Commutability of external quality assessment materials for serum magnesium and calcium measurements

Abstract

The commutability of pooled patient sera (PPS) and control materials (CM) should be evaluated to investigate their suitability for use in an external quality assessment (EQA) program. Individual human samples, PPS and CM were analyzed by four routine methods and inductively coupled plasma mass spectrometry reference methods for magnesium and calcium measurements. The commutability was analyzed according to EP14-A3 protocol and the difference in bias approach, respectively. For magnesium measurements, all PPS were commutable and 3/5?CM were commutable for all measurement systems according to the EP14-A3 protocol. For calcium measurements, most PPS were commutable for all measurement systems, but the CM were only commutable with the Cobas c702 system. The IFCC approach produced similar commutability profiles, except that a large number of inconclusive results appeared. The routine methods exhibited excellent linearity and precision. The majority of relative biases between the routine and reference methods were beyond the bias limits. The commutability of the CM and PPS vary depending on which evaluation approach and criterion is applied. Superiority in the commutability of PPS over CM was observed whichever evaluation approach is applied.     

Commutability and traceability in EQA programs

ObjectivesThe concept of commutability of samples has focused laboratories on the importance of traceability. However, the critical role of External Quality Assurance (EQA) in achieving the primary role of traceability (i.e. facilitating comparable patient results in different laboratories) has largely been lost. The aim of this paper is to review the role of EQA in achieving traceable/commutable results.Design and methodsThe role of commutability and traceability in EQA and Internal Quality Control (IQC) are discussed. Examples of commutable EQA samples are given to highlight the problem of assuming EQA material does not behave like patient samples.ResultsWe provide the conventional traceability chain (top down) and the role of EQA in a “bottom up” model using conventional EQA samples.ConclusionsThe quest for commutable samples has compromised the value of EQA without an understanding that some EQA materials are commutable for some measurands.EQA plays a key role in performance improvement, but laboratories need to understand the importance of using a range of values appropriate to the assay to identify areas of quality need. Traceability and EQA using conventional samples are not mutually exclusive concepts.     

Quality of serum creatinine measurement in light of EQA programs.

BACKGROUND: The aim of our study was to identify the role of External Quality Assessment (EQA) programs in improving the quality of serum creatinine measurement and glomerular filtration rate (GFR) estimation. Comparison of results achieved during EQA with National Kidney Disease Education Program and College of American Pathologists guidelines identified an urgent need for an improvement in measurement quality. We compared actual results for serum creatinine measurement within the Czech Republic EQA with the requirements of EC Directive 98/79. METHODS: We used the results for 2005-2006 EQA programs. There were seven surveys involved with two samples each, and a 2006 questionnaire on the post-analytical phase survey. RESULTS: Bias depended strongly on the creatinine concentration. However, this dependence varied for different in vitro diagnostic manufacturers, although they should all follow the same directive. We chose biological variation as the significance rate for bias and a resulting overall error of 6.9%. The proportion of results with total error <6.9% ranged from 11% to 80%. The total error for a reference sample of 94.8 mumol/L also showed significant dependence on the working calibrator used and ranged from 1% to 17%. CONCLUSIONS: The main role of EQA programs in improving the quality of creatinine measurement results and GFR calculation should be in monitoring the quality of IVD products, enabling users to adapt their use of these products accordingly. EQA programs can also educate on performing GFR estimation in a unified way. Highly commutable control materials with certified creatinine values or, alternatively, lyophilized materials with sufficient commutability proved by comparison with native frozen human sera, should become an important EQA tool.     

16种17-羟孕酮制备物基于两种评价方案的互通性研究

目的应用两种互通性评价方案评价16种17-羟孕酮制备物的互通性。方法互通性研究,收集2018年2月至2019年6月之间北京医院检验科的新鲜人血清共52份。根据美国临床和实验室间标准化研究所文件(CLSI)EP14-A3和国际临床化学和检验医学联合会(IFCC)互通性评价工作组报告,以血清17-羟孕酮同位素稀释液相色谱串联质谱法(ID-LC/MS/MS)为比对方法,3种临床常规分析系统(1种放射免疫法,2种LC/MS分析法)为待评方法,一同测定52个人血清样本和16种制备物的17-羟孕酮浓度,评价制备物质的互通性。结果综合两种互通性评价结果,所有正确度验证材料和国家甾体激素标准物质在LC/MS分析系统中都显示出良好的互通性,6/9的EQA材料在三种常规分析系统中都显示出互通性。其中所有材料在偏倚差值法中所有材料的LC/MS分析系统中都显示出良好的互通性。结论两种互通性评价结果有所差异,使用新鲜冰冻人血清作为血清17-羟孕酮的质评材料均能满足互通性要求。     

