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Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Homologous Recombination Repair (HRR) is the most reliable and important signaling pathway for repairing DNA damage. We initiated a calibration project to better understand the NGS landscape for HRR gene testing in China, provide indications for testing standardization, and guide clinical practice. Methods: A questionnaire was used to collect laboratory information, panel design for HRR gene testing, tissue sample test parameters, plasma ctDNA sample test parameters, and procedures for variant interpretation. The testing quality of the participating laboratories was further evaluated by external quality assessment (EQA), which provided 5 FFPE slices and 5 mimic ctDNA samples as standard references for evaluation. Test results and reports were collected to assess laboratory performance. Results: Our results showed that different laboratories had significant differences in sequencing platforms, library construction technologies, genes in the testing panel, detectable mutation types, probe coverage regions, sequencing parameters, variants interpretation guidelines, and positive test rates. For the EQA test, the overall pass rate was about 60%. The average accuracy for tissue samples and ctDNA samples was 79.55% and 74.13%, respectively. It is worth noting that variants in tandem repetition regions and splice sites, and those with low allele frequency were more prone to misdetection. The most common reasons for misdetection were as follows: the testing panel did not cover the genes or the whole exon and splice sites of the genes; the variants were misclassified as benign or likely benign, and the variants failed the QC criteria. Conclusions: The discrepancies observed in our survey and EQA test affect the authenticity of HRR gene test results for prostate cancer, underlining the need to establish guidelines for HRR gene testing and variant interpretation in China, and to optimize HRR gene testing in clinical practice to improve management and patient care.

Objective To analyze the difference of circulating threshold (Ct) of polymerase chain reaction (PCR) in blood station laboratories during the external quality assessment, and to put forward suggestions for the quality improvement of participating laboratories. Methods From 2018 to 2021, the blood station laboratories participated in the external laboratory quality assessment of CITIC including blood screening items with nucleic acid testing method. The data of Roche diagnostic reagent group were used as the source, and the detected Ct values of three groups of quality control samples of HBV A subtype (400 IU/mL), HCV 1b subtype (400 IU/mL) and HIV B genotype (500 IU/mL) were used as the objects. The data were grouped according to quality control (sample) batches, reagent batches and different laboratories. Using the statistical method of variance analysis (assuming P

[Objectives] The study aims to improve the ability of inspectors to recognize humoral moiphology and provide data reference for the improvement of EQA work of humoral morphology by Guangxi Clinical Laboratory Center. [Methods] A retrospective analysis was made on the EQA of humoral morphology by Guangxi Clinical Laboratory Center from 2010 to 2022, and the number of participating laboratories, the rate of return, sample types and maps of EQA of humoral morphology such as urine sediment, vaginal secretions and so on (except feces), and the reasons for the high error rate of the results of the participating laboratories were analyzed. [Results] The number of laboratories participating in the assessment of humoral morphology increased from 98 in 2010 to 371 in 2022. Except for 2011 (90.98%), the rate of return was more than 94%, and the highest rate of return was up to 100%. A total of 119 pictures of EQA of humoral moiphology were studied, including 101 urine sediment smears, 13 vaginal secretions smears and 5 other smears. The types of specimens were relatively comprehensive. The distribution of the maps was basically reasonable. The urinary sediment was mainly composed of crystalline salts, followed by tubes, and cells and fungi ranked third. The coverage was relatively complete. The error rate of return results from high to low were bacteria (error rate was equal to 40%), tubes and crystalline salts (error rate was close to 29%), and cells and fungi (error rate was about 14%). The main cases with high error rate of return results are as follows; the difference between different tubes was not clear, and the diversity of crystal moiphology was not understood enough; the phase division of cells in the same system was wrong. [Conclusions] The analysis and summary of the reasons for the high error rate of the data and results of Guangxi's EQA of humoral morphology is helpful for laboratory physicians to improve their awareness of morphological examination and identify clearly the error type and blurred concept, and lays a foundation for Guangxi Clinical Laboratory Center to cany' out EQA of humoral morphology more specifically. [ABSTRACT FROM AUTHOR]

Copyright of Enfermería Investiga: Investigaciin, Vinculación, Docencia y Gestiin is the property of Revista Enfermeria Investiga and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Tumor mutational burden (TMB) has recently been approved as an agnostic biomarker for immune checkpoint inhibitors. However, methods for TMB testing have not yet been standardized. The International Quality Network for Pathology (IQNPath) organized a pilot external quality assessment (EQA) scheme for TMB testing. The aim of this program was the validation of the materials and the procedures for the EQA of this complex biomarker. Five formalin-fixed paraffin-embedded (FFPE) cell lines were selected to mimic the various TMB values observed in clinical practice. The FFPE samples were tested with the FoundationOne CDx (F1CDx) assay as the reference test and three commercially available targeted sequencing panels. Following this internal validation, the five cell lines were sent to 29 laboratories selected on the basis of a previous survey. Nineteen of the 23 laboratories that submitted results (82.6%) used targeted sequencing for TMB estimation. Only two laboratories performed whole exome sequencing (WES) and two assessed TMB by clinical exome. A high variability in the reported TMB values was observed. The variability was higher for samples with the highest TMB value according to the F1CDx test. However, good reproducibility of the TMB score was shown by laboratories using the same panel. The majority of laboratories did not indicate a TMB cut-off value for clinical interpretation. In conclusion, this pilot EQA scheme suggests that it is feasible to run such an EQA program for TMB assessment. However, the results of our pilot highlight the numerous challenges for the standardization of this test. [ABSTRACT FROM AUTHOR]

IntroductionSeveral Proficiency Test (PT) or External Quality Assessment (EQA) schemes are currently available for assessing the ability of laboratories to detect and characterize enteropathogenic bacteria, but they are usually targeting one sector, covering either public health, food safety or animal health. In addition to sector-specific PTs/EQAs for detection, cross-sectoral panels would be useful for assessment of the capacity to detect and characterize foodborne pathogens in a One Health (OH) perspective and further improving food safety and interpretation of cross-sectoral surveillance data. The aims of the study were to assess the cross-sectoral capability of European public health, animal health and food safety laboratories to detect, characterize and notify findings of the foodborne pathogens Campylobacter spp., Salmonella spp. and Yersinia enterocolitica, and to develop recommendations for future cross-sectoral PTs and EQAs within OH. The PT/EQA scheme developed within this study consisted of a test panel of five samples, designed to represent a theoretical outbreak scenario.MethodsA total of 15 laboratories from animal health, public health and food safety sectors were enrolled in eight countries: Denmark, France, Italy, the Netherlands, Poland, Spain, Sweden, and the United Kingdom. The laboratories analyzed the samples according to the methods used in the laboratory and reported the target organisms at species level, and if applicable, serovar for Salmonella and bioserotype for Yersinia.ResultsAll 15 laboratories analyzed the samples for Salmonella, 13 for Campylobacter and 11 for Yersinia. Analytical errors were predominately false negative results. One sample (S. Stockholm and Y. enterocolitica O:3/BT4) with lower concentrations of target organisms was especially challenging, resulting in six out of seven false negative results. These findings were associated with laboratories using smaller sample sizes and not using enrichment methods. Detection of Salmonella was most commonly mandatory to notify within the three sectors in the eight countries participating in the pilot whereas findings of Campylobacter and Y. enterocolitica were notifiable from human samples, but less commonly from animal and food samples.DiscussionThe results of the pilot PT/EQA conducted in this study confirmed the possibility to apply a cross-sectoral approach for assessment of the joint OH capacity to detect and characterize foodborne pathogens.

