Next-Generation Patient-Based Real-Time Quality Control Models.

Patient-based real-time QC (PBRTQC) uses patient-derived data to assess assay performance. PBRTQC algorithms have advanced in parallel with developments in computer science and the increased availability of more powerful computers. The uptake of Artificial Intelligence in PBRTQC has been rapid, with many stated advantages over conventional approaches. However, until this review, there has been no critical comparison of these. The PBRTQC algorithms based on moving averages, regression-adjusted real-time QC, neural networks and anomaly detection are described and contrasted. As Artificial Intelligence tools become more available to laboratories, user-friendly and computationally efficient, the major disadvantages, such as complexity and the need for high computing resources, are reduced and become attractive to implement in PBRTQC applications.

Quality and resilience of clinical laboratories in Rwanda: a need for sustainable strategies.

BACKGROUND: Quality healthcare is a global priority, reliant on robust health systems for evidence-based medicine. Clinical laboratories are the backbone of quality healthcare facilitating diagnostics, treatment, patient monitoring, and disease surveillance. Their effectiveness depends on sustainable delivery of accurate test results. Although the Strengthening Laboratory Management Towards Accreditation (SLMTA) programme has enhanced laboratory quality in low-income countries, the long-term sustainability of this improvement remains uncertain. OBJECTIVE: To explore the sustainability of quality performance in clinical laboratories in Rwanda following the conclusion of SLMTA. METHODS: A quasi-experimental design was adopted, involving 47 laboratories divided into three groups with distinct interventions. While one group received continuous mentorship and annual assessments (group two), interventions for the other groups (groups one and three) ceased following the conclusion of SLMTA. SLMTA experts collected data for 10 years through assessments using WHO's StepwiseLaboratory Quality Improvement Process Towards Accreditation (SLIPTA) checklist. Descriptive and t-test analyses were conducted for statistical evaluation. RESULTS: Improvements in quality were noted between baseline and exit assessments across all laboratory groups (mean baseline: 35.3%, exit: 65.8%, p < 0.001). However, groups one and three experienced performance declines following SLMTA phase-out (mean group one: 64.6% in reference to 85.8%, p = 0.01; mean group three: 57.3% in reference to 64.7%, p < 0.001). In contrast, group two continued to enhance performance even years later (mean: 86.6%compared to 70.6%, p = 0.03). CONCLUSION: A coordinated implementation of quality improvement plan that enables regular laboratory assessments to pinpoint and address the quality gaps is essential for sustaining quality services in clinical laboratories.

Main findings: We found that continuous laboratory quality improvement was achieved by laboratories that kept up with regular follow-ups, as opposed to those which phased out these followups prematurely.Added knowledge: This study has affirmed the necessity of maintaining mentorship and conducting regular quality assessments until requisite quality routines are established to sustain laboratory quality services.Global health impact for policy and action: These findings emphasise the significance of instituting a laboratory quality plan, with regular assessments, as policy directives to uphold and enhance quality standards, which benefits both local and global communities, given the pivotal role of laboratories in patient treatment, disease prevention, and surveillance.

[Six Sigma driven QC management in hepatitis C serology]. / La méthodologie six sigma dans la gestion des contrôles de qualité en sérologie de l'hépatite C.

The Westgard quality control (QC) rules are often applied in infectious diseases serology to validate the quality of results, but this requires a reasonable tradeoff between maximum sensitivity to errors and minimum false rejections. This article, in addition to illustrate the six sigma methodology in the QC management of the (anti-HCV Architect®) test, it discusses the main influencing factors on sigma value. Data from low positive and in-kit control materials spreading over 6 months and using four reagent kits, were used to calculate the precision of the test. The difference between the control material reactivity and the cut-off defined the error budget. Sigma values were > 6, which indicates that the method produces four erroneous results per million tests. The application of the six sigma concept made it possible to argue the choice of the new QC strategy (use of 13S rule with one positive control) and to relax the existing QC rules. This work provides a framework for infectious diseases serology laboratories to evaluate tests performances against a quality requirement and design an optimal QC strategy.

Results of a Pilot External Quality Assessment Scheme for Genetic Testing of Newborns with Spinal Muscular Atrophy.

BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Quality assurance of SARS-CoV-2 testing laboratories during the pandemic period in India - An experience from a designated provider laboratory.

