Determination of serum soluble transferrin receptor (sTfR) is proposed to distinguish between iron-deficiency anemia and anemia of chronic disease. Here we conducted a meta-analysis of the literature to evaluate the diagnostic efficacy of sTfR and sTfR/log ferritin index. The meta-analysis included 18 sTfR and 10 sTfR index studies. Three sTfR index studies were, however, eliminated as outliers. The odds ratio was significant for both sTfR (22.9, 95% confidence interval [CI], 9.6-55.0) and sTfR index (9.5, 95% CI, 5.0-18.1) in a heterogeneous set of studies. Meta-analysis for sensitivity, specificity, and likelihood ratios (LRs) was performed only in a subset of 10 sTfR studies. The overall sensitivity, specificity, and positive and negative LRs were 86%, 75%, 3.85, and 0.19, respectively, with an area under summary receiver operating characteristic curve of 0.912 (standard error, 0.039). Additional studies are needed to define the overall diagnostic accuracy of sTfR.

Abstract:The measurement uncertainty budget should combine the uncertainty of higher order references, the uncertainty of commercial system calibration, the system imprecision and individual laboratory performance in terms of variability. Here we recommend that no more than one third of the total uncertainty budget, established by appropriate analytical performance specifications, is consumed by the uncertainty of references and approximately 50% of the total budget consumed by the manufacturer's calibration and value transfer protocol. The remaining 50% should be available for the commercial system imprecision (including the batch to batch variation of the reagents) and individual laboratory performance in order to fulfil the uncertainty goal. For commercial systems to work properly, in vitro diagnostics (IVD) manufacturers will need to take more responsibility and ensure the traceability of the combination of platform, reagents, calibrators and control materials for system alignment verification that only as such (as a whole) are certified ("CE marked") by the manufacturer itself in terms of traceability to the selected reference measurement system. Particularly, IVD manufacturers should report the combined (expanded) uncertainty associated with their calibrators when used in conjunction with other components of their analytical system (platform and reagents). This is more than what they are currently providing as traceability and uncertainty information.

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The goal of standardization for measurement of the catalytic concentration of enzymes is to achieve comparable results in human samples, independent of the reagent kits, instruments, and laboratory where the assay is performed. To pursue this objective, the IFCC has established reference systems for the most important clinical enzymes. These systems are based on the following requirements: a) reference methods, well described and evaluated extensively; b) suitable reference materials; and c) reference laboratories operating in a highly controlled manner. When these reference systems are used appropriately, the diagnostic industry can assign traceable values to commercial calibrators. Clinical laboratories that use procedures with validated calibrators to measure human specimens can now obtain values that are traceable to higher-order reference procedures. These reference systems constitute the structure of the traceability chain to which the routine methods can be linked via an appropriate calibration process, provided that they have a comparable specificity (i.e., they are measuring the same catalytic quantity).

International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has established reference measurement procedures (RMPs) for the most popular enzymes. Manufacturers should assign values to commercial calibrators traceable to these RMPs to achieve equivalent results in clinical samples, independent of reagent kits, instruments, and laboratory where the measurement is carried out. The situation is, however, far from acceptable. Some manufacturers continue to market assays giving results that are not traceable to internationally accepted RMPs. Meanwhile, end-users often do not abandon assays with demonstrated insufficient quality. Of the enzyme measurements, creatine kinase (CK) is satisfactorily standardized and a substantial improvement in performance of marketed γ-glutamyltranspeptidase (GGT) assays has been demonstrated. Conversely, aminotransferase measurements often exceed the desirable analytical performance because of the lack of pyridoxal-5-phosphate addition in the commercial reagents. Measurements of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and α-amylase (AMY) still show major disagreement, suggesting the need for improvement in implementing traceability to higher-order references. This is mainly the result of using assays with different analytical selectivities for these enzymes. The definition by laboratory professionals of the clinically acceptable measurement uncertainty for each enzyme together with the adoption by EQAS of commutable materials and use of an evaluation approach based on trueness represent the way forward for reaching standardization in clinical enzymology.

Laboratory medicine is amongst the fastest growing fields in medicine, crucial in diagnosis, support of prevention and in the monitoring of disease for individual patients and for the evaluation of treatment for populations of patients. Therefore, high quality and safety in laboratory testing has a prominent role in high-quality healthcare. Applied knowledge and competencies of professionals in laboratory medicine increases the clinical value of laboratory results by decreasing laboratory errors, increasing appropriate utilization of tests, and increasing cost effectiveness. This collective paper provides insights into how to validate the laboratory assays and assess the quality of methods. It is a synopsis of the lectures at the 15th European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Continuing Postgraduate Course in Clinical Chemistry and Laboratory Medicine entitled "How to assess the quality of your method?" (Zagreb, Croatia, 24-25 October 2015). The leading topics to be discussed include who, what and when to do in validation/verification of methods, verification of imprecision and bias, verification of reference intervals, verification of qualitative test procedures, verification of blood collection systems, comparability of results among methods and analytical systems, limit of detection, limit of quantification and limit of decision, how to assess the measurement uncertainty, the optimal use of Internal Quality Control and External Quality Assessment data, Six Sigma metrics, performance specifications, as well as biological variation. This article, which continues the annual tradition of collective papers from the EFLM continuing postgraduate courses in clinical chemistry and laboratory medicine, aims to provide further contributions by discussing the quality of laboratory methods and measurements and, at the same time, to offer continuing professional development to the attendees.

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