Performance Of Individual Laboratories Research Articles

Implementation, Evolution, and Laboratory Performance of Methods-Based Proficiency Testing for Next-Generation Sequencing Detection of Germline Sequence Variants.

Next-generation sequencing (NGS)-based assays are used for diagnosis of diverse inherited disorders. Limited data are available pertaining to interlaboratory analytical performance of these assays. To report on the College of American Pathologists (CAP) NGS Germline Program, which is methods based, and explore the evolution in laboratory testing practices. Results from the NGS Germline Program from 2016-2020 were analyzed for interlaboratory analytical performance. Self-reported laboratory testing practices were also evaluated. From 2016-2020, a total of 297 laboratories participated in at least 1 program mailing. Of the 289 laboratories that provided information on tests offered, 138 (47.8%) offered only panel testing throughout their enrollment, while 35 (12.1%) offered panels and exome testing, 30 (10.4%) offered only exomes, 9 (3.1%) offered only genomes, and 15 (5.2%) offered panels, exomes, and genomes. The remainder (62 laboratories, 21.4%) changed their test offerings during the 2016-2020 timeframe. Considering each genomic position/interval, the median detection percentage at variant positions across the 2016-2020 mailings ranged from 94.3% to 100%, while at reference positions (no variant detected), the median correct response percentage was 100% across all mailings. When considering performance of individual laboratories, 89.5% (136 of 152) to 98.0% (149 of 152) of laboratories successfully met the detection threshold (≥90% of the variants present), while 94.6% (87 of 92) to 100% (163 of 163) of laboratories met the 95% specificity threshold across mailings. Since the inception of this program, laboratories have consistently performed well. The median sensitivity and specificity of detection of sequence variants included in this program (eg, single nucleotide variants, insertions, and deletions) were 100.0%.

External quality control in laboratory medicine. Progresses and future.

An external quality control program distributes same control samples to various laboratories and evaluates results obtained with a common criterion. The aim of this work is to summarize the evolution of various types of external programs, to point out the progresses ant to preclude practical consequences of the participant laboratories. The material consists on a brief revision of the different types of external programs that have been used for the last forty years. The method is the critical analysis of the strong and weak points of each program model, from the light of our experience.External quality assessment (EQA) programs were initiated at half the XX century, evidencing big discrepancies among laboratory results. EQA were developed in various countries and some mechanisms to harmonize them were proposed: to establish common performance specifications derived from biological variation, to use EQS as educational tool. Since the 2000 important advances were seen: to focus EQA to assure the adequate clinical use of laboratory tests, to use commutable controls, to harmonize the different EQA models, to promote a forum for co-operation and exchange of knowledge on quality-related matters for EQA organizers. To participate in an EQA with commutable-reference method assigned values controls allows to know the real inaccuracy of results and their impact on patient' samples. To participate in a EQA with non commutable controls allows to know whether the individual laboratory performance agrees with that from other laboratories using same analytical method.

Assessment methods for interlaboratory comparisons of the dicentric assay

ABSTRACT Purpose To test the performance of different algorithms that can be used in interlaboratory comparisons based on dicentric chromosome analysis, and to evaluate the impact of considering a priori values different to calculate individual laboratory performance based on the ionizing radiation dose estimation. Methods Mean and standard deviation estimations in inter-laboratory comparisons are tested on simulated data and data from previously published inter-laboratory comparisons using three robust algorithms, algorithm A, Algorithm B and Q/Hampel, all programmed in R-project language and implemented in a Shiny application. The simulated data were generated assuming three different probabilities to contaminate inter-laboratory comparisons samples with atypical dose values. Comparison between different algorithms was also done using published exercises where blood samples were irradiated at 0 and 0.7 Gy that represent a challenge for the assessment of an inter-laboratory comparison. Results The best performance was obtained with the Q/Hampel algorithm for the estimation of the dose mean and with the algorithm B for the estimation of the dose standard deviation under the conditions tested in the simulations. The Q/Hampel algorithm showed the best performance when non-irradiated samples were evaluated and there was a high proportion of identical values. The presence identical values causes the Algorithm B to fail. Real examples illustrating the need to consider standard deviation priors, and the need to use algorithms resistant to a high proportion of identical values are presented. Conclusions Q/Hampel algorithm is a serious candidate to estimate the dose mean in the inter-laboratory comparisons, and to estimate both parameters when the proportion of identical values equals or higher than the half of the results. When the proportion of identical values is less than the half of the results, the Algorithm B should be considered as a candidate to estimate the standard deviation in the inter-laboratory comparisons with small number of laboratories. We remark that special attention is needed to establish prior definitions of standard deviation in the assessment of inter-laboratory dicentric assay comparisons.

