Improve Laboratory Performance Research Articles

An Integrated DAIDS Laboratory Oversight Framework: Application of the DAIDS GCLP Guidelines.

The Division of AIDS (DAIDS) Good Clinical Laboratory Practice (GCLP) Guidelines establish a framework to guide the oversight of laboratories supporting DAIDS-sponsored clinical research or trials. Compliance with these guidelines promotes data reliability, consistency, validity, and the safety of the clinical research or trial participants and laboratory staff, as well as ensures adherence to regulatory requirements. This article describes the application of the DAIDS GCLP Guidelines, the DAIDS Integrated Laboratory Oversight Framework, and the coordinated efforts of the collaborative oversight team of laboratory experts to support and monitor the performance of over 175 participating laboratories worldwide. Data from two self-administered online surveys conducted in 2017 and 2023 assessed the laboratory staff's experience implementing the GCLP Guidelines. The results of the 2017 survey were instrumental in informing changes to GCLP audit activities and promoting harmonization in the approach to laboratory oversight. A key finding from the 2023 survey results is the preference for hybrid GCLP training encompassing face-to-face and online modules. Overall, both surveys acknowledged satisfaction with applying and implementing GCLP Guidelines. The need to effectively disseminate information about DAIDS laboratory oversight requirements to support the improved implementation of GCLP Guidelines was notable from both survey results. The collaborative team of laboratory experts and the integrated oversight approach promote knowledge-sharing and accountability to support the application of the GCLP Guidelines and compliance monitoring. The systematic implementation of the integrated laboratory oversight activities helped identify valuable lessons for improving laboratory performance and opportunities to strengthen quality oversight for laboratories participating in clinical research or trials. .

Collaborative Study for Iodine Monitoring in Mandatory Direct-Iodized Sauce in Thailand.

Direct iodization in fish sauce, soy sauce, and seasoning sauces plays a crucial role in optimizing the iodine intake of Thailand's people. However, determining the iodine content to ensure that these sauces meet the standard of Thailand's Food and Drug Administration (FDA) is challenging. In this study, all local laboratories equipped with inductively coupled plasma-mass spectrometry (ICP-MS) and with experience in iodine analysis by any analytical method were invited to participate in a hands-on training workshop and two rounds of interlaboratory comparison. The aim was to improve laboratory performance and assess the potential for iodine monitoring for mandatory direct-iodized sauces. All target laboratories participated in this study. The hands-on training workshop harmonized the analytical method and increased the capacity of participating laboratories. Most laboratories (7/8) achieved satisfactory performance for six test samples based on interlaboratory comparison. Samples were extracted by tetramethylammonium hydroxide (TMAH), with the presence of 6% 2-propanol, 0.01% triton X-100, internal standard, and iodine determination in direct-iodized sauces by ICP-MS. The reproducibility standard deviation (SL), after the removal of outlier results for iodine content, was 7-22% iodine at a level of 0.03-4.81 mg/L. Moreover, the Thai FDA's judgment range for official control activities should expand the range of 2-3 mg per 1 L (ppm) by at least 22%.

Total error in lymphocyte subpopulations by flow cytometry-based in state of the art using Spanish EQAS data.

Flow cytometry analyses of lymphocyte subpopulations (T, B, NK) are crucial for enhancing clinical algorithms and research workflows. Estimating the total error (TE) values for the percentage and absolute number of lymphocyte subpopulations using the state-of-the-art (SOTA) approach with real data from an external proficiency testing (EPT) scheme was performed. A comparison with previously published Biological Variability (BV)-based specifications was carried out. A total of 44,998 results from 86 laboratories over 10 years were analysed and divided into two five-year periods (2012-2016) and (2017-2021). Data come from the IC-1 Lymphocytes scheme of the Spanish External Quality Assurance System (EQAS) GECLID Program. This quantitative scheme includes percentages and absolute numbers of CD3+, CD3+CD4+, CD3+CD8+, CD19+, and CD3-CD56+CD16+ NK cells. The percentage of TE was calculated as: |reported value-robust mean|*100/robust mean for each laboratory and parameter. The cut-off for TE is set at 80 % best results of the laboratories. A significant reduction in the SOTA-based TE for all lymphocyte subpopulations in 2017-2021 was observed compared to 2012-2016. The SOTA-based TE fulfils the minimum BV-based TE for percentages of lymphocyte subpopulations. The parameter with the best analytical performance calculated with SOTA (2017-2021 period)-based TE was the percentage of CD3+ (TE=3.65 %). The values of SOTA-based specifications from external quality assurance program data are consistent and can be used to develop technical specifications. The technological improvement, quality commitment, standardization, and training, reduce TE. An update of TE every five years is therefore recommended. TE assessment in lymphocyte subsets is a helpful and reliable tool to improve laboratory performance and data-based decision-making trust.

