EFLM Working Group Accreditation and ISO/CEN standards on dealing with ISO 15189 demands for retention of documents and examination objects.

Many aspects of the activity of a medical laboratory have to be documented so as to facilitate the maintenance of the ongoing quality of service. As a consequence, many documents, forms and reports are generated. The retention time for each of these has to be specified. In addition to medical laboratory reports as part of the patient's medical record, the medical laboratory has to retain many documents and specimens according to national legislation or guidance from professional organizations, if these exist. If not, the laboratory management needs to define a retention schedule, which shall define the storage conditions and period of storage, according to ISO 15189:2022 requirements for retention of general quality management documents and records. The EFLM Working Group on Accreditation and ISO/CEN standards provides here a proposal on retention periods of documentation and specimens based on a failure-mode-effects-analysis (FMEA) risk-based approach, a concept of risk reduction that has become an integral part of modern standards.

Comparison between radiometry and spectrophotometry for the determination of angiotensin-converting enzyme activity in cerebrospinal fluid.

Determination of angiotensin-converting enzyme (ACE) activity in cerebrospinal fluid (CSF) can help for establishing the diagnosis of neurosarcoidosis. We investigated the performance characteristics of two assays for ACE determination in 57 CSF, radiometry with [glycine-1-14C] benzoyl-L-histidyl-L-leucine and spectrophotometry with furylacryloyl-phenylalanyl-L-glycyl-L-glycine (FAPGG) as substrates. We compared both kinetic assays to an ELISA specific for human ACE. Within run and between run imprecisions were 14-17% for radiometry, 6-19% for spectrophotometry and 5-8% for ELISA. The limit of detection was 0.04 U/L for radiometry, 1.0 U/L for spectrophotometry and 0.156 µg/L for ELISA. The limit of quantification was 0.06 U/L for radiometry, 1.5 U/L for spectrophotometry, but not known for ELISA. The domain for quantification was 0.06-4.0 U/L for radiometry, 1.5-24 U/L for spectrophotometry and 0.156-10 µg/L for ELISA. Deming regression and Bland-Altman plots show good correlations between the three assays, but with high slopes, because both kinetic assays use different substrates and ELISA measures ACE molecule but not activity. Radiometry was more sensitive than spectrophotometry, which has a limit of detection above most pathological levels. ELISA could be an alternative to radiometry but only after complete evaluation, determination of normal values and assessment of its clinical value. We claim for standardization of ACE determination as well as in serum as in other biological fluids, in particular CSF.

Point-of-care testing performed by healthcare professionals outside the hospital setting: consensus based recommendations from the IFCC Committee on Point-of-Care Testing (IFCC C-POCT).

The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Committee on Point-of-Care Testing (C-POCT) supports the use of point-of-care testing (POCT) outside of the hospital setting performed by healthcare professionals without formal laboratory education because of its numerous benefits. However, these benefits are associated with risks that must be managed, to ensure the provision of reliable test results and minimize harm to the patient. Healthcare professionals, local regulatory bodies, accredited laboratories as well as manufacturers should actively be engaged in education, oversight and advice to ensure that the healthcare professional selects the appropriate equipment and is able to analyze, troubleshoot and correctly interpret the point-of-care (POC) test results.

[Precision intra-assay study in the absence of internal quality control: example of radioimmunoassay of procollagen III peptide]. / Étude de répétabilité en l'absence de contrôle interne de qualité : exemple du dosage radioimmunologique du peptide amino-terminal du procollagène de type III.

The first step to complete in a method validation of a biological analysis is the study of precision intra-assay. In the absence or insufficient quantity of control material, this study may be difficult to perform. This article proposes a methodology for preparing its own control samples for the radioimmunological assay of the amino-terminal peptide of procollagene type III (PIIIP). This methodology is easy to carry out, cost-effective and can be applied to analyses other than PIIIP. Furthermore, it allows the execution of control samples which have similar concentrations of analytes to those described in the precision studies of the datasheets provided by the manufacturers.

POCT management of neonatal bilirubinemia ­ guidelines for an optimization of kernicterus monitoring / Intérêt de la bilirubinémie en néonatalogie : recommandations pour une utilisation coordonnée par le LBM de la biologie délocalisée et des tests rapides d'orientation diagnostique

In pediatrics, accurate measurement of total serum bilirubin (TSB) is of major importance for reliable diagnosis and appropriate management of neonatal jaundice. However, several studies evidenced poor comparability of results obtained with the different available methods either in central lab or in POCT, on serum, capillary blood or transcutaneous. This situation is partly due to the lack of Reference Materials, especially for high bilirubin concentrations but also on poor communication between central lab and neonatology unit. To progress on these issues, we have compiled some data from CNRHP to propose guidelines for choice, use and management of POCT devices and to help clinical laboratories to achieve a better answer to clinical needs with specific local constraints. The results from several CNRHP studies are presented: traceability to International System of Units, inter-laboratories comparability, POCT vs central labs comparisons with POCT CO-oximeter or photometer, integration of transcutaneous bilirubinometer. We propose, based on an analysis of devices advantages and issues, guidelines to help labs either to improve neonates monitoring in their local context; we distinguished the choices inside laboratory for a better harmonization of results compared to published thresholds and outside lab contexts, to organize a coordinated chain with POCT devices, with capillary and/or transcutaneous approaches.