Continual Improvement of the Reliability of Next-Generation Sequencing-Based ctDNA Analysis: A Long-Term Comparison of ctDNA Detection in China.

Since circulating tumor DNA (ctDNA) sequencing is increasingly being applied in clinical management of patients with cancer, its testing accuracy has become a matter of serious concern. To address this issue, a long-term ctDNA analysis proficiency testing (PT) scheme for next-generation sequencing (NGS) was launched in China in 2018, serving as an educational tool for assessing and improving the testing quality of NGS-based ctDNA detection. Feedback from participating laboratories across 23 different PT samples containing different variants with varying variant allele frequency was collected between 2018 and 2021. To further show the landscape of changing conditions in accuracy and reliability of NGS-based ctDNA testing, performance was analyzed by evaluating the cfDNA extraction kits, testing panels, target enrichment strategies, and sequencing platforms. During the 4 years, 2745 results reported from 504 laboratories were evaluated. Only 66.3% of results from laboratories were entirely in concordance with the expected results. Nonetheless, along with an increasing number of participating laboratories, the number of errors occurring in laboratories, and the proportion of laboratories that experienced errors both showed a significant downward trend. No obvious differences in the error rates were found regarding the kit manufacturers or sequencing platform. Moreover, the individual performances of the laboratories improved when they participated in more PT scheme rounds. These data demonstrated that the performance of individual Chinese laboratories for NGS-based ctDNA analysis continuously improved over time with participation in PT schemes. However, further care must also be taken in standardized operations and validations.

Concordance of cerebrospinal fluid real‐time quaking‐induced conversion across the European Creutzfeldt–Jakob Disease Surveillance Network

Background and purposeCerebrospinal fluid (CSF) real‐time quaking‐induced conversion (RT‐QuIC) has a high degree of sensitivity and specificity for the diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD) and this has led to its being included in revised European CJD Surveillance Network diagnostic criteria for sCJD. As CSF RT‐QuIC becomes more widely established, it is crucial that the analytical performance of individual laboratories is consistent. The aim of this ring‐trial was to ascertain the degree of concordance between European countries undertaking CSF RT‐QuIC.MethodsTen identical CSF samples, seven from probable or neuropathologically confirmed sCJD and three from non‐CJD cases, were sent to 13 laboratories from 11 countries for RT‐QuIC analysis. A range of instrumentation and different recombinant prion protein substrates were used. Each laboratory analysed the CSF samples blinded to the diagnosis and reported the results as positive or negative.ResultsAll 13 laboratories correctly identified five of the seven sCJD cases and the remaining two sCJD cases were identified by 92% of laboratories. Of the two sCJD cases that were not identified by all laboratories, one had a disease duration >26 months with a negative 14‐3‐3, whilst the remaining case had a 4‐month disease duration and a positive 14‐3‐3. A single false positive CSF RT‐QuIC result was observed in this study.ConclusionsThis study shows that CSF RT‐QuIC demonstrates an excellent concordance between centres, even when using a variety of instrumentation, recombinant prion protein substrates and CSF volumes. The adoption of CSF RT‐QuIC by all CJD surveillance centres is recommended.

External quality assessment providers' services appear to more impact the immunohaematology performance of laboratories than national regulatory and economic conditions.

