Analytical Quality Specifications Research Articles

The biological variation of serum 1,25-dihydroxyvitamin D and parathyroid hormone, and plasma fibroblast growth factor 23 in healthy individuals

Background and aimsMeasuring 1,25-dihydroxyvitamin D (1,25(OH)2D), parathyroid hormone 1–84 (PTH 1–84) and intact FGF23 (iFGF23) is crucial for diagnosing a variety of diseases affecting bone and mineral homeostasis. Biological variability (BV) data are important for defining analytical quality specifications (APS), the usefulness of reference intervals, and the significance of variations in serial measurements in the same subject. The aim of this study was to pioneer the provision of BV estimates for 1,25(OH)2D and to improve existing BV estimates for iFGF23 and PTH 1–84. Materials and methodsSerum and plasma-EDTA samples of sixteen healthy subjects have been collected for seven weeks and measured in duplicate by chemiluminescent immunoassay on the DiaSorin Liaison platform. After variance verification, within-subject (CVI) and between-subject (CVG) BV estimates were assessed by either standard ANOVA, or CV-ANOVA. The APSs were calculated according to the EFLM-BV-model. ResultsWe found the following CVI estimates with 95% confidence intervals:1,25(OH)2D, 22.2% (18.9–26.4); iFGF23, 16.1% (13.5–19.5); and PTH 1–84, 17.9% (14.8–21.8). The CVG were: 1,25(OH)2D, 21.2% (14.2–35.1); iFGF23, 21.1% (14.5–35.8); and PTH 1–84, 31.1% (22.1–50.8). ConclusionsWe report for the first time BV estimates for 1,25(OH)2D and enhance existing data about iFGF23-BV and PTH 1–84-BV through cutting-edge immunometric methods.

Comparable analysis of six immunoassays for carcinoembryonic antigen detection

ObjectiveThis study aimed to assess the current status of carcinoembryonic antigen (CEA) detection. We evaluated the correlation, consistency, and comparability of CEA results among six automated immunoassays, and combined with the results of CEA trueness verification of the Beijing Center for Clinical Laboratories (BCCL) for further analysis. MethodsAbbott Architect i2000, Beckman DxI800, Roche Cobas E601, Diasorin Liaison XL, Maccura IS1200, and Autolumo A2000 were used to detect 40 individual serum CEA samples. Taking the optimal analytical quality specifications calculated from data on biological variation as the evaluation criterion. Passing-Bablok regression and Bland-Altman analysis were performed between each assay and all-assays median values to evaluate the correlation and relative difference. The concordance correlation coefficient (CCC) was used for consistency analysis. Additionally, the trueness verification program used samples at three concentration levels to assess the bias, coefficient of variation (CV), and total error (TE) between the average measured values and the target value. ResultsThe Spearman's rank correlation coefficient (rs) was ≥0.996 and the CCC ranged between 0.9448 and 0.9990 for each assay vs. all-assays median. Considering the all-assays median value of each sample as a reference, there were proportional and systematic differences according to the Passing-bablok regression analysis. The relative difference of the four assays (Abbott Architect i2000, Autolumo A2000, Diasorin Liaison XL, and Maccura IS1200) met the optimal analytical quality specifications. On the other hand, Beckman DxI800 (13.2 %) and Roche Cobas E601 (−9.0 %) were only able to fulfill the desirable analytical quality specifications. The average pass rates for bias, CV, and TE of the trueness verification program were 80 %, 98 %, and 96 %, respectively. ConclusionsThe six automated immunoassays vs. all-assays median have a good correlation in CEA detection. However, there is a lack of comparability of CEA results. Further improvements are needed in harmonization among CEA detections.

