External Quality Control Survey Research Articles

External quality control survey on identification of microorganisms using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry（ MALDI-TOF MS） is a bacterial typing tool that was approved as a medical device in 2011. However, external accuracy control examination of bacterial typing using mass spectrometry is still only performed on a small scale. In this study, E. faecium and S. maltophilia were selected and tested according to established procedures using Score Values at 228 institutions. The Score Values for MALDI Biotyper were 2.43±0.08 for E. faecium and 2.38±0.08 for S. maltophilia; and those for VITEK MS/PRIME were 99.9±0.0 for E. faecium and S. maltophilia. These results suggest that it is useful to evaluate external accuracy control with Score Values using the procedures we have developed.

External clinical laboratory quality control survey of clinical chemistry field from 2016 to 2018 in Aichi

External clinical laboratory quality control survey of clinical chemistry field from 2016 to 2018 in Aichi

In ECAT veritas?

The laboratory criteria of the antiphospholipid syndrome include one coagulation assay (lupus anticoagulant [LA]) and two solid phase assays (anticardiolipin [aCL] and anti-ß(2)glycoprotein I antibodies [aß(2)GPI]). External quality control (EQC) surveys show that negative and clearly positive LA samples are classified correctly by about 95% of laboratories. For 'weak' LA there is a wide variability in samples' classification. Furthermore, when a weak LA sample is used in two different EQC surveys more than 50% of laboratories classify it differently. In some surveys weak LA samples were found to be positive for aCL and for aß(2)GPI by a majority of laboratories; the main reason for laboratories which classified these samples as LA negative was a negative result in the mixing test. It is likely that, depending on the sensitivity of the assay, a weak LA cannot be detected anymore after 1:1 dilution of the sample with normal plasma. Therefore, we recommend the use of integrated assays, such as screen/confirm ratios, for the detection of weak LA samples.

Implementation of nine quality indicators in a hospital emergency clinical laboratory

Quality indicators are tools used to monitor specific activities within a process and improve it. In the area of clinical laboratories, the National Accreditation Standards for Providers of Health and the ISO 15189 standard recommend the implementation of indicators that monitor the test cycle with emphasis on those that contribute to a safer health care. To describe the implementation of nine indicators in a hospital clinical laboratory and their measurement during one year. The indicators implemented and measured were four of the pre-analytical phase (number of rejected samples, times of transport, blood culture contamination and blood cultures inoculated with adequate blood volumes), two of the analytical phase (coherence of Gram stains of blood culture with microorganism cultured and correct results in external quality control surveys) and three of the post-analytical phase (compliance with order to report lapse goals, corrected reports and alert values report). Two indicators of pre-analytical phase did not meet the per determined targets: number of rejected samples and blood cultures inoculated with adequate blood volume. All indicators of the analytical and post analytical phases were within the pre-determined targets. Coordinated work should be initiated especially with the nursing service to correct the two indicators that did not meet the target. The incorporation of quality indicators to monitor critical processes within the laboratory was undoubtedly an opportunity to identify areas for improvement.

How to deal with semi-quantitative tests? Application of an ordinal scale model to measurements of urine glucose

Background: The interpretation of semi-quantitative methods has always been difficult, because the different kitmanufacturers use varying concentration values and there is a considerable overlap between kit-defined concentrations within the same kit (Kit: ‘Ready-to-use’ measuring system specific for each manufacturer's product). Material: More than 2000 private practitioners and laboratories participated in three external quality control surveys on urine-glucose performed with a total of six control materials with known concentrations. Method: The ordinal scale model for evaluation of dichotomous methods based on rankit transformation of fractions of positive results (Petersen et al. Scand J Clin Lab Invest 2008;68:298–311) has been extended and modified to handle semi-quantitative data. Here, the percentages of results larger than the kit-concentration is calculated for each control sample and applied as a dichotomous method. Thereafter, these percentages are separated into all the defined kit-concentrations. Results: A total of eight kits had more than 50 measurements on at least four control materials which made them eligible for the calculations of logarithmic mean and standard deviation and thereby geometric mean and coefficient of variation for each of the kit-concentrations of each kit. Based on these parameters, the true concentration for selected percentages of each kit-concentration could be estimated. Moreover, the percentages of the different kit-concentrations could be calculated for each known true concentration. Conclusions: The present model is a powerful tool for improved characterization of semi-quantitative kits, which makes it possible to evaluate and validate kits and to optimize external quality control.