Medical laboratories may, at their own discretion, exceed but not undercut regulatory quality requirements. Available economic resources, however, may drive or hinder eagerness to exceed minimum requirements. Depending on the respective scopes of regulatory and economic framework conditions, differing levels of quality efforts to safeguard laboratory performance can be anticipated. However, this has not yet been investigated. Immunohaematology external quality assessment (EQA) results collected by 26 EQA providers from their participant laboratories in 73 countries from 2004 to 2019 were evaluated. Error rates were aggregated in groups according to the respective national regulatory and economic framework conditions, to whether or not expert advice was provided in case of incorrect results, and the frequency of EQA samples. These representative data indicate no association between national regulatory (mandatory participation in EQA, monitoring of performance of individual laboratories by authorities, financial consequences of incorrect results) and economic (level of national income, share of national health expenditure) conditions to the quality performance of medical laboratories in immunohaematology. However, EQA providers' support for laboratories in the event of incorrect results appear to be associated with lower error rates, but a high EQA sample frequency with higher error rates. Further research into the impact of introducing or changing services of EQA providers is needed to confirm the results found in this first of its kind study.

Establishment of a National Focal Point to Monitor the Performance of PCR Centres in Sri Lanka

<strong>Introduction: </strong>The number of confirmed cases of COVID -19 informs us about the development and magnitude of the global pandemic. Confirmation of COVID-19 infection is mainly by testing with PCR. The necessity of evaluating the performance of PCR laboratories was identified to understand how the pandemic was progressing, how to respond appropriately to the threat; either as individuals or as a society, to learn where countermeasures against the pandemic worked and for planning. Reliable data on testing was therefore necessary to assess spread of the pandemic. <strong> </strong> <strong>Objective: </strong>To establish a national focal point to collect quality, accurate, timely data of PCR test performance for planning and to make decision. <strong> </strong> <strong>Methods: </strong>Defining of data elements for collection and monitoring of the performance of PCR laboratories was done as the first step. Digital solution was identified after assessing the requirement. Agile development method was used to develop the digital solution, which consists of five modules. Entered data on PCR performance of laboratories were analyzed by the officer in charge of the focal point and disseminated timely, accurate, complete and compile data to the relevant officials on daily basis for further planning and implementation. <strong> </strong> <strong>Results: </strong>Performance of individual laboratories was identified on daily basis. Private sector performance was higher than public sector. Peaks showed the local clusters. <strong> </strong> <strong>Conclusion: </strong>A quality, accurate and real-time data and information helped for remarkable improvement in every step of planning and decision making to overcome the global challenge of COVID-19. <strong> </strong> <strong>Limitations: </strong>Computer literacy, close monitoring and duplication of data affected for accuracy.

Ultrastructural calibration model for proficiency testing

Proficiency testing (PT) determines the performance of individual laboratories for specific tests or measurements and it is used to monitor the reliability of laboratories measurements. PT plays a highly valuable role as it provides objective evidence of the competence of the participant laboratories. In this paper, we propose a multivariate calibration model to assess equivalence among laboratories measurements in PT. Our method allows to deal with multivariate data, where the item under test is measured at different levels. Although intuitive, the proposed model is nonergodic, which means that the asymptotic Fisher information matrix is random. As a consequence, a detailed asymptotic analysis was carried out to establish the strategy for comparing the results of the participating laboratories. To illustrate, we apply our method to analyze the data from the Brazilian engine test group, PT program, where the power of an engine was measured by eight laboratories at several levels of rotation.

Benchmarking the success of CCQM key comparisons for metrology institutes and their stakeholders

Key comparisons provide the means to assess the comparability of measurement capabilities at National Metrology Institutes and Designated Institutes worldwide. In addition, they provide a snapshot of the state of the art in measurement science and inform advances in metrology. Key comparisons provide essential information on assessing whether the metrology community can meet the needs of stakeholders. Using examples from gas metrology, we explore the mechanisms for benchmarking the success of a key comparison and a new approach for assessing individual laboratory performance.

