External Quality Assurance Providers Research Articles

Biomarker testing in oncology \u2013 Requirements for organizing external quality assessment programs to improve the performance of laboratory testing: revision of an expert opinion paper on behalf of IQNPath ABSL

In personalized medicine, predictive biomarker testing is the basis for an appropriate choice of therapy for patients with cancer. An important tool for laboratories to ensure accurate results is participation in external quality assurance (EQA) programs. Several providers offer predictive EQA programs for different cancer types, test methods, and sample types. In 2013, a guideline was published on the requirements for organizing high-quality EQA programs in molecular pathology. Now, after six years, steps were taken to further harmonize these EQA programs as an initiative by IQNPath ABSL, an umbrella organization founded by various EQA providers. This revision is based on current knowledge, adds recommendations for programs developed for predictive biomarkers by in situ methodologies (immunohistochemistry and in situ hybridization), and emphasized transparency and an evidence-based approach. In addition, this updated version also has the aim to give an overview of current practices from various EQA providers.

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.

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

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. 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). 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. 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.

An overview of the European Organization for External Quality Assurance Providers in Laboratory Medicine (EQALM).

The European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM) was founded in 1996 and currently has members from 29 European countries and 6 countries from outside Europe. EQALM provides a forum for co-operation and exchange of knowledge on quality-related matters in laboratory medicine, especially with regard to external quality assessment (EQA) programs in Europe. In addition, EQALM represent the EQA providers in laboratory medicine at European level vis-ŕ-vis political, professional, scientific and other bodies, including patients’ organisations. To this end EQALM promotes activities such as organizing meetings with scientific and practical themes for members and other interested parties, issuing scientific publications, developing EQA projects and representing laboratory medicine EQA activities within other organisations and networks. EQALM is active in scientific and educational activity in different fields such as survey frequency, haematology, haemostasis, microbiology, nomenclature, virtual microscopy, traceability, accreditation, and quality assurance of the total testing process. The aim of this paper is to give an overview of the EQALM organisation.

Interpretation of EQA results and EQA-based trouble shooting.

Important objectives of External Quality Assessment (EQA) is to detect analytical errors and make corrective actions. The aim of this paper is to describe knowledge required to interpret EQA results and present a structured approach on how to handle deviating EQA results. The value of EQA and how the EQA result should be interpreted depends on five key points: the control material, the target value, the number of replicates, the acceptance limits and between lot variations in reagents used in measurement procedures. This will also affect the process of finding the sources of errors when they appear. The ideal EQA sample has two important properties: it behaves as a native patient sample in all methods (is commutable) and has a target value established with a reference method. If either of these two criteria is not entirely fulfilled, results not related to the performance of the laboratory may arise. To help and guide the laboratories in handling a deviating EQA result, the Norwegian Clinical Chemistry EQA Program (NKK) has developed a flowchart with additional comments that could be used by the laboratories e.g. in their quality system, to document action against deviations in EQA. This EQA-based trouble-shooting tool has been developed further in cooperation with the External quality Control for Assays and Tests (ECAT) Foundation. This flowchart will become available in a public domain, i.e. the website of the European organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM).

Technical proficiency in cytopathology: assessment through external quality assurance.

To assess both the feasibility and value of conducting an external quality assurance programme concerning technical aspects of cytopathology laboratory practice, and the interest by laboratories in enrolling in such a programme. Six technical surveys, comprising staining exercises and questionnaires relating to laboratory practice, were distributed over a 4-year period to the approximately 220 laboratories enrolled in the RCPAQAP Cytopathology slide survey modules. Staining exercises using the Papanicolaou and Romanowsky techniques, the preparation of urine and body fluid specimens and immunocytochemistry on the cell block material were assessed. Accompanying relevant questionnaires were included, and one survey comprised a questionnaire alone concerning the collection of urinary tract and body fluid samples. Provision of an external cytopathology technical module was feasible for the RCPAQAP and participation rates (maximum of 87% per survey; average 68% for stained slides and 66% for questionnaires) were commendable, particularly considering these were optional undertakings with some exercises not applicable to all laboratories. The great majority of submitted slides were scored as satisfactory, and there was an especially high standard for the immunocytochemical staining exercise with 95% considered satisfactory, including 50.6% with a perfect score. Reasons for suboptimal scores were provided for potential quality improvement for interested laboratories. A wealth of information relating to laboratory practice was provided to the RCPAQAP which was collated and summarised for laboratory use. The provision of a technical module in cytopathology is both a feasible and valuable undertaking of interest to laboratories which should become standard practice for cytopathology external quality assurance providers.

