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Comprehensive genomic profiling (CGP) is increasingly used as a clinical laboratory test and being applied to cancer treatment; however, standardization and external quality assessments (EQA) have not been fully developed. This study performed cost-effective EQA and proficiency tests (PT) for CGP testing among multiple institutions those belong to the EQA working group of Japan Association for Clinical Laboratory Science (JACLS). This study revealed that preanalytical processes, such as derived nucleic acids (NA) extraction from formalin fixed paraffine embedded (FFPE) samples, are critical. First, EQA with extracted DNA from cell lines showed a detection rate of 100% (9 out of 9) in KRAS (c.38G > A; p.G13D), PIK3CA (p.H1047R), and B-Raf proto-oncogene, serine/threonine kinase (BRAF) (c.1799 T > A; p.V600E) in cases of > 10% variant allele frequency (VAF). However, BRAF (c.1799 T > A; p.V600E) detection decreased to 67% (6 out of 9) for a VAF of 4.9%. Second, when DNA was extracted from FFPE samples, pathogenic variants and variants with companion diagnostic indications were detected in all 10 participating laboratories. Each variant had < 20% VAFs on average (8.1–19.1%) and wide variability among laboratories was observed (relative standard deviation, 13–60%). Nonetheless, BRAF (c.1798_1799delinsAA; p.V600K) of 8.1% VAF, EGFR (c.2235_2249del; p.E746_A750del) of 9.7% VAF, and EGFR (c.2254_2277del; p.S752_I759del) of 9.8% VAF were detected with 70% (7/10), 70% (7/10), and 60% (6/10) frequency, respectively. Therefore, 10% VAF in pre-analytic processing for DNA extraction from FFPE was critical for variant detection in CGP analysis. Further, incorrect results were reported in case independent variant calling of BRAF; c.1798_1799delinsAA (p.V600K) was mistakenly interpreted as c.1798G > A, and c.1799 T > A was on the other strand. In conclusion, the EQA/PT among 10 institutes with common samples revealed the importance of VAF in pre-analysis and helped us understand the significance of the pipeline and common pitfalls usually ignored by the internal quality control in a single institute. [ABSTRACT FROM AUTHOR]

Abstract Comprehensive genomic profiling (CGP) is increasingly used as a clinical laboratory test and being applied to cancer treatment; however, standardization and external quality assessments (EQA) have not been fully developed. This study performed cost-effective EQA and proficiency tests (PT) for CGP testing among multiple institutions those belong to the EQA working group of Japan Association for Clinical Laboratory Science (JACLS). This study revealed that preanalytical processes, such as derived nucleic acids (NA) extraction from formalin fixed paraffine embedded (FFPE) samples, are critical. First, EQA with extracted DNA from cell lines showed a detection rate of 100% (9 out of 9) in KRAS (c.38G > A; p.G13D), PIK3CA (p.H1047R), and B-Raf proto-oncogene, serine/threonine kinase (BRAF) (c.1799 T > A; p.V600E) in cases of > 10% variant allele frequency (VAF). However, BRAF (c.1799 T > A; p.V600E) detection decreased to 67% (6 out of 9) for a VAF of 4.9%. Second, when DNA was extracted from FFPE samples, pathogenic variants and variants with companion diagnostic indications were detected in all 10 participating laboratories. Each variant had A, and c.1799 T > A was on the other strand. In conclusion, the EQA/PT among 10 institutes with common samples revealed the importance of VAF in pre-analysis and helped us understand the significance of the pipeline and common pitfalls usually ignored by the internal quality control in a single institute.

