Role of external quality assurance schemes in assessing and improving quality in medical laboratories.

Medical laboratories have a long tradition of external quality assessment. Starting from pure quality control of laboratory performances, most external quality schemes in Europe evolved into a powerful tool for improving quality of clinical outcome of results. External quality assurance in medical laboratories not only includes laboratory performance evaluation, but also evaluation of method performance, post-market vigilance, training and help. In the future, the quality of programmes will further be improved by accreditation of schemes international collaboration and by using IT applications.

External quality assessment (EQA) of Belgian clinical laboratories. The telematics paradigm.

Technology that enables communication between information systems has recently become cheaper and more powerful. It is therefore timely to consider the effects of the introduction of such techniques in external quality assessment (EQA) schemes on both users and organizers. Traditionally, results are returned to EQA organizers as hand-written numbers on structured forms. These data are then manually entered into a computer. The process is time-consuming, slow (as it depends on the postal service), prone to error at every transcription stage, and expensive, as clerical staff must be employed to input the data. Computer-to-computer communication allows this process to be improved. A telematics system for electronic data interchange has been developed for the Belgian EQA programme and it offers several advantages, such as the use of standardized semantics, expression of results in laboratory familiar units, possible interface with the Laboratory Information System, faster data analysis, shorter report time and long-term performance evaluation.

Simultaneous determination of p-aminobenzoic acid, acetyl-p-aminobenzoic acid and p-aminohippuric acid in serum and urine by capillary gas chromatography with use of a nitrogen-phosphorus detector.

In various studies during recent years, the use of p-aminobenzoic acid has been described in screening tests for exocrine pancreatic function. A synthetic three-unit compound N-benzoyl-L-tyrosyl-p-aminobenzoic acid has been administered orally and hydrolysed in the small intestine in the presence of chymotrypsin to N-benzoyl-L-tyrosine and p-aminobenzoic acid. This study describes a convenient procedure in which, after a selective extraction and derivatization with diazomethane, capillary gas chromatography is used combined with nitrogen-sensitive detection. With the proposed procedure, p-aminobenzoic acid and its major metabolites, acetyl-p-aminobenzoic acid and p-aminohippuric acid, can be monitored in serum and in urine samples.

GLC determination of pemoline in biological fluids.

A specific GLC method for the determination of microgram quantities of the central stimulant pemoline in biological fluids is described. Extraction problems due to the low solubility of pemoline are avoided by acid hydrolysis of the drug to 5-phenyl-2,4-oxazolidinedione, which then can be easily isolated by two-phase extraction with dichloromethane, ether, or chloroform. Amide-imide tautomerism enables a cleanup of the extract. Quantitative determination at the microgram level is done on a methylated fraction of the dichloromethane extract by GLC using a suitable internal standard. For supporting evidence of the GLC method's specificity, the compound is also identified by examining an aliquot of the final dichloromethane extract by TLC.

Report on a common survey in clinical laboratories in Belgium and in The Netherlands: immunoassays.

A common survey for immunoassays was organized for Belgian and Dutch laboratories. We compared the different statistical approaches used in the two schemes; both approaches lead to comparable results. Differences in overall consensus values and overall precision are related to a different selection of kits in the two countries. When analyzing results from users of representative kits in both countries, we found a very good correlation in accuracy but detected also some significant differences in precision for some samples for cortisol and theophylline determinations. For some observed differences there is actually no acceptable explanation.

Quality assurance in Belgium.

Clinical laboratories in Belgium working within the social security system require to be licensed. Internal quality control and participation in external quality assessment (EQA) belong to the licensing conditions. The evolution of the Belgian EQAs is outlined, including a performance evolution over the last ten years. Halving of interlaboratory CVs is observed for most clinical chemistry and immunoassay analytes. Improvement is less spectacular for haematological analytes and is missing for coagulation analytes. Using the results of EQAs 1989-1991 the mean overall method interlaboratory CVs could be estimated. Using data from a commercial internal quality control program for clinical chemistry and a request in 145 laboratories, current intralaboratory CVs are estimated.

Analytical evaluation of twenty assays for determination of thyrotropin (TSH).