PURPOSE: Indian Council of Medical Research (ICMR) initiated an Inter-Laboratory Quality Control testing (ILQC) program for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing. Under this program, SARS-CoV-2 testing laboratories across the country submit specimens to the assigned State Quality Control (SQCs) laboratories for ILQC testing. This study aimed to investigate the performance of public and private SARS-CoV-2 testing laboratories in Delhi and highlights the country's effort in ramping up testing facility with close monitoring of the quality of Covid-19 testing results. METHODS: In the present study, two-years of SARS-CoV-2 testing data is included. During July 2020 through February 2022, a total of 1791 anonymised specimens were received from 56 public and private laboratories. These specimens were processed by reverse transcriptase - polymerase chain reaction (RT-PCR) tests as per National Institute of Virology (NIV) protocol and the results were uploaded on the ICMR quality control/quality assurance (QC/QA) portal without directly conveying the results to respective participating laboratories. This portal generated a final report stating concordance and intimate results to individual laboratories. RESULTS: Among the 1791 specimens, 25 were rejected and the remaining 1766 were tested. Among these specimens 1691 (95.75%) revealed concordance, and 75 (4.24%) were discordant. A total of 29 laboratories had 100% concordance, 21 laboratories had over 90% concordance and six laboratories had over 80% concordance. CONCLUSIONS: The study demonstrates that the establishment of an inter-laboratory comparison program for SARS-CoV-2 testing helped in monitoring quality of SARS-CoV-2 testing in the country.

Critical test result management at Danish hospital laboratories: a national survey.

Critical test results in clinical laboratories are crucial for timely patient care, serving as indicators of potentially life-threatening conditions. Despite their importance, a notable heterogeneity in management practices exists globally. This study investigates the current practices of managing critical results at Danish clinical biochemistry laboratories and identifies areas prone for improvement. A comprehensive online survey was distributed to all 21 Danish clinical biochemistry laboratories regarding their critical result management, including documentation practices, critical limit selection, and quality assurance measures. A total of 17 laboratories (81%) responded. The answers revealed a generally uniform approach to managing critical results, with all laboratories having 24-h reporting, local instructions and using the telephone as communication channel. However, variations were noted in documentation practices and critical limit selection. Notably, 23.5% of the laboratories reported that one out of every ten critical results was not reported, indicating a significant risk of delayed critical results. This is further complicated by the limited use of predefined timeframes for reporting and also, only few laboratories actively monitored response times. The findings emphasize the need for more standardized documentation and evaluation practices to align with international standards and to enhance patient safety. While the laboratories showed a commitment to standardized procedures, the study emphasizes the necessity of a National or Nordic guideline to supplement the ISO 15189:2022. This study is a step towards optimizing critical result management, not only in Danish clinical biochemistry laboratories but also across various laboratory specialties, thereby improving overall laboratory quality, efficiency, and patient safety.

The role of analytical performance specifications in international guidelines and standards dealing with metrological traceability in laboratory medicine.

The goal of metrological traceability is to have equivalent results for a measurand in clinical samples (CSs) irrespective of the in-vitro diagnostic medical device (IVD-MD) used for measurements. The International Standards Organization standard 17511 defines requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples used with IVD-MDs. Each step in metrological traceability has an uncertainty associated with the value assigned to a material. The uncertainty at each step adds to the uncertainty from preceding steps such that the combined uncertainty gets larger at each step. The combined uncertainty for a CS result must fulfil an analytical performance specification (APS) for the maximum allowable uncertainty (umax CS). The umax CS can be partitioned among the steps in a metrological traceability calibration hierarachy to derive the APS for maximum allowable uncertainty at each step. Similarly, the criterion for maximum acceptable noncommutability bias can be derived from the umax CS. One of the challenges in determining if umax CS is fulfilled is determining the repeatability uncertainty (u Rw) from operating an IVD-MD within a clinical laboratory. Most of the current recommendations for estimating u Rw from internal quality control data do not use a sufficiently representative time interval to capture all relevant sources of variability in measurement results. Consequently, underestimation of u Rw is common and may compromise assessment of how well current IVD-MDs and their supporting calibration hierarchies meet the needs of clinical care providers.

Using analytical performance specifications in a medical laboratory.