As hormonal disorders are linked to several diseases, the accurate quantitation of steroid hormone levels in serum is crucial in order to provide patients with a reliable diagnosis. Mass spectrometry-based methods are regarded as having the highest level of specificity and sensitivity. However, immunoassays are more commonly used in routine diagnostics to measure steroid levels as they are more cost effective and straightforward to conduct. This study analyzes the external quality assessment results for the measurement of testosterone, progesterone and 17β-estradiol in serum using immunoassays between early 2020 and May 2022. As reference measurement procedures are available for the three steroid hormones, the manufacturer-specific biases were normalized to the reference measurement values. The manufacturer-specific coefficients of variation were predominantly inconspicuous, below 20% for the three hormones when outliers are disregarded, however there were large differences between the various manufacturer collectives. For some collectives, the median bias to the respective reference measurement value was repeatedly greater than ±35%, which is the acceptance limit defined by the German Medical Association. In the case of testosterone and progesterone determination, some collectives tended to consistently over- or underestimate analyte concentrations compared to the reference measurement value, however, for 17β-estradiol determination, both positive and negative biases were observed. This insufficient level of accuracy suggests that cross-reactivity continues to be a fundamental challenge when antibody detection is used to quantify steroids with a high structural similarity. Distinct improvements in standardization are required to provide accurate analysis and thus, reliable clinical interpretations. The increased accuracy of the AX immunoassay for testosterone measurement, as observed in the INSTAND EQAs between 2020 and 2022, could be the result of a recalibration of the assay and raises hope for further improvement of standardization of immunoassay-based steroid hormone analyses in the coming years.

Introduction: External Quality Assessment (EQA) schemes are designed to provide a snapshot of laboratory proficiency, identifying issues and providing feedback to improve laboratory performance and inter-laboratory agreement in testing. Currently there are no international EQA schemes for seasonal influenza serology testing. Here we present a feasibility study for conducting an EQA scheme for influenza serology methods. Methods: We invited participant laboratories from industry, contract research organizations (CROs), academia and public health institutions who regularly conduct hemagglutination inhibition (HAI) and microneutralization (MN) assays and have an interest in serology standardization. In total 16 laboratories returned data including 19 data sets for HAI assays and 9 data sets for MN assays. Results: Within run analysis demonstrated good laboratory performance for HAI, with intrinsically higher levels of intra-assay variation for MN assays. Between run analysis showed laboratory and strain specific issues, particularly with B strains for HAI, whilst MN testing was consistently good across labs and strains. Inter laboratory variability was higher for MN assays than HAI, however both assays showed a significant reduction in inter-laboratory variation when a human sera pool is used as a standard for normalization. Discussion: This study has received positive feedback from participants, highlighting the benefit such an EQA scheme would have on improving laboratory performance, reducing inter laboratory variation and raising awareness of both harmonized protocol use and the benefit of biological standards for seasonal influenza serology testing. [ABSTRACT FROM AUTHOR]

Background: Emerging infectious diseases pose an increasing threat to all nations around the world, including to developed countries. By definition, because they are rare or unknown, public health systems are not well prepared against these emerging diseases. To be fully prepared, countries must have implemented surveillance systems to monitor rare or unusual sanitary events. Methods: The capacity of diagnostic laboratories is a key component of surveillance systems since they are in charge of identifying the pathogens responsible for outbreaks in a timely manner. The MediLabSecure project aims at implementing a comprehensive surveillance system for vector-borne diseases around the Mediterranean and Black Sea regions. From 2014 to 2018, the human-virology group of MediLabSecure notably supported the implementation of molecular diagnostic capacities for eight arboviruses and one coronavirus in 19 laboratories of its network through sharing of protocols and reagents, and technical training of the scientific staff of beneficiary laboratories. Results: We report the results of External Quality Assessments for four of these viruses to assess the efficiency of the diagnostic for these threats emerging in the geographic area. The results for these EQA demonstrate the success of the project in the implementation of diagnostic technics for the identification of Dengue, Chikungunya, Zika, and West Niles viruses in laboratories that did not have the capacity before. However, results also show that some work is still to be done to strengthen the newly acquired capacity. Conclusion: The MediLabSecure project deployed an effort to build an efficient capacity in identifying and survey the emergence of arboviruses in the Mediterranean area. Diagnostic technics were successfully implemented in many of the laboratories of the network, but the effort must be maintained over time to strengthen these capacities.

