Pediatric reference interval verification for endocrine and fertility hormone assays on the Abbott Alinity system

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mary Kathryn Bohn ◽  
Siobhan Wilson ◽  
Alexandra Hall ◽  
Khosrow Adeli
Keyword(s):  
Clinical Decision Making ◽  
De Novo ◽  
Reference Interval ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Healthy Children ◽  
Confidence Limits ◽  
Test Results ◽  
Serum Samples ◽  
Abbott Architect

Abstract Objectives The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has developed an extensive database of reference intervals (RIs) for several biomarkers on various analytical systems. In this study, pediatric RIs were verified for key immunoassays on the Abbott Alinity system based on the analysis of healthy children samples and comparison to comprehensive RIs previously established for Abbott ARCHITECT assays. Methods Analytical performance of Alinity immunoassays was first assessed. Subsequently, 100 serum samples from healthy children recruited with informed consent were analyzed for 16 Alinity immunoassays. The percentage of test results falling within published CALIPER ARCHITECT reference and confidence limits was determined. If ≥ 90% of test results fell within the confidence limits, they were considered verified based on CLSI guidelines. If <90% of test results fell within the confidence limits, additional samples were analyzed and new Alinity RIs were established. Results Of the 16 immunoassays assessed, 13 met the criteria for verification with test results from ≥ 90% of healthy serum samples falling within the published ARCHITECT confidence limits. New CALIPER RIs were established for free thyroxine and prolactin on the Alinity system. Estradiol required special considerations in early life. Conclusions Our data demonstrate excellent concordance between ARCHITECT and Alinity immunoassays, as well as the robustness of previously established CALIPER RIs for most immunoassays, eliminating the need for de novo RI studies for most parameters. Availability of pediatric RIs for immunoassays on the Alinity system will assist clinical laboratories using this new platform and contribute to improved clinical decision-making.

Pediatric reference interval verification for common biochemical assays on the Abbott Alinity system

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mary Kathryn Bohn ◽  
Siobhan Wilson ◽  
Alexandra Hall ◽  
Youssef Massamiri ◽  
Ed Randell ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Package Insert ◽  
Reference Interval ◽  
Reference Intervals ◽  
Confidence Limits ◽  
Serum Samples ◽  
Laboratory Service ◽  
Biochemical Assays ◽  
Pediatric Healthcare ◽  
Abbott Architect

Abstract Objectives The quality of clinical laboratory service depends on quality laboratory operations and accurate test result interpretation based on reference intervals (RIs). As new analytical systems continue to be developed and improved, previously established RIs must be verified. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has established comprehensive RIs for many biomarkers on several analytical systems. Here, published CALIPER RIs for 28 chemistry assays on the Abbott ARCHITECT were assessed for verification on the newer Alinity system. Methods An analytical validation was first completed to assess assay performance. CALIPER serum samples (100) were analyzed for 28 chemistry assays on the Alinity system. The percentage of results falling within published pediatric ARCHITECT reference and confidence limits was determined for each analyte. Based on Clinical and Laboratory Standards Institute (CLSI) guidelines, if ≥90% of test results fell within confidence limits of ARCHITECT assay RIs, they were considered verified. Results Of the 28 assays assessed, 26 met the criteria for verification. Reference values for calcium and magnesium did not meet the criteria for verification with 87% and 35% falling within previously established ARCHITECT confidence limits, respectively. However, both assays could be verified using pediatric RIs provided in the Abbott Alinity package insert. Conclusions In this study, CALIPER ARCHITECT RIs were verified on the Alinity system for several chemistry assays. These data demonstrate excellent concordance for most assays between the Abbott ARCHITECT and Alinity systems and will assist in the implementation of the Alinity system in pediatric healthcare institutions.

Pediatric reference intervals for 1,25-dihydroxyvitamin D using the DiaSorin LIAISON XL assay in the healthy CALIPER cohort

2018 ◽  
Vol 56 (6) ◽  
pp. 964-972 ◽  
Author(s):  
Victoria Higgins ◽  
Dorothy Truong ◽  
Nicole M.A. White-Al Habeeb ◽  
Angela W.S. Fung ◽  
Barry Hoffman ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Critical Role ◽  
Reference Interval ◽  
Reference Intervals ◽  
Biologically Active ◽  
Specific Reference ◽  
Healthy Children ◽  
Serum Samples ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D

Abstract Background: 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active vitamin D metabolite, plays a critical role in calcium and phosphate homeostasis. 1,25(OH)2D is measured to assess calcium and phosphate metabolism, particularly during periods of profound growth and development. Despite its importance, no reliable pediatric reference interval exists, with those available developed using adult populations or out-dated methodologies. Using the fully automated chemiluminescence immunoassay by DiaSorin, we established 1,25(OH)2D pediatric reference intervals using healthy children and adolescents from the CALIPER cohort. Methods: Serum samples from healthy subjects (0 to <19 years) were analyzed for 1,25(OH)2D using the DiaSorin LIAISON XL assay and age-specific reference intervals were established. The Mann-Whitney U-test was used to determine seasonal differences. Pooled neonatal and infantile samples were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine if elevated concentrations during the first year of life may be attributed to cross-reacting moieties. Results: Three reference interval age partitions were required with highest levels in subjects 0 to <1 year (77–471 pmol/L), which declined and narrowed after 1 year (113–363 pmol/L) and plateaued at 3 years (108–246 pmol/L). 1,25(OH)2D concentration was not significantly affected by seasonal variation or sex. Elevated 1,25(OH)2D concentrations in neonatal and infantile samples may be the result of an interfering substance. The absence of 3-epi-1,25-dihydroxyvitamin D in the pooled samples makes it unlikely to be the interfering moiety. Conclusions: Pediatric reference intervals for 1,25(OH)2D were established to improve test result interpretation in children and adolescents. 1,25(OH)2D is elevated in a proportion of neonates and infants, which may be the result of a cross-reacting moiety.

