Analytical performance specifications for trace elements in biological fluids derived from six countries federated external quality assessment schemes over 10 years.

OBJECTIVES: This article defines analytical performance specifications (APS) for evaluating laboratory proficiency through an external quality assessment scheme. METHODS: Standard deviations for proficiency assessment were derived from Thompson's characteristic function applied to robust data calculated from participants' submissions in the Occupational and Environmental Laboratory Medicine (OELM) external quality assurance scheme for trace elements in serum, whole blood and urine. Characteristic function was based on two parameters: (1) ß - the average coefficient of variation (CV) at high sample concentrations; (2) α - the average standard deviation (SD) at low sample concentrations. APSs were defined as 1.65 standard deviations calculated by Thompson's approach. Comparison between OELM robust data and characteristic function were used to validate the model. RESULTS: Application of the characteristic function allowed calculated APS for 18 elements across three matrices. Some limitations were noted, particularly for elements (1) with no sample concentrations near analytical technique limit of detection; (2) exhibiting high robust CV at high concentration; (3) exhibiting high analytical variability such as whole blood Tl and urine Pb; (4) with an unbalanced number of robust SD above and under the characteristic function such as whole blood Mn and serum Al and Zn. CONCLUSIONS: The characteristic function was a useful means of deriving APS for trace elements in biological fluids where biological variation data or outcome studies were not available. However, OELM external quality assurance scheme data suggests that the characteristic functions are not appropriate for all elements.

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.

The risk of clinical misinterpretation of HbA1c: Modelling the impact of biological variation and analytical performance on HbA1c used for diagnosis and monitoring of diabetes.

BACKGROUND: The validity of clinical interpretation of HbA1c depends on the analytical performance of the method and the biological variation of HbA1c in patients. The contribution of non-glucose related factors to the biological variation of HbA1c (NGBVA1c) is not known. This paper explores the cumulative impact of analytical errors and NGBVA1c on the risk of misinterpretation. METHODS: A model has been developed to predict the risk of misinterpretation of HbA1c for diagnosis and monitoring with variables for analytical performance and levels of NGBVA1c. RESULTS: The model results in probabilities of misinterpretation for a given HbA1c. EXAMPLE: for an HbA1c 43 mmol/mol (6.1%), bias 1 mmol/mol (0.09%), CV 3% (2%) used for diagnosis, the probabilities of misinterpretation range from 1 to 19% depending on the contribution of NGBVA1c to the biological variation of HbA1c. CONCLUSIONS: In addition to analytical bias and imprecision, NGBVA1c contributes to the risk of misinterpretation, but the relative impact is different per clinical application of HbA1c. For monitoring, imprecision is the predominating factor, for diagnosis both biological variation and analytical bias. Given the increasing use of HbA1c for diagnosis, increase of knowledge on NGBVA1c, decrease of analytical bias, and awareness of the risk of misinterpretation are required.

Evaluation of the ARKRAY HA-8190V instrument for HbA1c.

OBJECTIVES: Hemoglobin A1c (HbA1c) is a valuable parameter in the monitoring of diabetic patients and increasingly in diagnosis of diabetes. Manufacturers continuously optimize instruments, currently the main focus is to achieve faster turnaround times. It is important that performance specifications remain of high enough standard, which is evaluated in this study for the new ARKRAY HA-8190V instrument. METHODS: The Clinical and Laboratory Standards Institute (CLSI) protocols EP-5, EP-9 and EP-10 were applied to investigate imprecision, bias and linearity. In addition potential interferences, performance in External Quality Assessment (EQA) and performance against the HA-8180V instrument in 220 clinical samples was evaluated. RESULTS: The HA-8190V demonstrates a CV of ≤0.8% in IFCC SI units (≤0.6% National Glycohemoglobin Standardization Program [NGSP]) at 34 and 102 mmol/mol levels (5.3 and 11.5% NGSP) and a bias of -0.1 mmol/mol (-0.01% NGSP) at a concentration of 50 mmol/mol (6.7% NGSP), but with a significant slope as compared to target values. This results in a bias of -1.0 and 0.9 mmol/mol (-2.0 and 0.9% NGSP) at the 30 and 70 mmol/mol (4.9 and 8.6% NGSP) concentration level. Simulation of participation in the IFCC certification programme results in a Silver score (bias -0.1 mmol/mol, CV 1.1%). Interference in the presence of the most important Hb variants (AS, AC, AE, AD) and elevated HbA2 and HbF concentrations is less than 3 mmol/mol (0.3% NGSP) at a concentration of 50 mmol/mol (6.7% NGSP). CONCLUSIONS: Analytical performance of the HA-8190V is very good, especially with respect to precision and HbA1c quantification in the presence of the most common Hb variants.