A-161 Analytical Performance of Reagents for Determination of Activated Partial Thromboplastin Time: A Sigma Metric Perspective

Abstract Background Sigma Metric (SM) assesses the degree of deviation of lab. tests from established specifications, combining Total Acceptable Error (ETa), imprecision and analytical bias. Quality criteria, defined by models of desirable specification, are used to determine the analytical performance of lab. tests. The concepts of biological variation are used as the preferred approach for establishing specifications. Reagents (RE) for the determination of activated partial thromboplastin time (APTT) use thromboplastin obtained from different tissue extracts and activation factors, being standardized to reduce the variability of the tests, and ensure equivalence of clinical diagnosis. This work evaluated three RE for APTT and the fulfillment of the desirable specifications of analytical quality, using the SM as an analysis tool. Material & methods APTT determinations were performed on the Sysmex®CS-2500 (Siemens Healthineers) with Actin®FS (AFS), Actin®FSL (FSL), and Pathromtin®SL (PSL) RE and bi-level Control Plasma N (CN) and Ci-Trol®2 Control (CI). Two different lots were used for each RE and control (CT), and the results were analyzed in RE-CT combination. We determined (a)analytical bias (Bias), from intra-assay imprecision determined by 30 repetitions in a single analytical run and by comparison with manufacturer's data, and (b)analytical coefficient of variation (CVa), from inter-assay imprecision, by triplicate in 3 periods each 3 h, for the 2 CT levels. Analytical quality specifications for APTT were selected in the literature, adopting desirable ETa values of 4.5% and minimum of 6.7%, obtained from a database for biological variation and acceptable limit of 15%, based on CLIA-CAP. SM was calculated with formula: Sigma = ETa–Bias/CVa, with graphic representation adapted from the Westgard’s model. Results For CVa, AFS and FSL results with CN and CI were <1.0%. PSL presented results above 1.0% for CN and CI. All RE presented results lower than those recommended by the manufacturer, respectively 4.0% for AFS; 3.0% for FSL; and 2.8% for PSL. For bias, a greater variation was observed for the combinations of RE and CT, ranging from 1.16% to 4.07%, being related to the differences between the averages obtained and the values defined in the leaflets. For the desirable specification of ETa (4.5%), 3 combinations of RE and CT level AFS-CN, FSL-CN and PSL-CI presented Sigma values >3 (respectively, 3.61, 3.87 and 3.33). When using the minimum specification (6.7%), the PSL-CN combination presented a Sigma = 2.06. With the CLIA-CAP specification, all RE and CT combinations had Sigma >6. Discussion All RE showed similar analytical performance when compared by SM, demonstrating that different commercial formulations for APTT determination do not show differences in analytical Bias and CVa determinations. The graphical representation by SM allows you to visually compare analytical imprecision and inaccuracy values. Conclusion All RE showed no differences in analytical performance, with SM being a visual tool for analyzing and comparing RE performance.

The possibility of automatic capillary blood testing in routine blood tests: an evaluation of the automatic mode of the Mindray BC-7500 CRP Auto Hematology Analyzer for capillary blood testing.

Capillary blood is a common specimen type used for infant blood routine tests. Until now, this specimen type could only be tested with the manual mode in hematology analyzers. Manual sample mixing and loading increases the amount labor force and can be more easily affected by human factors. This study was designed to investigate the proficiency of the automatic mode of the Mindray BC-7500 CRP Auto Hematology Analyzer for capillary blood testing. The complete blood count (CBC) results for capillary blood were compared between the automatic and manual modes. Special types of samples, including samples with high or low volume, thalassemia red cells, high fibrinogen, high hematocrit (HCT), or high triglyceride levels, were compared and evaluated. The intraclass correlation coefficient (ICC) was used to define the agreement between the 2 modes. The industry standard Analytical Quality Specifications for Routine Tests in Clinical Hematology (WS/T 406-2012), published by the National Health Commission of China, was used to evaluate the correlation between the results from the 2 modes. There was good correlation between the automatic and manual modes for every type of sample, and the ICCs were all higher than 0.9. Except for high HCT or high triglyceride samples, there were no differences found between the 2 modes based on the WS/T 406-2012 standard. This new automatic mode utilized in the Mindray BC-7500 CRP Auto Hematology Analyzer for capillary blood yielded the same results as the manual mode except in the case of samples with high HCT or triglycerides. Capillary blood might be routinely tested automatically with hematology analyzers in the near future, which might reduce the labor required and improve standardization.

Evaluation of Laboratory Performance in Consideration with Pre analytical and Post analytical Quality Indicators.

