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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]

External quality assessment (EQA) cycles are the smallest complete units within EQA programs that laboratories can use to obtain external assessments of their performance. In each cycle, several samples are distributed to the laboratories registered for participation, and ideally, EQA programs not only cover the examination procedures but also the pre- and post-examination procedures. The properties and concentration range of measurands in individual samples are selected with regard to the intended challenge for the participants so that each sample fulfils its purpose. This aims to ensure the most significant possible information gain in every cycle using the lowest possible number of EQA samples and thus, under economically optimal conditions. Participants examine samples and the results are reported to the EQA provider, who compares them with the target values for individual measurands in every sample. The EQA provider assesses the laboratory performance, and finally communicates the assessment results to the participant. The participants evaluate the outcomes of the assessment of their examination results and can draw conclusions in the case of both failing and passing and, if necessary, define improvement measures. After completion, each cycle is evaluated by the provider so that limitations and weaknesses of the EQA program can be identified and appropriate measures taken, or to confirm its continued suitability and appropriateness. [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.

The article discusses the importance of External Quality Assessment (EQA) in Laboratory Medicine, highlighting its benefits and challenges. It emphasizes the need for wider recognition and understanding of EQA beyond experts in the field. The authors call for collaboration between EQA providers and users to improve patient care and standards in laboratory practices. The future of EQA involves adapting to new technologies and evolving healthcare practices, with a focus on enhancing patient pathways and diagnostic accuracy. [Extracted from the article]

BackgroundC-reactive protein (CRP) is an established serum biomarker for different pathologies such as tissue injury and inflammatory events. One rising area of interest is the incorporation of low concentrations of CRP, so called high-sensitive (hs-) CRP, in the risk assessment and treatment monitoring of cardiovascular diseases (CVDs). Many research projects and the resulting meta-analyses have reported controversial results for the use of hs-CRP, especially in the risk assessment of CVDs. However, since these analyses used different assays to detect hs-CRP, it is important to assess the current level of assay harmonization.MethodsThis paper analyzes data from 17 external quality assessment (EQA) surveys for hs-CRP conducted worldwide between 2018 and 2023. Each EQA survey consisted of two blinded samples. In 2020 the sample material changed from pooled serum to single-donor samples. The aim was to assess the current status of assay harmonization by a manufacturer-based approach, taking into consideration the clinical decision limits for hs-CRP risk-stratification of CVDs as well as the scatter of results.ResultsOur analyses show that harmonization has increased in recent years from median differences of up to 50% to below 20%, with one exception that showed an increasing bias throughout the observed period. After changing sample materials from pools to single-donor samples, the coefficient of variation decreased to below 10% with one exception. Nevertheless, even these differences in the clinical setting could lead to disparate classification of patients depending on the assay used.ConclusionWhile there was a positive trend towards harmonization, meta-analysis of different risk-score publications should stratify their analysis by assay to account for the manufacturer-specific differences observed in this paper. Furthermore, assays are currently traceable to different international standard preparations, which might have a negative impact on future harmonization.

The S-score is a new performance score applicable to proficiency testing (PT) for binary data. It allows the proficiency test provider to choose how the assigned value (AV) is defined, e.g., positive versus negative, either by the PT provider or by laboratory consensus based on participating laboratories. It is a flexible tool that can be used to select as a maximum four types of proficiency test items (PTIs) depending on the required correct results and expected correct results predefined by the PT provider. Regarding the required correct results, for an easy tasks, e.g., easy analyte detection, correct results matching with the assigned value are required for all PTI1s. For difficult tasks, e.g. close to the limit of detection (LOD) with replicated samples and for mixed tasks with unreplicated, an acceptable range of correct results is required using the binomial probability density from at least six PTI2s. Regarding correct results expected but not required for difficult tasks, results matching with the assigned value are requested by the PT provider for all PTI3s and by a participating laboratory consensus (LC) for all PTI4s. The S-score was designed as a numerical indicator taking into account all the combinations of the different types of PTIs. The decimal part summarizes the laboratory results indicating the rate of incorrect results in relation to the different PTIs assigned values. The integer part provides a similar interpretation to the one of the z-score for quantitative PT, with 'satisfactory' (1 ≤ S-score < 2), 'questionable' (2 ≤ S-score < 3), and 'unsatisfactory' (S-score ≥ 3) performance, respectively. [ABSTRACT FROM AUTHOR]

