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En el laboratorio clínico, la calibración de los procedimientos de medición es un aspecto clave a la hora de garantizar la fiabilidad de los resultados del paciente. A lo largo de los años, se han publicado multitud de publicaciones y procedimientos para la evaluación del control de calidad y la interpretación de sus resultados. En esta publicación, nos centraremos en un aspecto crítico, la calibración, ya que no existen publicaciones o directrices claras sobre metodologías de calibración. Por lo general, solo están disponibles las recomendaciones del fabricante del reactivo o instrumento. El propósito de esta revisión es ahondar en esta deficiencia, con el fin de suscitar un debate y mejorar la situación actual.

Calibration of an analytical measurement procedure is an important basis for the reliability of patient results. Many publications and as well as procedures on how to estimate quality control and interpret those results have been become available over the years. In this publication we are focusing on the critical part of the calibration as there are no clear communication or guidelines on how to perform it. Usually only the recommendation of the reagent or instrument manufacturer is available. We would like to point out this gap to invite for a discussion and improvement of the current situation.

Reporting a measurement procedure and its analytical performance following method evaluation in a peer-reviewed journal is an important means for clinical laboratory practitioners to share their findings. It also represents an important source of evidence base to help others make informed decisions about their practice. At present, there are significant variations in the information reported in laboratory medicine journal publications describing the analytical performance of measurement procedures. These variations also challenge authors, readers, reviewers, and editors in deciding the quality of a submitted manuscript. The International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Method Evaluation Protocols (IFCC WG-MEP) developed a checklist and recommends its adoption to enable a consistent approach to reporting method evaluation and analytical performance characteristics of measurement procedures in laboratory medicine journals. It is envisioned that the LEAP checklist will improve the standardisation of journal publications describing method evaluation and analytical performance characteristics, improving the quality of the evidence base that is relied upon by practitioners. [ABSTRACT FROM AUTHOR]

Emerging technology in laboratory medicine can be defined as an analytical method (including biomarkers) or device (software, applications, and algorithms) that by its stage of development, translation into broad routine clinical practice, or geographical adoption and implementation has the potential to add value to clinical diagnostics. Paediatric laboratory medicine itself may be considered an emerging area of specialisation that is established relatively recently following increased appreciation and understanding of the unique physiology and healthcare needs of the children. Through four clinical (neonatal hypoglycaemia, neonatal hyperbilirubinaemia, sickle cell disorder, congenital adrenal hyperplasia) and six technological (microassays, noninvasive testing, alternative matrices, next generation sequencing, exosome analysis, machine learning) illustrations, key takeaways of application of emerging technology for each area are summarised. Additionally, nine key considerations when applying emerging technology in paediatric laboratory medicine setting are discussed. [ABSTRACT FROM AUTHOR]

In this computer simulation study, we examine four different statistical approaches of linearity assessment, including two variants of deviation from linearity (individual (IDL) and averaged (AD)), along with detection capabilities of residuals of linear regression (individual and averaged). From the results of the simulation, the following broad suggestions are provided to laboratory practitioners when performing linearity assessment. A high imprecision can challenge linearity investigations by producing a high false positive rate or low power of detection. Therefore, the imprecision of the measurement procedure should be considered when interpreting linearity assessment results. In the presence of high imprecision, the results of linearity assessment should be interpreted with caution. Different linearity assessment approaches examined in this study performed well under different analytical scenarios. For optimal outcomes, a considered and tailored study design should be implemented. With the exception of specific scenarios, both ADL and IDL methods were suboptimal for the assessment of linearity compared. When imprecision is low (3 %), averaged residual of linear regression with triplicate measurements and a non-linearity acceptance limit of 5 % produces <5 % false positive rates and a high power for detection of non-linearity of >70 % across different types and degrees of non-linearity. Detection of departures from linearity are difficult to identify in practice and enhanced methods of detection need development. [ABSTRACT FROM AUTHOR]