Implementation of Quality indicators (QIs) plays an imperative role in improving the total testing process, as it provides a quantitative basis for evaluating the laboratory performance. Besides monitoring of analytical quality specifications, several lines of experimental and clinical evidence have alluded a pivotal role of extra-analytical phases in improving the quality of laboratory services and therefore a relevance of pre- and post-analytical steps have been speculated on the overall quality in the total testing process and consequently on clinical decision-making. This was a retrospective study designed to evaluate and review different extra-analytical quality indicators in NABL accredited clinical biochemistry laboratory at BJ Medical College and Civil Hospital, Ahmedabad, Gujarat in an endeavour to ameliorate the performance of the laboratory. All Clinical Chemistry Laboratory test requests with their respective samples from January 2018 to December 2021 were included in the study. A total of 1,439,011samples were processed, and were evaluated for seven QIs [(% of number of suitable samples not received; QI-8), (% of number of samples received in inappropriate container; QI-9), (% of number of samples hemolysed; QI-10), (% of number of samples with inadequate sample volume; QI 12) (% of number of samples received mismatched; QI 15), (% of number of samples reported after turnaround time; QI 21) and (% of number of samples with critical values informed; QI 22)] based on defined criteria of Quality Specification given by International Federation of Clinical Chemistry. Total number of preanalytical errors was 53,669 (3.72%). Among the preanalytical errors, inadequate sample volume (2.37% of total samples; 63.49% of total pre-analytical errors) was the most common anomaly followed by Not received samples (24.18%) hemolysis (8.26%) mismatched (3.91%) and 0.14% samples were received in Inappropriate container; manifesting that the error frequency was unacceptable for QI 21 and QI 8, acceptable for QI 10, minimally acceptable for QI 15 and optimum for QI QI 9. Furthermore, there was year-wise progressive decline in error rate of inadequate sample volume, hemolysed sample received and mismatched samples. Total number of post analytical errors were 19,002 (1.32%). TAT outlier and critical values communicated were the two QIs evaluated for this phase and results of both QI were within acceptable limits. Quality indicators serve as a tool to monitor process performance and consequently derived error rates warrant active intervention to improve the laboratory services and patient health care. Dissemination of certified documents, regular staff training and evaluation needs to be conducted.

COMPARISON BETWEEN THE PARAMETERS OF THROUGHFALL AND BULK DEPOSITION MEASURED IN TWO LABORATORIES USING THE SAME METHODS

Among the main concerns of the researchers is the comparability of the analysis methods, in order to highlight possible errors. Several statistical approaches and graphical tools are available to investigate sources of analytical error and for decision-making. In this article, we present an operative protocol for the comparison of the precision for two laboratories with the same quantitative analytical methods. This paper describes the importance of achieving sequential stages, including experimental design, familiarization with the method of optimal research analysis, quality evaluation, selection of sample, definition of acceptability criteria. Sample measurement, data analysis and evaluation, final decision and reporting are also discussed and exemplified. The reason for performing a comparison experiment is to estimate the type and magnitude of systematic error between two laboratories with the same method and to judge if the two laboratories are identical within the inherent imprecision methods or within preset analytical quality specifications. Finally, the purpose was to check if same ranges of concentrations and fluxes of pollutants are obtained using the same methods of analysis, but in two different labs.

Analytical quality specifications in semen analysis according to the state of the current methodologies.

The aim of this study was to establish analytical quality specifications for human semen measurands according to the state of the current methodologies. Measurement errors were estimated based on data from participating laboratories in the External Quality Program (PEEC) led by the Argentine Biochemistry Foundation using the "Analytical Quality Minimum Specifications" model established in Spain for other biochemical collection parameters. Semen samples from the PEEC were analyzed according to WHO procedures. Analytical quality specifications were established according to the most recent results obtained by the External Quality Evaluation Program of the Fundación Bioquímica Argentina. Morphology, progressive motility, total motility and sperm concentration were 75%, 30%, 21% and 43%, respectively, for samples with assigned values between 6 and 15% of normal forms, 35-89% for progressive motility, 43-92% for total motility and for sperm count in the range of 1.8×106-65×106 spermatozoa/mL. Our allowable total error specification may affect medical conduct at certain dose levels, compromising clinical test validity. The measurement system employed is closely associated with the number of elements evaluated. The use of manual methods, where the fatigue of the operator counteracts their ability to evaluate a considerable number of elements, leads to errors typical of the poisson and binomial distribution characteristics of these measurands. This work reflects the laboratory performance in our region. The proposed specifications are a statement of minimums that every laboratory should comply with to ensure analytical performance of clinical utility with the current methodology available.

