Harmonization status of procalcitonin measurements: what do comparison studies and EQA schemes tell us?

Sepsis represents a global health priority because of its high mortality and morbidity. The key to improving prognosis remains an early diagnosis to initiate appropriate antibiotic treatment. Procalcitonin (PCT) is a recognized biomarker for the early indication of bacterial infections and a valuable tool to guide and individualize antibiotic treatment. To meet the increasing demand for PCT testing, numerous PCT immunoassays have been developed and commercialized, but results have been questioned. Many comparison studies have been carried out to evaluate analytical performance and comparability of results provided by the different commercially available immunoassays for PCT, but results are conflicting. External Quality Assessment Schemes (EQAS) for PCT constitute another way to evaluate results comparability. However, when making this comparison, it must be taken into account that the variety of EQA materials consist of different matrices, the commutability of which has not yet been investigated. The present study gathers results from all published comparison studies and results from 137 EQAS surveys to describe the current state-of-the-art harmonization of PCT results. Comparison studies globally highlight a significant variability of measurement results that nonetheless seem to have a moderate impact on medical decision-making. For their part, EQAS for PCT provides highly discrepant estimates of the interlaboratory CV. Due to differences in commutability of the EQA materials, the results from different peer groups could not be compared. To improve the informative value of the EQA data, the existing limitations such as non-harmonized conditions and suboptimal and/or unknown commutability of the EQA materials have to be overcome. The study highlights the need for commutable reference materials that could be used to properly evaluate result comparability and possibly standardize calibration, if necessary. Such an initiative would further improve the safe use of PCT in clinical routine.

Pre-analytical practices for routine coagulation tests in European laboratories. A collaborative study from the European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM).

Background Correct handling and storage of blood samples for coagulation tests are important to assure correct diagnosis and monitoring. The aim of this study was to assess the pre-analytical practices for routine coagulation testing in European laboratories. Methods In 2013-2014, European laboratories were invited to fill in a questionnaire addressing pre-analytical requirements regarding tube fill volume, citrate concentration, sample stability, centrifugation and storage conditions for routine coagulation testing (activated partial thromboplastin time [APTT], prothrombin time in seconds [PT-sec] and as international normalised ratio [PT-INR] and fibrinogen). Results A total of 662 laboratories from 28 different countries responded. The recommended 3.2% (105-109 mmol/L) citrate tubes are used by 74% of the laboratories. Tube fill volumes ≥90% were required by 73%-76% of the laboratories, depending upon the coagulation test and tube size. The variation in centrifugation force and duration was large (median 2500 g [10- and 90-percentiles 1500 and 4000] and 10 min [5 and 15], respectively). Large variations were also seen in the accepted storage time for different tests and sample materials, for example, for citrated blood at room temperature the accepted storage time ranged from 0.5-72 h and 0.5-189 h for PT-INR and fibrinogen, respectively. If the storage time or the tube fill requirements are not fulfilled, 72% and 84% of the respondents, respectively, would reject the samples. Conclusions There was a large variation in pre-analytical practices for routine coagulation testing in European laboratories, especially for centrifugation conditions and storage time requirements.

Analytical performance specifications for external quality assessment - definitions and descriptions.

External Quality Assurance (EQA) is vital to ensure acceptable analytical quality in medical laboratories. A key component of an EQA scheme is an analytical performance specification (APS) for each measurand that a laboratory can use to assess the extent of deviation of the obtained results from the target value. A consensus conference held in Milan in 2014 has proposed three models to set APS and these can be applied to setting APS for EQA. A goal arising from this conference is the harmonisation of EQA APS between different schemes to deliver consistent quality messages to laboratories irrespective of location and the choice of EQA provider. At this time there are wide differences in the APS used in different EQA schemes for the same measurands. Contributing factors to this variation are that the APS in different schemes are established using different criteria, applied to different types of data (e.g. single data points, multiple data points), used for different goals (e.g. improvement of analytical quality; licensing), and with the aim of eliciting different responses from participants. This paper provides recommendations from the European Federation of Laboratory Medicine (EFLM) Task and Finish Group on Performance Specifications for External Quality Assurance Schemes (TFG-APSEQA) and on clear terminology for EQA APS. The recommended terminology covers six elements required to understand APS: 1) a statement on the EQA material matrix and its commutability; 2) the method used to assign the target value; 3) the data set to which APS are applied; 4) the applicable analytical property being assessed (i.e. total error, bias, imprecision, uncertainty); 5) the rationale for the selection of the APS; and 6) the type of the Milan model(s) used to set the APS. The terminology is required for EQA participants and other interested parties to understand the meaning of meeting or not meeting APS.