En néonatalogie, la mesure précise de la bilirubinémie est essentielle pour le diagnostic et le suivi de l'ictère, en regard de seuils consensuels internationaux. Toutefois, une faible comparabilité des résultats est observée entre les laboratoires de biologie médicale (LBM) et avec les dispositifs délocalisés ou transcutanés. Cette situation est en partie due à des défauts de standardisation des méthodes, mais aussi à une coordination insuffisante entre les laboratoires et les unités de soins. L'objectif de ce travail est de progresser dans l'optimisation de la prise en charge des nouveau-nés en proposant des critères de choix et d'articulation des différentes réponses biologiques, EBM, EBMD et TROD, en fonction des besoins cliniques locaux et des moyens disponibles. Les résultats de plusieurs études ciblées sur la bilirubinémie néonatale sont présentés : raccordement au système international, harmonisation interlaboratoires, comparabilité EBMD-CNRHP d'un CO-oxymètre délocalisé en maternité, comparabilité EBMD-CNRHP d'un photomètre délocalisé en maternité, intégration d'un bilirubinomètre transcutané. Nous proposons ensuite, sur la base d'une analyse critique des différents types de dispositifs, des recommandations pour aider les LBM à améliorer la prise en charge des nouveau-nés dans leur contexte local, d'une part sur la mesure de la bilirubinémie néonatale au sein du LBM et d'autre part sur l'organisation d'une chaîne coordonnée EBM ­ EBMD ­ TROD en concertation avec les unités de soins.

Improving the laboratory result release process in the light of ISO 15189:2012 standard.

The ISO 15189:2012 standard section 5.9.1 requires laboratories to review results before release, considering quality control, previous results, and clinical information, if any, and to issue documented procedures about it. While laboratory result reporting is generally regarded as part of the post-analytical phase, the result release process requires a general view of the total examination process. Reviewing test results may follow with troubleshooting and test repetition, including reanalyzing an individual sample or resampling. A systematic understanding of the result release may help laboratory professionals carry out appropriate test repetition and ensure the plausibility of laboratory results. In this paper, we addressed the crucial steps in the result release process, including evaluation of sample quality, critical result notification, result reporting, and recommendations for the management of the result release, considering quality control alerts, instrument flags, warning messages, and interference indexes. Error detection tools and plausibility checks mentioned in the present paper can support the daily practice of results release.

[Analytical and clinical guidelines on neonatal bilirubinemia]. / Recommandations analytiques et cliniques pour l'utilisation de la bilirubinémie en néonatalogie.

The SFBC-CNBH-CNRHP "Neonatal bilirubin" working group performed a biological and clinical study on bilirubin use in neonates for reliable diagnosis and appropriate management of neonatal jaundice. A brief report of a national survey on analytical and biological practices in France is shown. The guidelines of the French Society of Neonatology (SFN) founded the decision of phototherapy set up upon an accurate lab measurement of total serum bilirubin. An abacus is proposed with defined thresholds, as a function of neonate lifetime in hours. However, several studies evidenced poor comparability of results obtained with the different available methods. This situation is partly due to the lack of reference materials, especially for high bilirubin concentrations. Clinical consequences might be observed. We present in this paper the results of a national harmonization study to progress on this issue. Beyond the analytical aspects, the clinical consequences of harmonization defects were investigated. Finally, guidelines for clinical laboratories are proposed, to be locally adapted.

Validation and verification of examination procedures in medical laboratories: opinion of the EFLM Working Group Accreditation and ISO/CEN standards (WG-A/ISO) on dealing with ISO 15189:2012 demands for method verification and validation.

This paper reflects the opinion of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group Accreditation and ISO/CEN standards (WG-A/ISO). It aims to provide guidance for drawing up local/national documents about validation and verification of laboratory methods. We demonstrate how risk evaluation can be used to optimize laboratory policies to meet intended use requirements as well as requirements of standards. This is translated in a number of recommendations on how to introduce risk evaluation in various stages of the implementation of new methods ultimately covering the whole process cycle.

Documenting metrological traceability as intended by ISO 15189:2012: A consensus statement about the practice of the implementation and auditing of this norm element.