Impact of Individualized Hemolysis Management Based on Biological Variation Cut-offs in a Clinical Laboratory.

BackgroundHemolysis is the most common type of preanalytical interference. Cut-offs based on the hemolysis index level can be established using different approaches. The Working Group for Preanalytical Phase of the European Federation of Laboratory Medicine has developed a protocol for hemolysis management based on cut-offs estimated from biological variation (BV) and the use of interpretative comments. We developed and assessed the implementation of the protocol in our laboratory.MethodsHemolysates from whole blood were prepared following the Meites method, and pooled serum samples with known Hb concentrations were prepared. For each analyte (42 ), interferograms were generated and used to establish cut-offs desirable analytical quality specification and reference change value. This protocol was assessed, both pre- and post-implementation, according to expert rules in the Laboratory Information System.ResultsAmong the analytes evaluated, we selected those that showed the highest degree of hemolysis interference lactate dehydrogenase (LDH), aspartate aminotransferase, direct bilirubin, potassium, and folic acid. The cut-offs for LDH and direct bilirubin were the lowest. Only 28.16% of all LDH values were adequately reported in the pre-implantation retrospective study, but this percentage improved in the post-implementation stage.ConclusionsThe development and implementation of a harmonized protocol for hemolysis management based on BV cut-offs and result reporting significantly improve hemolysis detection and lead to a decrease in the number of hemolyzed samples over time.

Biological variation of cardiac myosin-binding protein C in healthy individuals.

Cardiac myosin-binding protein C (cMyC) is a novel biomarker of myocardial injury, with a promising role in the triage and risk stratification of patients presenting with acute cardiac disease. In this study, we assess the weekly biological variation of cMyC, to examine its potential in monitoring chronic myocardial injury, and to suggest analytical quality specification for routine use of the test in clinical practice. Thirty healthy volunteers were included. Non-fasting samples were obtained once a week for ten consecutive weeks. Samples were tested in duplicate on the Erenna® platform by EMD Millipore Corporation. Outlying measurements and subjects were identified and excluded systematically, and homogeneity of analytical and within-subject variances was achieved before calculating the biological variability (CVI and CVG), reference change values (RCV) and index of individuality (II). Mean age was 38 (range, 21-64) years, and 16 participants were women (53%). The biological variation, RCV and II with 95% confidence interval (CI) were: CVA (%) 19.5 (17.8-21.6), CVI (%) 17.8 (14.8-21.0), CVG (%) 66.9 (50.4-109.9), RCV (%) 106.7 (96.6-120.1)/-51.6 (-54.6 to-49.1) and II 0.42 (0.29-0.56). There was a trend for women to have lower CVG. The calculated RCVs were comparable between genders. cMyC exhibits acceptable RCV and low II suggesting that it could be suitable for disease monitoring, risk stratification and prognostication if measured serially. Analytical quality specifications based on biological variation are similar to those for cardiac troponin and should be achievable at clinically relevant concentrations.

Performance evaluation of optical platelet counting of BC-6000Plus automated hematology analyzer.

BackgroundThe BC-6000Plus (Mindray, Shenzhen, China) is a recently developed hematology analyzer that utilizes fluorescent technology. Based on fluorescent nucleic acid stain and optical detection, the optical platelet counting (PLT-O) on the BC-6000Plus has strong anti-interference potential in platelet (PLT) detection. Its Auto 8×PLT-O Counting Tech can be automatically triggered in low-PLT samples, which enables the PLT-O on the BC-6000Plus to count low PLT more efficiently. Here, we evaluated the performance of the BC-6000Plus automated hematology analyzer in optical PLT counting.MethodsThe basic features (including blank counting, carryover, trueness, and accuracy) of the BC-6000Plus for PLT counting were evaluated according to the Analytical Quality Specifications for Routine Tests in Clinical Hematology (WST 406-2012). Low-PLT samples with a PLT count of below 100×109/L were selected for repeatability tests. Meanwhile, the potential correlations of BC-6000Plus with the XN-L 350 and manual microscopy within different PLT ranges or under interferences of small red blood cells (RBCs) or PLT aggregation were analyzed.ResultsThe PLT-O on BC-6000Plus met the technical requirements of PLT counting in terms of blank count, carryover, trueness, and accuracy. The repeatability of the enhanced mode (PLT-O 8×) on the BC-6000Plus was better than that of the XN-L 350 in three low PLT count ranges, including 10–20, 20–60, and 60–100 (×109/L). Under the interference-free conditions, the BC-6000Plus correlated well with the XN-L 350 in different PLT counting ranges. Under the interferences of small RBCs and PLT aggregation, the PLT-O on BC-6000Plus correlated better with microscopy than with the platelet impedance count (PLT-I).ConclusionsThe PLT-O on BC-6000Plus can meet the technical requirements of PLT counting in terms of blank counting, carryover rate, trueness, and accuracy. The PLT-O 8× has good repeatability, correlates well with the XN-L 350, and demonstrates good anti-interference ability. It can thus meet the needs of blood cell analysis in clinical settings.