Optimizing hepcidin measurement with a proficiency test framework and standardization improvement.

Objectives: Hepcidin measurement advances insights in pathophysiology, diagnosis, and treatment of iron disorders, but requires analytically sound and standardized measurement procedures (MPs). Recent development of a two-level secondary reference material (sRM) for hepcidin assays allows worldwide standardization. However, no proficiency testing (PT) schemes to ensure external quality assurance (EQA) exist and the absence of a high calibrator in the sRM set precludes optimal standardization. Methods: We developed a pilot PT together with the Dutch EQA organization Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek (SKML) that included 16 international hepcidin MPs. The design included 12 human serum samples that allowed us to evaluate accuracy, linearity, precision and standardization potential. We manufactured, value-assigned, and validated a high-level calibrator in a similar manner to the existing low- and middle-level sRM. Results: The pilot PT confirmed logistical feasibility of an annual scheme. Most MPs demonstrated linearity (R2>0.99) and precision (duplicate CV>12.2%), although the need for EQA was shown by large variability in accuracy. The high-level calibrator proved effective, reducing the inter-assay CV from 42.0% (unstandardized) to 14.0%, compared to 17.6% with the two-leveled set. The calibrator passed international homogeneity criteria and was assigned a value of 9.07±0.24 nmol/L. Conclusions: We established a framework for future PT to enable laboratory accreditation, which is essential to ensure quality of hepcidin measurement and its use in patient care. Additionally, we showed optimized standardization is possible by extending the current sRM with a third high calibrator, although international implementation of the sRM is a prerequisite for its success.

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.

IFCC Working Group Recommendations for Correction of Bias Caused by Noncommutability of a Certified Reference Material Used in the Calibration Hierarchy of an End-User Measurement Procedure.

Establishing metrological traceability to an assigned value of a matrix-based certified reference material (CRM) that has been validated to be commutable among available end-user measurement procedures (MPs) is central to producing equivalent results for the measurand in clinical samples (CSs) irrespective of the clinical laboratory MPs used. When a CRM is not commutable with CSs, the bias due to noncommutability will be propagated to the CS results causing incorrect metrological traceability to the CRM and nonequivalent CS results among different MPs. In a commutability assessment, a conclusion that a CRM is commutable or noncommutable for use with a specific MP is made when the difference in bias between the CRM and CSs meets or does not meet a criterion for that specific MP when compared to other MPs. A conclusion regarding commutability or noncommutability requires that the magnitude of the difference in bias observed in the commutability assessment remains unchanged over time. This conclusion requires the CRM to be stable and no substantive changes in the MPs. These conditions should be periodically reverified. If an available CRM is determined to be noncommutable for a specific MP, that CRM can be used in the calibration hierarchy for that MP when an appropriately validated MP-specific correction for the noncommutability bias is included. We describe with examples how a MP-specific correction and its uncertainty can be developed and applied in a calibration hierarchy to achieve metrological traceability of results for CSs to the CRM's assigned value.

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.

External quality assessment schemes for inorganic elements in the clinical laboratory: Lessons from the OELM scheme.