Performance of malaria microscopy external quality assessment and networking among health facilities in west Amhara region, Ethiopia

BackgroundMicroscopic examination of peripheral blood smear produces reliable results both about the malaria infection status and level of parasitemia. However, test results are affected by skill of the laboratory personnel, workload, condition of microscopes and quality of laboratory supplies. Therefore, continuous monitoring of the performance of laboratories is of pivotal importance in order to make timely correction.MethodsA facility based cross-sectional study was conducted from July 2017 to July 2019 to assess malaria microscopy performance among thirty malaria diagnostic laboratories in west Amhara region. Thirty slides were collected from participating laboratories every quarter. Collected slides were taken to Amhara Public Health Institute reference laboratory and re-checked by malaria microscopists who were blind to the results from health facilities. Percentage of test agreement, rates of false positive, false negative and species misdiagnosis were calculated using Excel 2010.ResultsAmong a total of 6689 slides re-checked, results of 6146 slides were the same with that of participating laboratories. The test agreement was 97.31 and 94.6% for parasite detection and species identification, respectively. Variations in the overall performance of individual laboratories were seen within a range of 81.55 to 97.27% test agreement. Results of 543 (8.12%) slides were discordant, of which 363 (5.4%), 93 (1.4%) and 87 (1.3%) slides were due to species misdiagnosis, false positive and false negative results, respectively.ConclusionThere was good test agreement between participated laboratories and Amhara Public Health Institute. More accurate performance is expected as the country is tracking to malaria elimination. Hence, further strengthening the external quality assurance program is recommended.

Continual Improvement of the Reliability of EML4-ALK Rearrangement Detection in Non–Small-Cell Lung Cancer: A Long-Term Comparison of ALK Detection in China

The results of EML4-ALK testing are critical to manage ALK tyrosine kinase receptor inhibitor treatment. Thus, the accurate detection of ALK rearrangement is increasingly becoming a matter of serious concern. To address this issue, a long-term EML4-ALK proficiency testing (PT) scheme was launched in China in 2015, serving as an educational tool for assessing and improving the testing quality of EML4-ALK fusion detection. Responses across 20 different PT samples interrogating three different variants and wild-type samples were collected between 2015 and 2019. Performance was analyzed by evaluating the detection methods, kits, and pre-analytic practices used to further display the landscape of changing conditions of the reliability of EML4-ALK testing. During the 5 years, 3224 results reported from 988 laboratories were evaluated, with an overall error rate of 5.36%. Along with an increasing number of participating laboratories, the error rate within each of the different methods showed a significantly downward trend over the years. No obvious differences in the error rates were found regarding the testing methods or kit manufacturers. Moreover, the individual performance of the laboratories improved when they participated in more PT scheme rounds. The data demonstrated that the performance of individual Chinese laboratories for EML4-ALK testing continuously improved over time by participating PT schemes, regardless of their method. However, care must be taken in standardized operations and validations.

The utility of measurement uncertainty in medical laboratories.

The definition and enforcement of reference measurement systems, based on the implementation of metrological traceability of patient results to higher-order (reference) methods and/or materials, together with a clinically acceptable level of measurement uncertainty (MU), are fundamental requirements to produce accurate and equivalent laboratory results. The MU associated with each step of the traceability chain should be governed to obtain a final combined MU on clinical samples fulfilling the requested performance specifications. MU is useful for a number of reasons: (a) for giving objective information about the quality of individual laboratory performance; (b) for serving as a management tool for the medical laboratory and in vitro diagnostics (IVD) manufacturers, forcing them to investigate and eventually fix the identified problems; (c) for helping those manufacturers that produce superior products and measuring systems to demonstrate the superiority of those products; (d) for identifying analytes that need analytical improvement for their clinical use and ask IVD manufacturers to work for improving the quality of assay performance and (e) for abandoning assays with demonstrated insufficient quality. Accordingly, the MU should not be considered a parameter to be calculated by medical laboratories just to fulfill accreditation standards, but it must become a key quality indicator to describe both the performance of an IVD measuring system and the laboratory itself.

Clinical Exome Studies Have Inconsistent Coverage.

