Practical assessment of the suitability of IQC control materials in haemocytometry based on biologic goals

We have assessed short and long-term imprecision goals based on biological variation in haemocytometry through internal quality control (IQC) for the following parameters: white blood cell (WBC), red blood cell (RBC) and platelet (Plt) counts, concentration of haemoglobin (Hb) and mean cell volume (MCV). The attainment of short-term imprecision goals in the IQC system with our own and commercial control blood (between-day control) presents problem for MCV, where minimum performance is achievable, the analytical coefficient of variation (CV) being less than three-quarter of the average within-subject variation (CV _I), i.e. CV<0.75 CV _I. For the other four parameters desirable performance (CV<0.50 CV _I) and even optimum performance—CV<0.25 CV _I (for WBC and Hb) is achievable. The long-term desirable imprecision goals (CV _L) based on within- and between-subject variation (CV _G) seem to be too loose. However optimum performance is attainable for all five basic haemocytometry parameters. In the IQC system with retained patient specimens (within-day control), short-term imprecision goals for optimum performance are surpassed for WBC and Hb and desirable performance is achieved for RBC, MCV and Plt.     

Comparison of evaluation procedures used by European external quality assessment scheme organizers for haemoglobin concentration and leukocyte concentration

This study aimed to assess currently used evaluation procedures for haemoglobin concentration and leukocyte concentration in European external quality assessment schemes (EQAS). Participating EQAS organizers were asked to complete a questionnaire gathering information on the statistical procedures used to assess the performance of participants, and to analyse an Excel file with 262 results for haemoglobin concentration and leukocyte concentration. Responses were received from the New York State Proficiency Testing programme in the US and from 11 European EQAS: Belgium, Croatia, Finland, France, Germany, Hungary, Russia, Slovenia, Spain (two organizers), and Switzerland. Five of the 11 European EQAS use fixed limits based upon experience, biological variation, state of the art, or professional consensus. The other EQAS use variable limits based upon statistical analysis of the performance attained. With the exception of the German, Hungarian, and Slovenian schemes, all European EQAS use consensus target values. The percentage of unsatisfactory results obtained by the European EQAS organizers for the given set of data varied between 0.4 and 15.6% for haemoglobin concentration and between 0 and 19.8% for leukocyte concentration.     

The effects of quality-management systems on external quality-assessment performance in Finnish clinical chemistry laboratories

The effects of the implementation of quality-management systems and technological changes on the performance of 23 Finnish clinical chemistry laboratories were studied in external quality-assessment (EQA) schemes organized by Labquality Ltd., Finland, during 1993 to 1999. The investigated serum analytes were sodium, calcium, glucose, cholesterol, and alanine aminotransferase. According to the results, the improvements in analytical quality due to the quality programs were rather small. The effects to the proportions of satisfactory results in terms of precision and deviation from the target value were 5–15% (95% confidence intervals for the proportions ±1–5%). At the same time the laboratories were implementing quality-management systems new technology and characteristics of quality-control materials affected the EQA performance. Both improvements and deteriorations in analytical quality due to these factors were identified. The effects and their total outcomes differed substantially between the five analytes.     

Anti-HIV quality assurance programs in Australia and the southeast Asian and Western Pacific regions

Anti-HIV testing is the most regulated area of laboratory medicine in Australia. These regulations have placed the National Sero-logy Reference Laboratory, Australia (NRL) in a unique position to implement a comprehensive quality assurance (QA) program for HIV testing. The elements of our QA program include pre-market evaluation of assays, external quality assessment schemes (EQAS), quality control, specificity monitoring, consultations, and training workshops. The results of the NRL EQAS for Australian laboratories were compared with those of a program developed by the NRL for reference laboratories in the Southeast Asian and Western Pacific (SEAWP) regions. For laboratories authorized to use tests for HIV in Australia, participation in the entire QA program is mandatory, whereas the SEAWP EQAS program is voluntary. While the overall percentage of discrepant results for these programs are similar, the percentage of false negatives, variation in laboratory results, and choice of assay differ. These differences have decreased with time with improvements in assays and laboratory testing practices. The educational component of both EQAS, which comprises workshops, laboratory questionnaires, consultancies, and newsletters, has had a critical impact on the testing practices of laboratories. Received: 30 October 2000 Accepted: 9 December 2000     

Proficiency testing in occupational and environmental health – Current practice and international initiatives for harmonisation

An increasing number of proficiency testing schemes (PT schemes) related to occupational and environmental health have been organised. Most schemes emphasise the importance of the validation of analytical results. With regards to harmonisation of the schemes, there are many differences between the schemes at many levels. These include factors concerning their relationship with legislation, national status, type and quality of proficiency testing material, analytical range and priorities for future development. Since differences between PT schemes have been recognised at the European level by organisers of PT schemes and external quality assessment schemes (EQASs) it seems appropriate to reinforce collaboration between scheme organisers in order to improve the quality of analytical performance in occupational and environmental health.     