In May, 2023, the International Organization for Standardization (ISO) and the International Electrotechnical Commission (IEC) published the international standard ISO/IEC 17043:2023 Conformity assessment—General requirements for the competence of proficiency testing providers. This article describes the 100 % online revision process from the perspective of the Working Group (WG) members, explains the latest changes, and explores the potential impact of these changes on interested parties. [ABSTRACT FROM AUTHOR]

For the accreditation according ISO/IEC 17025, the participation in the interlaboratory comparisons and proficiency testing is required as long as there exist suitable reference devices and providers. In order to contribute to the developments in this area, we have recently developed a new device, which can be used for the assessment of the test capabilities of laboratories for IEC 61000-4-4 (EFT/Burst Immunity). In this publication, we present the whole project of the proficiency testing for this EMC test standard: From the design of the reference equipment and its capability for identifying erroneous testing, to the interlaboratory comparison realized in Switzerland in 2023, including all the details on the evaluation procedure for the proficiency assessment, the results and the benefits for the community. This paper proves how proficiency testing, as shown in the case of Burst Immunity, can contribute to the quality of EMC testing.

This paper presents the results of two proficiency testing (PT) rounds conducted by the Export Inspection Agency (EIA) Chennai laboratory in 2021 for food testing laboratories in India. The PT program was designed in accordance with ISO/TS 22117, a standard for proficiency testing in food microbiology, and targeted Listeria monocytogenes and Salmonella spp as the organisms of focus. The samples were found to be stable and recoverable during the analysis, and all PT sample packages were delivered to participant laboratories in good condition. The participant laboratories reported high sensitivity rates of 100% for PT round 061021 M and 96.49% for PT round 050721 M. The accuracy rate in PT round 061021 M was 91.89% and 92.10% in case of PT round 050721 M. However, there were some false positive and false negative results reported by some participant laboratories in both PT rounds, which may have been caused by operational errors or inconsistencies in analysis. During the PT round 061021 M, out of a total of 38 participant laboratories, five laboratories reported false positive results and one laboratory reported a false negative result. Similarly, during the PT round 050721 M, six laboratories reported false positive results which resulted in their results being deemed unsatisfactory. [ABSTRACT FROM AUTHOR]

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.

This article presents the results of the interlaboratory comparison (ILC) study of the following four characteristics of ceramic tile adhesives (CTAs): initial tensile adhesion strength, tensile adhesion strength after heat ageing, tensile adhesion strength after immersion in water, and tensile adhesion strength after freeze–thaw cycles. The results showed that the objective of the ILC was achieved—the z-score analysis carried out following ISO 13528 allowed for classifying all results obtained by 23 laboratories out of 27 as satisfactory. The results of the remaining four laboratories were rated worse. Despite the achieved goal, the ILC notes high heterogeneity of the results in terms of failure patterns, as well as significant differences between the lowest and the highest values of tensile adhesion strength for various measurement conditions. The results of the ILC were discussed in terms of the possibility of including them in the risk analysis conducted by the manufacturer. The results of the ILC are also valuable information for market surveillance authorities, who, in the authors' opinion, should be more cautious about results on samples taken from the market. The ILC results for CTAs are also a valuable recommendation for a possible revision of EN 12004. [ABSTRACT FROM AUTHOR]