Exome sequencing has become a commonly used clinical diagnostic test. Multiple studies have examined the diagnostic utility and individual laboratory performance of exome testing; however, no previous study has surveyed and compared the data quality from multiple clinical laboratories. We examined sequencing data from 36 clinical exome tests from 3 clinical laboratories. Exome data were compared in terms of overall characteristics and coverage of specific genes and nucleotide positions. The sets of genes examined included genes in Consensus Coding Sequence (CCDS) (n = 17723), a subset of genes clinically relevant to epilepsy (n = 108), and genes that are recommended for reporting of secondary findings (n = 57; excludes X-linked genes). The average exome nucleotide coverage (≥20×) of each laboratory varied at 96.49% (CV = 3%), 96.54% (CV = 1%), and 91.68% (CV = 4%), for laboratories A, B, and C, respectively. For CCDS genes, the average number of completely covered genes varied at 12184 (CV = 29%), 11687 (CV = 13%), and 5989 (CV = 37%), for laboratories A, B, and C, respectively. With smaller subsets of genes related to epilepsy and secondary findings, the CV revealed low consistency, with a maximum CV seen in laboratory C for both epilepsy genes (CV = 60%) and secondary findings genes (CV = 71%). Poor consistency in complete gene coverage was seen in the clinical exome laboratories surveyed. The degree of consistency varied widely between the laboratories.

Detecting reagent lot shifts using proficiency testing data

Clinically significant systematic analytical shifts can evade detection despite between-lot reagent verification, quality control and proficiency testing systems practiced by most laboratories. Through numerical simulations, we present two methods to determine whether there has been a shift in the proficiency testing peer group of interest, peer group i, using the measurements from peer group i and J other peer groups. In method 1 ('group mean'), the distance of peer group i from the mean of the other J peer groups is used to determine whether a shift occurs. In method 2 ('inter-peer group' method), the distances of peer group i from each of the means of the other J peer groups are used to determine whether a shift has occurred. The power of detection for both methods increases with the magnitude of systematic shift, the number of peer groups, the number of laboratories within the peer groups and the proportion of laboratories within the affected peer group, and a smaller analytical imprecision. When the number of peer groups is low, the power of detection for the group mean method is comparable to the inter-peer group method, using the m= 1 criterion (a single inter-peer group comparison that exceeds the control limit is considered a flag). At larger peer groups, the inter-peer group method using the same (m= 1) criterion outperforms the group mean method. The proposed methods can elevate the professional role of the proficiency testing program to that of monitoring the peer group method on top of the performance of individual laboratories.

Determination of Quality outcome indicators in National Quality Assurance Standards (NQAS) accredited Hematology and Clinical Pathological laboratory

Background: Laboratory plays a vital role in disease control and prevention by providing timely data or information for patient management and disease surveillance. Quality in laboratory has huge impact on diagnosis and patient management as about 80% of all diagnosis is made on the basis of laboratory tests. Methods: The study was conducted in Central Diagnostic Laboratories of GMERS Medical College, Junagadh which is NQAS (National Quality Assurance Standards). The hospital uses internet and data is retrieved by the systems department. The study was conducted from January 2015 to December 2018. A total of 2,13,476 samples were received in the hematology and clinical pathology section. Different quality outcome indicators of hematology and clinical pathology laboratory were studied. Result: All Quality parameters were consistently improved from 2015 to 2018 due to new instrumentation, IQC, EQC, timely instrument maintenance, laboratory information system (LIS), telephonic communications and monthly-yearly quality improvement meetings. Some important indicators like TAT, critical alert were not reach up to the target value but due continuous improvement plane we soon reach target level. Conclusion: The concept of quality indicators has revolutionized the field of laboratory medicine. These indicators are of most importance in the comparison of individual laboratory performance with the aim of improving laboratory services and quality.

Six-Year Experience (2013-2018) With College of American Pathologists Programs at King Hussein Cancer Center in Jordan