The Importance of Reagent Lot Registration in External Quality Assurance/Proficiency Testing Schemes.

Providers of external quality assurance (EQA)/proficiency testing schemes have traditionally focused on evaluation of measurement procedures and participant performance and little attention has been given to reagent lot variation. The aim of the present study was to show the importance of reagent lot registration and evaluation in EQA schemes. Results from the Noklus (Norwegian Quality Improvement of Primary Care Laboratories) urine albumin/creatinine ratio (ACR) and prothrombin time international normalized ratio (INR) point-of-care EQA schemes from 2009-2015 were used as examples in this study. The between-participant CV for Afinion ACR increased from 6%-7% to 11% in 3 consecutive surveys. This increase was caused by differences between albumin reagent lots that were also observed when fresh urine samples were used. For the INR scheme, the CoaguChek INR results increased with the production date of the reagent lots, with reagent lot medians increasing from 2.0 to 2.5 INR and from 2.7 to 3.3 INR (from the oldest to the newest reagent lot) for 2 control levels, respectively. These differences in lot medians were not observed when native patient samples were used. Presenting results from different reagent lots in EQA feedback reports can give helpful information to the participants that may explain their deviant EQA results. Information regarding whether the reagent lot differences found in the schemes can affect patient samples is important and should be communicated to the participants as well as to the manufacturers. EQA providers should consider registering and evaluating results from reagent lots.

Analytical performance specifications for EQA schemes - need for harmonisation.

External Quality Assurance (EQA) is a vital tool in laboratory medicine to assess individual laboratory analytical performance and also the differences between the results from different laboratories. This information is also useful for professional bodies and manufacturers as part of post-market surveillance. The process involves the measurement of one or more samples by many laboratories and then assessment of the results. Individual results are generally assessed by how far they lie from a target, which may be established using reference methods or a median of some or all of the submitted results. The distance of a result from the target is compared with analytical performance specifications in order to assess the analytical quality. One of the uses of the Stockholm hierarchy of performance goals is to set the performance specifications for analysis of EQA results. Fifteen years after the Stockholm consensus meeting, EQA analytical performance specifications appear to still vary widely between EQA providers. This can be due to a range of factors, including the rationale for setting the criteria, the expected response to a failure to meet the specified performance, the clinical meaning behind meeting the specifications, and the possible need for further analytical improvements. There are also differences in the models chosen to set the criteria, usually either state of the art or biological variation, and then differences in how these are applied. While harmonisation of EQA performance specifications may be some time off, all EQA providers should define the nature of their specifications and the basis for their selection and make this information available to customers.

Performance monitoring and transfusion QAP performance levels

This presentation will endeavour to provide an understanding of Performance Monitoring in Quality Assurance of Transfusion as measured by a project undertaken by the Royal College of Pathologists of Australasia (RCPA) Quality Assurance Program (QAP) in 2012. In 2001 the Commonwealth Department of Health and Ageing (DoHA) sought proposals to undertake an evaluation of Australian pathology laboratory accreditation arrangements. Recommendations from the report were that (1) the DoHA and the Health Insurance Commission seek the cooperation of the RCPA QAP to establish explicit external quality assurance performance criteria and a mechanism for the RCPA QAP to identify relatively poorly performing laboratories; (2) RCPA QAP and other external quality assurance providers regularly submit to the National Association of Testing Authorities (NATA) reports identifying laboratories that are poorly performing according to these agreed performance criteria. The review process included establishment of a methodology/scoring system; a retrospective data analysis; establishment of criteria for acceptable performance based on the retrospective data analysis and reasonable expectations for completing a corrective action. Information and results from QAP surveys was used to assess individual participant data against established criteria to provide laboratories of an objective measure of their performance relative to their peers whilst meeting the needs of the performance review process.