How to deal with semi-quantitative tests? Application of an ordinal scale model to measurements of urine glucose

Background: The interpretation of semi-quantitative methods has always been difficult, because the different kitmanufacturers use varying concentration values and there is a considerable overlap between kit-defined concentrations within the same kit (Kit: ‘Ready-to-use’ measuring system specific for each manufacturer's product). Material: More than 2000 private practitioners and laboratories participated in three external quality control surveys on urine-glucose performed with a total of six control materials with known concentrations. Method: The ordinal scale model for evaluation of dichotomous methods based on rankit transformation of fractions of positive results (Petersen et al. Scand J Clin Lab Invest 2008;68:298–311) has been extended and modified to handle semi-quantitative data. Here, the percentages of results larger than the kit-concentration is calculated for each control sample and applied as a dichotomous method. Thereafter, these percentages are separated into all the defined kit-concentrations. Results: A total of eight kits had more than 50 measurements on at least four control materials which made them eligible for the calculations of logarithmic mean and standard deviation and thereby geometric mean and coefficient of variation for each of the kit-concentrations of each kit. Based on these parameters, the true concentration for selected percentages of each kit-concentration could be estimated. Moreover, the percentages of the different kit-concentrations could be calculated for each known true concentration. Conclusions: The present model is a powerful tool for improved characterization of semi-quantitative kits, which makes it possible to evaluate and validate kits and to optimize external quality control.

Technical Aspects in Laboratory Testing for Antiphospholipid Antibodies: Is Standardization an Impossible Dream?

Anticardiolipin (aCL) and anti-beta2 glycoprotein I (anti-beta2GPI) assays are widely performed because they are part of the laboratory criteria for the antiphospholipid syndrome (APS). Despite several standardization workshops and the availability of a worldwide accepted calibrator material for aCL, a high variability in numerical assay results and in sample classification is still observed in comparative studies and external quality control surveys. For anti-beta2GPI assays, comparison of numerical values is impeded by the absence of a common calibrator material, and external quality surveys similarly show a large overlap in sample classification. Numerous variables impact assay results, among them the source and integrity of beta2GPI, the secondary calibration process, and the assessment and derivation of cutoff values. For both assays, the vast majority of laboratories use commercial kits whose number has risen considerably in the past years. However, many problems persist, and there is a need to improve the comparability in assay results. The use of monoclonal antibodies as reference calibrators has to be especially considered, with their suitability evaluated by future collaborative studies and external quality controls surveys. Manufacturers should provide more precise information on results obtained when testing control groups for establishing reference ranges and cutoff values. From the customers' perspective, it is important that each laboratory, even if using commercial kits, assesses its local cutoff value whenever possible. In the field of autoimmunity, assay standardization is a difficult but nevertheless important task. Much more effort is needed to reduce the high interlaboratory variability in assay results even if absolute standardization cannot be feasibly achieved.

External quality control results of urine dip-slide devices

Urinary tract infections are frequently diagnosed by using urine dip-slide devices, especially in medical practices and small laboratories. We performed a retrospective analysis of more than 3000 results obtained by several urine dip-slide devices during external quality control surveys. We found that an underestimation of bacterial counts and a difficulty in identifying mixed flora were relatively more frequent in medical practices than in specialized laboratories, and that regular participation in external quality control surveys correlates with better performances.

