Commutability of possible external quality assessment materials for progesterone measurement

BackgroundThe commutability of control materials used for external quality assessment (EQA) programs is of great importance. Evaluating the commutability of control materials is crucial to assess their suitability for EQA programs.MethodsForty-eight individual patient serum samples, commercial EQA samples, human serum pools (HSPs), commercially available sterile filtered charcoal stripped serum (CS) and swine serum were analyzed using the isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS) comparative method and six immunoassays for progesterone. The commutability was assessed according to the EP14-A2 guideline and the difference in bias approach, respectively.ResultsAccording to the EP14-A2 guideline, HSPs and CS were commutable for all the tested immunoassays, while swine serum showed positive matrix effects in some assays. Based on the difference in bias approach, a large number of inconclusive and noncommutable results appeared.ConclusionsThe commutability of the processed materials varied depending on which evaluation approach and criterion was applied. Noncommutability of the EQA materials was observed. And HSPs and CS were possible commutable candidate control materials according to the EP14-A2 guideline.     

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.     

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.     

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.     

临床生化检验参考方法的主要作用

参考方法是临床检验参考系统的主要组成部分.参考方法主要用于评价常规方法和为标准物质定值,从而建立和保证检验结果的溯源性.常规方法的校准偏倚和非特异性及参考物质的互通性是临床检验标准化中的重要问题,标准化工作也需要互通的参考物质.参考方法在鉴定和纠正常规方法主要质量问题及参考物质研制中发挥不可替代的作用.     

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.     

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。     

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.     

Preliminary performance evaluation of blood gas analyzers.

BACKGROUND: We evaluated the imprecision and bias of three instruments for the determination of blood gases, pH and ionized calcium (Ca(2+)) in human arterial blood samples, in comparison with the performance of an established methodology. METHODS: The ABL 735, Omni S and Rapidpoint 405 blood gas analyzers were evaluated and compared to the ABL 620 analyzer. Imprecision was determined according to the NCCLS EP10-A2 evaluation protocol. The NCCLS EP9-A2 evaluation protocol was used to determine bias relative to the ABL 620 system. Experimental data were compared against preset quality specifications. RESULTS: The three new instruments showed excellent imprecision for the measurement of pH, but only the ABL 620 met the preset imprecision goals for all analytes tested. All new instruments showed good correlation with the comparative instrument. The slope of the regression equation was significantly different from 1.0 in six out of the 12 comparisons, indicating systematic differences between the instruments. Nevertheless, the predicted bias values relative to the comparative instrument did not exceed the preset quality specifications for two out of the three new instruments. CONCLUSIONS: Preliminary evaluation using the NCCLS evaluation protocols EP10-A2 and EP9-A2, may provide valuable information on performance characteristics of blood gas analyzers.     

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...     

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.     

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.     

血清葡萄糖参考方法的复现及与临床常用检测方法的比对研究

目的 复现血清葡萄糖测定己糖激酶的参考方法 (紫外分光光度法),对此方法 进行性能验证,并评价5种临床常用检测方法 .方法 按照美国CDC推荐的血清葡萄糖测定己糖激酶参考方法 的要求,建立参考方法 ;通过测定标准参考物质(SRM),以及参加国际临床化学与检验医学联合会(IFCC)主办的参考实验窒间的国际环形比对试验(ring-trial),来验证参考方法 的准确性;按照美国临床和实验室标准委员会(CLSI)EP9-A2试验方案,己糖激酶参考方法 作为比对方法 ,5种临床常用检测方法 作为待评方法 ,同时测定40份血清样品.结果 用己糖激酶参考方法 测定SRM965a,水平2和水平3与靶值的偏倚分别为0.93%、-0.23%;参加参考实验室国际比对,血清葡萄糖检测结果 在可接受范围内;5种常用检测方法 在医学决定点(Xc=6.11 mmol/L)预期偏差的95%可信区间在实验窜定义的可接受偏差(10%)范围内,也在生物学变异的可接受偏差(6.9%)范围内.结论 本室已复现并验证了血清葡萄糖测定己糖激酶参考方法 ;5种常用血清葡萄糖检测方法 的测定结果 与参考方法 的测定结果 有差异,但误差在临床可接受范围,不会影响临床检测结果 .     

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.     

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。     

AST不同方法间血清与人红细胞提纯酶结果互换性

目的 研究门冬氨酸氨基转移酶（AST）不同测定方法间人血清标本与纯化人红细胞c-AST结果的互换性。方法 采用八种常用的AST测定方法（试剂盒）测定99份血清标本及提纯AST，以IFCC推荐的方法（不含磷酸吡哆醛）为基准，其它七种方法测定的血清AST值与之进行相关分析，并对血清AST及纯化人红细胞c-AST的反应性进行比较。结果 八种方法间血清AST测定值的相关性较好，相关系数（r)接近1．0，截距接近0。提纯的c-AST在以上各方法间均与人血清AST反应性相近，具互换性；且提纯的c-AST测定值受辅基磷酸吡哆醛的影响较小。结论 提纯的 c-AST在各方法间与血清AST反应相似，可以作为AST参考品的酶制剂应用于临床生化检验。     

Commutability of calibration and control materials for serum lipase.