Since December 2019, the worldwide public health has been threatened by a severe acute respiratory syndrome caused by Coronavirus-2. From the beginning, a turning point has been the identification of new cases of infection, in order to minimize the virus spreading among the population. For this reason, it was necessary introducing a panel of tests able to identify positive cases, which became crucial for all countries. As a Regional Reference Centre, the CRQ Laboratory (Regional Laboratory for the Quality Control) developed and conducted an External Quality Assessment (EQA) panel of assay, so as to evaluate the quality of real-time reverse transcription polymerase chain reaction (PCR), which were used by 62 Sicilian laboratories, previously authorized to issue certificates for the COVID-19 diagnosis, on behalf of the Public Health Service. The qualitative performance test was based on pooled samples with different viral loads of SARS-CoV-2 or human Coronavirus OC43. 75% of the participating laboratories tested all core samples correctly, while the remaining 25% interpreted incorrectly the EQA exercise samples matching negatively the standards required. Subsequent inspection visits confirmed the issue of incorrect positive and negative certifications for COVID-19 by private and public laboratories, despite the possession of the authorization requirements currently provided for by current regulations, with a significant impact on the SSR. [ABSTRACT FROM AUTHOR]

Introduction: The haematology external quality assessment (EQA) scheme is the most commonly used service of quality assurance. The provision of complete blood count (CBC) materials must meet the quality requirements at a reasonable cost. These requirements are the most significant challenges for EQA organisers in Vietnam. This study’s objective was to evaluate the homogeneity, long-term stability, and peer-group performance of 10-parameter stabilised CBC EQA samples. Methods: The CBC EQA material was prepared using the following steps, including (1) adjusting levels of stabilised erythrocyte, leukocyte, and platelet samples, (2) mixing those cells into batches at three levels, and (3) dispensing and storing them at 2–6 °C. A set of 10 and 30 specimens were randomly chosen from each batch to study the homogeneity and long-term stability following ISO 13528:2015. In total, 166 samples at two levels were randomly distributed to 40 participants, which reported 83 automatic cell counters among six automated analyser models in the CBC EQA program. Results: The 10-parameter stabilised CBC EQA materials at three levels became homogeneous and stable in 12 weeks when preserved at 2–6 °C. Meanwhile, for five parameters (RBC, Hb, MCH, MCV, and MPV), this process was prolonged for up to 16 weeks in stock condition. In terms of peer-group performance, the CV (%) values increased at the low concentration for almost all parameters, especially in platelet counts. Conclusions: The stabilised CBC EQA samples prepared using the partial fixation method with aldehyde and gutaraldehyde in this study meet the ISO 13528:2015 requirements of homogeneity and long-term stability for the CBC EQA scheme. Analytical performance evaluation should categorise participant methods into peer groups.

Objectives: We conducted a nationwide external quality assessment (EQA) study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid amplification testing in Japan. Methods: A total of 563 public health and private sector laboratories participated. The EQA samples comprised 6 RNA and full-process controls. Results: The overall agreements were 99.3% and 97.9% for the RNA and full-process controls, respectively. A total of 530/563 (94.1%) laboratories reported correct results; public health laboratories had the highest accuracy. Thirty-three laboratories reported at least one incorrect result (26 laboratories of medical facilities, 5 commercial laboratories, 1 public health laboratory, and 1 other). Sixteen laboratories of medical facilities that used a fully automated assay system failed to detect the presence of the full-process control, due to inherent insufficiency in the limit of detection (LOD). Other causes of incorrect results included failure to ensure the LOD (n = 13), error in result judging or reporting (n = 3), and error in sample handling (n = 1). Conclusions: Performance was mostly dependent on the laboratory category and assay evaluation, particularly the LOD. Guidance should be developed based on these results, particularly in the phase of new entry into laboratory services for SARS-CoV-2.

• D-dimer is routinely used for excluding venous thromboembolism. • This study provides EQA design and laboratory performance for D-dimer assay in China for the first time. • Expression unit should be required to label in package inserts by regulatory authority. • Laboratory professionals should follow instructions for use and prefer unmodified test systems for clinical safely application. • Harmonization of reporting units through collaborative efforts is the promising step. To investigate performance of D-dimer assays in China and address analytical quality issues. D-dimer assays data were collected from China National External Quality Assessment Scheme (China NEQAS) from 2014 to 2022. We analyzed reagents, assay results, reporting unit and cutoffs in 2022 China NEQAS. Interlaboratory coefficient variations (CVs) and influence of modified/unmodified test systems on CVs were investigated over 9 years. There were 82 reagent brands in China NEQAS, but 55 reagent instructions did not indicate expression unit (DDU or FEU). Up to 7-fold of the ratio of max-to-min mean results was shown among different assays with same unit on the same sample. A prevalence of FEU (63.4%) over DDU (17.1%) was observed. Although 669 laboratories (37.9%) among 1766 laboratories used reagents without VTE exclusion claim, they also reported cutoffs. The CVs of only two assays were decreasing over years. CVs of modified test systems were higher than those of unmodified systems before improvement. Expression unit should be required to label in package inserts by regulatory authority. Laboratory professionals should follow instructions for use and prefer unmodified test systems for clinical safely application. Harmonization of reporting units through collaborative efforts is the promising step. [ABSTRACT FROM AUTHOR]

As one of the most requested profiles of blood tests, there is a need for standardization among liver function tests (LFT). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are key markers of hepatocellular injury. ALT and AST are used to calculate a Fibrosis-4 (FIB-4) score for assessing liver fibrosis. Despite recommendations by the International Federation of Clinical Chemistry (IFCC) to include pyridoxal-5-phosphate in ALT and AST assay methodologies, most laboratories continue to omit this.Data from the UK NEQAS for Clinical Chemistry Scheme, Distribution 1160 (November 2023), was reviewed to investigate variation in practice regarding liver blood tests in relation to ALT, AST and FIB-4. In addition, a series of questions audited laboratory practice in relation to liver enzymes.Wide variation was seen in LFT profiles offered by laboratories, with 32 different combinations of tests used. The IFCC-recommended methods for ALT and AST are used by one-third of laboratories and give significantly higher results than non-IFCC methods. Laboratories using IFCC methods also reported significantly higher FIB-4 scores. Reference ranges and cut-offs for these tests also varied, and did not account for method-related differences in results.The lack of standardization of LFTs can have a significant impact on patient care. The difference in results for ALT, AST and FIB-4 in laboratories not using IFCC-recommended methods may lead to misdiagnosis. This issue should be addressed by laboratories using methods including pyridoxal-5-phosphate. Until then, method-related reference ranges and cut-offs for ALT, AST and FIB-4 are required. [ABSTRACT FROM AUTHOR]

New psychoactive substances (NPS) are uncontrolled analogues of existing drugs or newly synthesized chemicals that exhibit psychopharmacological effects. Due to their diverse nature, composition, and increasing prevalence, they present significant challenges to the healthcare system and drug control policies. In response, healthcare system laboratories have developed analytical methods to detect NPS in biological samples. As a Regional Reference Centre, the Sicilian CRQ Laboratory (Regional Laboratory for Quality Control) developed and conducted an External Quality Assessment (EQA) study to assess, in collaboration with the Istituto Superiore di Sanità (ISS), the ability of different Italian laboratories to identify NPS and traditional drugs of abuse (DOA) in biological matrices. Two blood samples were spiked with substances from various drug classes, including synthetic cannabinoids, cathinones, synthetic opiates, and benzodiazepines, at concentrations ranging from 2 to 10 ng/mL. The blood samples were freeze-dried to ensure the stability of DOA and NPS. Twenty-two laboratories from the Italian healthcare system participated in this assessment. The information provided by the laboratories during the registration in an in-house platform included a general description of the laboratory, analytical technique, and the chosen panels of analytes. The same platform was employed to collect and statistically analyze the data and record laboratory feedback and comments. The evaluation of the results revealed that the participating laboratories employed three different techniques for analyzing the samples: GC-MS, LC-MS, and immunoenzymatic methods. Approximately 90 % of the laboratories utilized LC-MS techniques. Around 40 % of false negative results were obtained, with the worst results in the identification of 5-chloro AB PINACA. The results showed that laboratories that used LC-MS methods obtained better specificity and sensitivity compared to the laboratories using other techniques. The results obtained from this first assessment underscore the importance of external quality control schemes in identifying the most effective analytical techniques for detecting trace molecules in biological matrices. Since the judicial authorities have not yet established cut-off values for NPS, this EQA will enable participating laboratories to share their analytical methods and expertise, aiming to establish common criteria for NPS identification. • NPS pose challengesto healthcare and drug control policies due to their diverse nature and increasing prevalence. • EQA study to evaluate the identification NPS and traditional drugs of abuse in biological matrices in Italian laboratories. • GC-MS, LC-MS, and immunoenzymatic methodswere reported, with LC-MS showing higher specificity and sensitivity. • The absence of cut-off values for NPS emphasizes the need to establish common criteria for their identification. [ABSTRACT FROM AUTHOR]