This paper summarises the results of the evaluation of several assays of thyrotropin in serum. The authors assessed 8 radioimmunoassays (IRMA techniques) and 10 enzyme immunoassays, including ELISA, luminescent immunometry and fluoroimmunometry, also covering a broad spectrum of actual assays. An unique protocol based on identical human samples for all assays was used in order to compare precision, linearity, detection limit, matrix effects and correlation. The authors found a wide spread in precision results between the evaluated assays; as distinct from enzyme immunoassays, discrepant analytical results of the radioimmunoassays are mainly due to differences in standardization procedures. All assays were linear in a smaller or larger range. Sensitivity was generally in agreement with the manufacturer's specification. One assay was not acceptable for clinical use because the practical detection limit only reached 1.5 mU/l. Three other assays (from the same origin) demonstrated particular problems with the stability of the chromogenic reagent. The study of matrix effects was performed using different artificial matrices and the results varied from one assay to another; in the test conditions, some assays were not sensible to matrix manipulations, others were extremely influenced by ion strength or protein concentration. The correlation study confirmed the results of the precision study: assays with a good intraassay precision had also the best correlations. In a general appreciation of the evaluated methods the authors notice that most of the evaluated "classical" enzyme immunoassays operate around the sensitivity limits of spectrophotometry, explaining also the inferior results. Some radioimmunoassays and the enhanced luminescent technique gave the best results in this evaluation study.

External quality assessment in the measurement of haemoglobin by blood gas analysers in Belgium.

OBJECTIVE: The Belgian national External Quality Assessment Scheme (EQAS) for haematology organized a survey to assess the reliability of haemoglobin (Hb) measurements with the blood gas analysers (BGAs) currently available in Belgian hospitals. MATERIAL AND METHODS: All hospital laboratories received two specimens of fresh EDTA anticoagulated whole blood and were asked to determine the Hb concentration using both the conventional haematology analyser (HA) and all BGAs in the hospital. Ninety-seven hospital laboratories participated in the study and a total of 166 results were reported. The BGAs used (grouped according to technology) were Rapidlab 845, 855, 865 (Bayer 1, n = 41), Rapidlab 1245, 1265, Rapidpoint 405 (Bayer 2, n = 19), GEM Premier 3000 (Instrumentation Laboratory, IL, n = 13), ABL 500 and 600 series (Radiometer 1, n = 13), ABL 700 and 800 series (Radiometer 2, n = 35), Omni C, S5 (Roche 1, n = 7), Omni 3, 6, 9, S2, S4, S6 (Roche 2, n = 21). RESULTS: For the BGAs from Bayer, Radiometer and Roche, interlaboratory variation ranged from 0.6 % to 4.1 %, indicating good precision and close agreement between centres. A significant negative bias observed on the GEM Premier 3000 using the EDTA anticoagulated blood samples did not appear to be present in fresh heparinized whole blood samples. There was no significant difference in imprecision and bias between Hb measurements on BGA situated in and outside the central laboratory.

Total quality management for clinical laboratories: a need or a new fashion?

In most European countries, concepts of quality management in medical laboratories have been proposed. These concepts are based on general standards for test laboratories (EN 45001, ISO 25) or specific adapted standards. Improvement of quality lays on the foundation of the implementation of quality systems in medical laboratories. This new approach will have consequences on management style and on working conditions. Efficacy on the implementation can only be tested by external audits. During this audit, not only the quality system and analytical competence must be examined, but also if there is a real contact between pathologists and clinicians and if laboratory results are clinically validated (clinical audit). This new vision on quality in medical laboratories will ask a reconsideration of the tasks, duties and knowledge of clinical pathologists.

Effect of accreditation schemes on the setting of quality specifications by laboratories.

In the future, there will be a universal standard for quality management in medical laboratories: ISO 15189. This standard follows the basic principles of ISO 17025, the general standard for test laboratories, but also adds several specific aspects. A comparison between these standards is given. The language of ISO 15189 is designed to be understood by medical laboratory professionals. As this standard is applicable to all medical laboratory fields, requirements are given in general terms requiring the laboratory to implement them correctly. Because it is essential that information provided by laboratory results is useful for healthcare, the requirements covered by ISO 15189 are compared with those needed for providing good medical laboratory services. The capabilities of the personnel at the laboratory clinic interface are the most difficult to assess and evaluate in an adequate quality management system.

Solid phase chemistry in clinical laboratory tests: a literature review.

The present review attempts to summarize and discuss the systems based on solid phase chemistry reagent carriers. The development and the principles of the different systems are first discussed, followed by a survey of the literature on different analytes, and a discussion of possible sources of interference in each of the most important commercial systems.

Factitiously low urate recoveries in control sera with the Beckman Synchron Systems.