Objective To evaluate the laboratory's NAT ability by analyzing the feedback reports of nucleic acid test (NAT) results of external quality assessment (EQA) of National Center for Clinic Laboratories (NCCL), so as to improve the laboratory management details and ensure blood safety. Methods The data of NCCL NAT EQA of blood screening laboratory of Tianjin Blood Center (a total of five occasions from Jan 2019 to Jun 2021) were statistically analyzed. Results From Jan 2019 to Jun 2021, the laboratory participated in EQA for five times and all the results were qualified. The test results of NAT EQA HIV RNA/HCV RNA/HBV DNA detected by R1, R2 and R4 were consistent with the reference results. R3 showed false positive results (CT value 40.46) in the single donation detection of sample No.1925 in HCV RNA. Unreported data of the laboratory was that in the first EQA in 2021, the R4 showed false positive results (CT value 35.8) in in the single donation detection of sample No.2113 in HIV RNA. Conclusion The performance of each NAT screening system in our laboratory is relatively stable except occasional false positive results influenced by every factor. Potential problems can be found and continuously improved by assaying EQA reports and the extended experimental results of EQA samples to further improve the detection ability.

IntroductionExternal Quality Assessment (EQA) schemes are designed to provide a snapshot of laboratory proficiency, identifying issues and providing feedback to improve laboratory performance and inter-laboratory agreement in testing. Currently there are no international EQA schemes for seasonal influenza serology testing. Here we present a feasibility study for conducting an EQA scheme for influenza serology methods.MethodsWe invited participant laboratories from industry, contract research organizations (CROs), academia and public health institutions who regularly conduct hemagglutination inhibition (HAI) and microneutralization (MN) assays and have an interest in serology standardization. In total 16 laboratories returned data including 19 data sets for HAI assays and 9 data sets for MN assays.ResultsWithin run analysis demonstrated good laboratory performance for HAI, with intrinsically higher levels of intra-assay variation for MN assays. Between run analysis showed laboratory and strain specific issues, particularly with B strains for HAI, whilst MN testing was consistently good across labs and strains. Inter-laboratory variability was higher for MN assays than HAI, however both assays showed a significant reduction in inter-laboratory variation when a human sera pool is used as a standard for normalization.DiscussionThis study has received positive feedback from participants, highlighting the benefit such an EQA scheme would have on improving laboratory performance, reducing inter laboratory variation and raising awareness of both harmonized protocol use and the benefit of biological standards for seasonal influenza serology testing.

For diagnosing SARS-CoV-2 infection and for monitoring its spread, the implementation of external quality assessment (EQA) schemes is mandatory to assess and ensure a standard quality according to national and international guidelines. Here, we present the results of the 2020, 2021, 2022 EQA schemes in Lombardy region for assessing the quality of the diagnostic laboratories involved in SARS-CoV-2 diagnosis. In the framework of the Quality Assurance Programs (QAPs), the routinely EQA schemes are managed by the regional reference centre for diagnostic laboratories quality (RRC-EQA) of the Lombardy region and are carried out by all the diagnostic laboratories. Three EQA programs were organized: (1) EQA of SARS-CoV-2 nucleic acid detection; (2) EQA of anti-SARS-CoV-2-antibody testing; (3) EQA of SARS-CoV-2 direct antigens detection. The percentage of concordance of 1938 molecular tests carried out within the SARS-CoV-2 nucleic acid detection EQA was 97.7%. The overall concordance of 1875 tests carried out within the anti-SARS-CoV-2 antibody EQA was 93.9% (79.6% for IgM). The overall concordance of 1495 tests carried out within the SARS-CoV-2 direct antigens detection EQA was 85% and it was negatively impacted by the results obtained by the analysis of weak positive samples. In conclusion, the EQA schemes for assessing the accuracy of SARS-CoV-2 diagnosis in the Lombardy region highlighted a suitable reproducibility and reliability of diagnostic assays, despite the heterogeneous landscape of SARS-CoV-2 tests and methods. Laboratory testing based on the detection of viral RNA in respiratory samples can be considered the gold standard for SARS-CoV-2 diagnosis. [ABSTRACT FROM AUTHOR]