Hepatitis B surface Antigen (HBsAg) and hepatitis C antibody (anti-HCV) assays have been performed in most laboratories using a variety of analytical methods with different reagents for Hepatitis B virus (HBV) and Hepatitis C virus (HCV) screening1-2. The purpose of this study was to develop an EQA program for dual HBsAg and anti-HCV serological testing to ensure the accuracy and reliability of serological assays. A serum panel of 12 samples containing three negative, three positives for each virus and three positives for both of HBsAg and anti-HCV. These panels were distributed to 102 laboratories in the South of Vietnam. They were required to report their results and any problems encountered on EQA panel. The results show that performance of HBsAg and anti-HCV tests is not only different in terms of method used but also in the types of biological products. Rapid tests (RTs) to detect HBsAg and anti-HCV were most commonly used to screen for HBV and HCV in laboratories. The coincidence rates of RTs for HBsAg and anti-HCV serological assays were 88.24% and 89.86% respectively, while electrochemiluminescence (ECLs) and chemiluminescent immunoassays (CLIAs), Enzyme-linked immunosorbent assay (ELISA) showed the best performance for both HBsAg and anti-HCV testing. The most challenging was failed to detect weak positive samples. In conclusion, the differences in test results within and between groups of HBsAg and anti-HCV assay methods indicated a need to improve test conditions at laboratories in Viet Nam.

Accurate diagnosis of von Willebrand disease (VWD) depends on the quality, precision, and variability of the laboratory assays. The North American Specialized Coagulation Laboratory Association (NASCOLA) is a provider of external quality assessment (EQA) for approximately 60 specialized coagulation laboratories in North America. In this report, NASCOLA EQA data from 2010 to 2021 are reviewed for trends in methodology and precision among various assays. In particular, recent ASH ISTH NHF WFH (American Society of Hematology, International Society on Thrombosis and Haemostasis, National Hemophilia Foundation, and World Hemophilia Federation) guidelines for diagnosis of VWD are reviewed in light of EQA data. In contrast to other geographic regions, laboratories in North America predominantly use three-assay screening panels (antigen, platelet-binding activity, and factor VIII [FVIII] activity) rather than four-assay panels (antigen, platelet-binding activity, FVIII activity, and collagen-binding activity). They also use latex immunoassays rather than chemiluminescence immunoassays, and the classic ristocetin cofactor (VWF:RCo) assay and monoclonal antibody (VWF:Ab) assay to assess VWF platelet-binding activity over newer recommended assays (VWF:GPIbM and VWF:GPIbR). Factors that may be influencing these North American practice patterns include lack of Food and Drug Administration approval of the VWF:GPIbM, VWF:GPIbR, collagen binding assays, and chemiluminescence methodologies, and the influence of the 2008 National Heart, Lung, and Blood Institute guidelines on laboratory practice. Lastly, systems-based solutions are urgently needed to improve the overall accuracy of laboratory testing for VWD by minimizing preanalytical variables and adopting assay standardization. [ABSTRACT FROM AUTHOR]

Background  Reduced or dysfunctional von Willebrand factor (VWF) may lead to von Willebrand disease (VWD), which is a common inherited bleeding disorder. VWD is classified into three major types: type 1 is a partial quantitative deficiency of VWF, type 3 is a complete quantitative deficiency of VWF, and type 2 consists of qualitative abnormalities of VWF. To arrive at a correct VWD diagnosis, multiple tests and a correct interpretation of these tests are needed. Aim  The aim of the present study was to gain insight into the approach of laboratories toward VWD diagnosis. Methods  Data from four samples of the external quality assessment (EQA) VWF surveys of the ECAT (External Quality Control for Assays and Tests) were evaluated. Furthermore, results were analyzed of a questionnaire that was sent to hemostasis laboratories about VWD diagnostic approaches. Results  For most EQA samples, the majority of participants indicated the correct classification. However, 6 to 60% indicated another classification. For all samples, significant differences in VWF results were observed between the correct and incorrect classifications. The questionnaire demonstrated that the testing approach varied between the laboratories, especially for parameters that were essential for discrimination between VWD type 1 and healthy individuals, as well as the cutoff values used to discriminate VWD types 1 and 2. Conclusions  Diagnosis of VWD is heterogeneous in diagnostic approach, guidelines, and cutoff values within large ranges of VWF results between laboratories. Harmonization of approaches and increased accuracy of VWF measurements may help to establish a correct diagnosis. [ABSTRACT FROM AUTHOR]

von Willebrand disease (VWD) is a common bleeding disorder that arises from deficiency and/or defects of von Willebrand factor (VWF). Appropriate diagnosis of VWD, including differential identification of qualitative (types 2A, 2B, 2M, 2N VWD) versus quantitative (types 1 and 3 VWD) defects remains problematic but has important management implications, given differential therapy. Complete assessment for VWD in a patient with a bleeding history requires comprehensive test panels, including VWF activity and antigen. We describe the Australasian experience, using data from the Royal College of Pathologists of Australasia (RCPA) Quality Assurance Program (QAP) related to VWF testing in their VWD test module. The RCPAQAP has been providing samples for VWF testing since 1998, representing 25 years of proficiency testing related to VWD diagnosis. A total of 109 samples have been dispatched to participants over these years, with current assessment involving dispatches of two samples (=4 samples) per year. Samples have represented all types of VWD, as well as normal or other samples, including acquired von Willebrand syndrome and plasma VWF concentrates as used in VWD therapy. Different VWF assays and activity/antigen ratios show different utility in VWD and type identification. In the past 9 years of data capture, a total of 166 errors were identified from a total of 1,839 interpretations, representing a base error rate of 9.0%. Identification errors were highest for type 2 VWD samples (15.3%), intermediate for type 1 VWD samples (7.5%), and lowest for normal samples (2.4%). Errors can be linked to assay limitations, including assay variability and low-level VWF detection limits, as well as laboratory issues (including test result misinterpretation, which accounts for approximately 40% of all errors for type 2 VWD). For test-associated errors, VWF:RCo and VWF:GPIbM were associated with the highest variability and error rate, which was up to 10x higher than that using VWF:CB. As a test group, chemiluminescence-based procedures were associated with lowest inter-laboratory variability, best low-level VWF detection (down to <1 U/dL), and least errors overall. These findings inform on reasons behind high rates of errors associated with VWD diagnosis, with some assays and methodologies performing substantially better than others. [ABSTRACT FROM AUTHOR]

von Willebrand disease (VWD) is reportedly the most common inherited bleeding disorder, and can also arise as an acquired (von Willebrand) syndrome (AVWS). The hemostasis laboratory plays a key role in the diagnosis or exclusion of VWD/AVWS, which may otherwise be suspected due to the patient's clinical (bleeding) history. VWD/AVWS arise from deficiency and/or defects in the adhesive plasma protein, von Willebrand factor (VWF). VWF undertakes various roles within hemostasis, but principally acts within primary hemostasis to anchor platelets to sites of vascular damage, thereby facilitating thrombus formation to arrest bleeding. The diagnosis or exclusion of VWD/AVWS requires laboratory testing for both VWF level and activity, with the latter potentially comprising several of a potential plethora of different assays. Complete diagnosis of VWD also requires the differentiation of VWD type, with six types comprising the current classification (i.e., qualitative [types 2A, 2B, 2M, 2N VWD] vs. quantitative [types 1 and 3 VWD] deficiency/defects). Although appropriate diagnosis and type classification hold important therapeutic consequences, these remain problematic and sometimes elusive for some laboratories to achieve. This report reviews the laboratory aided diagnosis or exclusion of VWD from a geographic perspective, and focuses on the disparities of approaches and methods in different regions of the world. This is primarily done from the perspective of data available from published reports related to external quality assessment (or proficiency testing) from different geographic localities. Moreover, differences in approaches between laboratories may arise due to differential adherence of particular guidelines, as well as regulatory aspects and predominance of local manufacturers and suppliers. [ABSTRACT FROM AUTHOR]