Abstract TC1-3-1: Ki 67 Ki67 – a clinically relevant biomarker or just nice to have information?

Abstract Ki67 is an immunohistochemical marker indicating the growth fraction of cycling cells from G1 to S-phase in tumor specimens. In breast cancer, Ki67 is a prognostic marker with high values indicating poor outcome. Over the last decades, obstacles for its wide-spread use in clinical practice included lack of methodological standardization and lack of specific cut-off values for clinical decision making, i.e. discrimination of luminal A vs. B early breast cancer (EBC), chemotherapy indication in HR+/HER2- EBC. However, recently, the International Ki67 working group has put forward consensus statements for a standardized methodology. In general, reproducibility of Ki67 values at extreme sides of the spectrum such as 10% or ≥ 35% is much higher than in the intermediate range and quality assurance programs substantially improve laboratory performance. Moreover, clinical utility has also become apparent in two specific settings of HR±/HER2- EBC. First, the monarchE trial evaluating adjuvant abemaciclib in node-positive high-risk disease used a Ki67 cut-off of 20% as a criterion for aggressive disease and as a sole inclusion criterion for patients with 1-3 lymph nodes (cohort2). While data for this cohort have not yet been reported, Ki67 was a strong prognostic factor in the overall trial population with patients with high Ki67 having worse outcome than those with Ki67 < 20%. Benefit from abemaciclib was independent of Ki67 index. Nevertheless, some health authorities included Ki67 in their abemaciclib label as the absolute benefit was greater in tumors with Ki67 ≥ 20%. Second, Ki67 response after a short (2-4 week) preoperative endocrine therapy allows endocrine response assessment by determining Ki67 in the surgical specimen. This information is widely used in drug development. Ki67post 10% has been defined as endocrine response. In the POETIC trial, endocrine response was associated with improved outcome compared to tumors with Ki67 ≥ 10% after 2-weeks of preoperative AI in postmenopausal patients. In the WSG ADAPT trial, patients with 0-3 lymph nodes, Recurrence Score 25 and endocrine response had excellent outcome with adjuvant endocrine therapy alone independent of menopausal status (5-year dDFS ≥ 95%). In postmenopausal women, probability of endocrine response with an AI is around 80% whereas in premenopausal patients with tamoxifen it is only around 40%. Yet, in premenopausal women addition of GnRH substantially improves endocrine response probability reaching about 80% with GnRH and AI as recently shown by interim analysis of the WSG ADAPTcycle trial (about 2500 patients). Endocrine response probabilities seen in the ADAPT trial (≥ 5000 patients) were validated in ADAPTcycle demonstrating clinical validity of this biomarker. In conclusion, Ki67 is a clinically relevant biomarker that can be used for clinical decision making, particularly in HR+/HER2- EBC. As there is no single generally accepted Ki67 cut-off value to discriminate prognostically favorable from aggressive EBC, Ki67 needs to be used in the context of tumor burden and tumor biology. Currently, next to its use in allocating patients to adjuvant abemaciclib in countries where Ki67 index is included in the label, it provides clinically important information after short-term preoperative endocrine therapy regarding endocrine response in HR+/HER2 EBC. Given its easy and inexpensive determination method, its analytical validity within quality assurance programs, and its clinical usefulness, Ki67 needs to be integrated in our biomarker portfolio in EBC. Citation Format: Nadia Harbeck, Torsten Nielson. Ki 67 Ki67 – a clinically relevant biomarker or just nice to have information? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr TC1-3-1.