Trueness assessment of routine electrolytes measuring systems using the candidate reference method by ion chromatography

Electrolytes for sodium, potassium, magnesium, and calcium are important serum ions that are frequently assayed in clinical laboratories. In this study, we assessed the trueness of routine analytical systems for four cations using an inexpensive candidate reference method aimed to promote the standardization of serum electrolyte detection. An ion chromatography (IC) method with Cesium as an internal standard was developed and evaluated. The residual clinical serum samples at Chaoyang Hospital were collected and prepared into three human serum pools of electrolytes, which were used for the trueness evaluation of five routine analytical systems. Furthermore, the agreement between routine methods and the IC method was verified using 40 individual human samples. The recovery rates of sodium, potassium, magnesium and calcium were 99.69%, 100.34%, 100.43% and 99.89%, respectively. The intra-batch standard deviation and intra-laboratory precision of NIST SRM 956c were all less than 1% for the four ions. The certified values were within the validation range, and the deviation between the results and the certified values were less than 0.5%. The three serum pools were homogeneous and stable. All routine systems aligned with the IC method for four cations and achieved the analytical quality specifications for potassium and magnesium at 3 different concentrations. The developed IC method is simple, practical, accurate, and precise, which can be used as a candidate reference method for serum electrolytes measurement. Five routine analytical systems for electrolytes measurement had the acceptable bias for potassium and magnesium and their results showed good concordance.

Definition of analytical quality specifications for serum total folate measurements using a simulation outcome-based model

Article Definition of analytical quality specifications for serum total folate measurements using a simulation outcome-based model was published on March 1, 2020 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 58, issue 3).

Pre-analytical quality indicators in laboratory medicine: Performance of laboratories participating in the IFCC working group “Laboratory Errors and Patient Safety” project

Quality indicators (QIs) are key tools for improving the quality of laboratory services, by reducing error rates and safeguarding patient safety. A body of accumulated evidence confirms the relevance of QIs and their impact on the overall quality of laboratory information. The consensus achieved on a list of “harmonized” QIs, along with the system used for data collection and reporting throughout an international benchmarking programme, has enabled achieving realistic performance targets, based on knowledge of the state-of-the-art. Data collected in 2017 and 2018 have been analyzed and performance measures obtained by laboratories participating in the project are summarized in the present article. The laboratory performance measures have been classified into three levels (optimum, desirable or minimum) in agreement with the widely accepted model of analytical quality specifications.

Analytical and Biological Variability of Urinary Epidermal Growth Factor-to-Creatinine Ratio in Patients with Chronic Kidney Disease and in Healthy Volunteers.