Analytical performance specifications (APS) based on outcomes refer to how 'good' the analytical performance of a test needs to be to do more good than harm to the patient. Analytical performance of a measurand affects its clinical performance. Without first setting clinical performance requirements, it is difficult to define how good analytically the test needs to be to meet medical needs. As testing is indirectly linked to health outcomes through clinical decisions on patient management, often simulation-based studies are used to assess the impact of analytical performance on the probability of clinical outcomes which is then translated to Model 1b APS according to the Milan consensus. This paper discusses the related key definitions, concepts and considerations that should assist in finding the most appropriate methods for deriving Model 1b APS. We review the advantages and limitations of published methods and discuss the criteria for transferability of Model 1b APS to different settings. We consider that the definition of the clinically acceptable misclassification rate is central to Model 1b APS. We provide some examples and guidance on a more systematic approach for first defining the clinical performance requirements for tests and we also highlight a few ideas to tackle the future challenges associated with providing outcome-based APS for laboratory testing. [ABSTRACT FROM AUTHOR]

Analytical performance specifications (APS) are used for decisions about the required analytical quality of pathology tests to meet clinical needs. The Milan models, based on clinical outcome, biological variation, or state of the art, were developed to provide a framework for setting APS. An approach has been proposed to assign each measurand to one of the models based on a defined clinical use, physiological control, or an absence of quality information about these factors. In this paper we propose that in addition to such assignment, available information from all models should be considered using a risk-based approach that considers the purpose and role of the actual test in a clinical pathway and its impact on medical decisions and clinical outcomes in addition to biological variation and the state-of-the-art. Consideration of APS already in use and the use of results in calculations may also need to be considered to determine the most appropriate APS for use in a specific setting. [ABSTRACT FROM AUTHOR]

Reference intervals depend on the distribution of results within a reference population and can be influenced by subclinical disease. Functional reference limits present an opportunity to derive clinically relevant reference limits from routinely collected data sources, which consist of mixed populations of unhealthy and healthy groups. Serum ferritin is a good example of the utility of functional reference limits. Several studies have identified clinically relevant reference limits through examining the relationship between serum ferritin and erythrocyte parameters. These ferritin functional limits often represent the inflection point at which erythrocyte parameters change significantly. Comparison of ferritin functional reference limits with those based on population distributional reference limits reveals that the lower reference limit may fall below the point at which patients become clinically unwell. Functional reference limits may be considered for any biomarker that exhibits a correlated relationship with other biomarkers.

Calibration of an analytical measurement procedure is an important basis for the reliability of patient results. Many publications and as well as procedures on how to estimate quality control and interpret those results have been become available over the years. In this publication we are focusing on the critical part of the calibration as there are no clear communication or guidelines on how to perform it. Usually only the recommendation of the reagent or instrument manufacturer is available. We would like to point out this gap to invite for a discussion and improvement of the current situation. [ABSTRACT FROM AUTHOR]

Interference from isomeric steroids is a potential cause of disparity between mass spectrometry-based 17-hydroxyprogesterone (17OHP) results. We aimed to assess the proficiency of mass spectrometry laboratories to report 17OHP in the presence of known isomeric steroids. A series of five samples were prepared using a previously demonstrated commutable approach. These samples included a control (spiked to 15.0 nmol/L 17OHP) and four challenge samples further enriched with equimolar concentrations of 17OHP isomers (11α-hydroxyprogesterone, 11β-hydroxyprogesterone, 16α-hydroxyprogesterone or 21-hydroxyprogesterone). These samples were distributed to 38 participating laboratories that reported serum 17OHP results using mass spectrometry in two external quality assurance programs. The result for each challenge sample was compared to the control sample submitted by each participant. Twenty-six laboratories (68 % of distribution) across three continents returned results. Twenty-five laboratories used liquid chromatography-tandem mass spectrometry (LC-MS/MS), and one used gas chromatography-tandem mass spectrometry to measure 17OHP. The all-method median of the control sample was 14.3 nmol/L, ranging from 12.4 to 17.6 nmol/L. One laboratory had results that approached the lower limit of tolerance (minus 17.7 % of the control sample), suggesting the isomeric steroid caused an irregular result. Most participating laboratories demonstrated their ability to reliably measure 17OHP in the presence of the four clinically relevant isomeric steroids. The performance of the 12 (32 %) laboratories that did not engage in this activity remains unclear. We recommend that all laboratories offering LC-MS/MS analysis of 17OHP in serum, plasma, or dried bloodspots determine that the isomeric steroids are appropriately separated. [ABSTRACT FROM AUTHOR]

