Evaluation of a Reference Material for Glycated Haemoglobin

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The global impact of the International Federation of Clinical Chemistry and Laboratory Medicine, Education and Management Division: engaging stakeholders and assessing HbA1c quality in a multicentre study across China

Background: Diabetes mellitus is a major global issue and high quality testing is essential for the diagnosis and treatment of the disease. The IFCC Committee for the Education in the Utility of Biomarkers in Diabetes (C-EUBD) plays a global role in improving knowledge and understanding around diabetes testing. This paper describes a multi-stakeholder approach, to improving diagnostic and therapeutic testing for diabetes, using a multicentre study in China as an example of the global impact of the group. Methods: Educational workshops were developed to support the scientific aims of the study in which 30 centres around China received identical, fresh frozen whole blood samples with values assigned using IFCC secondary reference methods and undertook precision (EP-5) and trueness studies. Performance was assessed using sigma metrics. Results: A successful multi-stakeholder group was developed and sustained throughout the study through several educational workshops, which enabled the formation of a long-term collaboration with key opinion leaders and policy makers in China. All 30 centres showed good performance with within and between laboratory coefficient of variations (CVs) below 3% in SI units at both low and high haemoglobin A1c (HbA1c) levels. All individual laboratories met the criteria of a sigma of two or more at a total allowable error (TAE) of 5 mmol/mol (0.46% NGSP). Conclusions: The study led to a successful multi-partner approach to improving diabetes testing in China. All centres involved in the study meeting the published IFCC quality criteria, paving the way for future clinical trials and an expanded role for HbA1c testing across the country

Performance of laboratory tests used to measure blood phenylalanine for the monitoring of patients with phenylketonuria

Analysis of blood phenylalanine is central to the monitoring of patients with phenylketonuria (PKU) and age‐related phenylalanine target treatment‐ranges (0‐12 years; 120‐360 μmol/L, and >12 years; 120‐600 μmol/L) are recommended in order to prevent adverse neurological outcomes. These target treatment‐ranges are based upon plasma phenylalanine concentrations. However, patients are routinely monitored using dried bloodspot (DBS) specimens due to the convenience of collection. Significant differences exist between phenylalanine concentrations in plasma and DBS, with phenylalanine concentrations in DBS specimens analyzed by flow‐injection analysis tandem mass spectrometry reported to be 18% to 28% lower than paired plasma concentrations analyzed using ion‐exchange chromatography. DBS specimens with phenylalanine concentrations of 360 and 600 μmol/L, at the critical upper‐target treatment‐range thresholds would be plasma equivalents of 461 and 768 μmol/L, respectively, when a reported difference of 28% is taken into account. Furthermore, analytical test imprecision and bias in conjunction with pre‐analytical factors such as volume and quality of blood applied to filter paper collection devices to produce DBS specimens affect the final test results. Reporting of inaccurate patient results when comparing DBS results to target treatment‐ranges based on plasma concentrations, together with inter‐laboratory imprecision could have a significant impact on patient management resulting in inappropriate dietary change and potentially adverse patient outcomes. This review is intended to provide perspective on the issues related to the measurement of phenylalanine in blood specimens and to provide direction for the future needs of PKU patients to ensure reliable monitoring of metabolic control using the target treatment‐ranges

A Review of the Challenge in Measuring Hemoglobin A1c

The attraction of the simple biochemical concept combined with a clinical requirement for a long-term marker of glycolic control in diabetes has made hemoglobin A1c (HbA1c) one of the most important assays undertaken in the medical laboratory. The diversity in the biochemistry of glycation, clinical requirements, and management demands has resulted in a broad range of methods being developed since HbA1c was described in the late 1960s. A range of analytic principles are used for the measurement of HbA1c. The charge difference between hemoglobin A0 and HbA1c has been widely utilized to separate these two fractions, most notably found these days in ion-exchange high-performance liquid chromatography systems; the difference in molecular structure (affinity chromatography and immunochemical methods) are becoming widely available. Different results found in different laboratories using a variety of HbA1c analyses resulted in the need for standardization, most notably in the United States, Japan, and Sweden. Designated comparison methods are now located in these three countries, but as they are arbitrarily chosen and have differences in specificity, results of these methods and the reference values and action limits of the methods differ and only harmonized HbA1c in specific geographic areas. A reference measurement system within the concept of metrological traceability is now globally accepted as the only valid analytic anchor. However, there is still discussion over the units to be reported. The consensus statement of the International Federation of Clinical Chemistry (IFCC), the American Diabetes Association, the International Diabetes Federation, and the European Association for the Study of Diabetes suggests reporting HbA1c in IFCC units (mmol/mol), National Glycohemoglobin Standardization Program units (%), and estimated average glucose (either in mg/dl or mmol/liter). The implementation of this consensus statement raised new questions, to be answered in a concerted action of clinicians, biochemists, external quality assessment organizers, patient groups, and manufacturers