Urinary levels of epidermal growth factor to creatinine ratio are considered as an early predictor of interstitial kidney fibrosis but so far no data are available on their biological variation (BV) and derived parameters. The aim of this study is to determine the BV of epidermal growth factor to creatinine ratio in patients with chronic kidney disease and in healthy volunteers. This cross-sectional study included 150 patients with chronic kidney disease (CKD) and 150 healthy volunteers (HV). In both groups, spot second-morning urine samples were collected once a week for 4 consecutive weeks. Measurements of EGF were done by ELISA and expressed as EGF/creatinine ratio. The components of BV, individuality index (II), and reference change values (RCV) were calculated. The analytical coefficient of variation (CVa) of EGF/creatinine ratio was 3.8% in patients with CKD and 3.9% in HV. The within-patient variation coefficient (CVw) was 11.2% in CKD and 12.1% in HV. The between-patient coefficient of variation (CVg) was 34% in CKD and 22% in HV. In both groups, CVa met the optimum analytical quality specifications for imprecision, since it was lower than 25% of CVw. There were no significant differences between CKD and HV in the analytical or in the within-patient variances of the EGF/creatinine ratio. The between-patient EGF/creatinine ratio variance was significantly higher in patients with CKD than in HV (F: 48.3, p: 0.000). The EGF/creatinine ratio showed an individuality index (II) of 0.3 in CKD and 0.5 in HV. The reference change value (RCV) was 29.2% in CKD and 31.6% in HV. The CVa associated with the measurement techniques used in our study meets the optimal criteria of analytical imprecision. The urine EGF/creatinine ratio shows a high index of individuality both in patients with CKD and in HV, so the comparison of an isolated value with a reference interval is of little use. In the monitoring of repeated levels in the same individual or patient, the changes can only be considered significant when they are greater than 30% in relation to the previous values.

External quality assessment programs in the context of ISO 15189 accreditation.

AbstractEffective management of clinical laboratories participating in external quality assessment schemes (EQAS) is of fundamental importance in ensuring reliable analytical results. The International Standard ISO 15189:2012 requires participation in interlaboratory comparison [e.g. external quality assessment (EQA)] for all tests provided by an individual laboratory. If EQAS is not commercially available, alternative approaches should be identified, although clinical laboratories may find it challenging to choose the EQAS that comply with the international standards and approved guidelines. Great competence is therefore required, as well as knowledge of the characteristics and key elements affecting the reliability of an EQAS, and the analytical quality specifications stated in approved documents. Another skill of fundamental importance is the ability to identify an alternative approach when the available EQAS are inadequate or missing. Yet the choice of the right EQA program alone does not guarantee its effectiveness. In fact, the fundamental steps of analysis of the information provided in EQA reports and the ability to identify improvement actions to be undertaken call for the involvement of all laboratory staff playing a role in the specific activity. The aim of this paper was to describe the critical aspects that EQA providers and laboratory professionals should control in order to guarantee effective EQAS management and compliance with ISO 15189 accreditation requirements.

Short- and medium-term biological variation estimates of leukocytes extended to differential count and morphology-structural parameters (cell population data) in blood samples obtained from healthy people

BackgroundRecent studies showed that some cell population data (CPD) parameters of neutrophils may be useful for diagnosing myelodysplastic syndromes and sepsis, for the differential diagnosis of acute promyelocytic leukemia, and some CPD parameters of lymphocytes may be a valuable tool for preliminary screening of B cell lymphoproliferative disease. Notwithstanding the knowledge, no information has been made available about their analytical quality specification. This study was aimed to define short- and medium-term biological variation (BV) estimates and reference change value (RCV) of leukocyte count, extended leukocyte differential and CPD. MethodsThe study population consisted of 43 healthy volunteers, who participated in the assessment of medium-term (21 volunteers; blood sampling once a week for 5 consecutive weeks) and short-term (22 volunteers; blood sampling once a day for 5 consecutive days) BV, using Sysmex XN. Outlier analysis was carried out before CV-ANOVA, to determine BV estimates and their confidence intervals. ResultsThe medium-term and short-term within-subject BV (CVI) was comprised between 0.6–19.7% and 0.2–21.9%, whereas the medium-term and short-term between-subjects BV (CVG) was comprised between 1.2–61.5% and 1.1–58.5%. The RCVs were found to be similar for all the parameters, in both arms of the study, except for some CPD parameters. ConclusionThis study allowed accurately estimating the BV of many leukocyte parameters, some of which have not been currently explored. The kinetics of some leukocyte turnover suggests the use of short-term BV data for calculating analytical goals and RCV.

Quality specifications of routine clinical chemistry methods based on sigma metrics in performance evaluation.