An emerging technology (ET) for laboratory medicine can be defined as an analytical method (including biomarkers) or device (software, applications, and algorithms) that by its stage of development, translation into broad routine clinical practice, or geographical adoption and implementation has the potential to add value to clinical diagnostics. Considering the laboratory medicine-specific definition, this document examines eight key tools, encompassing clinical, analytical, operational, and financial aspects, used throughout the life cycle of ET implementation. The tools provide a systematic approach starting with identifying the unmet need or identifying opportunities for improvement (Tool 1), forecasting (Tool 2), technology readiness assessment (Tool 3), health technology assessment (Tool 4), organizational impact map (Tool 5), change management (Tool 6), total pathway to method evaluation checklist (Tool 7), and green procurement (Tool 8). Whilst there are differences in clinical priorities between different settings, the use of this set of tools will help support the overall quality and sustainability of the emerging technology implementation. [ABSTRACT FROM AUTHOR]

Between-reagent lot, bias, bile acid, drift, lot-to-lot variation, pregnancy, reagent, reagent lot, lot-to-lot verification, shift Keywords: between-reagent lot; bias; bile acid; drift; lot-to-lot variation; lot-to-lot verification; pregnancy; reagent; reagent lot; shift EN between-reagent lot bias bile acid drift lot-to-lot variation lot-to-lot verification pregnancy reagent reagent lot shift e108 e111 4 05/31/23 20230601 NES 230601 To the Editor, Bile acids (BA) are synthesised in the liver through a multi-step process, beginning with cholesterol. [Extracted from the article]

Lot-to-lot verification is an integral component for monitoring the long-term stability of a measurement procedure. The practice is challenged by the resource requirements as well as uncertainty surrounding experimental design and statistical analysis that is optimal for individual laboratories, although guidance is becoming increasingly available. Collaborative verification efforts as well as application of patient-based monitoring are likely to further improve identification of any differences in performance in a relatively timely manner. Appropriate follow up actions of failed lot-to-lot verification is required and must balance potential disruptions to clinical services provided by the laboratory. Manufacturers need to increase transparency surrounding release criteria and work closer with laboratory professionals to ensure acceptable reagent lots are released to end users. A tripartite collaboration between regulatory bodies, manufacturers, and laboratory medicine professional bodies is key to developing a balanced system where regulatory, manufacturing, and clinical requirements of laboratory testing are met, to minimize differences between reagent lots and ensure patient safety. Clinical Chemistry and Laboratory Medicine has served as a fertile platform for advancing the discussion and practice of lot-to-lot verification in the past 60 years and will continue to be an advocate of this important topic for many more years to come. [ABSTRACT FROM AUTHOR]

Method evaluation is one of the critical components of the quality system that ensures the ongoing quality of a clinical laboratory. As part of implementing new methods or reviewing best practices, the peer-reviewed published literature is often searched for guidance. From the outset, Clinical Chemistry and Laboratory Medicine (CCLM) has a rich history of publishing methods relevant to clinical laboratory medicine. An insight into submissions, from editors' and reviewers' experiences, shows that authors still struggle with method evaluation, particularly the appropriate requirements for validation in clinical laboratory medicine. Here, we consider through a series of discussion points an overview of the status, challenges, and needs of method evaluation from the perspective of clinical laboratory medicine. We identify six key high-level aspects of clinical laboratory method evaluation that potentially lead to inconsistency. 1. Standardisation of terminology, 2. Selection of analytical performance specifications, 3. Experimental design of method evaluation, 4. Sample requirements of method evaluation, 5. Statistical assessment and interpretation of method evaluation data, and 6. Reporting of method evaluation data. Each of these areas requires considerable work to harmonise the practice of method evaluation in laboratory medicine, including more empirical studies to be incorporated into guidance documents that are relevant to clinical laboratories and are freely and widely available. To further close the loop, educational activities and fostering professional collaborations are essential to promote and improve the practice of method evaluation procedures. [ABSTRACT FROM AUTHOR]

