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Calibration 2.000 was initiated 20 years ago for standardization and harmonization of medical tests. The program also intended to evaluate adequate implementation of the In Vitro Diagnostics (IVD) 98/79/EC directive, in order to ensure that medical tests are fit-for-clinical purpose. The Calibration 2.000 initiative led to ongoing verification of test standardization and harmonization in the Netherlands using commutable external quality assessment (EQA)-tools and a type 1 EQA-design, where feasible. National support was guaranteed by involving all laboratory professionals as well as laboratory technicians responsible for EQA and quality officers. A category 1 EQA-system for general chemistry analytes, harmonizers for specific analytes like hGH and IGF-1, and commutable materials for other EQA-sections have been developed and structurally introduced in the EQA-schemes. The type 1 EQA-design facilitates the dialogue between individual specialists in laboratory medicine and the IVD-industry to reduce lot-to-lot variation and to improve standardization. In such a way, Calibration 2.000 sheds light on the metrological traceability challenges that we are facing and helps the laboratory community to get the issues on the table and resolved. The need for commutable trueness verifiers and/or harmonizers for other medical tests is now seen as paramount. Much knowledge is present in the Netherlands and for general chemistry, humoral immunology and protein chemistry, a few endocrinology tests, and various therapeutic drug monitoring (TDM) tests, commutable materials are available. Also the multi sample evaluation scoring system (MUSE) and the category 1 EQA-design offer many possibilities for permanent education of laboratory professionals to further improve the between and within laboratory variation and the test equivalence. [ABSTRACT FROM AUTHOR]

Background: For the analysis of 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine ribonucleotides (6-MMPR), no external quality assessment scheme (EQAS) is currently available and no quality control samples can be made because of the absence of pure substances. An experimental design is tested to compare laboratory analytical results. Methods: In this EQAS, participating laboratories were asked to select patient samples from their routine analysis and exchange these with a coupled laboratory. Because of large differences in results between laboratories, all standard operating procedures were reviewed, revealing that the origin of these differences could be in the method of hydrolysis and the preparation of calibrators. To investigate the contribution of the calibrators to these differences, one participating laboratory was asked to prepare a batch of calibrators to be shipped to the participating laboratories for analysis. Results: Results for 6-TGN differed more between laboratories, compared with results for 6-MMPR. For 6-TGN and 6-MMPR 43% and 24% of the results, respectively, were out of the 80%-120% range. When correcting the results from the exchange of the patient samples with the results of the calibrators, the mean absolute difference for 6-TGN improved from 24.8% to 16.3% (p < 0.001), while the results for 6-MMPR worsened from 17.3% to 20.0% (p = 0.020). Conclusions: This first EQAS for thiopurine drugs shows that there is a difference between laboratories in the analysis of 6-TGN, and to a lesser extent in the analysis of 6-MMPR. This difference for 6-TGN can partially be explained by the use of in-house-prepared calibrators that differ among the participants. [ABSTRACT FROM AUTHOR]

Background: To provide its participants with an external quality assessment system (EQAS) that can be used to check trueness, the Dutch EQAS organizer, Organization for Quality Assessment of Laboratory Diagnostics (SKML), has innovated its general chemistry scheme over the last decade by introducing fresh frozen commutable samples whose values were assigned by Joint Committee for Traceability in Laboratory Medicine (JCTLM)-listed reference laboratories using reference methods where possible. Here we present some important innovations in our feedback reports that allow participants to judge whether their trueness and imprecision meet predefined analytical performance specifications. Methods: Sigma metrics are used to calculate performance indicators named 'sigma values'. Tolerance intervals are based on both Total Error allowable (TEa) according to biological variation data and state of the art (SA) in line with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Milan consensus. Results: The existing SKML feedback reports that express trueness as the agreement between the regression line through the results of the last 12 months and the values obtained from reference laboratories and calculate imprecision from the residuals of the regression line are now enriched with sigma values calculated from the degree to which the combination of trueness and imprecision are within tolerance limits. The information and its conclusion to a simple two-point scoring system are also graphically represented in addition to the existing difference plot. Conclusions: By adding sigma metrics-based performance evaluation in relation to both TEa and SA tolerance intervals to its EQAS schemes, SKML provides its participants with a powerful and actionable check on accuracy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Point-of-care glucose meters are used increasingly in semi- and non-professional context. The quality of glucose measurements depends on the quality of the equipment, the quality of use, and the pre-analytical conditions. In this article, a External Quality Assessment Scheme (SKML)-Quality Mark for point-of-care test (POCT) and self-test glucose meters is proposed, assessing analytical quality and technical quality. The analytical requirements are based on the biological variation concept, and a system to assess meters for the SKML-Quality Mark is described. Using the proposed system as an example, 14 meters were tested. Methods: The analytical quality of the POCT and self-test equipment was assessed for plasma calibrated glucose values by comparison with a trueness verified method traceable to the IFCC reference method in an accredited clinical laboratory. The concept is based on the biological variation system. The SKML-Quality Mark comprises the following criteria for blood glucose equipment: 1) Fulfilment of compliance with ISO 15197 and/or TNO guideline criterion; 2) Fulfilment of the total allowable error (TAE) criterion; 3) Fulfilment of the total allowable linearity bias criterion; 4) Fulfilment of the total allowable interfering substances bias criterion; and 5) Fulfilment of the haematocrit criterion. Results: The proposed SKML-Quality Mark system was tested on 14 commercial home-use meters. The TAE criterion is violated by two meters. The main reason for the violation is bias. For the majority of meters, the Passing and Bablok regression confidence interval does not include the intercept of 0.0 and slope of 1.0. In addition, Syx indicates dispersion around the line or non-linearity. The bias and total error at three different concentrations were investigated as part of the quality mark, resulting in disapproval of the Dicomed Sensocard Plus meter. The bias was significant for the Wellion Linus. With respect to interfering substances, bias of the same magnitude and sign as the bias without additive was seen for all meters for acetaminophen, indicating no additional interference. For ascorbic acid, an additional bias was seen for several meters. However, significant bias was demonstrated for the Sensocard Plus and Glucocard X-meter. Conclusions: The biological variation concept offers a scientific basis for assessment of acceptable deviation. The concept is extended in the SKML-Quality Mark correcting for the limited number of measurements that can be performed while assessing home-use or POCT meters. The results show that three out of 14 meters fail the proposed quality mark. Clin Chem Lab Med 2010;48:1021–7. [ABSTRACT FROM AUTHOR]