Abstract Objectives Proficiency testing (PT) includes interlaboratory comparisons that are organized regularly to assess the performance of individual laboratories for specific tests or measurements and it is used to monitor laboratories’ continuing performance. Background The College of American Pathologists (CAP) requires laboratories to participate in PT programs and to perform the investigation and root cause analysis for unsatisfactory PT results, which is valuable to improve the laboratory performance. Methods The data were extracted from the CAP PT results of the laboratory from 2013 to 2018 in the areas of Biochemistry, Immunology, Hematology, Microbiology, Anatomic Pathology and Cytology, and Blood Bank. The data were PT scores and consisted of values between 0 and 100, representing the percentage of correct response for each analyte. Results There were 211 analytes (502 event) in 2018, 215 analytes (547 event) in 2017, 204 analytes (531 event) in 2016, 210 analytes (519 event) in 2015, 228 analytes (443 event) in 2014, and 158 analytes (528 event) in 2013 that were covered by CAP PT surveys in different laboratory areas. Over the 6 years of experience, there were 57 (1.86%) unsatisfactory results for all PT events. It was seen that the rates of unsatisfactory results in that period were gradually decreased with each year of experience, which was 1.1% (2018), 1.6% (2017), 1.9% (2016), 1.5% (2015), 2.4% (2014), and 2.6% (2013). The top 3 reasons for unacceptable results were random error, analytical error, and procedural error, which accounted for 21.0% random error (2013 (9%), 2014 (4%), 2015, 2016, 2017, &amp; 2018 (2%)), 19.3% analytical error (2013 (2%), 2014 (5%), 2015 (5%), 2016 (3.5%), 2017 (2%), &amp; 2018 (1.8%)), and 17.5% procedural error (2013 (4%), 2014 (4%), 2015 (0%), 2016 (2%), 2017 (5%), &amp; 2018 (3.5%)). Conclusion The proficiency testing performance showed a trend of improvement from 2013 to 2018, which contributed to the improvement of laboratory performance and declining the unacceptable results that affected positively on patient test performance.

Proficiency testing for pH measurements: a 3-year evaluation

Chemical Metrology Laboratory, LIPI, organizes an annual proficiency testing (PT) scheme with pH being one of the parameters investigated. This study presents and evaluates the performance of the laboratories that participated in the pH measurement during 3 consecutive years of the PT from 2014 to 2016. The PT test items were prepared by Chemical Metrology Laboratory, LIPI, from high-purity material. The homogeneity testing and stability testing of the PT test items were performed according to ISO 13528:2005. The measured reference value was directly traceable to the pH value of SRM® 185i and 187e produced by NIST, USA, and the expanded uncertainty was calculated according to ISO GUM:2008 with a coverage factor (k = 2), at a 95 % confidence level. Individual laboratory performance was reported in terms of z-scores. In the 2014 scheme, the reference buffer solution was not provided by provider, while in the 2015 and 2016 schemes, reference buffer solutions were distributed to participants alongside the PT test items. The best performance was achieved in 2015, where more than 90 % of the reported results were assessed as satisfactory. The laboratory performance in 2015 coincided with the distribution of two traceable pH standard solutions to participants which allowed them to satisfactorily calibrate their instrumentation. In conclusion, regular PT program is an effective way of demonstrating the effectiveness of quality assurance procedures applied in participating laboratories and provides opportunity for corrective action which will benefit measurements made in the future.

Laboratory Performance of Serum B12 Assay in the United Kingdom (UK) As Assessed By the UK National External Quality Assessment Scheme for Haematinics: Implications for Clinical Interpretation