Detection of between-lot reagent bias is clinically important and can be assessed by application of regression-based statistics on several paired measurements obtained from the existing and new candidate lot. Here, the bias detection capability of six regression-based lot-to-lot reagent verification assessments, including an extension of the Bland–Altman with regression approach are compared. Least squares and Deming regression (in both weighted and unweighted forms), confidence ellipses and Bland–Altman with regression (BA-R) approaches were investigated. The numerical simulation included permutations of the following parameters: differing result range ratios (upper:lower measurement limits), levels of significance (alpha), constant and proportional biases, analytical coefficients of variation (CV), and numbers of replicates and sample sizes. The sample concentrations simulated were drawn from a uniformly distributed concentration range. At a low range ratio (1:10, CV 3%), the BA-R performed the best, albeit with a higher false rejection rate and closely followed by weighted regression approaches. At larger range ratios (1:1,000, CV 3%), the BA-R performed poorly and weighted regression approaches performed the best. At higher assay imprecision (CV 10%), all six approaches performed poorly with bias detection rates <50%. A lower alpha reduced the false rejection rate, while greater sample numbers and replicates improved bias detection. When performing reagent lot verification, laboratories need to finely balance the false rejection rate (selecting an appropriate alpha) with the power of bias detection (appropriate statistical approach to match assay performance characteristics) and operational considerations (number of clinical samples and replicates, not having alternate reagent lot). [ABSTRACT FROM AUTHOR]

One approach to assessing reference material (RM) commutability and agreement with clinical samples (CS) is to use ordinary least squares or Deming regression with prediction intervals. This approach assumes constant variance that may not be fulfilled by the measurement procedures. Flexible regression frameworks which relax this assumption, such as quantile regression or generalized additive models for location, scale, and shape (GAMLSS), have recently been implemented, which can model the changing variance with measurand concentration. We simulated four imprecision profiles, ranging from simple constant variance to complex mixtures of constant and proportional variance, and examined the effects on commutability assessment outcomes with above four regression frameworks and varying the number of CS, data transformations and RM location relative to CS concentration. Regression framework performance was determined by the proportion of false rejections of commutability from prediction intervals or centiles across relative RM concentrations and was compared with the expected nominal probability coverage. In simple variance profiles (constant or proportional variance), Deming regression, without or with logarithmic transformation respectively, is the most efficient approach. In mixed variance profiles, GAMLSS with smoothing techniques are more appropriate, with consideration given to increasing the number of CS and the relative location of RM. In the case where analytical coefficients of variation profiles are U-shaped, even the more flexible regression frameworks may not be entirely suitable. In commutability assessments, variance profiles of measurement procedures and location of RM in respect to clinical sample concentration significantly influence the false rejection rate of commutability. [ABSTRACT FROM AUTHOR]

Lot-to-lot verification is an important laboratory activity that is performed to monitor the consistency of analytical performance over time. In this opinion paper, the concept, clinical impact, challenges and potential solutions for lot-to-lot verification are exained. [ABSTRACT FROM AUTHOR]

In a survey reported in 2018, up to 50% of laboratories using LC-MS/MS methods for serum 17OHP measurement did not know if their methods could separate isobaric isomers of 17OHP [[8]]. Keywords: 17-hydroxyprogesterone; congenital adrenal hyperplasia (CAH); endogenous interference EN 17-hydroxyprogesterone congenital adrenal hyperplasia (CAH) endogenous interference e64 e66 3 01/30/23 20230301 NES 230301 To the Editor, Serum 17 hydroxyprogesterone (OHP) is a key steroid for screening, diagnosis, and monitoring of congenital adrenal hyperplasia (CAH), a condition with 95% of cases due to 21 hydroxylase deficiency. If these two isomers coelute with 17OHP, they can potentially increase serum 17OHP up to 9 times the actual 17OHP concentration, resulting in falsely high 17OHP results that may affect patient management. [Extracted from the article]

Evaluation of the performance of the techniques To compare the performance of different techniques, the fractional error of the derived I CV i SB I i i sb is determined as below. HT ht Graph where I CV i SB I derived i sb and I CV i SB I actual i sb are the derived and actual I CV i SB I i i sb respectively. The coefficient of variation for the remaining data, I CV i SB I rr i sb , is calculated and from this the I CV i SB I i i sb is obtained as follows: HT ht Graph (3) 4) Modified result ratio method Here, a modification of the result ratio method [[19]] with more stringent outlier exclusion is examined. In general, the EMS, result ratio and modified result ratio yielded estimates of I CV i SB I i i sb within ±0.1 fractional error. [Extracted from the article]