Is Serological Testing a Reliable Tool in Laboratory Diagnosis of Syphilis? Meta-Analysis of Eight External Quality Control Surveys Performed by the German Infection Serology Proficiency Testing Program

The accuracy of diagnostic tests is critical for successful control of epidemic outbreaks of syphilis. The reliability of syphilis serology in the nonspecialist laboratory has always been questioned, but actual data dealing with this issue are sparse. Here, the results of eight proficiency testing sentinel surveys for diagnostic laboratories in Germany between 2000 and 2003 were analyzed. Screening tests such as Treponema pallidum hemagglutination assay (mean accuracy, 91.4% [qualitative], 75.4% [quantitative]), Treponema pallidum particle agglutination assay (mean accuracy, 98.1% [qualitative], 82.9% [quantitative]), and enzyme-linked immunosorbent assays (ELISAs) (mean qualitative accuracy, 95%) were more reliable than Venereal Disease Research Laboratory (VDRL) testing (mean accuracy, 89.6% [qualitative], 71.1% [quantitative]), the fluorescent treponemal antibody absorption test (FTA-ABS) (mean accuracy, 88% [qualitative], 65.8% [quantitative]), and immunoblot assays (mean qualitative accuracy, 87.3%). Clearly, immunoglobulin M (IgM) tests were more difficult to manage than IgG tests. False-negative results for samples that have been unambiguously determined to be IgM and anti-lipoid antibody positive accounted for 4.7% of results in the IgM ELISA, 6.9% in the VDRL test, 18.5% in the IgM FTA-ABS, and 23.0% in the IgM immunoblot assay. For negative samples, the mean percentage of false-positive results was 4.1% in the VDRL test, 5.4% in the IgM ELISA, 0.7% in the IgM FTA-ABS, and 1.4% in the IgM immunoblot assay. On average, 18.3% of participants misclassified samples from patients with active syphilis as past infection without indicating the need for further treatment. Moreover, 10.2% of laboratories wrongly reported serological evidence for active infection in samples from patients with past syphilis or in sera from seronegative blood donors. Consequently, the continuous participation of laboratories in proficiency testing and further standardization of tests is strongly recommended to achieve better quality of syphilis serology.

Japanese collaborative study for fibrinogen assay: variability of the fibrinogen assay between different laboratories does not improve when a common calibrator is used

Several national and local external quality assurance schemes have been developed to improve the plasma fibrinogen assay in Japan over the past 30 years. Now most commercial calibrant plasma may be calibrated against an International Standard preparation, in order to achieve agreement of results obtained by different laboratories. However, we have never achieved satisfactory results, according to an external quality control survey regarding the fibrinogen assay. Therefore, we distributed two kinds of fibrinogen standards to be used as common calibrators, along with three plasma samples, among 183 general laboratories in Japan. The results of this collaborative study showed that the assigned value for the commercially available calibrators remained problematic. Furthermore, it was concluded that the between-laboratory variability could not be improved beyond a certain degree of standardization, even if a common calibrator was used for the Clauss-derived assay carried out by an automatic coagulometer.

Standardization of Laboratory Test in the JPHC Study

The standardization committee has carried out standardization of 23 laboratories in the cohort area. They participated in the External Quality Control Survey by the Japan Medical Association. Most laboratories got A or B in evaluation criteria for most test items, but the results of AST, ALT and gamma-GTP were unsatisfactory. As for the lipid standardization, accuracy and precision of all 23 laboratories were satisfactory except for one. Close communication and collaborative study with reference laboratory improved the accuracy control.