Glucometer is the most commonly used POCT device and guides monitoring of blood glucose level in both clinical settings and outside. Inaccurate glucometer readings resulting in erroneous therapeutic intervention has critical consequences on patient care. Regulatory guidelines for performance evaluation of glucometers are not available in many countries. A robust program implemented by the hospital is essential to ensure accuracy and precision of glucometers to produce optimal results. The objective of this study was to design a quality assurance program for the evaluation of glucometers in a high volume tertiary care referral hospital and evaluate the results from July'18 to July'19. Seventy three glucometers used across the hospital were subjected to Internal Quality Control checks and Proficiency Testing performed once a month and every 3 months respectively. The results were reviewed and plotted on a Bland Altman Graph. Clarke Error Grid Analysis was done to evaluate the clinical significance of inaccuracies in the measurement of blood glucose concentration as per ISO 15197: 2013. Eight devices were identified as unacceptable by ISO standards and replaced subsequently. 96.83% and 3.17% of the values were in Zone A and B of Clarke Error Grid Analysis. The study complied with the standard which requires that 99% of the values fall within zones A and B. The review of the program after one year and its ability to identify defective glucometers has validated the efficacy of the model. The method used may be suggested as a prototype for quality management of glucometers in a clinical setting. [ABSTRACT FROM AUTHOR]

Background: C-reactive protein (CRP) is an established serum biomarker for different pathologies such as tissue injury and inflammatory events. One rising area of interest is the incorporation of low concentrations of CRP, so called high-sensitive (hs-) CRP, in the risk assessment and treatment monitoring of cardiovascular diseases (CVDs). Many research projects and the resulting meta-analyses have reported controversial results for the use of hs-CRP, especially in the risk assessment of CVDs. However, since these analyses used different assays to detect hs-CRP, it is important to assess the current level of assay harmonization., Methods: This paper analyzes data from 17 external quality assessment (EQA) surveys for hs-CRP conducted worldwide between 2018 and 2023. Each EQA survey consisted of two blinded samples. In 2020 the sample material changed from pooled serum to single-donor samples. The aim was to assess the current status of assay harmonization by a manufacturer-based approach, taking into consideration the clinical decision limits for hs-CRP risk-stratification of CVDs as well as the scatter of results., Results: Our analyses show that harmonization has increased in recent years from median differences of up to 50% to below 20%, with one exception that showed an increasing bias throughout the observed period. After changing sample materials from pools to single-donor samples, the coefficient of variation decreased to below 10% with one exception. Nevertheless, even these differences in the clinical setting could lead to disparate classification of patients depending on the assay used., Conclusion: While there was a positive trend towards harmonization, meta-analysis of different risk-score publications should stratify their analysis by assay to account for the manufacturer-specific differences observed in this paper. Furthermore, assays are currently traceable to different international standard preparations, which might have a negative impact on future harmonization., 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 authors 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., (Copyright © 2024 Weiss, Vierbaum, Kremser, Kaufmann-Stoeck, Kappler, Ballert, Kabrodt, Hunfeld and Schellenberg.)

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.

A long-term, envisioned, objective of the Customs laboratories (CLEN), is the acquisition of harmonization of tasks and laboratory practices and procedures. One such task was the enrichment of the CLEN methods with their performance characteristics (PChs).The aim of this investigation was to define a valid statistical estimation procedure of the (PChs) (Repeatability and Reproducibility limits) from existing Proficiency Testings’ (PT) data, whose implementation could become the basis for all the other CLEN methods.The procedure was based on the estimation of the in-between reproducibility, considered to represent the systematic error of all the variations between and within laboratory, promoting thus Harmonization.There was no rejection of any data and hence, there was no need to follow any statistical rejection rules. The effectiveness and validity of the results was assessed and supported by the conformance to the AOAC minimum analytical requirements and the verification to the comparison with standard methods.The estimation and evaluation of data for the Butyric Methyl Esters (BAME) and Total fat in biscuits and chocolates, were found to be for BAME at concentration range (1.7–4.0)%m/m, repeatability (r) 0.14 and Reproducibility (R) 0.38 and Total fat at concentration range (10–20)%, repeatability (r) 0.28 and Reproducibility (R) 0.84 and for Total fat at concentration range (20–30)%, repeatability (r) 0.48 and Reproducibility (R) 1.07,though, in the milk products of high protein content, for (BAME) and Total Fat below 1.5%, methods, gave not conforming results. It is suggested that implementation of this estimation procedure will be of great benefit for CLEN laboratories, not only for the method acceptance, but for further investigation in different matrices, aiming to amendments and hence Harmonization. It is proposed that this procedure is reliable and can be implemented to any CLEN method, provided that sufficient PT data are available.