Serum B12 assay is the most commonly used routine test for assessing cobalamin status in the body. In the United Kingdom, there are around 350 laboratories performing the assay using seven different platforms. External quality assessment of the assays is organised by UK NEQAS for Haematinics by sending a serum sample every 3 months. An ‘all participants’ consensus mean is calculated and used as the target value and the results analysed with respect to intra- and inter- group variation. The percentage bias from the target value is used to assess performance.We present data on one such assessment to demonstrate the problems of the serum B12 assay (Survey number 248, April 2018) and also how it is interpreted by the laboratory for clinical use.MethodA serum sample with a B12 target value of approximately 173 ng/L was sent to participating laboratories for analysis. Laboratories were also asked for an interpretation of their result which would be reported to the requesting clinician, namely from low to high.ResultsFig 1 shows an individual laboratory's result (indicated by the arrow) in relation to all laboratories using the same technology (shaded histogram) or all methods (open histogram). There is a significant variation ranging from 86 to 258 ng/L depending on the assay used, with an overall standard deviation of 28 and co-efficient of variation of 16%.Fig 2 shows the distribution of results in the different methodologies used and how each laboratory interpreted its result. It demonstrates the bias of results obtained by the different methods. The assays using Beckman Coulter Access/Dxl (SF5 and SF6) gave much lower results than other methods. In the group SF5, three laboratories interpreted the result as ‘normal’ and one as ‘indeterminate’.In the groups Abbot Architect (AB13) and Roche Cobas/Modular (BO5), although having higher results than other groups, there is a significant number of laboratories interpreting the result as ‘low’ and also ‘normal’ or ‘indeterminate’.Fig 3 shows a graphical representation of an individual laboratory's performance bias and the consistency of its individual and group bias over a period of 6 months. The Bias score (B score on y axis) is how far the result obtained deviated from the target value. The C score (on x axis) informs on consistency of the bias over the past 6 months. Hence, ideally both B score and C score should be as low as possible, and therefore all methodologies would harmonise towards similar results.DiscussionThese data demonstrate the limitations of the serum B12 assay in assessing body B12 status. The numerical value obtained of any sample can vary considerably between the different methodologies used. In addition, the interpretation provided by the laboratory can also be highly variable. This may have profound implications for clinical assessment and management. In addition, this is compounded by the fact that it is not quite clear what would be regarded as the normal or reference range. Laboratories in the United Kingdom use the manufacturers ranges and clinicians may consult the British Society for Haematology Guidelines (Devalia V et al (2014) BCSH Guidelines for the diagnosis and treatment of cobalamin and folate disorders. British Journal of Haematology, 166, 496-513) for help in clinical interpretation. Our data shows that the different reference ranges quoted by the kit manufacturers do not correspond to their assay bias, ie there is no simple direct correlation between the ranges provided against the bias of their particular assay.ConclusionThe UK NEQAS Haematinics Programme demonstrates problems associated with the serum B12 assay with data on variation of results obtained, bias and interpretation of results in a style that is unique across currently available Proficiency Testing/ External Quality Assessment schemes.Laboratories need to be aware of their performance in assessing serum B12 level in order to provide appropriate clinical advice. This needs collection of feedback and audit of data of the clinical situation for which the request was made.Clinicians need to be aware of the performance of their laboratories in order that they can interpret the result provided in a meaningful way in relation to the clinical picture. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

External quality assessment for CD4 + T-lymphocyte count test: Performance of the Brazilian public health laboratories network.

The National Network for CD4+ T-lymphocyte counting of Brazil comprises 93 laboratories. This study reports the laboratory performances achieved in external quality assessment (EQA) rounds provides by Ministry of Health to evaluate the quality of the kits used and the performance of test by the technicians.Ten EQA rounds were analyzed according the EQA criteria aimed to evaluate individual laboratory performance on the basis of the accuracy of their results compared to the general mean obtained by all participating laboratories and the reproducibility of the results obtained between 2 samples from the same donor.The percentage of approved and failed laboratories in the EQAs tends to follow a uniform pattern. Since 2011, approval has remained above 80% and the failure rate has never exceeded 15%.EQA is very important to evaluate the performance of the laboratories, to identify monitor, and to resolve errors as quickly as possible.

Defining permissible limits for the combined uncertainty budget in the implementation of metrological traceability

In addition to the correct implementation of calibration traceability, the definition and the achievement of an appropriate analytical performance specification for the total uncertainty budget (GU) is essential to ensure that laboratory measurements are clinically usable. To understand if it is possible to fulfil these specifications, limits for combined uncertainty across the entire metrological traceability chain should be defined. We recommended that no more than one third of GU should be consumed by the uncertainty of higher order references and ≤50% of GU by the combined measurement uncertainty at the manufacturer's calibration level. The remaining allowable uncertainty should be available for random sources, i.e. for the imprecision of the commercial measuring system (including the reagent batch-to-batch variation) and the individual laboratory performance, as a safety margin to fulfil GU. Based on this approach, it is of interest to assess for each analyte measured in the clinical laboratory the status of the uncertainty budget of its measurement associated with the selected metrological traceability chain. Accordingly, we report three didactic cases that could occur in the clinical practice. This approach is very helpful to identify those analytes for which further technological improvements are probably needed to reduce uncertainty associated with their measurement.