An external quality assessment feasibility study; cross laboratory comparison of haemagglutination inhibition assay and microneutralization assay performance for seasonal influenza serology testing: A FLUCOP study.

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. 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. 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. 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.

Saliva: An Economic and Reliable Alternative for the Detection of SARS-CoV-2 by Means of RT-qPCR

The current pandemic has generated the search for new reliable and economic alternatives for the detection of SARS-CoV-2, which produces the COVID-19 disease, one of the recommendations by the World Health Organization, is the detection of the virus by RT-qPCR methods from upper respiratory tract samples. The discomfort of the pharyngeal nasopharyngeal swab described by patients, the requirement of trained personnel, and the generation of aerosols, are factors that increase the risk of infections in this type of intake. It is known that the main means of transmission of SARS-CoV-2 is through aerosols or small droplets, which is why saliva is important as a relevant means of detecting COVID-19. In this study, a modified method based on SARS-CoV-2 RNA release from saliva is described, avoiding the isolation and purification of the genetic material and its quantification of viral copies; the results are compared with paired pharyngeal/nasopharyngeal swab samples (EF/EN). Results showed good agreement in saliva samples compared to EF/EN samples. On average, a sensitivity for virus detection of 80% was demonstrated in saliva samples competing with EF/EN samples. The use of saliva is a reliable alternative for the detection of SARS-CoV-2 by means of RT-PCR in the first days of infection, having important advantages over the conventional method. Saliva still needs to be studied completely to evaluate the detection capacity of the SARS-CoV-2 nucleic acid, however, the described process is viable, due to the decrease in materials and supplies, process times, the increment in the sampling and improvement of laboratory performance.

Six Sigma Metrics: An Evolving Indicator of Quality Assurance for Clinical Biochemistry

Introduction: The analytical phase of the total testing process is the one in which the clinical biochemist can directly intervene to improve the quality of tests reporting. The sigma metrics and Operational Process Specification (OPSpec) chart can specify to which category the laboratory belongs. Aim: To apply sigma metrics to analytical process of testing, do the root cause analysis and apply the corrective measures according to Westgard Rules to improve laboratory performance towards the quality assurances. Materials and Methods: This was a retrospective-prospective study carried out in a clinical laboratory of MKCG Medical College and Hospital, Berhampur, Odisha, India, from July 2020 to March 2021. A retrospective secondary data analysis of six months duration was carried out in a clinical chemistry laboratory with a follow-up prospective study for three months. During this period, 16 analytes were tabulated to analyse the Internal Quality Control (IQC). External Quality Control (EQC) for the same analytes were obtained on monthly basis and the sigma metrics was calculated for each analytes. For analytes with sigma value <3, appropriate measures were taken according to Westgard rules to improvise the quality of laboratory investigations. The statistical analysis of sigma metrics was performed in “R” v-3.6.3. Results: Out of total 16 analytes, three analytes at level 1 and two analytes at level 2 Quality control (QC) showed a world class performance whereas four analytes showed a poor performance at both the QC levels with sigma metrics value <3. From Quality Goal Index (QGI) and root cause analysis, the source of error was detected and corrected. Conclusion: The inaccuracy and imprecision of different parameters in the analytical phase of the testing process can be addressed by calculating the sigma metrics and do the root cause analysis. Application of corrective measures according to Westgard rule can improve the laboratory performance towards the quality assurance.