Measurements of inorganic elements in clinical laboratories produce results used for the diagnosis, the treatment and the monitoring of deficiencies or overloads. The main objective of External Quality Assessment Schemes is to verify, on a regular frequency, that clinical laboratory results correspond to the quality requirement for patient care. Therefore, External Quality Assessment Schemes represent an essential component of a laboratory's quality management system. However, External Quality Assessment Schemes within the same analytical field remain heterogeneous for different reasons such as samples, determination of assigned value, acceptable limits, content of the reports. The aim of this review was to describe and illustrate some major critical aspects of External Quality Assessment Schemes based on Occupational and Environmental Laboratory Medicine external quality assessment scheme experience.

EQA-based evaluation of metrological traceability of clinical chemistry test results in Argentina / EQA-based evaluation of metrological traceability of clinical chemistry test results in Argentina

Equivalence of results among laboratories is a major mission for medical laboratories. In the Netherlands, medical laboratories only use homogenous, commercial for general chemistry analytes, whereas in Argentina heterogenous, home brew test applications are common. The effect of this practice difference on test accuracy is studied using key features of the accuracy-based EQA program of the Netherlands. Six frozen, human-based, commutable poolsera, covering the (patho) physiological measuring range for 17 general chemistry analytes, were assayed by ~75 Argentinian labs and ~200 Dutch laboratories in 2014. After removal of outliers, harmonization status among laboratories was evaluated by calculating overall mean interlaboratory coefficients of variation (CVs, %) per analyte and per country for all 6 levels. Evenso, standardization status was evaluated after removal of outliers by calculating overall mean recoveries (%) as compared to the assigned target values per analyte per country for all 6 levels. Absolute median biases were compared to (minimal/desirable) biases derived from biological variation criteria. For serum enzymes interlaboratory CVs in the Argentinian laboratories ranged between 10 and 22%, as compared to 3-6% in the Netherlands. For serum uric acid, creatinine, glucose and total protein, interlaboratory CVs varied between 4.3 and 13.1% in Argentinian labs, as compared to <3.5% in the Netherlands. For serum electrolytes, interlaboratory CVs ranged between 1.8 and 3.8% for Na+; 2.9-5.8% for Cl-; 3.8-7.5% for K+; 9.4-10.4% for Ca2+ and 16.2-22.3% for Mg2+ as compared to ≤2% (Na+, K+, Cl-, Ca2+) and ≤3% (Mg2+) in the Netherlands. Mean recoveries in Argentinian laboratories for e.g. serum creatinine, glucose, CK, Ca2+ and Na+ were 95-119%; 95-104%; 98-102%; 98-102% and 96-100% respectively, whereas min-max recovery ranges were 65-155%; 58-126%; 47-132%; 66-132% and 85-115%. In the Netherlands, absolute mean recoveries were overall 98.9% with a SD of 2.0%. Median biases in Argentinian laboratories ranged from -2.9 to 18.2%; -3.1 - 2.6%; -3.3 - 0.5%; -1.1 - 3.8% and -4.3-0% for serum creatinine, glucose, CK, Ca2+ and Na+. In the Netherlands overall mean/median biases were 1.1% (SD=2.0%). Exchange of commutable, value- assigned EQA-materials was helpful for studying the harmonization and standardization status of medical tests in Argentina, and for revealing the future harmonization and standardization potential. The results clearly demonstrate that metrological traceability of test results in Argentina is on average in line with what is expected; yet, the spreading among laboratories is far too high and should be improved.