Data processing of microbial enumeration expressed as colony counts requires the use of specific statistical approaches due to the particular aspect of the analyte and the consideration of the variability related to the growth of microorganisms. A challenging matter in the organization of proficiency testing (PT) schemes for water microbiology is to provide representative, homogeneous and stable enough samples with the aim of assessing participants' performance but also characterizing the accuracy of measurement. As a consequence, the proficiency testing design may help to make clear distinction between the different sources of variation and facilitate the subsequent error analysis associated with the analytical procedures of the participants. Besides, the statistical tools may be selected to provide explicit outcomes which enable the participants to interpret the data in line with other existing indicators such as those arising from validation studies or measurement uncertainty procedures in the laboratory quality assurance system. In this paper, the suitability of a Poisson–Gamma hierarchical generalized linear model is tested in order to evaluate the interlaboratory error, the batch homogeneity and the repeatability error from water microbiology PT. A probabilistic approach deriving from the negative binomial distribution is proposed for assessing the participating laboratories performance in terms of generalized z-score. [ABSTRACT FROM AUTHOR]

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.)

The Asia Pacific Metrology Program (APMP) and the Asia Pacific Laboratory Accreditation Cooperation (APLAC) joint Proficiency Testing (PT) programs for toxic elements such as cadmium (Cd) and lead (Pb) or nutritional elements such as iron (Fe) and zinc (Zn) in food were organized by the Korea Research Institute of Standards and Science (KRISS) with the aim of enhancing the quality of measurement and metrological traceability in various economies of the Asia Pacific region by evaluating the performance with rigorous evaluation. Three APMP-APLAC joint PT programs for elemental analyses were carried out by KRISS sequentially, where candidate certified reference materials (CRMs) were used as the PT materials and metrologically traceable certified reference values (RVs) were used as the PT assigned values for the evaluation of participants' results, which allows reliable evaluation of participant performance. This article describes the operation of the PTs and the overall performance of the participating laboratories. The effectiveness of these joint PT programs and trends in PT performance assessment are also discussed. These PT programs confirm the significant importance of using the metrologically traceable RVs instead of the consensus values from participants as the PT assigned value for reliable assessment. The lack of understanding of the concept of coverage factor, degree of freedom, standard uncertainty, and expanded uncertainty was revealed by some participants in these PT programs. Interpreting the zeta-scores or E n scores, which are derived by using measurement uncertainties, in conjunction with the z-scores is highly meaningful for assessing participants' ability in measurement capabilities and measurement uncertainty evaluation. Assessment of participants' performance considering measurement uncertainties helps the participants to check how reasonable their measurement uncertainty estimation was. The results of PTs also demonstrated that these PT programs are useful for improving the measurement capability of the laboratories, whereas more capability-building in uncertainty evaluation is required for further improvement. [Display omitted] • The three APMP-APLAC joint PT programs were carried out sequentially with better regional linkage between NMIs and laboratories. • The metrological reference values traceable to SI were applied as the PT assigned reference values(RV). • Not just z -scores, but also ζ-scores and E n scores were calculated to assess the reported results. • The performance assessment considering measurement uncertainties helps participants to check their uncertainty estimation. [ABSTRACT FROM AUTHOR]

The Asia Pacific Metrology Program (APMP) and Asia Pacific Laboratory Accreditation Cooperation (APLAC) joint proficiency testing (PT) program was established to improve the ability of quantitative analysis and enhance the quality of the PT program through a better regional linkage between the national metrology institutes (NMIs) and the accreditation bodies (ABs) in the Asia-Pacific region. The first APMP-APLAC joint PT was carried out to quantify hazardous elements Cd and Pb in kimchi cabbage powder, where a candidate certified reference material (CRM) was used as the PT material. A total of 83 laboratories from 37 countries registered, of which 73 laboratories submitted their results. Certified reference values (RVs) provided by Korea Research Institute of Standards and Science (KRISS) were used to evaluate the z -scores ( z ) of participants' results. This program confirms significant importance of the use of metrologically traceable RVs as PT assigned values for rigorous evaluation and reliable assessment. [ABSTRACT FROM AUTHOR]