Von Willebrand disease (VWD) is one of the most common hereditary bleeding disorders. Effective management of patients and their families depends on accurate diagnosis and subtype classification, and quality assurance including participation in proficiency testing programs is essential to ensure the accuracy of the panel of assays required to achieve this diagnosis. We report here findings from recent external quality assessment (EQA) exercises, as well as from a questionnaire about diagnostic practices employed by centers in the United Kingdom National Quality Assessment Scheme (UK NEQAS) performing von Willebrand factor (VWF) assays. Plasma samples from donors with VWD, "normal" donors, the International Society for Thrombosis and Haemostasis Scientific Subcommittee (ISTH SSC) plasma standard, and whole blood samples were sent to participants in the UK NEQAS BC program for VWF investigation. Calibration of lot#5 of the ISTH SSC plasma standard was shown to give improved comparability between the recovered value from an EQA exercise and the assigned potency for VWF activity assays. Diagnostic accuracy and precision amongst UK NEQAS participants was good, with an average 99% of centers reporting the correct interpretation for normal, type 1 and type 2 VWD samples, 100% diagnostic accuracy for centers performing FVIII binding assays, and good agreement amongst centers performing multimeric analysis. Genetic analysis of the VWF gene by specialist centers demonstrated errors in the genotyping process in one center, but also demonstrated failings in the interpretation of results in other centers. Despite evidence of good laboratory accuracy and precision in their assays, a questionnaire identified marked variation in diagnostic criteria employed, underlining the importance of guidelines to support the diagnosis of VWD. [ABSTRACT FROM AUTHOR]

Detection of Syndecan 2 (SDC2) methylation in stool DNA is a novel method for the auxiliary diagnosis of early colorectal cancer (CRC). Currently, this method has been widely applied; however, its accuracy and reliability have not been determined. The objective of this pioneering study was to evaluate the performance of clinical laboratories in China for their ability to detect SDC2 methylation from stool DNA. We generated a sample panel consisting of clinical and cell samples. The clinical samples were stool specimens from patients with or without CRC, including four positives (prepared by serial dilution from one stool specimen), one negative and one interferential sample. Two cell samples, with positive or negative methylated SDC2, were used as controls. The panel was distributed to 32 clinical laboratories for analysis of SDC2 methylation, and the results were compared and scored. The sample panel was compatible with commercially available assays and it showed appropriate stability to be an external quality assessment material. There were four false results; one hospital laboratory and one commercial diagnostic laboratory had a false-positive and a false-negative result, respectively, and one commercial diagnostic laboratory had both a false-positive and false-negative result. Among the 32 participating laboratories, 29 (90.62%) obtained an acceptable or better performance score, while 3 (9.38%) laboratories required improvement. Our results demonstrate that the detection of SDC2 methylation from stool DNA was satisfactory in China. Additionally, the importance of external quality assessment was highlighted for monitoring the performance of clinical laboratories. [ABSTRACT FROM AUTHOR]

A trueness-based EQA/PT program for high density lipoprotein cholesterol (HDL-C) was initiated. We analyzed the 4 year EQA/PT program to overview the measurement standardization for HDL-C in China. Two levels of freshly frozen, commutable serum external quality assessment/proficiency testing (EQA/PT) materials were prepared and determined by reference measurement procedure each year. The samples were delivered to clinical laboratories and measured 15 times in 3 days. The precision [coefficient of variation (CV)], trueness (bias), and accuracy [total error (TE)] were calculated and used to evaluate measurement performance. The pass rates of individual laboratories and peer groups were analyzed using the acceptable performance from the National Cholesterol Education Program (NCEP) and biological variation as the evaluation criteria. More than 60% of laboratories use heterogeneous systems, and there was a decrease in the percentage from 2016 to 2019. About 95, 78, and 33% of laboratories met the minimum, desirable and optimum TE criteria derived from biological variation. The pass rates were 87.0% (84.7–88.8%), 58.7% (55.3–62.4%), and 97.3% (95.6–98.3%) that met the acceptable performance of TE, bias, and CV of NCEP. The homogeneous systems had higher pass rates of TE, bias, and CV than the heterogeneous groups in 2016, but they did not show apparent advantages in 2017–2019. The trueness-based EQA/PT program can be used to evaluate the accuracy, reproducibility, and trueness of results. For some IVD manufacturers and individual laboratories, accuracy, especially trueness, are still problems. Efforts should be made to improve the situation and achieve better HDL-C measurement standardization. [ABSTRACT FROM AUTHOR]

Background: It is crucial to improve the accuracy of HbA1c measurement as its essential role in diabetes diagnosis and treatment. We aimed to establish the biological variation (BV) and sigma metrics (SM) models and apply the models to evaluate the analytical performance of HbA1c in external quality assessment (EQA) program.Methods: Data of HbA1c EQA (2021) and internal quality control (IQC) (March-August 2021) were collected. The group-specific bias and coefficient of variance (CV) were computed for measuring systems with laboratory number >9 in EQA program. The analytical bias and CV for individual laboratory were estimated from EQA and IQC data. The CV% and bias% were plotted in the BV-SM models for performance evaluation of measuring system and individual laboratory.Results: Totally, 380 laboratories participated in EQA program. The overall inter-laboratory CV of five EQA samples ranged from 3.02% to 3.63%. There were five measuring systems that met the minimum performance for 5/5 samples: Arkary, Primus, Roche, Mindray and Tosoh, but none of them achieved the optimum performance. Half of the 196 laboratories that reported IQC and EQA results simultaneously achieved 3σ and minimum performance limits. Further analysis indicated that 88.8%, and 31.6% of the laboratories met the minimum performance for bias and CV, respectively.Conclusions: The biological variation and sigma metrics are appropriate quality management models for evaluating the performance of HbA1c in EQA program. The intra-laboratory and inter-laboratory imprecision need to be improved in order to achieve the required analytical goals for diabetes diagnosis. [ABSTRACT FROM AUTHOR]

The diagnostic work-up for non-small cell lung cancer (NSCLC) requires biomarker testing to guide therapy choices. This article is the second of a two-part series. In Part 1, we summarised evidence-based recommendations for obtaining and processing small specimen samples (i.e. pre-analytical steps) from patients with advanced NSCLC. Here, in Part 2, we summarise evidence-based recommendations relating to analytical steps of biomarker testing (and associated reporting and quality assessment) of small specimen samples in NSCLC. As the number of biomarkers for actionable (genetic) targets and approved targeted therapies continues to increase, simultaneous testing of multiple actionable oncogenic drivers using next-generation sequencing (NGS) becomes imperative, as set forth in European Society for Medical Oncology guidelines. This is particularly relevant in advanced NSCLC, where tissue specimens are typically limited and NGS may help avoid tissue exhaustion compared with sequential biomarker testing. Despite guideline recommendations, significant discrepancies in access to NGS persist across Europe, primarily due to reimbursement constraints. The use of increasingly complex testing methods also has implications for the reporting of results. Molecular testing reports should include clinical interpretation with additional commentary on sample adequacy as appropriate. Molecular tumour boards are recommended to facilitate the interpretation of complex genetic information arising from NGS, and to collaboratively determine the optimal treatment for patients with NSCLC. Finally, whichever testing modality is employed, it is essential that adequate internal and external validation and quality control measures are implemented. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients and clinicians often rely on the outcome of laboratory tests, but can we really trust these test results? Good quality management is key for laboratories to guarantee reliable test results. This review focusses on external quality assessment (EQA) schemes which are a tool for laboratories to examine and improve the quality of their testing routines. In this review, an overview of the role and importance of EQA schemes for clinical laboratories is given, and different types of EQA schemes and EQA providers available on the market are discussed, as well as recent developments in the EQA landscape. External quality assessment (EQA) schemes are a tool for clinical laboratories to evaluate and manage the quality of laboratory practice with the support of an independent party (i.e., an EQA provider). Depending on the context, there are different types of EQA schemes available, as well as various EQA providers, each with its own field of expertise. In this review, an overview of the general requirements for EQA schemes and EQA providers based on international guidelines is provided. The clinical and scientific value of these kinds of schemes for clinical laboratories, clinicians and patients are highlighted, in addition to the support EQA can provide to other types of laboratories, e.g., laboratories affiliated to biotech companies. Finally, recent developments and challenges in laboratory medicine and quality management, for example, the introduction of artificial intelligence in the laboratory and the shift to a more individual-approach instead of a laboratory-focused approach, are discussed. EQA schemes should represent current laboratory practice as much as possible, which poses the need for EQA providers to introduce latest laboratory innovations in their schemes and to apply up-to-date guidelines. By incorporating these state-of-the-art techniques, EQA aims to contribute to continuous learning. [ABSTRACT FROM AUTHOR]