La equivalencia de resultados entre laboratorios es una mision importante para los laboratorios medicos. En los Paises Bajos, los laboratorios medicos solo usan aplicaciones comerciales homogeneas, regulatoriamente aprobadas (CE-IVD) para analitos quimicos, mientras que en la Argentina son comunes las aplicaciones heterogeneas caseras. El efecto de esta diferencia practica en la precision de la prueba se estudia utilizando caracteristicas clave del programa EQA, basado en la precision, de los Paises Bajos. Se ensayaron seis pools de sueros, congelados, de origen humano, conmutables, que cubrian el rango de medidas (pato)fisiologicas para 17 analitos de quimica clinica. Estos analitos de quimica clinica fueron analizados por ~75 laboratorios argentinos y ~200 laboratorios holandeses en 2014. Despues de eliminar los valores atipicos, el estado de armonizacion entre los laboratorios fue evaluado calculando los coeficientes de variacion interlaboratorios medios globales (CV%) por analito y por pais para los 6 niveles. No obstante, el estado de estandarizacion se evaluo despues de la eliminacion de valores atipicos mediante el calculo de recuperaciones medias generales (%) en comparacion con los valores asignados por analito por pais para los 6 niveles. Los sesgos medios absolutos se compararon con los sesgos (minimos / deseables) derivados de los criterios de variacion biologica. Para enzimas sericas los CV interlaboratorio en los laboratorios argentinos oscilaron entre 10 y 22%, en comparacion con 3-6% en los Paises Bajos. Para el acido urico serico, creatinina, glucosa y proteinas totales, los CV entre laboratorios variaron entre 4,3 y 13,1% en los laboratorios argentinos, en comparacion con <3,5% en los Paises Bajos. Para los electrolitos sericos, los CV interlaboratorios oscilaron entre 1,8 y 3,8% para Na+; 2,9-5,8% para Cl-; 3,8-7,5% para K+; 9,4-10,4% para Ca2+ y 16,2-22,3% para Mg2+ en comparacion a ≤2% (Na+, K+, Cl-, Ca2+) y ≤3% (Mg2+) en los Paises Bajos. Las recuperaciones medias en laboratorios argentinos para, p.ej. la creatinina serica, glucosa, CK, Ca2+ y Na+ fueron 95-119%; 95-104%; 98-102%; 98-102% y 96-100% respectivamente, mientras que los rangos de recuperacion min-max fueron 65-155%; 58-126%; 47-132%; 66-132% y 85-115%. En los Paises Bajos, las recuperaciones medias absolutas fueron en general del 98,9% con una desviacion estandar (DE) del 2,0%. La mediana de los sesgos medios de los laboratorios argentinos oscilo entre -2,9 y 18,2%; -3,1 - 2,6%; -3,3 - 0,5%; -1,1 - 3,8% y -4,3-0% para creatinina serica, glucosa, CK, Ca2+ y Na+. En los Paises Bajos, las medias / medianas en general fueron de 1,1% (DE=2,0%). El intercambio de los valores asignados a los materiales EQA, conmutables fue de gran ayuda para la armonizacion y estandarizacion de los ensayos medicos en la Argentina y para revelar el potencial futuro de armonizacion y estandarizacion. Estos resultados claramente demuestran que la trazabilidad metrologica de los resultados de las pruebas en la Argentina esta, en promedio, de acuerdo con lo esperable; sin embargo, la dispersion entre laboratorios es muy grande y deberia ser mejorada.