Comparability of four clinical laboratory measurement methods for GGT and commutability of candidate reference materials

BackgroundThis study was conducted to evaluate the progress in the standardization of the gamma‐glutamyl transferase (GGT) to achieve metrological traceability of routine in vitro diagnosis (IVD) medical devices.MethodsWe collected 25 single fresh frozen serum samples for GGT analysis. Candidate reference materials (RMs), calibrators, internal quality controls (IQC), and external quality assessment (EQA) materials from the National Center for Clinical Laboratory (NCCL), Beijing Center for Clinical Laboratory (BCCL), and College of American Pathologists (CAP) were randomly added to these serum samples. A total of 42 samples were examined using IFCC reference method and four different IVD medical devices to perform the comparability and commutability study.ResultsThe four IVD medical devices achieved trueness assessment within the measurement range. Linear analysis showed the agreement of Siemens ADVIA 2400, Hitachi 7600‐020/BioSino, Beckman AU 5800, and Roche Cobas 501 with the reference method. These assay pairs were comparable at the medical decision levels. The GGT in‐house candidate RMs, and Beckmann and Roche calibrators were all within the limits of the 95% prediction intervals, the commutability of BioSino calibrators was indeterminate, and some internal and external quality controls were not commutable for comparisons of certain IVD medical devices vs the reference method.ConclusionsBy comparing with the reference method, we found that performance of GGT conventional measurement systems to be traceable to the higher order references was improved. The commutable materials for calibration and trueness controls of routine methods were significant to promote the standardization of GGT analysis.     

血浆纤维蛋白原不同检测系统间检测结果的一致性分析及质控品的互通性探讨

目的 比较7种不同检测系统测定血浆纤维蛋白原(Fib)结果的一致性,并观察不同厂家质控品的基质效应,评价互通性.方法 在Sysmex CS 5100,IL ACL TOP 700,STA-Compact,雷杜Rayto RAC 1830,众驰Zonci XL 1000i,赛科希德Succeeder SF 8100配套检...     

Commutability and traceability: their repercussions on analytical bias and inaccuracy

The commutability of calibrators and accuracy control materials affects the traceable link between patient sample results and standards. We sought to identify the repercussions of commutability on various aspects of laboratory practice (calibration, control of bias and accuracy assessment) and to discover the solutions that can reduce the problems produced by non-commutability with presently available resources. Ten serum constituents, ten comparison procedures and 37 analytical procedures were studied. The information concerning accuracy and bias provided from materials found to be commutable in previous works was challenged with native serum results for each routine and reference method compared, using Passing–Bablok regression and decision limits derived from biological variation. We found that: (1) Use of commutable control materials did not assure reliable information on the bias (systematic component of analytical error) of analytical procedures, and (2) Results from native serum and commutable controls were very highly concordant, indicating that these materials provide a good indication of the inaccuracy (total analytical error) of results. We suggest that the performance of individual laboratories would be better evaluated by occasional use of native sera with values assigned by reference methods in EQAS schemes. Moreover, our findings support the idea that manufacturers should assign values to calibrators using reference methods and native sera to reduce matrix effects and promote traceability.     

血清ALT与AST测定的基质效应评价

摘要：目的：评价7种室间质量评价（EQA）材料和4种市售材料在9个检测系统上测定血清ALT和AST的基质效应。 方法：参照美国临床实验室标准化协会(CLSI)EP14-A2指南,根据ALT和AST的参考方法建立不含磷酸吡哆醛的比对方法。9个检测系统的常规方法为待评方法。用比对方法和待评方法同时测定新鲜人血清、EQA材料及市售材料的ALT和AST水平,评价非血清样品的基质效应。 结果：ALT测定中1种EQA材料对所有检测系统均表现基质效应,AST测定中2种EQA材料对所有检测系统无基质效应,其他材料视系统的不同而表现出不同的情况。 结论：基质效应影响血清ALT和AST测定的准确性和可比性,应充分重视基质效应对临床检验量值溯源的影响。     

Myoglobin and creatine kinase isoenzyme MB mass assays: intermethod behaviour of patient sera and commercially available control materials

The low biological variation of myoglobin and creatine kinase isoenzyme MB mass (CK-MBm) requires accurate measurements. In the standardization process, in order to effectively measure and correct intermethod variability, the intermethod behaviour of control materials must be the same of patient sera, i.e. they must be commutable. In this work we checked the commutability of some commercially available control materials in pairs of methods for myoglobin and CK-MBm measurements; we assessed the impact of commutable and non-commutable control materials when used for equalizing patient sera results by two different methods and discussed the problems related to external quality assessment schemes. Myoglobin and CK-MBm were measured in sets of 49 and 56 patient sera and in 13 commercially available control materials with two automatic analytical systems. The non-commutability rate was 8.3% for myoglobin and 23.1% for CK-MBm. Recalculation of serum samples results with a control material as calibrator lowered or increased the bias originally present according to whether the material itself was commutable or not. We conclude that also for myoglobin and CK-MBm assays it is necessary to check the commutability of materials to be used in external quality assessment schemes, or to normalize patient results by different methods.     