Emerging infectious diseases pose an increasing threat to all nations around the world, including to developed countries. By definition, because they are rare or unknown, public health systems are not well prepared against these emerging diseases. To be fully prepared, countries must have implemented surveillance systems to monitor rare or unusual sanitary events. The capacity of diagnostic laboratories is a key component of surveillance systems since they are in charge of identifying the pathogens responsible for outbreaks in a timely manner. The MediLabSecure project aims at implementing a comprehensive surveillance system for vector-borne diseases around the Mediterranean and Black Sea regions. From 2014 to 2018, the human-virology group of MediLabSecure notably supported the implementation of molecular diagnostic capacities for eight arboviruses and one coronavirus in 19 laboratories of its network through sharing of protocols and reagents, and technical training of the scientific staff of beneficiary laboratories. We report the results of External Quality Assessments for four of these viruses to assess the efficiency of the diagnostic for these threats emerging in the geographic area. The results for these EQA demonstrate the success of the project in the implementation of diagnostic technics for the identification of Dengue, Chikungunya, Zika, and West Niles viruses in laboratories that did not have the capacity before. However, results also show that some work is still to be done to strengthen the newly acquired capacity. The MediLabSecure project deployed an effort to build an efficient capacity in identifying and survey the emergence of arboviruses in the Mediterranean area. Diagnostic technics were successfully implemented in many of the laboratories of the network, but the effort must be maintained over time to strengthen these capacities. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

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For diagnosing SARS-CoV-2 infection and for monitoring its spread, the implementation of external quality assessment (EQA) schemes is mandatory to assess and ensure a standard quality according to national and international guidelines. Here, we present the results of the 2020, 2021, 2022 EQA schemes in Lombardy region for assessing the quality of the diagnostic laboratories involved in SARS-CoV-2 diagnosis. In the framework of the Quality Assurance Programs (QAPs), the routinely EQA schemes are managed by the regional reference centre for diagnostic laboratories quality (RRC-EQA) of the Lombardy region and are carried out by all the diagnostic laboratories. Three EQA programs were organized: (1) EQA of SARS-CoV-2 nucleic acid detection; (2) EQA of anti-SARS-CoV-2-antibody testing; (3) EQA of SARS-CoV-2 direct antigens detection. The percentage of concordance of 1938 molecular tests carried out within the SARS-CoV-2 nucleic acid detection EQA was 97.7%. The overall concordance of 1875 tests carried out within the anti-SARS-CoV-2 antibody EQA was 93.9% (79.6% for IgM). The overall concordance of 1495 tests carried out within the SARS-CoV-2 direct antigens detection EQA was 85% and it was negatively impacted by the results obtained by the analysis of weak positive samples. In conclusion, the EQA schemes for assessing the accuracy of SARS-CoV-2 diagnosis in the Lombardy region highlighted a suitable reproducibility and reliability of diagnostic assays, despite the heterogeneous landscape of SARS-CoV-2 tests and methods. Laboratory testing based on the detection of viral RNA in respiratory samples can be considered the gold standard for SARS-CoV-2 diagnosis.

Objective: Medical laboratories encounter critical obstacles in External Quality Assessment (EQA) practices that are key to assessment of the analytical period. Present study aims to unveil the challenges in nationwide inter-laboratory harmonization and suggest practical solutions. Materials and methods: EQA results of 1941 laboratories participating in 18 different EQA-programs between 2010 and 2017 were examined. Standard Deviation Index (SDI) of each program calculated using 801,028 sample data from 24 different clinical chemical tests were used to conduct a process assessment. Results: There is a significant discrepancy in unsatisfactory performance ratio among different EAQ-programs with an average of 3.4% (27,074 cases) between 2010 and 2017 and a decreasing trend (~40–50%) in 7-years. Programs with higher SDI display lower discrepancy rates. Reasons for unaccepted results appear to be data entry errors (8.27–22.2%), material dilution errors (5–11.4%), technical problems (3.76–7.9%); while random or unidentified causes account for a major of 44.9–59.5%. In 7-years, 15.7% reduction was observed in average SDI of all tests. Conclusion: With the launch of national EQA follow-up program, increased awareness of the analytical processes led to a decrease in unaccepted results and variances in the analytical period. Staff training is suggested as a significant measure. In addition, simultaneous assessment of SDI and allowable total error rates would reduce the variation between programs. [ABSTRACT FROM AUTHOR]