Lipemia is the presence of abnormally high lipoprotein concentrations in serum or plasma samples that can interfere with laboratory testing. There is little guidance available from manufacturers or professional bodies on processing lipemic samples to produce clinically acceptable results. This systematic review summarizes existing literature on the effectiveness of lipid removal techniques in reducing interference in clinical chemistry tests. A PubMed search using terms relating to lipid removal from human samples for clinical chemistry tests produced 1,558 studies published between January 2010 and July 2021. 15 articles met the criteria for further analyses. A total of 66 analytes were investigated amongst the 15 studies, which showed highly heterogenous study designs. High-speed centrifugation was consistently effective for 13 analytes: albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatine kinase (CK), creatinine (Jaffe method), gamma-glutamyl transferase (GGT), glucose (hexokinase-based method), lactate dehydrogenase (LDH), phosphate, potassium, and urea. Lipid-clearing agents were uniformly effective for seven analytes: ALT, AST, total bilirubin, CK, creatinine (Jaffe method), lipase, and urea. Mixed results were reported for the remaining analytes. For some analytes, high-speed centrifugation and/or lipid-clearing agents can be used in place of ultracentrifugation. Harmonized protocols and acceptability criteria are required to allow pooled data analysis and interpretation of different lipemic interference studies. [ABSTRACT FROM AUTHOR]

In recent years, there has been renewed interest in the "old" average of normals concept, now generally referred to as moving average quality control (MA QC) or patient-based real-time quality control (PBRTQC). However, there are some controversies regarding PBRTQC which this review aims to address while also indicating the current status of PBRTQC. This review gives the background of certain newly described optimization and validation methods. It also indicates how QC plans incorporating PBRTQC can be designed for greater effectiveness and/or (cost) efficiency. Furthermore, it discusses controversies regarding the complexity of obtaining PBRTQC settings, the replacement of iQC, and software functionality requirements. Finally, it presents evidence of the added value and practicability of PBRTQC. Recent developments in, and availability of, simulation methods to optimize and validate laboratory-specific PBRTQC procedures have enabled medical laboratories to implement PBRTQC in their daily practice. Furthermore, these methods have made it possible to demonstrate the practicability and added value of PBRTQC by means of two prospective "clinical" studies and other investigations. Although internal QC will remain an essential part of any QC plan, applying PBRTQC can now significantly improve its performance and (cost) efficiency. [ABSTRACT FROM AUTHOR]

This letter to the editor discusses the use of sigma metrics in laboratory medicine. The authors analyze data from an external quality assurance program to examine the correlation between sigma metric, analytical imprecision, and bias. They find that sigma metric is more strongly correlated with analytical imprecision than bias. The study highlights the importance of considering both imprecision and bias when assessing laboratory performance. The accompanying table provides data on various laboratory measurements and their correlation with different testing methods, offering valuable information for researchers and library patrons interested in laboratory testing methods and their correlation. However, it is important to interpret the results with caution due to potential differences in sample material and study limitations. [Extracted from the article]

Despite a century of research, bilirubin metabolism and the transport mechanisms responsible for homeostasis of bilirubin in serum remain controversial. Emerging evidence on the hepatic membrane transporters and inherited disorders of bilirubin metabolism have contributed to a greater understanding of the various steps involved in bilirubin homeostasis and its associated excretory pathways. We discuss these recent research findings on hepatic membrane transporters and evaluate their significance on the newborn bilirubin metabolism and excretion. New insights gained speculate that a proportion of conjugated bilirubin is excreted via the renal system, as an alternative to the intestinal excretion, even in normal physiological jaundice with no associated pathological concerns. Finally, this paper discusses the clinical relevance of targeting the altered renal excretory pathway, as bilirubin in urine may hold diagnostic importance in screening for neonatal jaundice. [ABSTRACT FROM AUTHOR]

Urine albumin is measured in clinical laboratories by immunoturbidimetry. However, large biases are observed among the different routine methods. To standardize the measurement of urine albumin, a reference measurement procedure (RMP) and urine albumin certified reference materials (CRMs) are needed. A candidate RMP for urine albumin based on liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) using human serum albumin as calibration standard was developed. Isotope-labeled human albumin was used as internal standard. Urine samples were digested using trypsin and eight resulting "signature" peptides of albumin were quantified by LC-IDMS/MS. The candidate RMP was employed in value assignment of external quality assessment (EQA) samples and certification of urine albumin reference materials. The commutability of the developed CRMs was assessed against patient samples. The candidate RMP (recovery 101.5–103.2% and CV 1.2–3.3% at about 7–40 mg/L) met optimal performance goal. The lower limit of quantification was 0.03 mg/L as determined by signal-to-noise method. The EQA results from clinical laboratories using different immunoturbidimetric methods were generally comparable with assigned target values determined by the candidate RMP, with albumin concentrations ranging from 5 to 226 mg/L. Urine albumin reference materials (two levels) certified using the candidate RMP showed good commutability in a preliminary study. With optimal method precision and trueness, as well as comparability with routine methods, the developed RMP may be used for value assignment of EQA samples or certification of reference materials, which are important pillars in urine albumin method standardization. [ABSTRACT FROM AUTHOR]