The aim of this study was to establish analytical quality specifications for human semen measurands according to the state of the current methodologies. Measurement errors were estimated based on data from participating laboratories in the External Quality Program (PEEC) led by the Argentine Biochemistry Foundation using the "Analytical Quality Minimum Specifications" model established in Spain for other biochemical collection parameters. Semen samples from the PEEC were analyzed according to WHO procedures. Analytical quality specifications were established according to the most recent results obtained by the External Quality Evaluation Program of the Fundación Bioquímica Argentina. Morphology, progressive motility, total motility and sperm concentration were 75%, 30%, 21% and 43%, respectively, for samples with assigned values between 6 and 15% of normal forms, 35–89% for progressive motility, 43–92% for total motility and for sperm count in the range of 1.8 × 106 –65 × 106 spermatozoa/mL. Our allowable total error specification may affect medical conduct at certain dose levels, compromising clinical test validity. The measurement system employed is closely associated with the number of elements evaluated. The use of manual methods, where the fatigue of the operator counteracts their ability to evaluate a considerable number of elements, leads to errors typical of the poisson and binomial distribution characteristics of these measurands. This work reflects the laboratory performance in our region. The proposed specifications are a statement of minimums that every laboratory should comply with to ensure analytical performance of clinical utility with the current methodology available. [ABSTRACT FROM AUTHOR]

Introduction: Increased albuminuria is associated with elevated mortality. Urine albumin (U-ALB) above 20 mg/L or albumin-to-creatinine ratio (U-ACR) of 3 g/mol are indicative of moderately increased albuminuria. Due to limited standardization among U-ALB methods, diagnosis of increased albuminuria might prove difficult., Materials and Methods: Data from Equalis's external quality assessment scheme for low U-ALB levels during 2005-2023 were categorized according to manufacturer and divided into central laboratory (CLAB) and point-of-care testing (POCT) methods. Manufacturer median values were compared to total group mean consensus values and manufacturer CV% was compared at different U-ALB levels., Results: CLAB was generally closer to consensus values and had lower CV% than POCT at U-ALB levels around 20 mg/L. For CLAB, Roche methods were approximately equal to consensus U-ALB, Abbott 4 % above, and Siemens 5 % below. For POCT, HemoCue was 1 % below, Siemens 7 % above, and Abbott 8 % below. For U-Creatinine, all manufacturers generally had a good agreement differing on average by 1-4 % from consensus., Conclusions: Although U-ALB methods generally meet The National Kidney Disease Education Program (NKDEP) recommendations of method bias less than 13 % and imprecision less than 30 %, differences among manufacturers have increased over the last years, with 2023 showing the largest differences between methods. This highlights the need for guidelines for albuminuria and ACR to take method differences into consideration, but also for implementation of suitable urine reference materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In 2015, U.K. newborn screening (NBS) laboratory guidelines were introduced to standardize dried blood spot (DBS) specimen quality acceptance and specify a minimum acceptable DBS diameter of ≥7 mm. The UK 'acceptable' avoidable repeat rate (AVRR) is ≤2%. To assess inter-laboratory variability in specimen acceptance/rejection, two sets of colored scanned images ( n = 40/set) of both good and poor-quality DBS specimens were distributed to all 16 U.K. NBS laboratories for evaluation as part of an external quality assurance (EQA) assessment. The mean (range) number of specimens rejected in the first EQA distribution was 7 (1-16) and in the second EQA distribution was 7 (0-16), demonstrating that adherence to the 2015 guidelines was highly variable. A new minimum standard for DBS size of ≥8 mm (to enable a minimum of six sub-punches from two DBS) was discussed. NBS laboratories undertook a prospective audit and demonstrated that using ≥8 mm as the minimum acceptable DBS diameter would increase the AVRR from 2.1% (range 0.55% to 5.5%) to 7.8% (range 0.55% to 22.7%). A significant inverse association between the number of specimens rejected in the DBS EQA distributions and the predicted AVVR (using ≥8 mm minimum standard) was observed (r = -0.734, p = 0.003). Before implementing more stringent standards, the impact of a standard operating procedure (SOP) designed to enable a standardized approach of visual assessment and using the existing ≥7 mm diameter (to enable a minimum of four sub-punches from two DBS) as the minimum standard was assessed in a retrospective audit. Implementation of the SOP and using the ≥7 mm DBS diameter would increase the AVRR from 2.3% (range 0.63% to 5.3%) to 6.5% (range 4.3% to 20.9%). The results demonstrate that there is inconsistency in applying the acceptance/rejection criteria, and that a low AVVR is not an indication of good-quality specimens being received into laboratories. Further work is underway to introduce and maintain standards without increasing the AVRR to unacceptable levels.

Background and Aims: Testing for coagulation factors VIII (FVIII) and IX (FIX) plays significant importance in the diagnostic and treatment of hemophilia A and B. External quality assessment (EQA) scheme aimed to assess the participants' performance of testing for coagulation factors and identify shortcomings in clinical practice. This study aimed to investigate the performance trends of the participating laboratories in China national external quality assessment Scheme (China NEQAS) for FVIII and FIX over a five-year period (2019-2023)., Materials and Methods: A total of ten external quality assessment (EQA) rounds were conducted from 2019 to 2023 in the China NEQAS for FVIII and FIX. The distribution of method, reagent and instrument were calculated. The trends of method- specific inter-laboratory coefficient of variation (CV) and pass rates were analyzed over 5 years. The dilutions for coagulation factor testing were also investigated., Results: All laboratories use one-stage assays to detect FVIII and FIX activity. The inter-laboratory overall CV decreased year by year (10.9 % to 9.3 % for FVIII and 13.5 % to 10.2 % for FIX), and the laboratory pass rate steadily increased (88.0 % to 93.4 % for FVIII and 81.3 % to 92.7 % for FIX). The majority of laboratories employed a single dilution methodology for the assessment of FVIII and FIX activity. The interlaboratory CV was elevated for the Siemens reagent (Actin FSL) during analysis of moderately abnormal FIX concentrations of EQA samples in most batches., Conclusions: The implementation of the external quality assessment has contributed to facilitate the enhancement of testing quality. Chromogenic assay is a supplement to accurate determination when necessary. Laboratories may choose to perform dilution tests or direct assays to identify the presence of inhibitors, particularly when they are suspected., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Thailand National External Quality Assessment Scheme (NEQAS) for HbA1c was established to evaluate the quality of HbA1c assays in Thailand in 2016. Methods: HbA1c results from participating laboratories were compared to the target value assigned by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference system. Results: The pass rates of participating laboratories during 2016–2020 were72–88%. The mean bias ranged between −0.19 and 0.20% of HbA1c. SD ranged from 0.30 to 1.08% of HbA1c. The overall coefficients of variation ranged from 4.46-15.66%. Conclusions: Performance evaluation using IFCC assigned values indicated that different assay methods had an effect on HbA1c results. Participation in external quality assessment programs for HbA1c analysis is essential for improving laboratory quality and benefiting patient management.