Influence of calibration solutions on the results of available phosphorus measurement in soils

The aim of the study was to compare soil available phosphorus content as determined in a range of diverse soils using calibration solutions prepared with the extractant used for soil samples or distilled water. Location and time of the study. Soil chemical analyses were performed in 2021 with 54 soil samples collected in 2018-2020 of the podsolised chernozem (Luvic Greyzemic Chernozem) and meadow-chernozemic podsolised soil (Luvic Greyzemic Chernozem Colluvic) in the Toguchin district of the Novosibirsk region, Russia, and leached chernozem (Luvic Chernozem) in the Iskitim district of the same region and Pavlovsky district in Altaisky krai, Russia. The samples were collected at undisturbed, arable and abandoned arable sites. Methods. The method used to estimate available soil phosphorus content included extraction of phosphates by 0.5M acetic acid (1:25 soil:extractant ratio). Phosphate solutions (including both stock and working) for constructing the calibration curve were prepared either with the extractant or with the distilled water. Results. The values of soil available phosphorus content were shown to depend on the composition of calibration solutions: when the extractant was used, the values were on average 1,1 times lower as compared with those obtained using the distilled water to construct the calibration curve. The difference was statistically significant (р<0,01) for undisturbed, arable or abandoned arable soils. Conclusions. Solutions used to construct calibration curves for phosphates, including the stock and working ones, should be close in their chemical composition to the solutions used to extract phosphates from soil and hence should be prepared with the same solution as used for extracting phosphates from soil. At the same time a researcher should follow a specific protocol chosen for the analysis. Therefore, the peculiarities of soil chemical analyses should be carefully considered and compared, especially in the long-term surveys or meta-analysis of the spatially and temporally varying data. The use of reference soil standards, both internal and certified external, with known chemical composition, is indispensable for controlling the quality of chemical measurements. Preparation of internal laboratory standard soil samples in sufficient amounts and their routine use in analyses allows to decrease the number of analytical replicates and is a prerequisite for improving laboratory performance and making justified conclusions about soil fertility.

Development of Centrifugation Tool to Improve Laboratory Performance and Problem Solving Skills

This study aims to develop centrifugation tool to improve performance in the laboratory and problem solving skills. The research method used is Research and Development (R&D) with 4D model. The results showed that the developed centrifuge was declared according to the material, had educational value, was durable, precise in measurement, efficient and safe for students based on the responses of teachers and students respectively at 100% and 96.15% with very high criteria. Student performance scores in the laboratory have a distribution close to the average student performance score (91.52). The effectiveness of the application of centrifugation using the students’ worksheet obtained good results in improving problem solving skills with moderate criteria (0.60) and giving moderate effect (0.42). Based on these results, the developed centrifuge was declared effective for improving laboratory performance and problem solving skills. Keywords: centrifuge, student performance, problem solving. Abstrak: Penelitian ini bertujuan untuk mengembangkan alat sentrifugasi untuk meningkatkan kinerja di laboratorium dan keterampilan pemecahan masalah. Metode penelitian yang digunakan adalah metode Research and Development (R&D) dengan model 4D. Hasil penelitian menunjukan bahwa alat sentrifugasi hasil pengembangan dinyatakan sesuai materi, memiliki nilai pendidikan, tahan lama, tepat dalam pengukuran, efisien serta aman bagi siswa berdasarkan tanggapan guru dan siswa masing-masing sebesar 100% dan 96,15% dengan kriteria sangat tinggi. Nilai-nilai kinerja siswa di laboratorium memiliki persebaran yang dekat dengan nilai rata-rata kinerja siswa (91,52). Keefektifan penerapan alat sentrifugasi dengan mengguna¬kan lembar kerja siswa diperoleh hasil yang baik dalam meningkatkan keterampilan pemecahan masalah dengan kriteria sedang (0,60) dan memberikan pengaruh sedang (0,32). Ber¬dasarkan dari hasil tersebut, alat sentrifugasi hasil pengembang¬an dinyatakan efektif untuk meningkatkan kinerja di laboratorium dan keterampilan pemecahan masalah. Kata kunci: alat sentrifugasi, kinerja siswa, pemecahan masalah. DOI: http://dx.doi.org/10.23960/jpmipa/v23i2.pp853-865

Preanalytical errors in a satellite stat laboratory: A Six Sigma analysis of seven years’ data