Serological testing for the detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is emerging as an important component of the clinical management of patients with coronavirus disease 2019 (COVID-19) as well as the epidemiological assessment of SARS-CoV-2 exposure worldwide. In addition to molecular testing for the detection of SARS-CoV-2 infection, clinical laboratories have also needed to increase testing capacity to include serological evaluation of patients with suspected or known COVID-19. While regulatory approved serological immunoassays are now widely available from diagnostic manufacturers globally, there is significant debate regarding the clinical utility of these tests, as well as their clinical and analytical performance requirements prior to application. This document by the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Taskforce on COVID-19 provides interim guidance on: (A) clinical indications and target populations, (B) assay selection, (C) assay evaluation, and (D) test interpretation and limitations for serological testing of antibodies against SARS-CoV-2 infection. These evidence-based recommendations will provide practical guidance to clinical laboratories in the selection, verification, and implementation of serological assays and are of the utmost importance as we expand our pandemic response from initial case tracing and containment to mitigation strategies to minimize resurgence and further morbidity and mortality. [ABSTRACT FROM AUTHOR]

Routine biochemical and hematological tests have been reported to be useful in the stratification and prognostication of pediatric and adult patients with diagnosed coronavirus disease (COVID-19), correlating with poor outcomes such as the need for mechanical ventilation or intensive care, progression to multisystem organ failure, and/or death. While these tests are already well established in most clinical laboratories, there is still debate regarding their clinical value in the management of COVID-19, particularly in pediatrics, as well as the value of composite clinical risk scores in COVID-19 prognostication. This document by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on COVID-19 provides interim guidance on: (A) clinical indications for testing, (B) recommendations for test selection and interpretation, (C) considerations in test interpretation, and (D) current limitations of biochemical/hematological monitoring of COVID-19 patients. These evidence-based recommendations will provide practical guidance to clinical laboratories worldwide, underscoring the contribution of biochemical and hematological testing to our collective pandemic response. [ABSTRACT FROM AUTHOR]

The diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection globally has relied extensively on molecular testing, contributing vitally to case identification, isolation, contact tracing, and rationalization of infection control measures during the coronavirus disease 2019 (COVID-19) pandemic. Clinical laboratories have thus needed to verify newly developed molecular tests and increase testing capacity at an unprecedented rate. As the COVID-19 pandemic continues to pose a global health threat, laboratories continue to encounter challenges in the selection, verification, and interpretation of these tests. This document by the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on COVID-19 provides interim guidance on: (A) clinical indications and target populations, (B) assay selection, (C) assay verification, and (D) test interpretation and limitations for molecular testing of SARS-CoV-2 infection. These evidence-based recommendations will provide practical guidance to clinical laboratories worldwide and highlight the continued importance of laboratory medicine in our collective pandemic response. [ABSTRACT FROM AUTHOR]

Objectives: Our recent survey of 44 mass spectrometry laboratories across 17 countries identified variation in internal standard (IS) choice for the measurement of serum/plasma 17α-hydroxyprogesterone (17OHP) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The choice of IS may contribute to inter-method variations. This study evaluated the effect of two common isotopically labeled IS on the quantification of 17OHP by LC-MS/MS. Methods: Three collaborating LC-MS/MS laboratories from Asia, Europe and Australia, who routinely measure serum 17OHP, compared two IS, (1) IsoSciences carbon-13 labeled 17OHP-[2,3,4-13C3], and (2) IsoSciences deuterated 17OHP-[2,2,4,6,6,21,21,21-2H]. This was performed as part of their routine patient runs using their respective laboratory standard operating procedure. Results: The three laboratories measured 99, 89, 95 independent samples, respectively (up to 100 nmol/L) using the 13C- and 2H-labeled IS. The slopes of the Passing-Bablok regression ranged 0.98–1.00 (all 95% confidence interval [CI] estimates included the line of identity), and intercept of <0.1 nmol/L. Average percentage differences of −0.04% to −5.4% were observed between the two IS materials, which were less than the optimal bias specification of 7% determined by biological variation, indicating no clinically significant difference. The results of 12 Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) proficiency samples (1–40 nmol/L) measured by the laboratories were all within the RCPAQAP analytical performance specifications for both IS. Conclusions: Overall, the comparison between the results of 13C- and 2H-labeled IS for 17OHP showed good agreement, and show no clinically significant bias when incorporated into the LC-MS/MS methods employed in the collaborating laboratories. [ABSTRACT FROM AUTHOR]