Objective To conduct a retrospective analysis of HIV Ag-Ab detection by ELISA in our blood center, so as to provide reference for continuous improvement. Methods The reactive rate of HIV by each reagent, reactive rate of both reagents, re-test rate, concordance rate of initial-repeat test, and reagent utilization rate were counted, and the external quality assessment results were analyzed by PT score and z-ratio. Results The total reactive rate of HIV was 0.15%. The reactive rate by both reagents was 0.02%. The re-test rates, reactive rates, concordance rates and reagent utilization rates of the two reagents were 0.09% vs 0.08%, 0.07% vs 0.06%, 75.86% vs 78.21%, and 114.54% vs 113.92%, respectively. PT score was 100%, and z-ratio of 7 negative samples and 1 positive sample was less than 2, and of 2 positive samples was more than 3. Conclusion The laboratory quality monitoring indicators and external quality assessment can effectively monitor the operation of blood testing laboratory.

The glycoproteins alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) have long been approved as biomarkers for diagnosing and monitoring tumors. International Reference Preparations (IRPs) have been around since 1975. Nevertheless, manufacturer-dependent differences have been reported, indicating a lack of harmonization. This paper analyzes data from 15 external quality assessment (EQA) surveys conducted worldwide between 2018 and 2022. The aim was to gain insight into the longitudinal development of manufacturer-dependent differences for CEA and AFP. In each survey, participating laboratories received two samples with different tumor marker levels. Inter- and intra-assay variability was analyzed and the mean 80% and 90% of the manufacturer collectives were compared to the evaluation criteria of the German Medical Association (RiliBÄK). The median EQA results for CEA revealed manufacturer-dependent differences between the highest and lowest collective of up to 100%; for AFP, the median differences mostly remained below 40%. The coefficients of variation were predominantly low for both markers. We concluded that the current assays for AFP and CEA detection are better harmonized than previously reported. The assays displayed a good robustness; however, a narrowing of the current assessment limits in EQA schemes could further enhance the quality of laboratory testing.

Fast and reliable ethanol assays analysis are used in a clinical context for patients suspected of ethanol intoxication. Mostly, automated systems using an enzymatic reaction based on ethanol dehydrogenase are used. The manuscript focusses on the evaluation of the performance of these assays. Data included 30 serum samples used in the Belgian EQA scheme from 2019 to 2021 and concentrations ranged from 0.13 to 3.70 g/L. A regression line between target concentrations and reported values was calculated to evaluate outliers, bias, variability and measurement uncertainty. A total of 1,611 results were taken into account. Bias was the highest for Alinity c over the whole concentration range and the lowest for Vitros for low concentrations and Cobas 8000 using the c702 module for high concentrations. The Architect and Cobas c501/c502 systems showed the lowest variability over the whole concentration range. Highest variability was observed for Cobas 8000 using the 702 module, Thermo Scientific and Alinity c. Cobas 8000 using the c702 module showed the highest measurement uncertainty for lower concentrations. For higher concentrations, Alinity c, Thermo Scientific and Vitros were the methods with the highest measurement uncertainty. The bias of the enzymatic techniques is nearly negligible for all methods except Alinity c. Variability differs strongly between measurement procedures. This study shows that the Alinity c has a worse measurement uncertainty than other systems for concentrations above 0.5 g/L. Overall, we found the differences in measurement uncertainty to be mainly influenced by the differences in variability. [ABSTRACT FROM AUTHOR]

Results of earlier external quality assessment (EQA) rounds suggested remarkable differences in the sensitivity of SARS-CoV PCR assays. Although the test systems are intended to detect SARS-CoV-2 in individual samples, screening is often applied to sample pools to increase efficiency and decrease costs. However, it is unknown to what extent these tests actually meet the manufacturer's specifications for sensitivity and how they perform when testing sample pools. The sensitivity of assays in routine use was evaluated with a panel of positive samples in a round of a SARS-CoV-2 virus genome detection EQA scheme. The panel consisted of samples at or near the lower limit of detection ("weakly positive"). Laboratories that routinely test sample pools were asked to also analyze the pooled EQA samples according to their usual pool size and dilution method. All participants could detect a highly positive patient-derived sample (>106 copies/mL). Most (96%) of the test systems could detect at least 1,000 copies/mL, meeting the minimum acceptable benchmark, and many (94%) detected the vRNA in a sample with lower concentration (500 copies/mL). The false negative ratio increased to 16 and 26% for samples with 100 and 50 copies/mL, respectively. The performance of most assays met or exceeded their specification on sensitivity. If assays are to be used to analyze sample pools, the sensitivity of the assay and the number of pooled samples must be balanced. [ABSTRACT FROM AUTHOR]

• Classical Youden plots evaluate laboratory results with respect to state of the art. Evaluation limits based on total error do not take into account correlation between data, and have an increased chance of falsely flagging well performing laboratories. • Incorporating elliptical acceptance areas based on maximum allowed variability and maximum allowed variability and bias do take into account correlation between data and keep the chance of falsely flagging well performing laboratories under control. • The approach does not only allow to evaluate individual laboratory results but also method performance. Historically, Youden plots are made of a scatter plot of the results of two EQA samples with an elliptical confidence area around them. Because Youden plots compare individual laboratory results with respect to other laboratories, they intrinsically evaluate with state of the art. In the field of medical laboratory science, analytical performance specifications have been proposed and various EQA providers show these limits on Youden plots by horizontal and vertical lines near the limits of total error. This study shows the weaknesses of these limits of total error and proposes a new approach for drawing acceptance areas on Youden plots. The classical Youden plot is extended with two acceptance areas: A first acceptance area evaluates the reported results with respect to maximum allowed variability, a second acceptance area evaluates the results with respect to maximum allowed variability and bias. The ellipses are calculated using quantiles of the Chi-square and noncentral Chi-square distribution. Results show that the new approach allows evaluating results from individual laboratories and from measurement procedures by comparing the position and overlap of the confidence area and the acceptance areas. It is demonstrated that his approach controls the type I error better than the rectangular limits. [ABSTRACT FROM AUTHOR]

• dPCR protocol investigated measuring hCMV whole virus panels over four years. • First reference measurement procedure for human pathogenic DNA virus quantification. • High reproducibility and trueness confirmed Method for value assignment of viral materials for calibration and quality assurance. • Method has the potential for harmonization of routine hCMV load testing. • Method has the potential to harmonization for routine hCMV load testing. A candidate digital PCR (dPCR)-based reference measurement procedure for quantification of human cytomegalovirus (hCMV) was evaluated in 10 viral load comparison schemes (seven external quality assessment (EQA) and three additional training schemes) organized by INSTAND e.V. over four years (between September 2014 and March 2018). Four metrology institutes participated in these schemes using the same extraction method and dPCR measurement procedure for the hCMV specific target sequence of UL54 gene. The calibration independent reference measurement procedure results from the metrology institutes were compared to the results of the clinical diagnostic laboratories applying hCMV qPCR measurement procedures calibrated to reference materials. While the criteria for the acceptable deviation from the target value interval for INSTAND's EQA schemes is from −0.8 log 10 to +0.8 log 10 , the majority of dPCR results were between −0.2 log 10 to +0.2 log 10. Only 4 out of 45 results exceeded this interval with the maximum deviation of −0.542 log 10. In the training schemes containing samples with lower hCMV concentrations, more than half of the results deviated less than ±0.2 log 10 from the target value, while more than 95% deviated less than ±0.4 log 10 from the target value. Evaluation of intra- and inter-laboratory variation of dPCR results confirmed high reproducibility and trueness of the method. This work demonstrates that dPCR has the potential to act as a calibration independent reference measurement procedure for the value assignment of hCMV calibration and reference materials to support qPCR calibration as well as ultimately for routine hCMV load testing. [ABSTRACT FROM AUTHOR]