Results of proficiency testing (PT) undertaken to assess the analytical skills in Japanese laboratories are presented. The PT was coordinated jointly by the National Metrology Institute of Japan (NMIJ) and the National Food Research Institute (NFRI), in which the determination of As, Cd, Fe, Mn and Zn in a dried powdered squid powder was carried out in compliance with the international standard ISO/IEC 17043:2010. A prescribed protocol for the determination of the moisture content of the sample was given to the participants beforehand. Any sample preparation/extraction methods were not prescribed, and a variety of methods was thus applied by the 118 participants. Reported results were assessed using the E n -number and z -score approaches in accordance with ISO/IEC 17043 and the international harmonized protocol for PT. Results of this PT are reviewed in detail, and technical problems leading to some unsatisfactory results are discussed. [ABSTRACT FROM AUTHOR]

Proficiency testing (PT) for the determination of pesticide residues in soybean samples was organized by the National Metrology Institute of Japan (NMIJ). The candidate certified reference material, NMIJ CRM 7509-a, that was prepared from the raw soybeans containing target pesticides (diazinon, fenitrothion, chlorpyrifos, and permethrin) was used as the test sample. Forty participants submitted two sets of analytical results along with the details of the analytical method and conditions they applied. Two types of assigned values were established for each target pesticide: one was derived from the analytical results of the participants, and the other was provided from the analytical results by isotope-dilution mass spectrometry (IDMS). The latter values were 7.4–16% higher than the former values, plausibly because the analytical values from the IDMS measurements were not affected by the recovery ratio of the target pesticides during the analytical process. Thus, two kinds of z -scores were calculated for individual participants using the corresponding assigned values: one ( z 1 -score) showed the relative performance score for the present PT and the other ( z 2 -score) could be used for evaluation of the trueness of their analytical methods. [ABSTRACT FROM AUTHOR]

Abstract: Growth hormone (hGH) is a measurand belonging to ISO category 4, indicating intrinsic unavailability of a reference measurement procedure and primary standard material. Large between-method differences have been raising confusion, especially in the interpretation of results of stimulation tests for exclusion of juvenile growth hormone deficiency. Within the framework of the external quality assessment scheme (EQAS) of the SKML (Dutch Foundation for Quality Assessment in Clinical Laboratories), attempts to reduce between-method variation of hGH measurements have been made, starting in 1994 with an inter-laboratory comparison of 9 different immunoassays by using a panel of sera and standard materials available at that time. Methods appeared to differ from each other largely in a systematic, sample-independent manner. These systematic differences are reflected in the hGH measurement results obtained in commutable sera. A commutable serum pool was introduced as a consensus reference material, permitting correction of each method's results to a common scale. Pair wise comparisons (“twin studies”) were carried out to investigate and corroborate the effectiveness of this material for harmonization. A significant reduction of the between-laboratory coefficient (CV) of variation from 22 to 9.0% was attained. [Copyright &y& Elsevier]

Abstract: Phthalate metabolites are often measured in biomonitoring studies to evaluate a population's exposure to ubiquitous phthalates. During the course of national biomonitoring studies in Canada, we identified an issue with the accuracy of several commercial phthalate metabolite standards that are commonly used in such studies. The validity of the results from these studies was then questioned. Altogether, three (3) large studies were affected, involving a total of 9302 samples and 105000 individual phthalate metabolite measurements. Data from our previous investigation suggested that the inaccuracies in the commercially-available phthalate metabolite standards were compound- and lot-specific. Therefore, an approach was developed to derive correction factors for each lot of phthalate metabolite standard and was applied to the previously-acquired measurements with the goal of obtaining accurate and comparable data. A statistical analysis was performed to support the approach. It is expected that the corrected phthalate metabolite data from all three Canadian biomonitoring studies are comparable to one another. However, caution is still advised when comparing data obtained from biomonitoring studies for which the calibration standards have not been investigated for their accuracy. Suggestions are made based on quality assurance aspects to improve the validity of phthalate metabolite measurements. [Copyright &y& Elsevier]