Objectives: A global survey was conducted by the IFCC Task Force on COVID-19 to better understand how general biochemistry laboratories manage the pre-analytical, analytical and post-analytical processes to mitigate biohazard risks during the coronavirus disease 2019 (COVID-19) pandemic. Methods: An electronic survey was developed to record the general characteristics of the laboratory, as well as the pre-analytical, analytical, post-analytical and operational practices of biochemistry laboratories that are managing clinical samples of patients with COVID-19. Results: A total of 1210 submissions were included in the analysis. The majority of responses came from hospital central/core laboratories that serve hospital patient groups and handle moderate daily sample volumes. There has been a decrease in the use of pneumatic tube transport, increase in hand delivery and increase in number of layers of plastic bags for samples of patients with clinically suspected or confirmed COVID-19. Surgical face masks and gloves are the most commonly used personal protective equipment (PPE). Just >50% of the laboratories did not perform an additional decontamination step on the instrument after analysis of samples from patients with clinically suspected or confirmed COVID-19. A fifth of laboratories disallowed add-on testing on these samples. Less than a quarter of laboratories autoclaved their samples prior to disposal. Conclusions: The survey responses showed wide variation in pre-analytical, analytical and post-analytical practices in terms of PPE adoption and biosafety processes. It is likely that many of the suboptimal biosafety practices are related to practical local factors, such as limited PPE availability and lack of automated instrumentation. [ABSTRACT FROM AUTHOR]

Objectives: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on COVID-19 conducted a global survey to understand how biochemistry laboratories manage the operational challenges during the coronavirus disease 2019 (COVID-19) pandemic. Materials and methods: An electronic survey was distributed globally to record the operational considerations to mitigate biosafety risks in the laboratory. Additionally, the laboratories were asked to indicate the operational challenges they faced. Results: A total of 1210 valid submissions were included in this analysis. Most of the survey participants worked in hospital laboratories. Around 15% of laboratories restricted certain tests on patients with clinically suspected or confirmed COVID-19 over biosafety concerns. Just over 10% of the laboratories had to restrict their test menu or services due to resource constraints. Approximately a third of laboratories performed temperature monitoring, while two thirds of laboratories increased the frequency of disinfection. Just less than 50% of the laboratories split their teams. The greatest reported challenge faced by laboratories during the COVID-19 pandemic is securing sufficient supplies of personal protective equipment (PPE), analytical equipment, including those used at the point of care, as well as reagents, consumables and other laboratory materials. This was followed by having inadequate staff, managing their morale, anxiety and deployment. Conclusions: The restriction of tests and services may have undesirable clinical consequences as clinicians are deprived of important information to deliver appropriate care to their patients. Staff rostering and biosafety concerns require longer-term solutions as they are crucial for the continued operation of the laboratory during what may well be a prolonged pandemic. [ABSTRACT FROM AUTHOR]

Patient-based real-time quality control (PBRTQC) is a laboratory tool for monitoring the performance of the testing process. It includes well-established procedures like Bull's algorithm, average of nomals, moving median, moving average (MA) and exponentially (weighted) MAs. Following the setup and optimization processes, a key step prior to the routine implementation of PBRTQC is the verification and documentation of the performance of the PBRTQC as part of the laboratory quality system. This verification process should provide a realistic representation of the performance of the PBRTQC in the environment it is being implemented in, to allow proper risk assessment by laboratory practitioners. This document focuses on the recommendation on performance verification of PBRTQC prior to implementation. [ABSTRACT FROM AUTHOR]