ISO15189:2012 requires medical laboratories to document metrological traceability of their results. While the ISO17511:2003 standard on metrological traceability in laboratory medicine requires the use of the highest available level in the traceability chain, it recognizes that for many measurands there is no reference above the manufacturer's selected measurement procedure and the manufacturer's working calibrator. Some immunoassays, although they intend to measure the same quantity and may even refer to the same reference material, unfortunately produce different results because of differences in analytical selectivity as manufacturers select different epitopes and antibodies for the same analyte. In other cases, the cause is the use of reference materials, which are not commutable. The uncertainty associated with the result is another important aspect in metrological traceability implementation. As the measurement uncertainty on the clinical samples is influenced by the uncertainty of all steps higher in the traceability chain, laboratories should be provided with adequate and appropriate information on the uncertainty of the value assignment to the commercial calibrators that they use. Although the between-lot variation in value assignment will manifest itself as part of the long-term imprecision as estimated by the end-user, information on worst-case to be expected lot-lot variation has to be communicated to the end-user by the IVD provider. When laboratories use ancillary equipment that potentially could have a critical contribution to the reported results, such equipment needs verification of its proper calibration and criticality to the result uncertainty could be assessed by an approach based on risk analysis, which is a key element of ISO15189:2012 anyway. This paper discusses how the requirement for metrological traceability as stated in ISO15189 should be met by the medical laboratory and how this should be assessed by accreditation bodies.

[Critical care testing: SFBC recommendations in 2018]. / Biologie d'urgence : les recommandations 2018 de la SFBC.

The SFBC Working Group on critical care testing describes in this paper the SFBC recommendations for the determination of maximal turnaround times (TAT) for laboratory medicine examination in emergency conditions. The table presented in a previous paper was updated, taken into account the clinical situations, as well as the emergency response capabilities of the medical laboratory. These new French recommendations must to be based to each local situation in a clinical-biological context between the physicians and the specialist in Lab Medicine.

Diagnostic accuracy of the Coopscore© to predict liver fibrosis in human immunodeficiency virus/hepatitis B virus co-infection.

Background Non-invasive methods for assessing liver fibrosis are increasingly used as an alternative to liver biopsy. Recently, a score-based biochemical blood test (Coopscore©) was developed in a cohort of patients chronically infected with hepatitis C virus, showing higher diagnostic performances than Fibrometer®, Fibrotest®, Hepascore® and Fibroscan™. Here, we assess its performance in patients co-infected with the human immunodeficiency virus and hepatitis B virus. Methods Ninety-seven human immunodeficiency virus/hepatitis B virus co-infected patients with liver biopsies were included from a previously described cohort. Histological fibrosis staging using METAVIR criteria was used as the reference. Coopscore©, Fibrotest®, Fibrometer®, Hepascore® and Zeng score were computed and compared with the Coopscore© using the Obuchowski index and area under the receiving operator characteristic curves. Results The distribution of liver fibrosis levels was as follows: F0-F1 ( n = 42), F2 ( n = 25), F3 ( n = 15) and F4 ( n = 15). The Obuchowski index was higher for Coopscore© (0.774) than Fibrometer® (0.668), Hepascore® (0.690) and Zeng scores (0.704) ( P < 0.05), reflecting a better ability to discriminate between fibrosis stages. Similarly, when predicting significant fibrosis (≥F2), the AUROC was significantly greater for the Coopscore© (0.836) than the Hepascore® (0.727) and Zeng scores (0.746), but not for the Fibrotest® (0.778, P = 0.14) or Fibrometer® (0.790, P = 0.19). The Coopscore© did not show a higher capacity than other scores to predict advanced fibrosis (≥F3) or cirrhosis (F4). Conclusions This study supports the diagnostic value of the Coospcore© in fibrosis staging among human immunodeficiency virus/hepatitis B virus co-infected patients, especially to predict significant fibrosis.

Search for biomarkers of neurosarcoidosis by proteomic analysis of cerebrospinal fluid.

Sarcoidosis is a systemic granulomatous disease, which mostly affects lung. Central nervous system can be affected causing a neurosarcoidosis in 5 to 15% of all sarcoidosis patients. The definitive diagnosis is established on histological examination of brain granulomas. Angiotensin converting enzyme is currently the most relevant biomarker to confirm a probable diagnosis; however, it lacks sensitivity and specificity. We aim to find novel biomarkers of neurosarcoidosis in cerebrospinal fluid (CSF) by proteomic analysis, combining two-dimension electrophoresis (2-DE) and mass spectrometry. We performed CSF proteomic profile of both patients (group S) and control subjects (group H). The statistical analysis of 2-D gels highlighted 42 spots significantly different between the two groups. Twenty-five spots were subjected to tryptic digestion; the peptides were analyzed by MALDI-TOF and MALDI-TOF-TOF, giving rise to 10 identifications. Among the identified proteins, low-molecular-mass-kininogen and vitamin-D-binding-protein were increased, while transthyretin was decreased. These proteins have probably an intrathecal source and could be interesting candidates. This study led to the identification of several proteins which can be used for the diagnosis and/or monitoring of neurosarcoidosis. These putative biomarkers have to be confirmed on a larger cohort and assessed for their sensitivity and specificity.