Abstract: Objectives: Several previous studies have described the effects of interfering substances on clinical assay results; however, the effects of exogenous substances, particularly additives from blood collection tubes on quality control (QC) specimens and serum specimens have not been well examined. This study examines the effects of blood-collection tube additives on total triiodothyronine (TT3), and thyroxine (TT4), cortisol, and routine clinical chemistry tests in QC and serum specimens from apparently healthy volunteers. Methods: QC and serum specimens were poured or collected into different blood collection tubes. TT3 and TT4, cortisol, and routine chemistry tests were analyzed from the different blood-collection tube types. Results: The findings of this study demonstrate statistically and/or clinically significant blood collection tube-related alterations in the TT3, TT4, and cortisol concentrations of QC specimens and TT4 concentrations from serum specimens. Conclusions: These findings have important implications for clinical laboratories, demonstrating that QC specimens should ideally, like patients' specimens, be poured into blood collection tubes. This strategy would reveal any adverse effects caused by blood collection tubes, which otherwise would not likely be detected by most routine QC practices. The results of this study also show the importance of producing blood collection tubes that contain additives that are truly inert and do not adversely affect clinical laboratory testing. [Copyright &y& Elsevier]

Abstract: Background: There is current advocacy for change in Pb proficiency testing (PT) acceptance criterion from ±4μg/dl ([Pb] <40μg/dl; criterion a) to ±2μg/dl ([Pb] <20μg/dl, criterion b). We examined the effect of this proposed change on PT sample pass rates for point-of-care testing (POCT) as predicted by imprecision of POCT PT sample results. Methods: Inter-site standard deviations (s) of POCT PT results were tabulated as a function of [Pb] and characterized as a linear function of [Pb] (r2 >0.8). Given s, predicted minimum, random-error-only PT failure rates (Fp) as a function of [Pb] were computed as the fraction of a normal distribution of results ([Pb]± s) that would fall outside of boundaries of acceptance criterion a or b. Results: For [Pb]=2–20μg/dl, current observed PT sample failure rates using criterion a range from 3 to 6%, which are greater than the predicted minimum failure rates based on s alone (Fp(a)=0–6%). In contrast, predicted minimum failure rates based on s using criterion b are greatly increased (Fp(b)=5–35%). Conclusions: Given the degree of inter-site imprecision among POCT Pb PT results, adoption of criterion b for PT acceptance will dramatically increase Pb PT sample failure rates for POCT due to random-error alone. [Copyright &y& Elsevier]

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Abstract: Chemical oxygen demand (COD) is a critical analytical parameter in waste and wastewater treatment, more specifically in anaerobic digestion, although little is known about the quality of measuring COD of anaerobic digestion samples. Proficiency testing (PT) is a powerful tool that can be used to test the performance achievable in the participants’ laboratories, so we carried out a second PT of COD determination in samples considered “difficult” to analyze (i.e. solid samples and liquid samples with high concentrations of suspended solids). The results obtained (based on acceptable z-score values) may be considered satisfactory. When compared with the results of a previous similar scheme, the overall performance improved by around 30%, again demonstrating that analytical performance can be improved by regular participation in PT. [Copyright &y& Elsevier]

Abstract: In accordance with Article 8 of the European Union (EU) Water Framework Directive (WFD), EU Member States are required to establish monitoring programs for the quality of the surface water and the groundwater within each river-basin district. As such data are the basis for regulatory decisions and measures required to achieve WFD environmental objectives, appropriate analytical quality-assurance and quality-control tools have to be implemented by the monitoring laboratories. In this respect, reference materials (RMs) play a key role. Within the framework of the SWIFT-WFD project (Screening methods for Water data InFormation in support of the WFD), several approaches to the preparation of matrix RMs for the analysis of polycyclic aromatic hydrocarbons and pesticides in water have been used in wide-scale proficiency-testing (PT) schemes. We present the different strategies employed in preparing water-matrix RMs for organic analytes. By reviewing the results from the SWIFT-WFD PT schemes, we reflect on the applicability and the suitability of the different approaches. [Copyright &y& Elsevier]