BACKGROUND: To effectively assess and correct for intermethod variability, calibration and control materials (CCMs) must show the same intermethod behavior as patient sera, i.e., they must be commutable. We describe the commutability of selected CCMs for lipase assays, the impact of noncommutability of CCMs in normalizing patient results, and characteristics of reagents that affect assay specificity and commutability. METHODS: Lipase was measured in 98 patient sera and in 29 commercial CCMs, with 2 commercial methods using different substrates and with 4 experimental methods using 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester as substrate and colipase as cofactor, but differing in the stabilizing proteins used and in the size of the substrate micelles. RESULTS: The noncommutability rate, i.e., the frequency of aberrant intermethod behavior of CCMs in comparison with patient sera, was 27% for liquid CCMs and 47% for lyophilized CCMs. The normalized residuals, measuring the degree of noncommutability, were -2.3 to 2.4 for CCMs with "normal" lipase activity, and -3.5 to 21.7 for CCMs with higher lipase activity. Recalculation of patient results with CCMs as calibrators decreased or increased the original bias according to whether the CCMs were commutable. CONCLUSIONS: For the lipase methods in this study, the frequency of noncommutability of CCMs is affected by assay-specific characteristics, including size of substrate micelles and the presence or absence of added proteins.     

The Nordic Trueness Project 2002: use of reference measurement procedure values in a general clinical chemistry survey

Up to 136 laboratories participated in a joint effort to assess the trueness of routine measurements for 14 serum components. An unmodified, fresh-frozen human serum ("IMEP-17 Material 1"), produced for an international inter-laboratory comparison, served as the "master material". The serum had assigned values of the highest available metrological quality, and is assumed to involve no or negligible commutability problems. The material was used in the assignment of traceable values to two other reference sera, "CAL" and "X", through parallel measurements on the three materials according to a common protocol. In this transfer process, uncertainty estimates were provided for all values. The material CAL had been supplied with reference measurement procedure values in 1997, and the two sets of assigned values agreed well. A lyophilized control serum "HK02" was also included in the routine analysis series. It, too, had assigned values based on reference measurement procedures. Significant matrix effects were found. The project has provided: Assigned traceable values for 14 components in a fresh-frozen serum, available to Nordic laboratories for the coming years as "NFKK reference serum X"; Confirmation of earlier assigned reference measurement procedure values for a number of components in CAL, the main calibrator in the Nordic Reference Interval project (NORIP). The transferred values will now serve as the primary reference.; Evidence of long-term stability ( > or = 5 years) of the fresh-frozen serum CAL when stored at -80 degrees C; Evidence of substantial matrix effects in the processed serum HK02. The findings should be used to discuss to what extent reference measurement procedure values are useful and cost-efficient for this type of material.     

Validation of candidate reference methods based on ion chromatography for determination of total sodium, potassium, calcium and magnesium in serum through comparison with flame atomic emission and absorption spectrometry

Objectives: We report on the validation of candidate reference methods based on ion chromatography for the determination of total sodium, potassium, calcium, and magnesium in serum. The current study is a continuation of previous investigations in which we were able to show the potential of ion chromatography to serve as a reference method principle. The validation consisted of comparison of the ion chromatographic methods with generally recognized reference methods based on flame atomic emission (for sodium/potassium) and absorption (for calcium/magnesium) spectrometry.

Methods: Sample preparation consisted of acidic dilution and pre-purification with reversed phase cartridges. Ion chromatography with suppressed conductivity was performed with polymeric stationary phases chemically modified with carboxylate and sulfonate functional groups for sodium/potassium and calcium/magnesium, respectively. Single-point calibration was used in combination with individual adaptation of serum sampling and diluting to give similar responses in samples and standards. In the study, more than 25 control sera were analyzed in parallel with the ion chromatographic methods and the traditional reference methods. The measurement protocol consisted of quadruplicate analysis of each sample per run, in 3 different runs. In each measurement series, internal quality control with certified reference materials from the National Institute of Standards and Technology and the Bureau Communautaire de Référence was applied. The performance criteria to fulfill were predefined (i.e., the maximum within-day and overall coefficient of variation, the confidence interval, the daily and overall deviation from the certified value and the maximum total analytical error).

Results: The comparison is presented as difference plot (i.e., deviation of the results obtained with ion chromatography from those obtained with the respective traditional reference methods). The mean deviations were +0.9% for sodium, +1.0% for potassium, ±0.0% for calcium, and +0.1 % for magnesium. With the exception of 2 values each for sodium and potassium, all deviations were within the limit of 2 times the allowed total analytical error. From the data obtained for internal quality control during the different measurement campaigns, we further estimated the long-term precision and accuracy of our methods. The overall coefficient of variation (respectively the bias) amounted to 0.7% (+0.1%) for sodium, 0.9% (−0.3%) for potassium, 1.3% (−0.1 %) for calcium, and 1.0% (±0.0%) for magnesium.

Conclusion: From the precision and accuracy reached by our ion chromatographic methods, we conclude that they can be proposed as candidate reference methods for the determination of total sodium, potassium, calcium, and magnesium in serum.