[Display omitted] • RT-dPCR capable of reproducible quantification of HIV-1 RNA without calibration. • Viral RNA extraction kits evaluated to measuring viral RNA from whole virus. • Calibration independent procedure used to participate in quality assessment scheme. • Findings demonstrating RT-dPCR could act as a reference measurement procedure. • Potential role to support routine calibration of HIV-1 RNA measurement highlighted. Viral load monitoring in human immunodeficiency virus type 1 (HIV-1) infection is often performed using reverse transcription quantitative PCR (RT-qPCR) to observe response to treatment and identify the development of resistance. Traceability is achieved using a calibration hierarchy traceable to the International Unit (IU). IU values are determined using consensus agreement derived from estimations by different laboratories. Such a consensus approach is necessary due to the fact that there are currently no reference measurement procedures available that can independently assign a reference value to viral reference materials for molecular in vitro diagnostic tests. Digital PCR (dPCR) is a technique that has the potential to be used for this purpose. In this paper, we investigate the ability of reverse transcriptase dPCR (RT-dPCR) to quantify HIV-1 genomic RNA without calibration. Criteria investigated included the performance of HIV-1 RNA extraction steps, choice of reverse transcription approach and selection of target gene with assays performed in both single and duplex format. We developed a protocol which was subsequently applied by two independent laboratories as part of an external quality assurance (EQA) scheme for HIV-1 genome detection. Our findings suggest that RT-dPCR could be used as reference measurement procedure to aid the value assignment of HIV-1 reference materials to support routine calibration of HIV-1 viral load testing by RT-qPCR. [ABSTRACT FROM AUTHOR]

This study examines the imprecision of zinc (Zn) measurements across various clinical detection methods by analyzing the external quality assessment (EQA) data from 2018 to 2022. The findings of this study aim to offer recommendations for enhancing Zn measurements. Participating laboratories were grouped into peer categories based on the detection methods. The robust mean and coefficient of variation (CV) of the samples were calculated following ISO 13528 guidelines. The evaluation criteria for optimal, desirable, and minimum allowable imprecision in Zn estimation are 2.50 %, 5.05 %, and 7.55 %, respectively, based on biological variation. Furthermore, the study examined inter-lab CVs, inter-method bias, and the passing rate. The impact of sample concentration on CVs and the pass rate was also investigated. Over the past five years, 4283 laboratories participated in the EQA program, showing a high pass rate that improved as sample concentration increased. Differential pulse polarography (DPP) demonstrated stable and low CVs (0.61–1.86 %). Although differential pulse stripping (DPS) was less stable than DPP, it still exhibited a low CV (0.71–3.10 %). Graphite furnace atomic absorption spectrometry (GFAAS) and flame atomic absorption spectrometry (FAAS) performed similarly and displayed stable CVs (2.39–4.42 %) within the acceptable range of desirable imprecision (5.05 %). However, the CVs for ICP-MS were unacceptable in three out of the five years (5.28–6.20 %). In 2022, the number of participating laboratories for DDP, DPS, GFAAS, FAAS and ICP-MS is 131, 35, 35, 820 and 72, respectively. This study provides reliable insights into the imprecision of Zn measurements in clinical laboratories. The findings indicate that additional efforts are required to reduce the imprecision of ICP-MS in Zn measurements. [ABSTRACT FROM AUTHOR]

In 2019, the Italian National Institute of Health established an external quality assessment (EQA) program to evaluate the performance of laboratories of collaborative centres participating in the National Early Warning System in hair testing for classical and new psychoactive substances (NPS). The results obtained in the four rounds (2019–2023) and the evolution in hair testing performance for classic drugs of abuse and new psychoactive substances are presented. A total of 11 hair specimens, including 3 blank samples, were prepared by adding different classes of classical and NPS at known concentrations to pre-screened drug-free hair. False negative and false positive results were calculated for the qualitative data evaluation. The quantitative evaluation included the imprecision (as % coefficient of variation, CV%) and the accuracy (as % error, ERR%) of the results with respect to a mean value obtained by reference laboratories and Z-score values were assessed. Over the years, an improvement in false negative results (from 52.4% in the first year to 34.3% in the last one) and false positive results (from 55.0% in the first year to 30.8.% in the last one) was observed. In the first round, the mean ERR% ranged from 6.2% to 112.8% due to NPS determination. However, in the subsequent three rounds, the mean ERR% ranged from 10.4% to 22.4%, The mean CV% in the four rounds was approximately 41.5% (ranging from 44.3% to 53.3%). Between 12.0% and 56.6% of the reported results in all rounds should be considered satisfactory. EQA programs help laboratories to identify and correct problems within their processes by highlighting errors and variations. This ensures that the results produced are accurate and reproducible. • The identification of new psychoactive drugs is a constant challenge for laboratories. • Hair analysis detects past and chronic use of both classic drugs of abuse and NPS. • External quality assessment, a quality tool for evaluating laboratory performance. • EQA programmes are crucial for NPS hair analysis in clinical and forensic settings. [ABSTRACT FROM AUTHOR]

Background The aim of accreditation is to improve quality of care and patient safety. However, studies on the effectiveness of accreditation on clinical outcomes are limited and inconsistent. Comparative studies have contrasted accredited with non-accredited hospitals or hospitals without a benchmark, but assessments of clinical outcomes of patients treated at hospitals undergoing accreditation are sparse. The Faroe Islands hospitals were accredited for the first time in 2017, making them an ideal place to study the impact of accreditation. Objective We aimed to investigate the association between first-time hospital accreditation and length of stay (LOS), acute readmission (AR) and 30-day mortality in the unique situation of the Faroe Islands. Methods We conducted a before and after study based on medical record reviews in relation to first-time accreditation. All three Faroese hospitals were voluntarily accredited using a modified second version of the Danish Healthcare Quality Programme encompassing 76 standards. We included inpatients 18 years or older treated at a Faroese hospital with one of six clinical conditions (stroke/transient ischemic attack (TIA), bleeding gastic ulcer, chronic obstructive pulmonary disease (COPD), childbirth, heart failure and hip fracture) in 2012–2013 designated 'before accreditation'or 2017–2018' after accreditation'. The main outcome measures were LOS, all-cause AR and all-cause 30-day mortality. We computed adjusted cause-specific hazard rate (HR) ratios using Cox Proportional Hazard regression with before accreditation as reference. The analyses were controlled for age, sex, cohabitant status, in-hospital rehabilitation, type of admission, diagnosis and cluster effect at patient and hospital levels. Results The mean LOS was 13.4 days [95% confidence interval (95% CI): 10.8, 15.9] before accreditation and 7.5 days (95% CI: 6.10, 8.89) after accreditation. LOS of patients hospitalized after accreditation was significantly shorter [overall, adjusted HR = 1.23 (95% CI: 1.04, 1.46)]. By medical condition, only women in childbirth had a significantly shorter LOS [adjusted HR = 1.30 (95% CI: 1.04, 1.62)]. In total, 12.3% of inpatients before and 9.5% after accreditation were readmitted acutely within 30 days of discharge, and 30-day mortality was 3.3% among inpatients before and 2.8% after accreditation, respectively. No associations were found overall or by medical condition for AR [overall, adjusted HR = 1.34 (95% CI: 0.82, 2.18)] or 30-day mortality [overall, adjusted HR = 1.33 (95% CI: 0.55, 3.21)]) after adjustment for potential confounding factors. Conclusion First-time hospital accreditation in the Faroe Islands was associated with a significant reduction in LOS, especially of women in childbirth. Notably, shorter LOS was not followed by increased AR. There was no evidence that first-time accreditation lowered the risk of AR or 30-day mortality. [ABSTRACT FROM AUTHOR]

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• Correlation between External Quality Assessment schemes reduces the amount of information that can be drawn. • By modelling the correlation according to different scenarios, the number of samples negated due to correlation can be calculated and the frequency of EQA surveys optimized. No clear rules about the optimal frequency of organizing External Quality Assessment (EQA) rounds exist. More frequent challenges will facilitate faster responses and more reliable statistics. Adding extra samples leads to extra information, but the correlation between results from different samples reduces the extra information from additional samples. Data were used for ALT and Albumin from the RCPAQAP EQA scheme. Every two weeks, laboratories analysed two samples. Correlation between results of different samples was calculated to determine the power of distinguishing poorly from well-performing laboratories. The power was compared to hypothetical cases of no correlation and one-sample-per-week to estimate the number of samples negated due to correlation. Correlation leads to negation of a number of samples, but not more than 50% of samples were negated. The number of negated samples was positively related with the correlation between EQA results. The proposed framework provides a quantitative evaluation of the impact of adding more EQA rounds or samples. A correlation exists and is higher for analyses performed closer in time, but the examples shown here did not show a detrimental effect on correctly evaluating laboratories. [ABSTRACT FROM AUTHOR]