The increasing incidence of West Nile virus (WNV) in the Euro-Mediterranean area warrants the implementation of effective surveillance programs in animals. A crucial step in the fight against the disease is the evaluation of the capacity of the veterinary labs to accurately detect the infection in animal populations. In this context, the animal virology network of the MediLabSecure project organized an external quality assessment (EQA) to evaluate the WNV molecular and serological diagnostic capacities of beneficiary veterinary labs. Laboratories from 17 Mediterranean and Black Sea countries participated. The results of the triplex real time RT-PCR for simultaneous detection and differentiation of WNV lineage 1 (L1), lineage 2 (L2) and Usutu virus (USUV) were highly satisfactory, especially for L1 and L2, with detection rates of 97.9% and 100%, respectively. For USUV, 75% of the labs reported correct results. More limitations were observed for the generic detection of flaviviruses using conventional reverse-transcription polymerase chain reaction (RT-PCR), since only 46.1% reported correct results in the whole panel. As regards the serological panel, the results were excellent for the generic detection of WNV antibodies. More variability was observed for the specific detection of IgM antibodies with a higher percentage of incorrect results mainly in samples with low titers. This EQA provides a good overview of the WNV (and USUV) diagnostic performance of the involved veterinary labs and demonstrates that the implemented training program was successful in upgrading their diagnostic capacities.

As hormonal disorders are linked to several diseases, the accurate quantitation of steroid hormone levels in serum is crucial in order to provide patients with a reliable diagnosis. Mass spectrometry-based methods are regarded as having the highest level of specificity and sensitivity. However, immunoassays are more commonly used in routine diagnostics to measure steroid levels as they are more cost effective and straightforward to conduct. This study analyzes the external quality assessment results for the measurement of testosterone, progesterone and 17β-estradiol in serum using immunoassays between early 2020 and May 2022. As reference measurement procedures are available for the three steroid hormones, the manufacturer-specific biases were normalized to the reference measurement values. The manufacturer-specific coefficients of variation were predominantly inconspicuous, below 20% for the three hormones when outliers are disregarded, however there were large differences between the various manufacturer collectives. For some collectives, the median bias to the respective reference measurement value was repeatedly greater than ±35%, which is the acceptance limit defined by the German Medical Association. In the case of testosterone and progesterone determination, some collectives tended to consistently over- or underestimate analyte concentrations compared to the reference measurement value, however, for 17β-estradiol determination, both positive and negative biases were observed. This insufficient level of accuracy suggests that cross-reactivity continues to be a fundamental challenge when antibody detection is used to quantify steroids with a high structural similarity. Distinct improvements in standardization are required to provide accurate analysis and thus, reliable clinical interpretations. The increased accuracy of the AX immunoassay for testosterone measurement, as observed in the INSTAND EQAs between 2020 and 2022, could be the result of a recalibration of the assay and raises hope for further improvement of standardization of immunoassay-based steroid hormone analyses in the coming years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Vierbaum, Weiss, Kaiser, Kremser, Wenzel, Thevis, Schellenberg and Luppa.)

This review shows the current analytical quality for the following analytes used as tumour markers in the external quality assessment (EQA)-programmes of Instand e.V., a national EQA-organiser in Germany: Corticotropin (ACTH), growth hormone (GH, hGH), prolactin (PRL), chorionic gonadotropin (CG, hCG), calcitonin (CT, hCT), thyroglobulin (Tg), carcinoembryonic antigen (CEA), CA-Antigens 125, 72-4, 15-3 and 19-9, alpha foetoprotein (AFP) and prostate-specific antigen (PSA). The results from the participants show a large variation in the precision of the methods used as well as in the comparability of results between methods for the same analyte. In general, the hormones used as tumour markers show better performance than the "CA-markers", which are often inadequately standardised and defined. In the case of one CA-marker (CA 72-4/TAG 72-4), the differences between the lowest kit median concentration and highest kit median concentration for one sample pair were 440% and 580%. The corresponding figures for ACTH were 123% and 156% and for CEA 180% and 184%. The classical tumour markers such as carcinoembryonic antigen (CEA) and alpha foetoprotein (AFP) performed markedly better than the CA-markers and PSA with regards to both inter- and intra-method comparability. The inter-laboratory precision for a given kit and marker was acceptable in many cases. The results show that only results from the same kit/method for each tumour marker can be used for cumulative or time-dependent comparison of results - for example pre-operative and post-operative follow up. In the case of prostate specific antigen (PSA), the kits used for free and total PSA must come from the same producer, if the generally accepted ratios are to have any diagnostic value. The need for kit- and laboratory-specific reference ranges and cut-off values for setting diagnostic specificity and sensitivity is highlighted from the EQA-results. The situation for inter-method comparability for the CA-Markers has not improved over the past decade. With the exception of calcitonin for detecting medullary thyroid carcinoma, chorionic gonadotropin in germ-cell tumours in men and thyroglobulin after total thyroidectomy, none of the remaining analytes appear to be suitable for screening purposes.

