of Clinical Laboratory Test Results: The Role of the IVD Industry.

At the start of the 21st century, a dramatic change occurred in the clinical laboratory community. Concepts from Metrology, the science of measurement, began to be more carefully applied to the in vitro diagnostic (IVD) community, that is, manufacturers. A new appreciation of calibrator traceability evolved. Although metrological traceability always existed, it was less detailed and formal. The In Vitro Diagnostics Directive (IVDD) of 2003 required manufacturers to provide traceability information, proving assays were anchored to internationally accepted reference materials and/or reference methods. The intent is to ensure comparability of patient test results, regardless of the analytical system used to generate them. Results of equivalent quality allows for the practical use of electronic health records (EHRs) capture a patient's complete laboratory test history and allow healthcare providers to diagnose and treat patients, confident the test results are suitable for correct interpretation, i.e., are "fit for purpose" and reflect a real change in a patient's condition and not just "analytical noise." The healthcare benefits are obvious but harmonization of test systems poses significant challenges to the IVD Industry. Manufacturers must learn the theory of metrological traceability and apply it in a practical manner to assay calibration schemes. It's difficult to effect such a practical application because clinical laboratories do not test purified analytes using reference measurement procedures but instead deal with complex patient samples, e.g., whole blood, serum, plasma, urine, etc., using "field methods." Harmonization in the clinical laboratory is worth the effort to achieve optimal patient care.

Sigma metrics used to assess analytical quality of clinical chemistry assays: importance of the allowable total error (TEa) target.

BACKGROUND: Six Sigma metrics were used to assess the analytical quality of automated clinical chemistry and immunoassay tests in a large Belgian clinical laboratory and to explore the importance of the source used for estimation of the allowable total error. Clinical laboratories are continually challenged to maintain analytical quality. However, it is difficult to measure assay quality objectively and quantitatively. METHODS: The Sigma metric is a single number that estimates quality based on the traditional parameters used in the clinical laboratory: allowable total error (TEa), precision and bias. In this study, Sigma metrics were calculated for 41 clinical chemistry assays for serum and urine on five ARCHITECT c16000 chemistry analyzers. Controls at two analyte concentrations were tested and Sigma metrics were calculated using three different TEa targets (Ricos biological variability, CLIA, and RiliBÄK). RESULTS: Sigma metrics varied with analyte concentration, the TEa target, and between/among analyzers. Sigma values identified those assays that are analytically robust and require minimal quality control rules and those that exhibit more variability and require more complex rules. The analyzer to analyzer variability was assessed on the basis of Sigma metrics. CONCLUSIONS: Six Sigma is a more efficient way to control quality, but the lack of TEa targets for many analytes and the sometimes inconsistent TEa targets from different sources are important variables for the interpretation and the application of Sigma metrics in a routine clinical laboratory. Sigma metrics are a valuable means of comparing the analytical quality of two or more analyzers to ensure the comparability of patient test results.

Defining acceptable limits for the metrological traceability of specific measurands.

Although manufacturers are compelled by the European IVD Directive, 98/79/EC, to have traceability of the values assigned to their calibrators if suitable higher order reference materials and/or procedures are available, there is still no equivalence of results for many measurands determined in clinical laboratories. The adoption of assays with metrological traceable results will have a significant impact on laboratory medicine in that results will be equivalent across different laboratories and different analytical platforms. The IFCC WG on Allowable Errors for Traceable Results has been formed to define acceptable limits for metrological traceability chains for specific measurands in order to promote the equivalence of patient results. These limits are being developed based on biological variation for the specific measurands. Preliminary investigations have shown that for some measurands, it is possible for manufacturers to assign values to assay calibrators with a measurement uncertainty that allows the laboratory enough combined uncertainty for their routine measurements. However, for other measurands, e.g., plasma sodium, current assays are too imprecise to fulfil limits based on biological variation. Although an alternative approach based on probability theory is being investigated, the most desirable approach would be for industry to improve measurement methods so that they meet clinical requirements.