血清肌酐测定基质效应的研究

目的 评价血清肌酐测定常规方法的校准偏差及肌酐制备物常在常规方法上的基质效应.方法 根据美国临床实验室和标准化协会(CLSI)EP14-A2评价方案,同位素稀释液相色谱串联质谱法(ID-LC/MS/MS)测定血清肌酐的方法为比对方法,15种常规肌酐测定系统(7种酶法,8种苦味酸法)为待评方法,测定40个新鲜冰冻人血清和36种制备物的肌酐浓度,评价制备物的基质效应和测定系统的校准偏差.结果 大部分商品制备物(29/30)在苦味酸法系统上表现出基质效应,少部分商品制备物(13/30)在部分酶法系统上表现出基质效应.我中心6个制备物在所有15个系统上均未观察到基质效应.所有常规系统新鲜冰冻血清测定值与比对方法测定值间均呈较好的直线相关,所有苦味酸法和部分酶法测定肌酐方法存在校准偏差.结论 基质效应和校准偏差存在于常规肌酐测定方法,必须重视这些因素,提高肌酐测定结果的正确度和可比性.     

Intermethod variation in serum carcinoembryonic antigen (CEA) measurement. fresh serum pools and control materials compared.

This study was undertaken to evaluate the feasibility of using commercial control materials in a regional external quality assessment scheme (EQAS) for serum carcinoembryonic antigen (CEA) measurement. We have assessed the commutability of 12 commercial control materials using five automated immunochemical systems. We compared the intermethod behavior of the materials with that of 12-14 patient serum pools. In a total of 48 comparisons (12 materials x 4 pairs of analytical systems), seven instances of non-commutability were apparent, as shown by normalized residuals falling outside the +/-3 interval. The use of non-commutable materials generates two negative effects. In EQAS, the interlaboratory variation recorded is not representative of the variation expected in the assay of patient sera; in interlaboratory harmonization programs, recalibration with non-commutable materials increases, instead of decreasing, the interlaboratory variation. Both these effects were shown to occur in CEA measurement with the tested materials and systems. The materials planned to be used in our EQAS turned out to be commutable: this gave us the guarantee of measuring realistic interlaboratory variation values, although the check for commutability should be extended to all the analytical systems used by the participants in the scheme.     

Evaluation of commutability of control materials.

The commutability of 13 control materials was evaluated by performing parallel measurements on two different analysers: a Synchron CX-5 Delta from Beckman-Coulter and a Vitros 950 from Ortho-Clinical Diagnostics. Twenty three clinical chemistry analytes (substrates, electrolytes and enzymatic activities) were determined in plasma from 15 different patients in order to define intermethod relationship for each analyte. The relationship observed for each control material was compared to those obtained for patients' specimens. The results show that commutability depends both on the tested analyte and on the control material. No totally commutable material has been found for the whole set of tested parameters. Most control materials were commutable for inorganic phosphate, glucose, chloride, triglycerides, alanine aminotransferase, amylase and y-glutamyltransfera-se, but less than a quarter of control materials were commutable for sodium, calcium, creatinine, alkaline phosphatase and lipase. Seven materials were commutable for more than half of the analytes, whereas five control materials were commutable for less than a quarter of these analytes. We propose to verify the commutability of materials before their use in an external quality control assessement.     

Metrological traceability of values for α-amylase catalytic concentration assigned to a commutable calibrator materials

BackgroundThe International Standard ISO 18153 describes how to assure the metrological traceability of catalytic concentration values assigned to commercial calibration materials following the reference measurement system. We applied this approach to the standardization of α-amylase measurements.MethodsTraceable values of catalytic activity with measurement uncertainty were assigned to three commercial calibrator materials using α-amylase primary reference measurement procedure described by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The metrological traceable to the SI units calibration was validated by measuring human serum and plasma samples using the primary reference procedure and two routine commercial measurement procedures using different substrates (4,6-ethylidene(G1)-4-nitrophenyl(G7)-α-(1→4)-d-maltoheptaoside (EPS) and 2-chloro-4-nitrophenyl-α-d-maltotrioside (CNP)) and calibrated with the traceable materials. Previously the commutability of the commercial calibration materials was verified.ResultsProcedures comparison showed that the primary reference procedure and routine procedures have the same analytical specificity. The commercial calibrators tested showed to be commutable and were used to recalibrate the routine measurement procedures. The agreement of procedures improves after recalibration with commutable calibrator materials.ConclusionsThe implementation of a reference system for α-amylase measurements was demonstrated that assures the traceability of patients' results to SI units and to harmonize the results obtained by two different routine procedures.     