The increasing incidence of West Nile virus (WNV) in the Euro-Mediterranean area warrants the implementation of effective surveillance programs in animals. A crucial step in the fight against the disease is the evaluation of the capacity of the veterinary labs to accurately detect the infection in animal populations. In this context, the animal virology network of the MediLabSecure project organized an external quality assessment (EQA) to evaluate the WNV molecular and serological diagnostic capacities of beneficiary veterinary labs. Laboratories from 17 Mediterranean and Black Sea countries participated. The results of the triplex real time RT-PCR for simultaneous detection and differentiation of WNV lineage 1 (L1), lineage 2 (L2) and Usutu virus (USUV) were highly satisfactory, especially for L1 and L2, with detection rates of 97.9% and 100%, respectively. For USUV, 75% of the labs reported correct results. More limitations were observed for the generic detection of flaviviruses using conventional reverse-transcription polymerase chain reaction (RT-PCR), since only 46.1% reported correct results in the whole panel. As regards the serological panel, the results were excellent for the generic detection of WNV antibodies. More variability was observed for the specific detection of IgM antibodies with a higher percentage of incorrect results mainly in samples with low titers. This EQA provides a good overview of the WNV (and USUV) diagnostic performance of the involved veterinary labs and demonstrates that the implemented training program was successful in upgrading their diagnostic capacities.

Laboratory preparedness with quality-assured diagnostic assays is essential for controlling the current coronavirus disease (COVID-19) outbreak. We conducted an external quality assessment study with inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples to support clinical laboratories with a proficiency testing option for molecular assays. To analyse SARS-CoV-2 testing performance, we used an online questionnaire developed for the European Union project RECOVER to assess molecular testing capacities in clinical diagnostic laboratories.

This review shows the current analytical quality for the following analytes used as tumour markers in the external quality assessment (EQA)-programmes of Instand e.V., a national EQA-organiser in Germany: Corticotropin (ACTH), growth hormone (GH, hGH), prolactin (PRL), chorionic gonadotropin (CG, hCG), calcitonin (CT, hCT), thyroglobulin (Tg), carcinoembryonic antigen (CEA), CA-Antigens 125, 72-4, 15-3 and 19-9, alpha foetoprotein (AFP) and prostate-specific antigen (PSA). The results from the participants show a large variation in the precision of the methods used as well as in the comparability of results between methods for the same analyte. In general, the hormones used as tumour markers show better performance than the "CA-markers", which are often inadequately standardised and defined. In the case of one CA-marker (CA 72-4/TAG 72-4), the differences between the lowest kit median concentration and highest kit median concentration for one sample pair were 440% and 580%. The corresponding figures for ACTH were 123% and 156% and for CEA 180% and 184%. The classical tumour markers such as carcinoembryonic antigen (CEA) and alpha foetoprotein (AFP) performed markedly better than the CA-markers and PSA with regards to both inter- and intra-method comparability. The inter-laboratory precision for a given kit and marker was acceptable in many cases. The results show that only results from the same kit/method for each tumour marker can be used for cumulative or time-dependent comparison of results - for example pre-operative and post-operative follow up. In the case of prostate specific antigen (PSA), the kits used for free and total PSA must come from the same producer, if the generally accepted ratios are to have any diagnostic value. The need for kit- and laboratory-specific reference ranges and cut-off values for setting diagnostic specificity and sensitivity is highlighted from the EQA-results. The situation for inter-method comparability for the CA-Markers has not improved over the past decade. With the exception of calcitonin for detecting medullary thyroid carcinoma, chorionic gonadotropin in germ-cell tumours in men and thyroglobulin after total thyroidectomy, none of the remaining analytes appear to be suitable for screening purposes.