BackgroundThere have been few reports regarding the frequency and types of preanalytical errors in stat laboratories, in particular those occurring in the satellite laboratory setting. The impact of this error type on laboratory performance in this environment is largely unknown. We assessed the performance of a stat laboratory serving a population of predominantly elderly patients with suspected or established diagnoses of cancer using Six Sigma methodology and compared the results to previous work on this subject. MethodsWe performed an observational retrospective study using data from the period 2013–2020. The clinical setting was a satellite laboratory supporting an outpatient medical clinic. The type and frequency of each type of preanalytical error were compiled and were used to derive the quarterly error rate. Overall and quarterly performance were calculated using Six Sigma methodology. ResultsDuring the study period 1314 preanalytical errors were identified from 247,271 laboratory tests (0.5% of total test volume). There was a steady decrease in the error rate over the course of the study period, ranging from 1.4% in 2013 to 0.14% in 2020, despite a 290% increase in quarterly test volume during this period. The most common error types encountered were order error, hemolysis, collection error, and lab accident. Conclusion1) The overall performance of a satellite laboratory with a stat testing menu is comparable to hospital-based laboratory stat testing. 2) The most frequent error types encountered in satellite laboratory stat testing differ from those found in hospital-based laboratories. 3) There was an overall improvement in laboratory performance based on Six Sigma methodology.

Predicted standard deviation of proficiency testing performance in animal nutrition methods

The empirical correlations of the results of over ten years of a proficiency testing of animal nutritional analysis conducted by Embrapa were evaluated. The results demonstrate the similarity of the Horwitz equation proposal, but it is desirable to use individual equations related to the different analyses performed by the laboratories. Using these equations enables a more realistic assessment of possible systematic errors and analytical processes, improving laboratory performance and providing the most reliable results.

In vivo test-driven upgrade of a time domain multi-wavelength optical mammograph.

A recent upgrade of the time domain multi-wavelength optical mammograph developed by Politecnico di Milano achieved good performance in laboratory tests [Biomed. Opt. Express9, 755 (2018).10.1364/BOE.9.000755]. However, it proved unsatisfactory when in vivo measurements were finally performed. That led to a further upgrade, including the replacement of the time-to-digital converter with a new model, and the related set-up changes. The new instrument version offers improved laboratory performance (as assessed through established protocols: BIP and MEDPHOT) and good in vivo performance (extension of the scanned breast area, repeatability, consistency of estimated tissue composition with physiology). Besides introducing the new set-up and detailing its laboratory and in vivo performance, we highlight the importance of systematic in vivo testing before entering clinical trials.

Quality evaluation of molecular diagnostic tests for astrovirus, sapovirus and poliovirus: A multicenter study

BackgroundAstrovirus (AstV), Sapovirus (SaV) and Poliovirus (PV) are important pathogens that cause infections in children under five years of age. It is a very important task to systematically monitor and evaluate the diagnostic performance of these viruses in clinical laboratories. MethodsIn our study, we performed a multicenter evaluation study among 21 laboratories across China using simulated stool samples spiked with self-designed AstV, SaV and PV pseudoviral particles. ResultsThe testing capability of 80.0% (16/20, AstV), 52.6% (10/19, SaV), and 25.0% (2/8, PV) of the participating laboratories were found to be “competent” in reporting correct results for all samples. The main type of errors were false negatives. None of the laboratories identified the subtypes of AstV and SaV, and six laboratories specifically identified the subtypes of PV. Lacking of well-trained personnel and adequate funding were the main challenges. From the questionnaire results, 55.6% laboratories (10/18) believe that training personnel could improve the laboratory testing performance. ConclusionsThe laboratories showed a competent diagnostic performance for AstV, but inferior diagnostic performances for SaV and PV. Sensitivity of detection and the ability for virus typing should be improved clinically. Professional and standardized personnel training is urgently needed to further improve laboratory performance.