A new approach to define acceptance limits for hematology in external quality assessment schemes.

BACKGROUND: A study performed in 2007 comparing the evaluation procedures used in European external quality assessment schemes (EQAS) for hemoglobin and leukocyte concentrations showed that acceptance criteria vary widely. For this reason, the Hematology working group from the European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM) decided to perform a statistical study with the aim of establishing appropriate acceptance limits (AL) allowing harmonization between the evaluation procedures of European EQAS organizers. METHODS: Eight EQAS organizers from seven European countries provided their hematology survey results from 2010 to 2012 for red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), white blood cells (WBC), platelets and reticulocytes. More than 440,000 data were collected. The relation between the absolute value of the relative differences between reported EQA results and their corresponding assigned value (U-scores) was modeled by means of an adaptation of Thompson's "characteristic function". Quantile regression was used to investigate the percentiles of the U-scores for each target concentration range. For deriving AL, focus was mainly on the upper percentiles (90th, 95th and 99th). RESULTS: For RBC, hemoglobin, hematocrit and MCV, no relation was found between the U-scores and the target concentrations for any of the percentiles. For WBC, platelets and reticulocytes, a relation with the target concentrations was found and concentration-dependent ALs were determined. CONCLUSIONS: The approach enabled to determine state of the art-based ALs, that were concentration-dependent when necessary and usable by various EQA providers. It could also easily be applied to other domains.

Retrospective analysis of 55,769 HbA1c EQA results obtained from professional laboratories and medical offices participating in surveys organized by two European EQA centers over a nine-year period.

External Quality Assessment (EQA) is an essential tool for laboratories to monitor the performances of their analyses. It also allows a comparison of methods and types of laboratories (professional laboratories vs. medical offices). We, therefore, compared 55,769 HbA1c EQA results obtained between 1999 and 2008 by laboratories participating in EQA schemes organized by two European centers, Switzerland (center 1) and France (center 2). We used simple, nonparametrical statistics suited to EQA results to calculate the yearly and global precision performances. All the results, including the outliers, were included in the calculations. The best global precision performances were obtained by professional laboratories and medical offices using DCA POCT devices, followed by professional laboratories with the Integra, Hitachi, Cobas Mira, and HPLC groups of devices, and finally by both types of laboratories with the NycoCard POCT devices. When considering yearly precision performances, an overall improvement over time was observed for almost all diagnostic devices of center 1, whereas the trend was less clear for center 2. The HbA1c EQA results collected and analyzed over a 9-year period showed that the DCA POCT devices used either by professional laboratories or medical offices had better reproducibility than laboratory devices (other than POCT) and that a general improvement of yearly precision performances was observed, especially when frequent EQA schemes were organized.

Retrospective analysis of 88,429 serum and urine glucose EQA results obtained from professional laboratories and medical offices participating in surveys organized by three European EQA centers between 1996 and 2007.

BACKGROUND: The aim of this study was to provide inter-laboratory imprecision comparisons of different groups of diagnostic systems as well as a comparison of professional laboratories with medical offices performance on the basis of 88,429 glucose results obtained in external quality assessment (EQA) schemes organized by three European EQA centers between 1996 and 2007. METHODS: A simple, non-parametrical statistical model suited to all EQA results, including outliers, was used to calculate yearly and global performance. RESULTS: The best performance was obtained from professional laboratories with a group of three diagnostic systems--Hitachi, Integra, and Vitros, followed by Cobas Mira, and finally by Reflotron. For medical offices, the best performance was achieved with the Cobas Mira diagnostic systems, followed by the Reflotron, SpotChem, and Vitros DT60 diagnostic systems. A slight but overall improvement in performance over time was observed for most diagnostic devices. CONCLUSIONS: The analysis of glucose EQA results collected over a 12-year period showed that professional laboratories obtained better performances than medical offices, and that a general improvement in yearly performance was observed for both types of laboratories.

[Not Available]. / Sterilisationsergebnisse bei mit Sporen versehenen Streifen.

The Swiss Center for Quality Control organizes external quality assessment schemes for medical laboratories as well as biological monitoring of the sterilization process for autoclaves. Over the period from 2008 to 2012, 209 dental offices performed 4,709 sterilizations of biological indicators – strips covered by Geobacillus stearothermophilus spores. The median number of sterilizations per participant was 20. Steam autoclaves obtained better results than the Chemiclave. It turned out that 99 strips (2.1%) failed to be properly sterilized, and that 61 participants (29.2%) experienced one or more sterilization failures. In addition, there was no performance improvement over time.