Blood lead monitoring in Italy: Assessment of the quality of results obtained between 1992 and 1994

Between 1992 and 1994, a new screening campaign for blood Pb monitoring in the Italian general population was carried out. Since the first campaign (started in 1978, in accomplishment of the European Community Directive 77/312/EEC) a working group of the Laboratory of Clinical Biochemistry at the Italian National Institute of Health (Istituto Superiore di Sanità), as the Reference Centre (RC), has coordinated the activity of various laboratories spread over the national territory. Appropriate quality assurance procedures, including an external quality assessment scheme (EQAS), were elaborated. Within the EQAS, three or four trials were carried out every year. Each laboratory participating in the trial analyzed eight control samples prepared from cow blood at different Pb concentrations. The results obtained by each peripheral laboratory and the RC between 1992 and 1994 have been compared by regression analysis. The same statistical method was adopted to compare the results obtained by each peripheral laboratory and the RC in the duplicate analysis of about 10 per cent of the human samples collected during the 1992–1994 monitoring campaign. There was no evidence of systematic differences between the regression lines obtained on control and human samples. In spite of the lower Pb concentration in the control samples analyzed during the 1992–1994 campaign, the analytical performance of the laboratories was better than that obtained in the previous screening campaign (1985–1986). Blood Pb levels observed in human samples collected between 1992 and 1994, confirm the downward time trend observed in the campaigns carried out in 1978–1979, 1980–1981 and 1985–1986. This study confirms that the results obtained in an EQAS are representative of the actual performance in the analysis of real (human) samples.     

Gene network coherence based on prior knowledge using direct and indirect relationships

Gene networks (GNs) have become one of the most important approaches for modeling biological processes. They are very useful to understand the different complex biological processes that may occur in living organisms. Currently, one of the biggest challenge in any study related with GN is to assure the quality of these GNs. In this sense, recent works use artificial data sets or a direct comparison with prior biological knowledge. However, these approaches are not entirely accurate as they only take into account direct gene–gene interactions for validation, leaving aside the weak (indirect) relationships.We propose a new measure, named gene network coherence (GNC), to rate the coherence of an input network according to different biological databases. In this sense, the measure considers not only the direct gene–gene relationships but also the indirect ones to perform a complete and fairer evaluation of the input network. Hence, our approach is able to use the whole information stored in the networks. A GNC JAVA-based implementation is available at: http://fgomezvela.github.io/GNC/.The results achieved in this work show that GNC outperforms the classical approaches for assessing GNs by means of three different experiments using different biological databases and input networks. According to the results, we can conclude that the proposed measure, which considers the inherent information stored in the direct and indirect gene–gene relationships, offers a new robust solution to the problem of GNs biological validation.     

Proficiency testing in analytical chemistry, microbiology and laboratory medicine: working group discussions on current practice and future directions

A summary of the working group (WG) discussions on proficiency testing (PT) and external quality assessment (EQA) held at the joint EURACHEM/CITAC/EQALM workshop, Bracknell, UK, 16–18 February 2003 is provided. The nine WGs covered a range of issues concerned with current practice and future directions; PT/EQA as a tool for regulators (WG1); PT/EQA as a tool for accreditation (WG2); evaluation of performance and uncertainty (WG3); frequency of PT/EQA participation (WG4); selection of appropriate PT/EQA schemes (WG5); added value of PT/EQA and cost benefit evaluation (WG6); global harmonisation and rationalisation (WG7); new technical areas and challenges in PT/EQA (WG8); and accreditation of PT/EQA providers (WG9). Participants with different backgrounds were on each WG in order to capture a range of views and experience from different sectors. The discussions reflected on the keynote lectures and built, in many cases, on discussions at previous workshops in 2000 and 2002.     

Calibration services in the frame of accredited coagulation EQA schemes – Meeting the IVD directive

Organisers of external quality assurance programmes may, for various reasons, also manufacture in vitro diagnostic medical devices, or provide calibration services. This paper describes measures taken by a Swedish organiser to meet the requirements of the European Commission's directive 98/79/EC for a national calibration of prothrombin time. Quality management system requirements and interactions with coagulation experts are summarised.Presented at the Eurachem PT Workshop September 2005, Portorož, Slovenia     

External quality assessment schemes for clinical analysis in Russia

 The history and the present condition of external quality assessment (EQA) schemes for clinical laboratories in Russia are described briefly. The creation of EQA programmes started in Russia in the 1980s. Now almost 20 years later these schemes have been transformed. The National External Quality Assessment Scheme ensures quality control in the clinical chemistry sector (more than 2000 laboratories) and is the most powerful scheme in Russia. The (Sistema Vneshnego Kontrola Katchestva, *) (BKK) system, covering about 120 Russian laboratories, and a lot of local regional programmes (mainly in Siberia), is also very active. The purposes and design of the operating programs, reference materials used, algorithms of estimation, modes of result representation and development prospects are considered. The basic obstacle to the development of EQA schemes in Russia is financial restriction.     