The estimation of uncertainty in organic elemental analysis for C, H, N and S is reported. Both “bottom up” and “top down” strategies are used for uncertainty calculations. The bottom up approach used the results of C, H, N, and S obtained from the homogeneity study of two pure chemicals (toluene-4-sulfonamide and 4(6)-methyl-2-thiouracil). Two calibration systems, K factor and calibration curve, were applied in this study and no significant differences were obtained. For the “top down” approach, we used the data obtained from a proficiency test on both pure chemicals from among 45 Spanish laboratories. Both approaches are compared and discussed below. [ABSTRACT FROM AUTHOR]

Abstract: An approach to the estimation of possible different sources of variation found in proficiency testing experiments is described. Four errors namely, technique, analyst, laboratory and geographical location are considered and calculated by using a rational experimental design based on hierarchical classification. The treatment of the confidence of the design over different experimental arrangements is explored and visualised by calculating a function that depends only on the design and not on the experimental response. An illustrative example based on simulated data is used to show how the theory could be applied in practice. [Copyright &y& Elsevier]

Background: The objective of external quality assessment is to evaluate clinical acceptability of laboratory results. It is desirable to evaluate intermethod harmonization and traceability to a reference system. Methods: Conventional matrix-modified processed materials are used in most programs, because they can be produced in large quantities, can have multiple abnormal analytes in the same vial and have excellent stability. The principal limitation of these materials is non-commutability which makes them unsuitable for traceability or harmonization evaluation. Peer group evaluation is used which allows an individual laboratory to confirm appropriate use of a measurement technology and a manufacturer to monitor uniformity in their calibration transfer process. Authentic clinical specimen pools provide commutability but are limited by the quantity available and number of analytes at pathologic levels in the same vial. Hybrid approaches have used authentic clinical specimen pools in conjunction with non-commutable processed materials to determine method-specific matrix-corrected target values which have enabled evaluation of traceability to reference methods. Conclusions: Conventional processed materials are limited by non-commutability. Pooled clinical specimens are limited by availability. When used together, external quality assessment can evaluate traceability to reference systems and harmonization between test procedures. [Copyright &y& Elsevier]

In this study, the results obtained by 19 laboratories participating in 2 editions of the interlaboratory comparison (ILC) determining 2 properties of ceramic tiles adhesives (CTAs), i.e., initial tensile adhesion strength and tensile adhesion strength after water immersion following EN 12004, were analyzed. The results show that participating laboratories maintain a constant quality of their work. The use of z-score analysis, under ISO 13528, allows for classifying 89.5% to 100% of laboratories as satisfactory, depending on the measurement's kind and edition. The remaining laboratories are classified as questionable. The investigation of the predominant mode of failure of the CTA's samples tested in the two editions shows significant differences. From the perspective of laboratories, the goal of the ILC has been achieved. From the standpoint of a manufacturer who evaluates a product's properties when placing it on the market, the results indicate the necessity of a particular treatment of the product evaluation process because the variability of the obtained results is significant. It increases the possibility of the product failing to meet the assessment criteria verified by the construction market supervision authorities. The manufacturer must consider all possible variations in the risk analysis, including the ILC results, to improve the assessment process of CTAs. [ABSTRACT FROM AUTHOR]