Background: The delta check time interval limit is the maximum time window within which two sequential results of a patient will be evaluated by the delta check rule. The impact of time interval on delta check performance is not well studied. Methods: De-identified historical laboratory data were extracted from the laboratory information system and divided into children (≤18 years) and adults (>21 years). The relative and absolute differences of the original pair of results from each patient were compared against the delta check limits associated with 90% specificity. The data were then randomly reshuffled to simulate a switched (misidentified) sample scenario. The data were divided into 1-day, 3-day, 7-day, 14-day, 1-month, 3-month, 6-month and 1-year time interval bins. The true positive- and false-positive rates at different intervals were examined. Results: Overall, 24 biochemical and 20 haematological tests were analysed. For nearly all the analytes, there was no statistical evidence of any difference in the true- or false-positive rates of the delta check rules at different time intervals when compared to the overall data. The only exceptions to this were mean corpuscular volume (using both relative- and absolute-difference delta check) and mean corpuscular haemoglobin (only absolute-difference delta check) in the children population, where the false-positive rates became significantly lower at 1-year interval. Conclusions: This study showed that there is no optimal delta check time interval. This fills an important evidence gap for future guidance development. [ABSTRACT FROM AUTHOR]

Background: The measurement of hemoglobin A1c (HbA1c) is important for diagnosing diabetes mellitus as well as assessing glycemic control in diabetic patients. Commutable whole blood certified reference materials (CRMs) are needed in the measurement of HbA1c for method validation and/or as quality controls. Methods: We developed three levels of hemolyzed whole blood CRMs for HbA1c. The certified values were determined using liquid chromatography-isotope dilution tandem mass spectrometry method (LC-IDMS/MS) where two "signature" hexapeptides of HbA1c and hemoglobin A0 (HbA0) were used as the calibration standards. The concentrations of the hexapeptide solutions were determined by amino acid analysis by the LC-IDMS/MS method using amino acid CRMs as the calibration standards. The commutability study was conducted by measuring 25 patient specimens and the whole blood CRMs by both LC-IDMS/MS method and various routine methods using six different clinical analyzers. Results: The certified values were determined to be 35.1±2.0, 50.3±1.9 and 65.8±2.6 mmol/mol, respectively. These CRMs showed good commutability on five of the six clinical analyzers but showed poor commutability on one of the clinical analyzers that used similar method as two other analyzers where good commutability was observed. Conclusions: With certified target values based on metrological traceability and good commutability on most of the clinical analyzers, the developed whole blood CRMs can be used for method validation or as quality control materials in the measurement of HbA1c. The commutability study results also underscored the need of commutability testing of clinical CRMs using various clinical analyzers. [ABSTRACT FROM AUTHOR]

Reference intervals are a vital part of the information supplied by clinical laboratories to support interpretation of numerical pathology results such as are produced in clinical chemistry and hematology laboratories. The traditional method for establishing reference intervals, known as the direct approach, is based on collecting samples from members of a preselected reference population, making the measurements and then determining the intervals. An alternative approach is to perform analysis of results generated as part of routine pathology testing and using appropriate statistical techniques to determine reference intervals. This is known as the indirect approach. This paper from a working group of the International Federation of Clinical Chemistry (IFCC) Committee on Reference Intervals and Decision Limits (C-RIDL) aims to summarize current thinking on indirect approaches to reference intervals. The indirect approach has some major potential advantages compared with direct methods. The processes are faster, cheaper and do not involve patient inconvenience, discomfort or the risks associated with generating new patient health information. Indirect methods also use the same preanalytical and analytical techniques used for patient management and can provide very large numbers for assessment. Limitations to the indirect methods include possible effects of diseased subpopulations on the derived interval. The IFCC C-RIDL aims to encourage the use of indirect methods to establish and verify reference intervals, to promote publication of such intervals with clear explanation of the process used and also to support the development of improved statistical techniques for these studies. [ABSTRACT FROM AUTHOR]

A letter to the editor on point mutation in the thiopurine S-methyltransferase gene that led to exon 5 deletion in the transcribed mRNA is presented.

A letter to the editor is presented about a study which analyzed the racial differences and relationships between gestational thyrotropin and free thyroxine in a multiracial Asian population.

A letter to the editor is presented in response to the article on the high concentration of IgM-κ paraprotein causes over-estimation of serum total protein by certain biuret method.