PT community meet in Istanbul: proficiency testing workshop

The historic city of Istanbul, known for where the East meets the West, became the meeting place for the global proficiency testing (PT) and external quality assurance (EQA) community for 4 days in October 2011. This was the 7th international PT workshop on Proficiency Testing in Analytical Chemistry, Microbiology and Laboratory Medicine organized by the EURACHEM Proficiency Testing Working Group in association with EQALM and CITAC. The workshop was supported locally by several Turkish organizations including the Middle East Technical University (METU), the Petroleum Research Center, EURACHEM-Turkiye, TUBITAK UME and TURKAK. The wonderful setting on the coast of the Sea of Marmara provided the perfect location for this successful workshop which once again provided an excellent opportunity for providers, users and regulators of PT/EQA to come together to discuss a wide range of key issues across the three disciplines of analytical chemistry, microbiology and laboratory medicine. The 233 delegates attending from 54 different counties ensured a truly global perspective. Since the last (6th) PT workshop held in Rome during October 2008, there have been a number of developments in the field of proficiency testing, one of the most notable being the publication of ISO/IEC 17043, the new international standard for the competence of PT/EQA providers, addressing the requirements for the development and operation of PT/EQA schemes. This new standard has been adopted by the International Laboratory Accreditation Cooperation (ILAC) as the requirements against which PT/ EQA providers should be accredited. With the publication and its subsequent adoption by ILAC, this has led to an increase in the number of PT/EQA providers being accredited around the world. This workshop, therefore, specifically addressed the experiences of implementing ISO/IEC 17043 both from the views of the PT/EQA providers and the accreditation bodies. In addition to addressing the implementation of ISO/IEC 17043, this workshop focused on further developments in performance assessment in microbiology and qualitative schemes, the status and needs of PT/EQA in developing areas of the world and advancements in preand postanalytical PT/EQA. These important topics addressed at this workshop were explored and discussed through a series of lectures and working group discussions. The diverse range of international delegates attending from different sectors provided a beneficial environment for the cross-fertilization of ideas. The workshop was enriched further with 52 poster contributions covering a wide range of topics and experiences concerned with PT/EQA. In conjunction with the workshop, training sessions on ‘‘Establishing Traceability and Uncertainty of Assigned Values’’ and ‘‘Assisting Participants to Assess/Estimate Their Measurement Uncertainty Using PT Results’’ were provided. This latest workshop once again proved a great success thanks to the hard work of the local organizers, the quality of the presentations and posters and just as importantly the active participation of all the delegates leading to lively debate and fruitful discussions. We are pleased to provide the papers on many of the presentations, posters and working group discussions in this Topical Focus on PT/ EQA issue of the Journal. B. Brookman (&) LGC Standards Proficiency Testing, Bury, UK e-mail: Brian.Brookman@lgcpt.com

Monitoring performance of nucleic acid-based diagnostic measurement system users by EQA

External quality assurance (EQA) programmes allow a laboratory to monitor independently its performance and provide feedback to identify and investigate potential areas of concern. However, both the definition of appropriate ‘performance indicators’ and their statistical analysis vary across EQA providers. Typically, performance scores have an unknown statistical distribution and hence arbitrary thresholds are used to measure performance. In this paper, we introduce a scoring system based on well-known statistical principles. The system is simple, flexible and easy to interpret. It can be used to measure performance for single samples or across a panel so providing useful and meaningful information to participants in EQA programmes. The score is illustrated using the 2005 QCMD Hepatitis B Virus Proficiency programme.

External quality assessment schemes for toxicology

A variety of external quality assurance (EQA) schemes monitor quantitative performance for routine biochemical analysis of agents such as paracetamol, salicylate, ethanol and carboxyhaemoglobin. Their usefulness for toxicologists can be lessened where the concentrations monitored do not extend fully into the toxic range or where the matrix is synthetic, of animal origin or serum as opposed to whole human blood. A scheme for quantitative determinations of a wider range of toxicological analytes such as opioids, benzodiazepines and tricyclics in human blood has been piloted by the United Kingdom National External Quality Assessment Scheme (UKNEQAS). Specialist schemes are available for drugs of abuse testing in urine and for hair analysis. Whilst these programmes provide much useful information on the performance of analytical techniques, they fail to monitor the integrated processes that are needed in investigation of toxicological cases. In practice, both qualitative and quantitative tests are used in combination with case information to guide the evaluation of the samples and to develop an interpretation of the analytical findings that is used to provide clinical or forensic advice. EQA programs that combine the analytical and interpretative aspects of case studies are available from EQA providers such as UKNEQAS and the Dutch KKGT program (Stichting Kwaliteitsbewaking Klinische Geneesmiddelanalyse en Toxicologie).