Ongoing improvements in laboratory performance of coagulation factors VIII and IX: recent experience from the RCPAQAP

Ongoing improvements in laboratory performance of coagulation factors VIII and IX: recent experience from the RCPAQAP

94P - Two years of BRCA1 and BRCA2 somatic external quality assessment with Gen&Tiss scheme in France

BackgroundTesting for germline BRCA1/2 mutations has an established predictive role in breast and ovarian cancer risk assessment and EQA on germline mutation testing have been performed for a long time. With the European extension of indication for the PARP inhibitors, the screening of tumors first is increasingly important. However, tumoral BRCA1/2 testing is a different analytical process on formalin-fixed, paraffin-embedded (FFPE) material and with some challenging variants as large rearrangements. Validation of the test method and participation in external quality assessment programs are therefore required. MethodsIn the French national quality control programs (Gen&tiss) of 2017 and 2018, laboratories received 5 samples from ovarian cancer patients and 1 educational artificial sample with mutations present at different variant allelic frequencies in BRCA1/2 and a large rearrangement in BRCA1. ResultsThe number of participants was 21 in 2017 and 26 in 2018. The number of labs with severe error was 3 in 2017 (14%) and 4 in 2018 (15%). For BRCA1, the average score remained stable between 2017 [9.6/10 (N=21)] and 2018 [9.6/10 (N=26)]. In both years, 2 laboratories made severe errors (false positive/false negative). In 2017 only 11 laboratories (N=20) identified the educational variant present at 7% VAF. For BRCA2 the score slightly decreased from 9.8/10 (N=22) to 9.4/10 (N=26) and the number of laboratories with severe errors increased from 1 to 3. Half of the laboratories (N=20) detected all three mutations present in the educational sample (VAF 10% to 30%) in the 2017 scheme. In 2018 a large deletion in BRCA1 present in the educational sample was only detected by 4 out of 20 laboratories. Three out of 26 laboratories detected the additional RAD51C variant and none the RAD51D variant. The main methods applied in France focus on BRCA1 and BRCA2 genes and amplification-based enrichment. ConclusionsThe genotype results were very similar between 2017 and 2018: acceptable but there are still more than 14% with severe errors. The limit of detection is a critical point. Few labs are ready to extend testing beyond BRCA1/2 genes. The question of large rearrangements is not yet solved for tumoral screening. EQA on tumoral BRCA1/2 testing is therefore essential to improve laboratory performance. Legal entity responsible for the studyGen&tiss - GFCO and AFAQAP. FundingAstraZeneca. DisclosureAll authors have declared no conflicts of interest.

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

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

External Quality Assurance of Current Technology for the Testing of Cancer-Associated Circulating Free DNA Variants.

Liquid biopsy testing is rapidly emerging as a diagnostic means of identifying circulating free DNA (cfDNA) disease-associated variants. However, the reporting of cfDNA variants remains inconsistent due in part to the application of multiple testing pipelines which raise uncertainty about current cfDNA detection efficiency. External quality assurance (EQA) programs are required to monitor, evaluate and help improve laboratory performance for cfDNA variant detection and in clinical interpretation. This study therefore evaluated the performance of diagnostic laboratories currently performing cfDNA testing in China, Australia and New Zealand. A total of 89 laboratories participated in this EQA program. Reference testing material comprised of cfDNA manufactured to contain six different genotypes in four different genes (EGFR, KRAS, BRAF, NRAS). The predicted genotypic variant allelic frequencies ranged between 0.5% - 2.5%. Proficiency testing used a z-score on the laboratory consensus allelic frequency data to compare laboratory performance for the detection of the different genotypes. Allelic frequency genotyping data were received from 88 of the 89 laboratories. Next generation sequencing and digital PCR testing platforms were primarily used by participants in this pilot EQA. The average consensus data for each cfDNA genotype identified allelic frequencies ranging between 0.39% - 4.4%. Z-score proficiency testing found that >92% of clinical laboratories were concordant for detecting the cfDNA variants. The data from this pilot study suggest that current cfDNA testing platforms can detect cfDNA allelic frequency variants from 0.39% and above with high levels of confidence. In addition, these data highlight the importance of laboratories enrolling on EQA programs so that proficiency in cfDNA diagnostic testing can be determined and potential sources of error identified and addressed.