HbA1c Standardisation: History, Science and Politics

Significant analytical improvements have occurred since glycated haemoglobin (GHb), measured as total HbA1, was first used in routine clinical laboratories around 1977. Following the publication of the Diabetes Control and Complications Trial (DCCT) study in 1993 the issue of international standardisation became an important objective for scientists and clinicians. The lack of international standardisation led several countries to develop national standardisation programs. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Working Group on Standardisation of HbA1c established a true international reference measurement system for HbA1c and the successful preparation of pure HbA1c calibration material that should lead to further improvements in inter-method and inter-laboratory variability. Reporting of HbA1c has been agreed using the units of mmol/mol (IFCC) and percent (National Glycohemoglobin Standardization Program, NGSP)

Optimizing hepcidin measurement with a proficiency test framework and standardization improvement

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Feasibility for aggregation of commutable external quality assessment results to evaluate metrological traceability and agreement among results.

Objectives External quality assessment (EQA) with commutable samples is used for assessing agreement of results for patients' samples. We investigated the feasibility to aggregate results from four different EQA schemes to determine the bias between different measurement procedures and a reference target value. Methods We aggregated EQA results for creatinine from programs that used commutable EQA material by calculating the relative difference between individual participant results and the reference target value for each sample. The means and standard errors of the means were calculated for the relative differences. Results were partitioned by methods, manufacturers and instrument platforms to evaluate the biases for the measurement procedures. Results Data aggregated for enzymatic methods had biases that varied from -8.2 to 3.8% among seven instrument platforms for creatinine at normal concentrations (61-85 μmol/L). EQA schemes differed in the evidence provided about the commutability of their samples, and in the amount of detail collected from participants regarding the measurement procedures which limited the ability to sub-divide aggregated data by instrument platforms and models. Conclusions EQA data could be aggregated from four different programs using different commutable samples to determine bias among different measurement procedures. Criteria for commutability for EQA samples as well as standardization of reporting the measurement methods, reagents, instrument platforms and models used by participants are needed to improve the ability to aggregate the results for optimal assessment of performance of measurement procedures. Aggregating data from a larger number of EQA schemes is feasible to assess trueness on a global scale

Allergy: Evaluation of 16 years (2007–2022) results of the shared external quality assessment program in Belgium, Finland, Portugal and The Netherlands

Objectives: This paper evaluates 16 year results of the Allergy EQA program shared by EQA organisers in Belgium, Finland, Portugal, and The Netherlands. Methods: The performance of Thermo Fisher and Siemens user groups (in terms of concordance between both groups, between laboratory CV, prevalence of clinically significant errors) and suitability of samples (stability and validity of dilution of patient samples) are evaluated using data of 192 samples in the EQA programs from 2007 to 2022. Measurands covered are total IgE, screens and mixes, specific IgE extracts and allergen components. Results: There is perfect (53 %), acceptable (40 %) and poor (6 %) concordance between both method groups. In case of poor concordance the best fit with clinical data is seen for Thermo Fisher (56 %) and Siemens (26 %) respectively. The between laboratory CV evolves from 7.8 to 6.6 % (Thermo Fisher) and 7.3 to 7.7 % (Siemens). The prevalence of blunders by individual laboratories is stable for Siemens (0.4 %) and drops from 0.4 to 0.2 % for Thermo Fisher users. For IgE, the between year CV of the mean of both user groups is 1 %, and a fifteen-fold dilution of a patient sample has an impact of 2 and 4 % on the recovery of Thermo Fisher and Siemens user groups. Conclusions: The analytical performance of Thermo Fisher is slightly better than that of Siemens users but the clinical impact of this difference is limited. Stability of the sample and the low impact of dilution on the recovery of measurands demonstrates the suitability for purpose of the EQA program.info:eu-repo/semantics/publishedVersio