Analytical performance specifications (APS) are used for the quantitative assessment of assay analytical performance, with the aim of providing information appropriate for clinical care of patients. One of the major locations where APS are used is in the routine clinical laboratory. These may be used to assess and monitor assays in a range of settings including method selection, method verification or validation, external quality assurance, internal quality control and assessment of measurement uncertainty. The aspects of assays that may be assessed include imprecision, bias, selectivity, sample type, analyte stability and interferences. This paper reviews the practical use of APS in a routine clinical laboratory, using the laboratory I supervise as an example.

Analysis of hematology quality control using six sigma metrics.

INTRODUCTION: Clinical laboratories serve a critical role in increasing the efficiency of patient care. Choosing the right test, getting trustworthy results and appropriate interpretation are of utmost importance in improving the patient's well-being. Quality management strategies should be applied in routine patient care because laboratory errors have a major impact on the quality of patient care. In sigma metrics, errors identified are quantified as percentage errors or defects per million (DPM). It aims at improving the quality control (QC) process by forming an appropriate strategy. AIM AND OBJECTIVES: To analyze the internal quality control (IQC) of hematology analytes using the sigma metrics method and to devise the frequency of IQC by the results of six sigma metric analysis. MATERIALS AND METHODS: This study was conducted in a tertiary care center of western India. Internal quality control (IQC) data sets of five analytes- Red Blood Cell count (RBC), Hemoglobin (Hb), Hematocrit (Hct), White blood cell count (WBC), and Platelet count (PLT) were analyzed retrospectively of six months using Beckman Coulter DXH 800 hematology analyzers. RESULTS: The observed sigma value was >6 for Hb, TLC, and PLT, indicating excellent results and requiring no modification in IQC. The Sigma value was between 3 and 4 for RBC and Hct suggested the need for improvement in quality control (QC) processes. No analytes showed a Sigma value of <3. CONCLUSION: Sigma metrics provide a quantitative framework that helps to assess analytic methodologies and can serve as an important self-assessment tool for quality assurance in the clinical laboratory.

Whole blood clotting time: Current practices among Thailand National External Quality Assessment Scheme for blood coagulation member laboratories.

INTRODUCTION: The Thai National Guidelines for Hemostatic Laboratory Testing were established in 2018. The guidelines recommend that the 20-min whole blood clotting time (20WBCT) method be used to diagnose/monitor snake bites. The aim of this study was to survey members of the Thailand National External Quality Assessment Scheme (NEQAS) for Blood Coagulation to investigate the use of 20WBCT testing compared between the 2021 post-guideline and 2007 pre-guideline periods. METHODS: In July 2021, questionnaires were sent from the Faculty of Medicine Siriraj Hospital, Mahidol University to 521 Thailand NEQAS for Blood Coagulation member laboratories to survey their WBCT practices. Current WBCT practices were compared with pre-guideline WBCT practices, and chi-square test (x2) was used to test for differences between groups. RESULTS: Ninety-seven (18.6%) of 521 surveys were returned. Seventy-one laboratories (73.2%) reported knowing about 20WBCT from the Thai national guidelines. The reported average frequency of overall WBCT testing in 2021 was 12.4 times/month. The proportion of laboratories that reported using the 20WBCT test increased from 2.0% in 2007 to 46.4% in 2021 (p < 0.001), and the indications for performing WBCT were virtually unchanged from 2007 to 2021. The proportion of laboratories that reported having problems with WBCT testing decreased from 32.7% in 2007 to 16.5% in 2021. CONCLUSION: Despite our findings that almost three-quarters of respondent laboratories reported knowing about 20WBCT testing from the WBCT guidelines, and that WBCT-specific problems decreased significantly from 2007 to 2021, more work and training is needed to improve WBCT guideline dissemination, understanding, and adherence in Thailand.

A Novel Approach for Routinely Assessing Laboratory Sigma Metrics for a Broad Range of Automated Assays.