Quality assurance in clinical chemistry laboratories in the UK

 Since the mid-1960s quality assurance in clinical chemistry has progressed from a need to define and improve precision and accuracy in analytical test procedures to an all-embracing process of assuring that the whole process of pre-analytical, analytical and post-analytical phases of handling patient samples is managed effectively and efficiently. Automated and computer-controlled equipment has reduced many of the analytical errors, in particular in imprecision, that were present in manual analysis. New management techniques have been developed to control the quality and appropriateness of results. Developments in internal quality control and external quality assessment procedures have enabled laboratories to continually improve the quality of assays. Laboratory accreditation and external quality assessment scheme accreditation have ensured that peer review and peer pressure have been applied to both laboratory and external quality assessment scheme performance. As the NHS reviews its priorities and places more emphasis on primary care provider demands, hospital laboratories will of necessity assist with near patient testing outside the laboratory. This will provide new challenges to the quality of the service provided. Received: 2 July 1998 · Accepted: 1 August 1998     

The Swiss External Quality Assessment Scheme in Bacteriology and Mycology 1992–1996

 The Swiss External Quality Assessment Scheme in Bacteriology and Mycology was created in 1980 and has been organised since 1983 by the Department of Medical Microbiology in Zurich. The number of Swiss participants has steadily risen from 66 in 1989 to 92 in 1996. Twelve bacterial and fungal strains are sent to the participants in four despatches, each containing three specimens, per year. Scores are allocated per specimen and range between 0 and 1. Participants with mean scores of ≤0.75 are considered poor performers. The mean scores increased from 0.85 in 1992 to 0.91 in 1996. This improvement can be attributed to the educational effect of the external quality control scheme, since all participants receive a detailed discussion for each specimen together with their individual results. On average, both large University and Cantonal (state) laboratories as well as private laboratories show satisfactory performance. In particular, laboratories officially recognised by the Swiss Federal Office of Public Health (SFOPH) rate better than non-recognised participants. Many small regional hospital laboratories, most of them not SFOPH-recognised, are often among the poor performers. They are often managed by technical staff and lack a trained microbiologist. The recently introduced legislation in Switzerland renders participation in external quality assessment schemes compulsory, and all clinical microbiology laboratories are required to employ qualified microbiologists. This will certainly help to improve the quality standards of all laboratories performing microbiological tests. Received: 13 November 1997 · Accepted: 28 December 1997     

Advances in microbiology EQA

External quality assessment for microbiology laboratories has seen many changes over the past ten years. EQA is much less focused on the pure analytic process of identifying single organisms submitted in an artificial medium. Samples are more realistic, and can be used to address clinical relevancy. Samples can be supplemented with a variety of non-traditional challenges to extend testing to include a wider range of the pre- and post-analytic aspects of the laboratory cycle. A look to the future sees a broad range of newer targets, with increasing interest in virology and point-of-care testing. Received: 13 April 2002 Accepted: 24 June 2002     

Quality in clinical laboratory measurements

 Clinical chemistry deals with measurements and observations using samples from patients in order to supply clinicians with information to support their decisions in diagnosis and treatment. The discipline utilizes advanced chemical and biochemical methods and also sophisticated instrumentation which allows a high throughput. Clinical chemistry has a long tradition of quality assessment and improvement. The major tools have been proficiency testing or external quality assessment and internal quality control. Nowadays, total quality management has become widely recognized, and accreditation according to international, regional or national schemes has contributed to the design of quality systems and improvement of the reliability of results from clinical laboratories.     

Proficiency testing in analytical chemistry, microbiology, and laboratory medicine – working group discussions on current status, problems, and future directions

Working group (WG) discussions on proficiency testing (PT) held at the joint Eurachem/ EQALM workshop, Borås, Sweden, 24–26 September 2000 are summarized. The discussions focused on aspects of PT and accreditation (WG 1), general aspects of PT in analytical chemistry (WG 2), microbiology (WG 3), and laboratory medicine (WG 4), incorporation of measurement uncertainty into PT schemes (WG 5), international harmonization of PT schemes (WG 6), and the role of PT in the international structure of chemical measurement (WG 7). Current status, problems and future directions are identified. Each WG contained a majority of participants experienced in the subject being covered by that WG, and a few participants with different expertise. This was done to promote cross-fertilization of ideas between sectors, a key objective of the workshop. The WG issues reflected the content of the keynote lectures and some issues were covered from different perspectives by more than one group.     