血清尿素测定基质效应研究

目的 评价2007年全国室间质量评价(EQA)临床化学项目材料和13种市售制备物血清尿素测定在7种脲紫外速率法测定系统上的基质效应,并考察这些测定系统的校准偏差.方法 按美国临床和实验室标准协会(CLSI)EP 14-A2试验方案,同位素稀释气相色谱质谱法作比对方法,7种尿素酶常规方法为待评方法,用比对方法和待评方法同时测定25份新鲜冰冻人血清和EQA材料及市售制备物.考察常规方法和比对方法测定EQA材料(或市售制备物)结果间的数量关系与它们测定新鲜冰冻人血清样品数量关系的一致程度,评价样品的基质效应.考察新鲜冰冻人血清样品常规方法和比对方法结果的差异,评价测定系统的校准偏差.结果 8种EQA材料和3种市售制备物对参加评价的所有测定系统无基质效应,1种市售制备物对所有系统都表现基质效应,其他样品视系统的不同而表现出不同的情况.7种测定系统中的6种都存在不同程度的校准偏差:同直线Y=X相比,系统A的斜率、截距偏差均小于5%,不存在明显校准偏差.系统B、C、D、F、G的斜率偏差小于5%,截距偏差大于5%,存在一定的校准偏差.系统E的斜率和截距偏差均大于5%,表现为存在校准偏差.结论 样品的基质效应和测定系统的校准偏差影响血清尿素测定的准确性和可比性.应充分重视基质效应和校准偏差对临床检验量值溯源的影响.     

5水平冰冻混合人血清尿酸候选二级标准物质的研制

目的 研制5水平尿酸(UA)冰冻混合人血清候选二级标准物质,为UA常规检测方法的准确度验证提供稳定和互通性良好的真实值控制品.方法 收集无肉眼可见脂血、溶血和黄疸的5个UA浓度混合血清,过滤并分装后,-70℃保存.参照《标准物质/标准样品定值的一般原则和统计方法》(简称ISO Guide 35)用常规方法进行均匀性和稳...     

Commutability assessment of potential reference materials using a multicenter split-patient-sample between-field-methods (twin-study) design: study within the framework of the Dutch project "Calibration 2000"

BACKGROUND: The Dutch project "Calibration 2000" aims at harmonization of laboratory results via calibration by development of commutable, matrix-based, secondary reference materials. An alternative approach to the NCCLS EP14 protocol for studying commutability of reference materials is presented, the "twin-study design", which in essence is a multicenter, split-patient-sample, between-field-methods protocol. METHODS: The study consisted of the simultaneous analysis of fresh patient sera and potential reference materials (PRMs) for HDL-cholesterol (HDL-C) by 86 laboratories forming 43 laboratory couples. Six subgroups of method combinations were formed. The patient sera were selected and interchanged by each laboratory couple. The PRMs consisted of three types: C37, prepared according to the NCCLS C37 protocol; Fro, frozen selectively pooled human serum; and Lyo, which was the same serum pool as Fro but lyophilized in the presence of sucrose. All PRMs were provided in three HDL-C concentrations. The regression line residuals for the PRMs were normalized by expressing them as multiples of the state-of-the-art within laboratory SD (SD(SA)). In addition, the extra contribution of each PRM to the total measurement uncertainty, CV(Netto), was calculated. RESULTS: Averaged over the three PRM concentrations, 1.6% of the C37 residuals were outside the 3 SD(SA) limit. For the Fro and Lyo PRMs, these values were 2.4% and 11.1%. CV(Netto) values for C37, Fro, and Lyo were 2.9%, 4.3%, and 5.3%, respectively. CONCLUSIONS: The present twin-study design, as a practical alternative to the NCCLS EP14 protocol, is a viable way of studying commutability characteristics of PRMs. The study suggests that the C37 PRMs are the best candidates for a future reference material.     

Creatine kinase 2 mass measurement: methods comparison and study of the matrix effect.