BACKGROUND: Sigma metrics have been adapted for the clinical laboratory to incorporate observed accuracy, precision, and total error allowed. The higher the Sigma level for a process, the better performance that process has. A limitation of studies assessing Sigma metrics is that they are performed on a small number of well-controlled systems. METHODS: An algorithm was developed to extract QC data and derive the Sigma metric for 115 analytes from sites connected to the QuidelOrtho E-Connectivity® database. The median of these results was then used to derive the Sigma metric for each assay. RESULTS: In this analysis, 79 out of 115 (68.7%) of the assays assessed achieved 6 Sigma or better and 98 out of 115 (85.2%) achieved 5 Sigma or better. CONCLUSIONS: This study has demonstrated a methodology that can be used to condense Sigma metrics from hundreds of analyzers into a single metric of assay quality. Because these analyzers are running in working laboratories from around the world, this analysis can serve as a baseline for understanding the assay performance achieved in the presence of variabilities such as lab-to-lab, instrument-to-instrument, material handling, environmental conditions, and reagent lot. The significant number of assays demonstrating high Sigma levels did so despite this variation. The ability of the methods reported here to include hundreds of analyzers represents a novel approach for assessing Sigma metrics in clinical laboratories.

Issues in assessing analytical performance specifications in healthcare systems assembling multiple laboratories and measuring systems.

Analytical performance specifications (APS) are usually compared to the intermediate reproducibility uncertainty of measuring a particular measurand using a single in vitro diagnostic medical device (IVD MD). Healthcare systems assembling multiple laboratories that include several IVD MDs and cater to patients suffering from long-term disease conditions mean that samples from a patient are analyzed using a few IVD MDs, sometimes from different manufacturers, but rarely all IVD MDs in the healthcare system. The reproducibility uncertainty for results of a measurand measured within a healthcare system and the components of this measurement uncertainty is useful in strategies to minimize bias and overall measurement uncertainty within the healthcare system. The root mean squares deviation (RMSD) calculated as the sample standard deviation (SD) and relative SD includes both imprecision and bias and is appropriate for expressing such uncertainties. Results from commutable stabilized internal and external control samples, from measuring split natural patient samples or using big-data techniques, are essential in monitoring bias and measurement uncertainties in healthcare systems. Variance component analysis (VCA) can be employed to quantify the relative contributions of the most influential factors causing measurement uncertainty. Such results represent invaluable information for minimizing measurement uncertainty in the interest of the healthcare system's patients.

How clinical laboratories select and use Analytical Performance Specifications (APS) in Italy.

OBJECTIVES: Even if the topic of the analytical quality required to provide laboratory results "fit for purpose" exists since the beginning of the modern medical laboratory, there is the suspect that the expression "Analytical Performance Specifications" (APS) is not well-known. To investigate this aspect a survey was conducted. METHODS: A questionnaire with seven questions related to the knowledge about the topic, the sources of information and the criteria used by the laboratories to set the APS and their applications was prepared. It was distributed to all the clinical pathology laboratories of Lombardy Region (143) and to the members of SIBioC Laboratory Medicine (excluding Lombardy). RESULTS: We received 201 replies: 127 from Lombardy and 74 from the rest of Italy. Fifteen percent declared to ignore the meaning of APS and only 64 % of those knowing the meaning of the term declared to use them in the daily practice. The state-of-the-art was the principle used more frequently to set APS (about 48 %) followed by biological variation (41 %), and APS were typically applied to set goals for Internal Quality Control for selected measurands. Usually imprecision or total error APS were used, much less frequently uncertainty APS. In fact only 27 % of the laboratories declared to have calculated the measurement uncertainty for part or the majority of their measurands. CONCLUSIONS: Even considering the limits of a survey that relies upon self-declarations, it appears clearly that, at list in Italy, there is some work to be done to promote the concept and the use of APS.

A survey of total IgE reference intervals reported by Scandinavian and British medical laboratories - a need for harmonisation.

OBJECTIVES: There appears to be marked discrepancies between total IgE reference intervals (RIs) in use by many laboratories and those recommended by published studies. The aim of this study was therefore to review total IgE RIs currently reported by Scandinavian and British laboratories and to compare these to published RIs identified by a literature review. METHODS: Relevant laboratories were identified by test directories provided by the national accreditation bodies in Norway, Sweden, Denmark and the UK. Total IgE RIs and their sources were acquired by accessing laboratory user handbooks or by an electronic survey. In addition a literature review of published total IgE RI studies was performed. RESULTS: From 172 accredited laboratories providing total IgE analysis, data was acquired from 122 laboratories. An adult upper reference limit between 81 to 150 kU/L was reported by 89% of these. Denmark and Sweden reported the most harmonised RIs whilst Norway and the UK exhibited the least degree of harmonisation. Published adult (n = 6) and paediatric (n = 6) RI studies reported markedly higher upper limits than those currently in use by the laboratories included in this study. There were also large variations in the number of age strata in use for paediatric RIs. CONCLUSION: This study demonstrates large variations in currently utilised IgE RIs by Scandinavian and British accredited laboratories and most report markedly lower RIs than those recommended by recent RI publications. Many laboratories likely utilise outdated RIs and should consider critically reviewing and updating their RIs.