Interference From Digitoxin-like Immunoreactive Factors Reduced in a New Monoclonal Chemiluminescent Digitoxin Assay

Endogenous digoxin-like immunoreactive factors (DLIF) can interfere with some digoxin immunoassays. We looked for similar interference, called digitoxin-like immunoreactive factors (DTLIF) in two digitoxin immunoassays: A new chemiluminescent assay (CLIA), processed on the automated random access immunoassay system ACS:180, and a fluorescent polarization assay (FPIA), processed on the semiautomated TDx batch analyzer. One hundred thirty-seven samples of sera were tested from nondigitalized pregnant women, patients with liver or kidney diseases, and cord blood. The CLIA digitoxin assay uses a murine monoclonal antibody and requires no sample pretreatment; the FPIA digitoxin assay uses a polyclonal rabbit antibody and requires sample precipitation. Both assays have a similar dynamic range and sensitivity and give comparable results with commercial controls and external quality control survey samples. Although the CLIA detected no digitoxin in any sample tested, the FPIA showed apparent digitoxin concentrations of more than 2.0 ng/ml for 100% and 44% among cord blood and liver disease specimens, respectively. The highest DTLIF concentration was found in serum from a patient with liver disease (18.1 ng/ml). When spiked with 32 ng/ml digitoxin, six of the samples containing DTLIF generated FPIA digitoxin values of 6% to 27.5% more than the expected digitoxin levels. Two specimens with no detectable DTLIF activity were run as controls, and when spiked with digitoxin, showed target digitoxin concentrations in the FPIA. The CLIA recovered near the target digitoxin values (32 ng/ml) in all spiked samples. It was concluded that the polyclonal FPIA digitoxin assay may give discordant digitoxin concentrations in some patient groups because of interference from digitoxin-like immunoreactive factors. The CLIA digitoxin assay is not affected by DTLIF interference.

General approach to correction for bias in analytical performance in longitudinal studies illustrated by estimating the effect of age on gamma-glutamyltransferase activity

For studying trends in blood biochemistry analytes of an individual or a group of individuals, the outcome may be influenced by analytical changes that may have occurred during the study. An observed trend may well represent a drift in analytical performance instead of a truly biological finding. We developed a model that allows for retrospective correction of analytical changes with time. This model is based on the concept of adjustment of an individual's longitudinal blood biochemistry data by comparing the long-term results of the laboratory with those of other laboratories in an external quality-control survey program. Factors responsible for the analytical bias of our laboratory were identified by multiple regression analysis. The resulting procedure for assessing analytical bias and variability was applied to study in two mutually exclusive cohorts of employees of the Shell petrochemical complex in Rotterdam (a) the true nature of the changes (analytical or biological) in gamma-glutamyltransferase (GGT) and (b) the effect of age on GGT. The first cohort consisted of employees who attended a periodic health assessment in 1984 and in 1989; the second, employees who attended periodic health assessments in 1985 and in 1988. Thus we studied 3- and 5-year changes of GGT corrected for analytical bias. Whereas standard cross-sectional results apparently showed an increase of GGT up to age 50 years, the longitudinal findings corrected for analytical changes, as indicated above, do not support these cross-sectional results.

Quality control program on biological monitoring by Japan Federation of Occupational Health Organizations

Since 1980, the Japan Federation of Occupational Health Organizations has been conducting an external quality control survey for biological monitoring under a contract with the Ministry of Labour of the Japanese Government. The number of participating organizations has increased from 91 in 1980 to 179 in 1987. The items in the program were lead and free erythrocyte protoporphyrin concentrations in blood, and lead, coproporphyrin, delta-aminolevulinic acid, chromium, hippuric acid, methylhippuric acid, total trichloro-compounds, mandelic acid, and phenol concentrations in urine. Evaluation was based on a scoring system. The scores were on the slope of major axis for probable ellipse, the slope of regression line, square root of error mean square for regression, performance indices, and the difference between 'true' and observed values of each sample. There was a gradual improvement in the evaluation scores as a function of time. The improvement was paralleled by the adoption of modern analytical methods such as flameless atomic absorption spectrometry for blood-lead measurement and high-performance liquid chromatography for urinary hippuric acid determination in many participants. These methods are simple in operation and reliable in performance. It was considered very probable that the program promoted the adoption.