• SARS-CoV-2 nucleic acid amplification tests were assessed for quality in Japan • Agreements were 99.3% and 97.9% for the RNA and full-process controls, respectively • A total of 530/563 (94.1%) laboratories reported correct results • Public health laboratories had higher performance than private sector laboratories • Failure to ensure the limit of detection was the most common cause of error We conducted a nationwide external quality assessment (EQA) study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid amplification testing in Japan. A total of 563 public health and private sector laboratories participated. The EQA samples comprised 6 RNA and full-process controls. The overall agreements were 99.3% and 97.9% for the RNA and full-process controls, respectively. A total of 530/563 (94.1%) laboratories reported correct results; public health laboratories had the highest accuracy. Thirty-three laboratories reported at least one incorrect result (26 laboratories of medical facilities, 5 commercial laboratories, 1 public health laboratory, and 1 other). Sixteen laboratories of medical facilities that used a fully automated assay system failed to detect the presence of the full-process control, due to inherent insufficiency in the limit of detection (LOD). Other causes of incorrect results included failure to ensure the LOD (n = 13), error in result judging or reporting (n = 3), and error in sample handling (n = 1). Performance was mostly dependent on the laboratory category and assay evaluation, particularly the LOD. Guidance should be developed based on these results, particularly in the phase of new entry into laboratory services for SARS-CoV-2. [ABSTRACT FROM AUTHOR]

• To guarantee the NIPS reproducibility in laboratories. • Performance validation, enrichment operations, and reporting content should be standardized. Non-invasive prenatal screening (NIPS) has been introduced as a routine screening technique for aneuploidies in the clinic. To evaluate its reliability and reporting standardization, the National Center for Clinical Laboratories launched an external quality assessment (EQA) program based on highly simulated samples. Maternal and child paired cell lines were digested by enzymes to obtain DNA fragments for the analysis panel, which were composed of 5% T21, 5% T18, 10% T13, 10% euploid, and 20% T18 samples. The samples were validated and distributed to laboratories along with scenarios and questionnaires for analysis. Out of 350 participating laboratories, 98.6% correctly identified all samples. The concurrence rates of laboratories for the 5% T21, 5% T18, 10% T13, 10% euploid, and 20% T18 samples were 98.9%, 99.7%, 99.7%, 100%, and 100%, respectively. Enrichment increased the foetal fraction (FF) values by 2 ∼ 3-fold, but the z scores generated by the enrichment group fluctuated greatly. Other FF estimation techniques, such as the size-based and FF-QuantSC methods, generated slightly different FF values from the chr Y-based method. Furthermore, some laboratories omitted the suggestions of results in reports. The participating laboratories provided highly reliable results for samples with relatively higher FF values. However, the absence of performance validation, laboratory errors, and low FF values were potential reasons for false-negative results. In addition, enrichment operations should be validated and normalized to guarantee NIPS reproducibility, plus further efforts are required to standardize the NIPS reports. [ABSTRACT FROM AUTHOR]

The importance of laboratory performance evaluation in qualitative and interpretative proficiency testing (PT) and external quality assessments (EQA) has increased significantly over recent years. Unfortunately, the relevant ISO standards provide limited guidance on how these assessments could be harmonised. In 2014, the Eurachem PT Working Group performed an initial survey on current practices applied by PT/EQA providers in these areas. This paper presents the results of this survey along with the findings of an extensive literature review on the subject extended to 2020. Both the survey results and the literature search show that, even though a majority of scoring systems are based on simple yes/no or absence/presence responses, multiple types of performance evaluation criteria are in use for qualitative and interpretative PT/EQA schemes. This represents a clear disadvantage compared to the more aligned approach in quantitative PT/EQA schemes since laboratory proficiency between schemes is not as easily comparable. The paper presents current practices and scoring systems grouped by categories with defined criteria and may serve as a basis for further discussion and investigation towards the harmonisation of performance evaluation in qualitative and interpretative PT/EQA schemes. [ABSTRACT FROM AUTHOR]

Background: The accurate measurement of α-fetoprotein (AFP) is critical for clinical diagnosis. However, different AFP immunoassays may yield different results. Appropriate AFP reference materials (RMs) were selected and assigned accurate values for applications with external quality assessment (EQA) programs to standardize AFP measurements., Methods: Forty individual clinical samples and six different concentrations of candidate RMs (Can-RMs, L1-L6) were prepared by the Beijing Center for Clinical Laboratories. The Can-RMs were assigned target values by performing five immunoassays, using WHO International Standard 72/225 as a calibrator, and sent to 45 clinical laboratories in Beijing for AFP measurements. The commutability of all RMs was assessed based on CLSI and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) approaches. Analytical performance was assessed for compliance based on accuracy (total error, TE), trueness (bias), and precision (CV)., Results: The Can-RMs were commutable for all immunoassays using the CLSI approach and for 6 of 10 assay combinations using the IFCC approach. RMs diluted in WHO RM 72/225 were commutable among all assays with the CLSI approach, except for serum matrix (Autolumo vs. Roche analyzer) and diluted water matrix (Abbott vs. Roche/Mindray analyzer), whereas some inconclusive and non-commutable results were found using the IFCC approach. The average pass rates based on the TE, bias, and CV were 91%, 81%, and 95%, respectively., Conclusions: The commutability of the RMs differed between both evaluation approaches. The Can-RMs exhibited good commutability with the CLSI approach, suggesting their suitability for use with that approach as commutable EQA materials with assigned values and for monitoring the performance of AFP measurements.

Background: In recent decades, the analytical quality of clinical laboratory results has substantially increased because of collaborative efforts. To effectively utilize laboratory results in applications, such as machine learning through big data, understanding the level of harmonization for each test would be beneficial. We aimed to develop a quantitative harmonization index that reflects the harmonization status of real-world laboratory tests., Methods: We collected 2021-2022 external quality assessment (EQA) results for eight tests (HbA1c, creatinine, total cholesterol, HDL-cholesterol, triglyceride, alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], and prostate-specific antigen [PSA]). This EQA was conducted by the Korean Association of External Quality Assessment Service, using commutable materials. The total analytical error of each test was determined according to the bias% and CV% within peer groups. The values were divided by the total allowable error from biological variation (minimum, desirable, and optimal) to establish a real-world harmonization index (RWHI) at each level (minimum, desirable, and optimal). Good harmonization was arbitrarily defined as an RWHI value ≤ 1 for the three levels., Results: Total cholesterol, triglyceride, and CEA had an optimal RWHI of ≤ 1, indicating an optimal harmonization level. Tests with a desirable harmonization level included HDL-cholesterol, AFP, and PSA. Creatinine had a minimum harmonization level, and HbA1c did not reach the minimum harmonization level., Conclusions: We developed a quantitative RWHI using regional EQA data. This index may help reflect the actual harmonization level of laboratory tests in the field.

Mutation-specific PCR assays have quickly found their way into laboratory diagnostics due to their capacity to be a fast, easy to implement and high-throughput method for the detection of known SARS-CoV-2 variants of concern (VoCs). However, little is known about the performance of such assays in routine laboratory analysis. The results reported in a recent round of an external quality assessment (EQA) scheme for SARS-CoV-2 mutation-specific PCR were retrospectively analyzed. For the determination of individual variant-specific sequences as well as for the interpretation results for certain virus variants, correct, incorrect, and unreported results were evaluated, and their possible causes were investigated. A total of 34 laboratories participated in this study. For five samples containing the VoC Alpha + E484K, Beta, Gamma, Delta, or B.1.1.318 (as a variant of interest), 848 results for SARS-2-CoV mutation detection were reported, 824 (97.2%, range per sample 88–100%) of which were correct. Melting curve assays gave 99% correct results, real-time RT-qPCR 94%, microarray-based assays 100%, and MALDI-TOF MS 96%. A total of 122/167 (73%) reported results for SARS-CoV-2 variant determination were correct. Of the 45 inconclusive or incorrect results, 33 (73%) were due to inadequate selection of targets that did not allow identification of contemporary VoC, 11 (24%) were due to incorrect results, and one (3%) was due to correct results of mutation-specific PCR. Careful and up-to-date selection of the targets used in mutation-specific PCR is essential for successful detection of current SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]