In this study, the results obtained by 19 laboratories participating in 2 editions of the interlaboratory comparison (ILC) determining 2 properties of ceramic tiles adhesives (CTAs), i.e., initial tensile adhesion strength and tensile adhesion strength after water immersion following EN 12004, were analyzed. The results show that participating laboratories maintain a constant quality of their work. The use of z-score analysis, under ISO 13528, allows for classifying 89.5% to 100% of laboratories as satisfactory, depending on the measurement's kind and edition. The remaining laboratories are classified as questionable. The investigation of the predominant mode of failure of the CTA's samples tested in the two editions shows significant differences. From the perspective of laboratories, the goal of the ILC has been achieved. From the standpoint of a manufacturer who evaluates a product's properties when placing it on the market, the results indicate the necessity of a particular treatment of the product evaluation process because the variability of the obtained results is significant. It increases the possibility of the product failing to meet the assessment criteria verified by the construction market supervision authorities. The manufacturer must consider all possible variations in the risk analysis, including the ILC results, to improve the assessment process of CTAs.

Proper quality assessment of ready-mixed concrete, which is currently the principal material for construction, land engineering and architecture, has an impact on the optimisation and verification of correct functioning of individual stages of the production process. According to the European Standard EN 206 "Concrete–Specification, performance, production and conformity", obligatory conformity control of concrete is carried out by the producer during its production. In order to verify the quality of concrete, investors generally commission independent laboratory units to perform quality assessment of both concrete mix and hardened concrete, which guarantees a high quality of construction works. One of the essential tools for ensuring the quality of test results is the participation of laboratories in the so-called proficiency testing (PT) or inter-laboratory comparisons (ILC). Participation in PT/ILC programmes is, on the one hand, a tool for demonstrating the laboratory's performance, on the other hand an aid for maintaining the quality of available concrete tests and validating test methods. Positive evaluation is a confirmation of the laboratory's capability for performing the tests. The paper presents the results of laboratory proficiency tests carried out by means of inter-laboratory comparisons, as shown in the example of quality assessment of ready-mixed concrete for nine participating laboratories. The tests were performed for concrete of the following parameters: strength class C30/37, consistency S3, frost resistance degree F150, and water resistance degree W8. This involved determining consistencies, air content and density of the concrete mix, and compressive strength of hardened concrete. For the evaluation of laboratory performance results, z-score, ζ-score and En-score were applied. The innovation of the proposed study lies in employing both classical and iterative robust statistical methods. In comparison with classical statistical methods, robust methods ensure a smaller impact of outliers and other anomalies on the measurement results. Following the analyses, clear differences were found between the types of detected discrepancy of test results, which occurred due to the nature of individual parameters. For two laboratories, two scores revealed unsatisfactory results for concrete mix consistency. The main reasons can be pouring into the cone-shaped form a concrete mixture that is too dry, or incorrect use of a measuring tool also creating a possibility that the obtained value can be wrongly recorded. Other possible reasons are discussed in the paper. Participation in inter-laboratory comparison programmes is undoubtedly a way to verify and raise the quality of tests performed for concrete mix and hardened concrete, whereas individual analysis of the results allows the laboratory quality system to be improved. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Newborn screening for biotinidase deficiency can be performed using a fluorometric enzyme assay on dried blood spot specimens. As a pre-requisite to the consolidation of different enzymatic assays onto a single platform, we describe here a novel analytical method for detecting biotinidase deficiency using the same digital microfluidic cartridge that has already been demonstrated to screen for five lysosomal storage diseases (Pompe, Fabry, Gaucher, Hurler and Hunter) in a multiplex format. Methods: A novel assay to quantify biotinidase concentration in dried blood spots (DBS) was developed and optimized on the digital microfluidic platform using proficiency testing samples from the Centers for Disease Control and Prevention. The enzymatic assay uses 4-methylumbelliferyl biotin as the fluorogenic substrate. Biotinidase deficiency assays were performed on normal (n=200) and deficient (n=7) newborn DBS specimens. Results: Enzymatic activity analysis of biotinidase deficiency revealed distinct separation between normal and affected DBS specimens using digital microfluidics and these results matched the expected activity. Conclusions: This study has demonstrated performance of biotinidase deficiency assays by measurement of 4-methylumbelliferyl product on a digital microfluidic platform. Due to the inherent ease in multiplexing on such a platform, consolidation of other fluorometric assays onto a single cartridge may be realized. [Copyright &y& Elsevier]