In the Belgian national external quality assessment scheme, we observed significantly lowered recoveries for urate in the group of Beckman Synchron users in comparison with the overall median values of the uricase/peroxidase colorimetric methods. These effects were linked to control sera of some manufacturers and we could demonstrate that these sera contained large amounts of pyridoxal-5-phosphate (PLP) as activator for transaminases. By spiking normal human serum with increasing PLP concentrations from 62.5 to 1000 mumol l-1, we observed a decrease in the urate recovery from 125 mumol l-1 (-11%). At 1000 mumol l-1 PLP, only 40% of the urate concentration was measured. An explanation for this effect was found in the polychromatic corrections of the Beckman Sychron system only applied with the Beckman urate method. This study demonstrates that EQAS organizers must carefully distinguish in their peer groups, not only the analytical principle and the measurement equipment, but also the reagent origin. Finally, the use of EQA control sera without PLP addition is strongly recommended if these sera are intended to be used as accuracy controls in EQA schemes including Beckman Synchron users.

De Laboratoria Van Klinische Biologie in Belgie: Evolutie En Situatie Na Organisatie Van De Verpl1Chte Externe KWaliteitscontrole.

The evolution and the situation of the laboratories of clinical biology in Belgium is described. This paper gives a point of view of the locality, the activity and the employment in these laboratories.

Inter-laboratory external quality assessment schemes for specific IgE antibodies. The results of a European scheme for 1992.

External quality assessment programmes for specific IgE have been organised for some years in the United Kingdom, Belgium and the Netherlands but independently. This paper describes a co-operation scheme whereby the same samples were circulated simultaneously from each of the three countries and subsequent results combined to produce a single "EURO EQAS" report. Serum pools were prepared each containing antibodies, at differing concentrations, to 4 different allergens. The allergens surveyed represented the 10 most commonly encountered in Northern Europe. Results were submitted in grades (or classes) and in quantitative units and they showed some similarity by grade regardless of method used but differed greatly in units probably due to method differences. This paper shows how results could be treated to produce statistical data for the participants to help them be aware of their performance internally and also in comparison to other users.

Characterisation and evaluation of external quality assessment scheme serum. Discussion paper from the European External Quality Assessment (EQA) Organisers Working Group C.

This work reviews the procurement, specification and manufacture of serum for external quality assessment (EQA) and provides a checklist for scheme organisers. Guidance on the assessment of commutability and notes on the use of EQA materials to assess assay problems are provided. The importance of the appropriateness of materials in respect of scheme design and objectives, and the essential nature of a detailed specification prior to manufacture are emphasised.

Factors influencing between-laboratory variability of C-reactive protein results as evidenced by the Belgian External Quality Assessment(EQA) Scheme.

Based on results from the Belgian External Quality Assessment (EQA) Scheme, we studied the main factors affecting the between-laboratory variation of C-reactive protein determination. Participants using homogeneous systems with several calibration points generally achieved better performance. Working temperatures influenced the results to a lesser extent. The present study stresses the importance for EQA organizers to collect more detailed information about CRP analytical methods used by the participants. It also suggests that manufacturers should be more involved in the management of quality, in particular by striving for standardization of the material (kit and calibrator) they produce for CRP assay.

Positive interference of merthiolate in the TDx digoxin assay in control samples used in the Belgian External Quality Assessment (EQA) Scheme.

We investigated the possible origin of the spuriously high results observed with the Abbott TDx Immunoassay in the 1991 Belgian external quality assessment scheme for digoxin. The present work ascribes this discrepancy to a matrix effect induced by the addition of merthiolate as preservative to the control samples. It consequently stresses the importance of avoiding the use of this compound for preparing such samples.

Desirable routine analytical goals for quantities assayed in serum. Discussion paper from the members of the external quality assessment (EQA) Working Group A on analytical goals in laboratory medicine.

The aim of the Working Group was to describe guidelines for deriving desirable analytical goals in laboratory medicine. First, a literature review is given of the different approaches used until now, and some of the most important studies are presented in detail. These approaches are then discussed critically, and the analytical goals proposed by the group are outlined with respect to monitoring and diagnostic testing. The group recommends that, most realistically, analytical quality specifications be biologically based. For diagnostic testing, the aim is achievement of accuracy, allowing the use of common reference intervals when populations are homogeneous for a given quantity. For monitoring (within an individual laboratory and performed with the same instrument), analytical performance should aim at stable operation and low imprecision compared with the within-subject biological variation. Method accuracy is also very important for the comparability of results from different laboratories or instruments.