Five-Year Performance of Improved Open-Graded Friction Course on the NCAT Pavement Test Track

Open Graded Friction Course (OGFC) mixtures are used as the final riding surface on roadways as they offer many benefits, such as reducing hydroplaning, reducing splash and spray behind vehicles for improved driver visibility, improving wet-pavement friction, and reducing surface reflectivity during wet-weather conditions. Despite these benefits, the use of OGFC has diminished over the years due to durability and service-life issues. The typical OGFC pavements in Alabama have exhibited premature distresses (e.g., raveling) after approximately six or seven years in service. Therefore, there is a need to change the current OGFC mix design procedure to improve the mix durability. In this study, three modified OGFC mixtures were designed based on a 12.5-mm OGFC mix design previously approved by the Alabama Department of Transportation (ALDOT) and paved in three test sections (E9A, E9B, and E10) on the National Center for Asphalt Technology pavement test track to evaluate possible changes to ALDOT’s OGFC mix design procedure. The ALDOT-approved mix design lasted less than 20 million equivalent single-axle loads (ESALs) on I-85, a few miles from the test track, whereas the three modified OGFC mixtures lasted more than 20 million ESALs and remained in place for another research cycle (10 millions ESALs) on the test track. The three modified OGFC mixtures also showed improved laboratory performance characteristics compared with those of the ALDOT-approved OGFC mixture. Based on the field and laboratory test results, adjustments made in the three modified OGFC mixtures can potentially improve the long-term field performance of OGFC mixtures in Alabama.

External Quality Assessment (EQA) for Molecular Diagnostics of Zika Virus: Experiences from an International EQA Programme, 2016⁻2018.

Quality Control for Molecular Diagnostics (QCMD), an international provider for External Quality Assessment (EQA) programmes, has introduced a programme for molecular diagnostics of Zika virus (ZIKV) in 2016, which has been continuously offered to interested laboratories since that time. The EQA schemes provided from 2016 to 2018 revealed that 86.7% (92/106), 82.4% (89/108), and 88.2% (90/102) of the participating laboratories reported correct results for all samples, respectively in 2016, 2017, and 2018. The review of results indicated a need for improvement concerning analytical sensitivity and specificity of the test methods. Comparison with the outcomes of other EQA initiatives briefly summarized here show that continuous quality assurance is important to improve laboratory performance and to increase preparedness with reliable diagnostic assays for effective patient management, infection and outbreak control.

The implementation of Xpert MTB/RIF assay for diagnosis of tuberculosis in Nepal: A mixed-methods analysis.

BackgroundTuberculosis (TB) is a major public health problem in low and middle-income countries. Early detection and enrolment of TB cases is a challenge for National TB Programs.ObjectiveTo understand the performance and feasibility for scale-up of Xpert MTB/RIF assay for the TB diagnosis in Nepal.DesignImplementation research employed mixed-method sequential explanatory design. The results of Xpert MTB/RIF assay were analysed in 26 TB diagnostic centres where Xpert machines had been installed before 2015. In-depth interviews and focus group discussions were conducted with stakeholders, purposively selected to represent experiences in centres that were functioning well, poorly or not functioning.ResultsDuring a one-year period in 2015/16, 23,075 Xpert MTB/RIF assays were performed in 21 diagnostic centres with 22,288 people also tested by sputum microscopy. Among these, 77% had concordant (positive or negative) results, demonstrating fair agreement (Kappa score, 0.3) between test results. Test failure and positivity rates in diagnostic centres ranged from 2.6% to 13.4% and 6.5% to 49%, respectively. The number of cartridges per positive result varied from 2.3 to 10.2. Xpert assay was positive in 3314 (15% of all cases) sputum smear microscopy negative cases. Of 4280 bacteriologically confirmed cases by Xpert assay, 355 (8%) were rifampicin resistant. Xpert machines were no longer functioning regularly throughout the year in 5 diagnostic centres. The main barriers for effective implementation of Xpert in Nepal were the lack of: timely supply of cartridges; replacement of damaged modules; maintenance of Xpert machines; and stock verification for timely procurement of cartridges. Inadequate laboratory infrastructure for maintaining functional Xpert equipment further challenges implementation and scale-up.ConclusionThe implementation of Xpert MTB/RIF assay has increased case-finding of TB and MDR-TB in Nepal. However, there is a need to improve laboratory performance and strengthen laboratory infrastructure for optimal utilisation and scale-up of Xpert.