A equivalencia de resultados entre laboratorios e uma missao importante para os laboratorios medicos. Nos Paises Baixos, os laboratorios medicos so utilizam aplicacoes comerciais homogeneas, aprovadas por regulacoes (CE-IVD) para analitos quimicos, ao passo que na Argentina sao comuns as aplicacoes heterogeneas caseiras. O efeito desta diferenca pratica na exatidao do teste e estudado utilizando caracteristicas essenciais do programa EQA, dos Paises Baixos, baseado na exatidao. Foram ensaiados seis pools de soros, congelados, de origem humana, comutaveis, que abrangiam a faixa de medidas (pato)fisiologicas para 17 analitos quimicos gerais. Esses analitos quimicos foram analisados por ~75 laboratorios argentinos e ~200 laboratorios holandeses em 2014. Apos eliminar os valores atipicos, o estado de harmonizacao entre os laboratorios foi avaliado atraves do calculo dos coeficientes de variacao interlaboratorio meios globais (CV%) por analito e por pais para os 6 niveis. Nao obstante, o estado de padronizacao foi avaliado depois da eliminacao de valores atipicos pelo calculo de recuperacoes medias gerais (%) se comparados com os valores atribuidos por analito por pais para os 6 niveis. Os vieses medios absolutos foram comparados com os vieses (minimos / desejaveis) decorrentes dos criterios de variacao biologica. Para enzimas sericas, os CV interlaboratorio nos laboratorios argentinos oscilaram entre 10 e 22%, em comparacao com 3-6% nos Paises Baixos. Para o acido urico serico, creatinina, glicose e proteinas totais, os CV entre laboratorios variaram entre 4,3 e 13,1% nos laboratorios argentinos, em comparacao com <3,5% nos Paises Baixos para os eletrolitos sericos, os CV interlaboratorios oscilaram entre 1,8 e 3,8% para Na+; 2,9-5,8% para Cl-; 3,8-7,5% para K+; 9,4-10,4% para Ca2+ e 16,2-22,3% para Mg2+ em comparacao com ≤2% (Na+, K+, Cl-, Ca2+) e ≤3% (Mg2+) nos Paises Baixos. As recuperacoes medias em laboratorios argentinos para, p.ex. a creatinina serica, glicose, CK, Ca2+ e Na+ foram 95-119%; 95-104%; 98-102%; 98-102% e 96-100% respectivamente, enquanto que os intervalos de recuperacao min-max. foram 65-155%; 58-126%; 47-132%; 66-132% e 85-115%. Nos Paises Baixos, as recuperacoes medias absolutas foram em geral de 98,9% com um desvio padrao (DE) de 2,0%. A mediana dos vieses medios dos laboratorios argentinos oscilou entre -2,9 e 18,2%; -3,1 - 2,6%; -3,3 - 0,5%; -1,1 - 3,8% e -4,3-0% para creatinina serica, glicose, CK, Ca2+ e Na+. Nos Paises Baixos, as medias / medianas em geral foram de 1,1% (DE=2,0%). O intercambio dos valores atribuidos aos materiais EQA, comutaveis, foi de grande ajuda para a harmonizacao e padronizacao dos ensaios medicos na Argentina e para revelar o potencial futuro de harmonizacao e padronizacao. Esses resultados demonstram as claras que a rastreabilidade metrologica dos resultados dos testes na Argentina esta de acordo com o esperavel; a dispersao entre laboratorios ainda e muito grande e deveria ser melhorada.

Provisional standardization of hepcidin assays: creating a traceability chain with a primary reference material, candidate reference method and a commutable secondary reference material.

Background Hepcidin concentrations measured by various methods differ considerably, complicating interpretation. Here, a previously identified plasma-based candidate secondary reference material (csRM) was modified into a serum-based two-leveled sRM. We validated its functionality to increase the equivalence between methods for international standardization. Methods We applied technical procedures developed by the International Consortium for Harmonization of Clinical Laboratory Results. The sRM, consisting of lyophilized serum with cryolyoprotectant, appeared commutable among nine different measurement procedures using 16 native human serum samples in a first round robin (RR1). Harmonization potential of the sRM was simulated in RR1 and evaluated in practice in RR2 among 11 measurement procedures using three native human plasma samples. Comprehensive purity analysis of a candidate primary RM (cpRM) was performed by state of the art procedures. The sRM was value assigned with an isotope dilution mass spectrometry-based candidate reference method calibrated using the certified pRM. Results The inter-assay CV without harmonization was 42.1% and 52.8% in RR1 and RR2, respectively. In RR1, simulation of harmonization with sRM resulted in an inter-assay CV of 11.0%, whereas in RR2 calibration with the material resulted in an inter-assay CV of 19.1%. Both the sRM and pRM passed international homogeneity criteria and showed long-term stability. We assigned values to the low (0.95±0.11 nmol/L) and middle concentration (3.75±0.17 nmol/L) calibrators of the sRM. Conclusions Standardization of hepcidin is possible with our sRM, which value is assigned by a pRM. We propose the implementation of this material as an international calibrator for hepcidin.

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.

IFCC Working Group Recommendations for Assessing Commutability Part 1: General Experimental Design.