Performance of Cell Counters in Primary Health Care

The results are presented from two external quality control surveys of cell counters in primary health care. The precision of haemoglobin measurements in the normal range was better than that obtained by conventional haemometers. The analytical quality of leucocyte analyses was about the same as that performed by hospital instruments. The precision of cell counters with respect to thrombocytes was poorer than that obtained on hospital instruments, especially in the lower level. Celldyn and Sysmex instruments performed best among the instruments examined. Reliable cell counter results were associated with medical laboratory technicians as operators of the instruments. To improve the analytical quality of the laboratory in primary health care, it appears necessary to establish an external quality assurance programme, including a laboratory consultancy service.

External quality control in the determination of neonatal bilirubin. An approach to the improvement of results.

The reliability of bilirubin analyses is especially important in cases of neonatal hyperbilirubinaemia. However, when the means of the results of external quality control surveys and the method-dependent stated values for control sera were compared with reference method values, differences of up to 10% were found. Further inaccuracy arose from interlaboratory imprecision, which showed coefficients of variation of at least 7%, and from greater or lesser interference from contamination of samples with haemoglobin. The present work investigates whether the current situation can be improved by available means.

Report on a joint European quality control survey for neonatal thyrotropin determinations (1986).

This paper presents the results of a joint European external quality control survey for thyrotropin determinations in blood dried on filter paper, carried out in 1986 in cooperation with several national quality control organizations. For the evaluation, 124 participants presented their individual diagnostic classifications in addition to their analytical results. Although, in relation to earlier studies of this kind, there was a significant improvement in interlaboratory precision the results still showed variance which depended on the analytical method and, possibly on the country in which it was performed. Regional differences were also evident in the diagnostic classifications.

Progress report on a national quality-control survey of triiodothyronine and thyroxin assay.

In January 1980, a national external quality-control survey was organized to evaluate assays for triiodothyronine (T3) and thyroxin (T4). Currently, about 150 laboratories are involved. Each participant has received and assayed 100 quality-control samples during four periods of about six months each. The average analytical performance achieved by the participants in each six-month period was estimated by computing the average between-laboratory agreement (CVT), the overall average bias, and the average laboratory imprecision. During the 2.5 years of the survey, analytical performance has improved for both assays (CVT decreased from 17.0 to 15.7% for T3 and from 13.1 to 12.7% for T4). Analysis of survey results according to the method/kit used (mean kit bias and kit imprecision for the nine kits most used by participants) showed that the analytical reliability of the T4 assay is generally better than that observed for T3, mainly because of the larger systematic differences among T3 kits.

The First External Quality Control Survey (EQCS) for Antithyroglobulin- and Antimicrosomal Antibody Determination

Fourteen laboratories participated in an external quality control survey (EQCS) for antithyroglobulin- and antimicrosomal-antibody determination. Seventeen frozen serum samples from individuals suffering from various thyroid diseases were dispatched by mail. Different test systems were used by the participants including the haemagglutinatin test, radioimmunoassay (RIA), enzyme immunoassay (ELISA) and immunofluorescence test. The different test results of each participant were sized and could be compared by giving place numbers to each test result. Inter-laboratory quality control was performed by evaluation of a rank correlation coefficient. There was close agreement between the haemagglutination test results of antimicrosomal antibody determination with different test kits, and these tests showed good precision. Antithyroglobulin antibody titers from the two haemagglutination test-kits used, however, were not directly comparable. When sized by place numbers, antithyroglobulin antibody results from haemagglutinatin test, RIA and ELISA were in close agreement. The least correspondence was shown by the immunofluorescence test, in the antithyroglobulin antibody determination.

A Second External Quality Control Survey (EQCS) for Serum Triiodothyronine (T 3 ) and Thyroxine (T 4 ) Assays Using the “Munich Model”

Article A Second External Quality Control Survey (EQCS) for Serum Triiodothyronine (T3) and Thyroxine (T4) Assays Using the “Munich Model” was published on January 1, 1980 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 18, issue 8).