A new internal quality control chart based on biological variation

The instruments and analytical methods currently used in clinical laboratories today have better precision and stability than those used in the past. With the development of chemical and immunological methods and instrumentation technology, test precision has increased. However, the application of the Westgard multirule procedure to control sera in the Levey-Jennings chart may not be useful or cost-effective. We devised a new test-specific decision limit for accepting or rejecting runs based on the data of within-subject biological variation and prepared a control chart. We then applied these new limits and control chart to a group of tests performed in our laboratory. With the exception of the tests for albumin, total protein, and calcium, for which desirable performance standards could not be attained with the current technology and methodology, the application of these control limits was cost-effective and convenient. It is estimated that the value of healthy within-subject biological variations is constant, irrespective of the methodology, the area in which the study has been performed, and the number of subjects included in the study. We believe that control limits based on biological variation are reliable and cost-effective, and may be useful in modern and accredited laboratories.     

Establishing measurement traceability in clinical chemistry

Measurement traceability is probably the most important tool for achievement of comparability in clinical chemistry. As stipulated by the In Vitro Diagnostica Directive of the European Union and several ISO standards, values assigned to calibrators and control materials must be traceable to reference materials and/or reference procedures of higher order. In the German proficiency testing system, statutory use of reference measurement procedures for several measurands has been in force since 1988. As a result, reference procedures are now regularly applied for the setting up of target values in the control samples of internal and external quality assessment and for assigning values to the manufacturers calibrator and control materials. Noticeably, the comparability of results obtained by different diagnostic tests has greatly improved for the measurement of many metabolites and substrates, e.g. creatinine, cholesterol, uric acid, total glycerol and urea. For many measurands in laboratory medicine the implementation of the concept of traceability proves to be much more difficult; this mainly concerns the measurement of proteins, in particular enzymes, proteo-hormones, tumour markers and cardiac markers. For such measurands the analyte must first of all be distinctively defined before a reference system can be established which comprises reference procedures, reference materials and networks of reference laboratories.Presented at the CCQM Workshop on Traceability 16–17 April 2002 at the BIPM, Sèvres, France     

Quality assurance programs for countries in need: a global view from the College of American Pathologists

Providing laboratory external quality assessment (EQA) programs for countries in need requires special considerations not ordinarily part of EQA for laboratories in industrialized countries. Cultural, professional, service and economic factors must be understood and accommodated in order to carry out successful programs. Coordination of worldwide efforts for countries in need requires more resources and planning than have thus far been devoted to the enterprise.     

External quality assessment in microbiology: comparison of results from Belgian and Canadian laboratories with regard to their ability to identify <Emphasis Type="Italic">Streptococcus pyogenes</Emphasis>

Clinical Microbiology Proficiency Testing (CMPT; Canada) and the Institute of Public Health (IPH; Belgium) set up a joint external quality assessment (EQA) project in which they sent identical simulated clinical samples to their respective participants. Samples were sent out as throat swabs containing Streptococcus pyogenes (as pathogen) and viridans streptococci (as commensal). Results from identification by the Belgian laboratories were excellent: 99.5% detected the group A streptococci. About 10% of the Canadian laboratories reported the absence of reportable β-haemolytic streptococci, although for most of them the issue was one of non-examination of small or pin-point streptococci. Overall, Canadian and Belgian laboratories performed well in this EQA; the joint project clearly showed that although many similarities exist, there are differences between laboratories in treating EQA samples and reporting results.     

Rapid quality assessment of Gentianae Macrophyllae Radix based on near-infrared spectroscopy and capillary electrophoresis

The aim of this study was to establish a rapid quality assessment method for Gentianae Macrophyllae Radix (RGM) using near-infrared (NIR) spectra combined with chemometric analysis. The NIR spectra were acquired using an integrating sphere diffuse reflectance module, using air as the reference. Capillary electrophoresis (CE) analyses were performed on a model P/ACE MDQ Plus system. Partial least squares-discriminant analysis qualitative model was developed to distinguish different species of RGM samples, and the prediction accuracy for all samples was 91%. The CE response values at each retention time were predicted by building a partial least squares regression (PLSR) calibration model with the CE data set as the Y matrix and the NIR spectra data set as the X matrix. The converted CE fingerprints basically match the real ones, and the six main peaks can be accurately predicted. Transforming NIR spectra fingerprints into the form of CE fingerprints increases its interpretability and more intuitively demonstrates the components that cause diversity among samples of different species and origins. Loganic acid, gentiopicroside, and roburic acid were considered quality indicators of RGM and calibration models were built using PLSR algorithm. The developed models gave root mean square error of prediction of 0.2592% for loganic acid, 0.5341% for gentiopicroside, and 0.0846% for roburic acid. The overall results demonstrate that the rapid quality assessment system can be used for quality control of RGM.