Commutability is a property of a reference material (RM) that relates to the closeness of agreement between results for an RM and results for clinical samples (CSs) when measured by ≥2 measurement procedures (MPs). Commutability of RMs used in a calibration traceability scheme is an essential property for them to be fit for purpose. Similarly, commutability of trueness controls or external quality assessment samples is essential when those materials are used to assess trueness of results for CSs. This report is part 1 of a 3-part series describing how to assess commutability of RMs. Part 1 defines commutability and addresses critical components of the experimental design for commutability assessment, including selection of individual CSs, use of pooled CSs, qualification of MPs for inclusion, establishing criteria for the determination that an RM is commutable, generalization of commutability conclusions to future measurements made with the MPs included in the assessment, and information regarding commutability to be included in the certificate for an RM. Parts 2 and 3 in the series present 2 different statistical approaches to commutability assessment that use fixed criteria related to the medical decisions that will be made using the laboratory test results.

IFCC Working Group Recommendations for Assessing Commutability Part 3: Using the Calibration Effectiveness of a Reference Material.

A process is described to assess the commutability of a reference material (RM) intended for use as a calibrator based on its ability to fulfill its intended use in a calibration traceability scheme to produce equivalent clinical sample (CS) results among different measurement procedures (MPs) for the same measurand. Three sources of systematic error are elucidated in the context of creating the calibration model for translating MP signals to measurand amounts: calibration fit, calibrator level trueness, and commutability. An example set of 40 CS results from 7 MPs is used to illustrate estimation of bias and variability for each MP. The candidate RM is then used to recalibrate each MP, and its effectiveness in reducing the systematic error among the MPs within an acceptable level of equivalence based on medical requirements confirms its commutability for those MPs. The RM is declared noncommutable for MPs for which, after recalibration, the CS results do not agree with those from other MPs. When a lack of agreement is found, other potential causes, including lack of calibration fit, should be investigated before concluding the RM is noncommutable. The RM is considered fit for purpose for those MPs where commutability is demonstrated.

IFCC Working Group Recommendations for Assessing Commutability Part 2: Using the Difference in Bias between a Reference Material and Clinical Samples.

A process is described to assess the commutability of a reference material (RM) intended for use as a calibrator, trueness control, or external quality assessment sample based on the difference in bias between an RM and clinical samples (CSs) measured using 2 different measurement procedures (MPs). This difference in bias is compared with a criterion based on a medically relevant difference between an RM and CS results to make a conclusion regarding commutability. When more than 2 MPs are included, the commutability is assessed pairwise for all combinations of 2 MPs. This approach allows the same criterion to be used for all combinations of MPs included in the assessment. The assessment is based on an error model that allows estimation of various random and systematic sources of error, including those from sample-specific effects of interfering substances. An advantage of this approach is that the difference in bias between an RM and the average bias of CSs at the concentration (i.e., amount of substance present or quantity value) of the RM is determined and its uncertainty estimated. An RM is considered fit for purpose for those MPs for which commutability is demonstrated.

Evaluation of Performance of Laboratories and Manufacturers Within the Framework of the IFCC model for Quality Targets of HbA1c.

HbA1c is a key parameter in diabetes management. For years the test has been used exclusively for monitoring of long-term diabetic control. However, due to improvement of the performance, HbA1c is considered more and more for diagnosis and screening. With this new application, quality demands further increase. A task force of the International Federation of Clinical Chemistry and Laboratory Medicine developed a model to set and evaluate quality targets for HbA1c. The model is based on the concept of total error and takes into account the major sources of analytical errors in the medical laboratory: bias and imprecision. Performance criteria are derived from sigma-metrics and biological variation. This review shows 2 examples of the application of the model: at the level of single laboratories, and at the level of a group of laboratories. In the first example data of 125 individual laboratories of a recent external quality assessment program in the Netherlands are evaluated. Differences between laboratories as well as their relation to method principles are shown. The second example uses recent and 3-year-old data of the proficiency test of the College of American Pathologists. The differences in performance between 26 manufacturer-related groups of laboratories are shown. Over time these differences are quite consistent although some manufacturers improved substantially either by better standardization or by replacing a test. The IFCC model serves all who are involved in HbA1c testing in the ongoing process of better performance and better patient care.