Sigma metrics were applied to evaluate the performance of 20 routine chemistry assays, and individual quality control criteria were established based on the sigma values of different assays. Precisions were expressed as the average coefficient variations (CVs) of long-term two-level chemistry controls. The biases of the 20 assays were obtained from the results of trueness programs organized by National Center for Clinical Laboratories (NCCL, China) in 2016. Four different allowable total error (TEa) targets were chosen from biological variation (minimum, desirable, optimal), Clinical Laboratory Improvements Amendments (CLIA, US), Analytical Quality Specification for Routine Analytes in Clinical Chemistry (WS/T 403-2012, China) and the National Cholesterol Education Program (NECP). The sigma values from different TEa targets varied. The TEa targets for ALT, AMY, Ca, CHOL, CK, Crea, GGT, K, LDH, Mg, Na, TG, TP, UA and Urea were chosen from WS/T 403-2012; the targets for ALP, AST and GLU were chosen from CLIA; the target for K was chosen from desirable biological variation; and the targets for HDL and LDL were chosen from the NECP. Individual quality criteria were established based on different sigma values. Sigma metrics are an optimal tool to evaluate the performance of different assays. An assay with a high value could use a simple internal quality control rule, while an assay with a low value should be monitored strictly.

Evaluation of a new hemoglobin A1c analyzer for point-of-care testing.

There has been an increasing desire for the use of point-of-care testing (POCT) by both primary care clinicians and patients. This study aimed to evaluate the performance of a new POCT analyzer for hemoglobin A1c (HbA1c) testing. We assessed the accuracy, precision, and linearity of the POCT HbA1c analyzer (A1C EZ 2.0) with the Tosoh G8 Analyzer as comparative instrument, following the Clinical and Laboratory Standards Institute (CLSI) protocols. We evaluated sensitivity and specificity of the A1C EZ 2.0 in the clinical diagnosis of diabetes among 842 subjects from 79 communities in Beijing, China. Using regression analysis, the slope of the A1C EZ 2.0 vs the Tosoh G8 Analyzer was 0.9938, with an intercept of 0.0964 and a concordance correlation coefficient of 0.978. For precision, the reproducibility of CV (CVT ) were 3.7% and 2.7% at a lower (36mmol/mol (5.4%)) and higher (107mmol/mol (11.9%)) level of HbA1c respectively. The area under the receiver operating characteristic (ROC) curve for clinical diagnosis of diabetes was 0.911 with the HbA1c cut-off value of 44mmol/mol (6.14%). At the HbA1c level of 48mmol/mol (6.5%), the sensitivity and specificity were76.1% and 86.6%. The A1C EZ 2.0 has a high accuracy and precision, with a wide range of linearity, compared to a comparative laboratory instrument. It met analytical quality specifications and could be suitable for the clinical management of diabetes mellitus.

Quality Control of Structural Parameters (CELL POPULATION DATA) of Sysmex XN Series