A performance evaluation of sthemO 301 coagulation analyzer and associated reagents.

AIM: The study objective was to evaluate the performance of sthemO 301 system and to compare it with the analyzer used in our university hospital laboratory (STA R Max® 2), for a selection of hemostasis parameters. METHODS: Method comparison (according to CLSI EP09-A3), carryover (according to CLSI H57-A), APTT sensitivity to heparin (according to CLSI H47-A2), HIL level assessment, and productivity were performed using leftover samples from our laboratory (n > 1000). Commercial quality control materials were used to evaluate precision (according to CLSI EP15-A3) and accuracy. The assays tested on sthemO 301 were: PT, APTT (silica and kaolin activators), fibrinogen (Fib), thrombin time (TT), chromogenic and clotting protein C (PC) activity, and von Willebrand factor antigen (VWF:Ag) levels. RESULTS: All intra-assay and inter-assay precision CVs were below the maximal precision limit proposed by the French Group for Hemostasis and Thrombosis (GFHT). Accuracy was verified with bias below GFHT criteria and most Z-scores were between -2 and +2. No clinically relevant carryover was detected. Silica APTT reagent sensitivity to unfractionated heparin was moderate, as expected. Productivity results were consistent over the 10 repeats performed. The overall agreement between the two systems was excellent for all assays, with Spearman rank correlation coefficient all above 0.9 and slopes of Passing-Bablok correlation near 1 and intercepts close to 0. CONCLUSION: For the methods tested, sthemO 301 system met all the criteria to implement a novel coagulation analyzer in the laboratory and result comparability with STA R Max® 2 was good.

Reported Awareness and Adoption of 2021 Estimated Glomerular Filtration Rate Equations Among US Clinical Laboratories, March 2022.

This study includes clinical laboratories that participated in the first general chemistry proficiency testing survey in 2022 to assess awareness and adoption of new equations from the Chronic Kidney Disease Epidemiology Collaboration for estimated glomerular filtration rate (eGFR) that eliminated race-adjustment factors, including one based on creatinine and one based on creatinine and cystatin C.

Canadian Society of Clinical Chemists Harmonized Clinical Laboratory Lipid Reporting Recommendations on the Basis of the 2021 Canadian Cardiovascular Society Lipid Guidelines.

There is limited guidance on laboratory reporting and interpretation of lipids and lipoproteins used in cardiovascular risk stratification. This contributes to inconsistencies in lipid reporting across clinical laboratories. Recently, the Canadian Cardiovascular Society (CCS) published the 2021 CCS guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. A subcommittee of the Working Group on Reference Interval Harmonization of the Canadian Society of Clinical Chemists has developed harmonized lipid reporting recommendations that are aligned with the 2021 CCS guidelines, to improve the standardization of lipid assessment and clinical decision-making. The proposed harmonized lipid reporting recommendations were critically reviewed by a broad range of laboratory and clinical experts across Canada. Feedback from approximately 30 expert reviewers was reviewed by the Working Group on Reference Interval Harmonization lipid subcommittee, and consensus decisions were incorporated into the 2021 harmonized lipid reporting recommendations. In this position statement, we provide 6 recommendations for laboratory reporting of lipid parameters. These recommendations include implementing the new National Institutes of Health equation to replace the Friedewald equation for calculating low-density lipoprotein cholesterol, offering lipoprotein (a), either as an in-house or send-out test, and using assays that report lipoprotein (a) in molar units (nmol/L). We also developed a harmonized lipid reporting format with interpretive comments that includes flagging results based on screening patients using treatment decision thresholds in a primary prevention setting. Overall, harmonized lipid reporting will help bridge the gap between clinical guideline recommendations and clinical laboratory reporting and interpretation, and will improve cardiovascular risk assessment across Canada.