Five different commercial immunoassays for the measurement of creatine kinase isoenzyme 2 mass concentration were compared using human plasma samples covering a wide range of creatine kinase 2 concentrations. The immunoassays studied differ in the detection systems, in the specificity of the antibodies and in the calibrators used. Intermethod comparison by regression analysis showed differences in the results of creatine kinase 2 mass concentration. The following ratios were deduced from the obtained equations: Elecsys=1.10xImmulite=1.20xIMx=1.26xACS:180= 1.33 x Stratus. The commutability of different materials prepared by diluting purified human creatine kinase 2 in biological and synthetic matrices was studied using the different immunoassays in comparison with human plasma specimens. Almost all the materials tested were not commutable.     

External Quality Assessment in The Netherlands: time to introduce commutable survey specimens. Lessons from the Dutch "Calibration 2000" project.

The performance of suitable secondary reference material for the use of trueness control of six routinely measured clinical enzymes in the Dutch External Quality Assessment (EQA) scheme is described. The reference material of choice was selected using the split-patient-sample between-field method (twin study) design as described in an earlier study of the Calibration 2000 project in The Netherlands. This material, which was proven to be commutable for all wet chemistry systems, was implemented as the national enzyme calibrator. It consisted of a cryo-protected lyophilised serum with additions of recombinant human enzymes. Various batches of the frozen version of this material without cryo-protection additive, called native EQA samples, were used in the general EQA scheme for performance evaluation. The results of Calibration 2000 calibrated and non-Calibration 2000 calibrated laboratories were compared for both the regular (spiked with non-human enzymes) and native EQA samples in terms of precision and bias with established reference method values for the native samples. The regular samples showed mean between-laboratory CV ranges for all six enzymes involved (low-high) of 5.5-10.3% for the non-calibrated users vs. 4.6-10.8% for the calibrated users. For the native samples these respective ranges were 5.2-9.9% vs. 2.2-4.9%. Without exception, the group of Calibration 2000 calibrated users showed the lowest bias against the reference method values. Regular EQA samples (spiked with non-human enzymes) showed poorer performance than native samples and are not suitable for accuracy assessment purposes, the main aim of EQA schemes. Native samples that are commutable should be used for trueness control in current EQA schemes.     

总蛋白室间质评成绩不满意原因分析

目的查找2009年第1次全国常规化学总蛋白(TP)室间质评(EQA)成绩不满意原因。方法用贝克曼LX20 MC(A组)、DXC800 MC(B组)及DXC800 CC(C组)仪器检测40份患者新鲜血清样本、三个厂家定值室内质控(IQC)血清和2009年第1次剩余EQA血清TP,数据采用One-Way ANOVA分析,新鲜血清样本同时依据EP9-A2文件方法分析,以CLIA’88规定的允许误差(EA)1/2为标准,判断三组仪器检测结果可比性。结果 A、B组检测EQA血清TP仍不满意(PT<80%),C组满意(PT=100%);三个厂家质控血清TP均在控,但MC(A/B组)与CC(C组)部分差异有统计学意义(P<0.05);患者新鲜血清样本差异无统计学意义(P>0.05),MC(A/B组)与CC(C组)相关性均良好(r2>0.95、P<0.01),系统误差(SE)小于1/2 EA。结论 TP EQA成绩不满意原因是EQA血清基质效应造成的。     

Application of a six sigma model to the evaluation of the analytical performance of serum enzyme assays and the design of a quality control strategy for these assays: A multicentre study

BackgroundSix medical testing laboratories at six different sites in China participated in this study. We applied a six sigma model for (a) the evaluation of the analytical performance of serum enzyme assays at each of the laboratories, (b) the design of individualized quality control programs and (c) the development of improvement measures for each of the assays, as appropriate.MethodsInternal quality control (IQC) and external quality assessment (EQA) data for selected serum enzyme assays were collected from each of the laboratories. Sigma values for these assays were calculated using coefficients of variation, bias, and total allowable error (TEa). Normalized sigma method decision charts were generated using these parameters. IQC design and improvement measures were defined using the Westgard sigma rules. The quality goal index (QGI) was used to assist with identification of deficiencies (bias problems, precision problems, or their combination) affecting the analytical performance of assays with sigma values <6.ResultsSigma values for the selected serum enzyme assays were significantly different at different levels of enzyme activity. Differences in assay quality in different laboratories were also seen, despite the use of identical testing instruments and reagents. Based on the six sigma data, individualized quality control programs were outlined for each assay with sigma <6 at each laboratory.ConclusionsIn multi-location laboratory systems, a six sigma model can evaluate the quality of the assays being performed, allowing management to design individualized IQC programs and strategies for continuous improvement as appropriate for each laboratory. This will improve patient care, especially for patients transferred between sites within multi-hospital systems.