INTRODUCTION:Cell population data (CPD) measured by hematology analyzers (HA) describe morphological parameters of white blood cell (WBC) subpopulations and are reported to be as useful parameters in the screening of several hematological and non-hematological diseases. The Sysmex XN is an HA that uses fluorescence flow cytometry for WBC differential, combining forward scatter (FSC), side scatter (SSC) and fluorescence intensity (SFL) to identify WBC populations. These three measures, along with their Distribution Width (DW), are used to provide CPD of Neutrophils (NE), Lymphocytes (LY) and Monocytes (MO). Recent articles have shown that neutrophils CPD parameters (NE-SSC, NE-SFL) may be useful in the diagnosis of myelodysplastic syndromes [1,2] and sepsis [3]. However, little is known on their analytical quality specification, as the comparability of CPD between instruments and laboratories. The aim of the study was to evaluate the between-analyzers consistency of CPD provided by Sysmex XN comparing the results obtained in five different XN modules installed in the same laboratory. Here we present the results for NE-SSC and NE- SFL, the CPD parameters mainly used to support the diagnosis of suspected sepsis and myelodysplasiaM&MPeripheral blood samples collected in K3EDTA tubes (Becton Dickinson, NJ) in three different days from 30 healthy blood donors (HBD, 10 samples/daily) were analyzed within 30 minutes on each XN module. Additionally, all normal samples analyzed by the lab were selected from the routine workload of one month (November 2015) consisting of a total of 35.500 samples. The inclusion criteria (that led to a selection of 6,702 normal routine samples, NRS) were as follows: no morphological flags, WBC from 4.0 to 10.0 x 109/L; Hgb from 120 to 170 g/L; MCV from 84 to 98 fL, PLT from 150 to 450 x 109/L; RDW-CV < 14.0%; NRBC=0.00 x 109/L; NE from 2.00 to 5.60 x 109/L, LY from 1.50 to 3.50 x 109/L, MO from 0.30 to 0.80 x 109/L, EOS from 0.10 to 0.60 x 109/L, BASO <0.20 x 109/L. Finally, the daily results of XN-Chex control blood (Normal level) were included in the evaluation.For each group of samples (HBD, NRS, XN-Check) we compared the median values of CPD parameter obtained on each XN modules. The between-analyzers consistency of CPD parameter was assessed calculating the percentage of Bias (Bias%) between the median value of each XN module and the overall median value of all the five analyzers.To evaluate the stability over the time of CPD parameters, the same study on 30 HBD, 6,690 NRS and XN-Chex control blood was repeated after two months (January 2016).RESULTSThe median values of NE-SSC and NE-SFL obtained in each group of samples are shown in Table 1. The results highlight a good agreement between analyzers, with a maximum Bias of -3.85%. Interestingly, the median values of NE-SSC and NE-SFL were practically the same in HBD and NRS while, as expected, they were significantly different on XN-Chex (due to the presence of stabilized cells). However, the Bias observed for each module XN on control blood was similar to that observed on fresh blood (HBS and NRS groups). Median values of NE-SSC and NE-SFL were practically the same after two months both in HBD and NRS, proving that CPD parameters are stable over the time. Similar results were obtained on all the other CPD parameters provided by Sysmex XN (data not shown)CONCLUSIONSCPD parameters are stable over the time and their inclusion on the automated QC of the analyzer based on the moving average of normal may be a reliable and inexpensive method to assess the between-analyzers consistency of CPD parameters. Providing the expected values of CPD parameters, XN-Check could be useful for the daily QC, to assess the need of calibration and to improve the inter-laboratory comparability being the Neutrophils the best WBC population to control using XN-Check control blood. The moving average can be used too as a way to monitor the calibration and to decide what to do when the QC materials give a result out of range (moving average).The results of this study show the possibility to calibrate the CPD parameters. The availability of a calibration material also for CPD parameters would guarantee a further improvement of standardization and their use as reportable diagnostic parameters.1. Le Roux G, Vlad A, Eclache V et al. Int J Lab Hematol 2010;32:237-2432. Furundarena JR, Araiz M, Uranga M et al. Int J Lab Hematol 2010;32:360-3663. Park SH, Park CJ, Lee BR et al. Int J Lab Hematol 2014;37 [Display omitted] DisclosuresSimon-Lopez:Sysmex Corporation: Consultancy, Honoraria. Buoro:Sysmex EMEA: Research Funding. Pacioni:DASIT Diagnostica SpA: Employment, Other: Scientific Manager of DASIT (Distributor of Sysmex in Italy). Seghezzi:Sysmex EMEA: Research Funding. Manenti:Sysmex EMEA: Research Funding.

Biological variation of 20 analytes measured in serum from clinically healthy domestic cats.

The applications of data on biological variation include assessment of the utility of population-based reference intervals, evaluation of the significance of change in serial results, and setting of analytical quality specifications. We investigated the biological variation of 19 biochemistry analytes and total T4, measured in serum from 7 clinically healthy domestic cats sampled once weekly for 5 weeks. Samples were frozen and analyzed in random order in the same analytical run. Results were analyzed for outliers, and the components of variance, subsequently generated by restricted maximum likelihood, were used to determine within-subject and between-subject variation (CVI and CVG, respectively), as well as analytical variation (CVA) for each analyte. Indices of individuality, reference change values, and analytical performance goals were calculated. The smallest CVI and CVG were found for calcium, chloride, and sodium, whereas the largest values were calculated for bile acids. Nine analytes (albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, cholesterol, creatinine, phosphate [phosphorus], total protein, total T4) demonstrated high individuality, indicating limited utility of population-based reference intervals. Individuality was low, and population-based reference intervals were thereby considered appropriate for 5 analytes (bile acids, calcium, fructosamine, glucose, potassium). The intermediate individuality observed for 4 analytes (creatine kinase, iron, magnesium, urea) indicated that population-based reference intervals should be used with caution.