scholarly journals Data mining of pediatric reference intervals

2021 ◽  
Vol 45 (6) ◽  
pp. 311-317
Author(s):  
Jakob Zierk ◽  
Markus Metzler ◽  
Manfred Rauh
Keyword(s):  
Data Mining ◽  
Information Systems ◽  
Statistical Methods ◽  
Clinical Decision Making ◽  
Reference Intervals ◽  
Healthy Children ◽  
Test Results ◽  
Young Infants ◽  
Age Related ◽  
Laboratory Test Results

Abstract Laboratory tests are essential to assess the health status and to guide patient care in individuals of all ages. The interpretation of quantitative test results requires availability of appropriate reference intervals, and reference intervals in children have to account for the extensive physiological dynamics with age in many biomarkers. Creation of reference intervals using conventional approaches requires the sampling of healthy individuals, which is opposed by ethical and practical considerations in children, due to the need for a large number of blood samples from healthy children of all ages, including neonates and young infants. This limits the availability and quality of pediatric reference intervals, and ultimately negatively impacts pediatric clinical decision-making. Data mining approaches use laboratory test results and clinical information from hospital information systems to create reference intervals. The extensive number of available test results from laboratory information systems and advanced statistical methods enable the creation of pediatric reference intervals with an unprecedented age-related accuracy for children of all ages. Ongoing developments regarding the availability and standardization of electronic medical records and of indirect statistical methods will further improve the benefit of data mining for pediatric reference intervals.

NUMBER: standardized reference intervals in the Netherlands using a ‘big data’ approach

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Wendy P.J. den Elzen ◽  
Nannette Brouwer ◽  
Marc H. Thelen ◽  
Saskia Le Cessie ◽  
Inez-Anne Haagen ◽  
...  
Keyword(s):  
General Chemistry ◽  
Big Data ◽  
The Netherlands ◽  
Clinical Laboratory ◽  
Reference Interval ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Test Results ◽  
Study Population ◽  
Set Up

AbstractBackgroundExternal quality assessment (EQA) programs for general chemistry tests have evolved from between laboratory comparison programs to trueness verification surveys. In the Netherlands, the implementation of such programs has reduced inter-laboratory variation for electrolytes, substrates and enzymes. This allows for national and metrological traceable reference intervals, but these are still lacking. We have initiated a national endeavor named NUMBER (Nederlandse UniforMe Beslisgrenzen En Referentie-intervallen) to set up a sustainable system for the determination of standardized reference intervals in the Netherlands.MethodsWe used an evidence-based ‘big-data’ approach to deduce reference intervals using millions of test results from patients visiting general practitioners from clinical laboratory databases. We selected 21 medical tests which are either traceable to SI or have Joint Committee for Traceability in Laboratory Medicine (JCTLM)-listed reference materials and/or reference methods. Per laboratory, per test, outliers were excluded, data were transformed to a normal distribution (if necessary), and means and standard deviations (SDs) were calculated. Then, average means and SDs per test were calculated to generate pooled (mean±2 SD) reference intervals. Results were discussed in expert meetings.ResultsSixteen carefully selected clinical laboratories across the country provided anonymous test results (n=7,574,327). During three expert meetings, participants found consensus about calculated reference intervals for 18 tests and necessary partitioning in subcategories, based on sex, age, matrix and/or method. For two tests further evaluation of the reference interval and the study population were considered necessary. For glucose, the working group advised to adopt the clinical decision limit.ConclusionsUsing a ‘big-data’ approach we were able to determine traceable reference intervals for 18 general chemistry tests. Nationwide implementation of these established reference intervals has the potential to improve unequivocal interpretation of test results, thereby reducing patient harm.

Influence of ethnicity on biochemical markers of health and disease in the CALIPER cohort of healthy children and adolescents

2020 ◽  
Vol 58 (4) ◽  
pp. 605-617 ◽  
Author(s):  
Houman Tahmasebi ◽  
Shervin Asgari ◽  
Alexandra Hall ◽  
Victoria Higgins ◽  
Ashfia Chowdhury ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Clinical Decision Making ◽  
Pediatric Population ◽  
Statistical Significance ◽  
Immunoglobulin A ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Immunoglobulin M ◽  
Healthy Children ◽  
Pediatric Study

AbstractBackgroundAccurate pediatric reference intervals (RIs) for laboratory tests determined in a healthy pediatric population are essential for correct laboratory test interpretation and clinical decision-making. In pediatrics, RIs require partitioning by age and/or sex; however, the need for partitioning based on ethnicity is unclear. Here, we assessed the influence of ethnicity on biomarker concentrations in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents and compared the results with the National Health and Nutrition Examination Survey (NHANES).MethodsA total of 52 biomarkers were measured in a multiethnic population of 846–1179 healthy children (aged 5 to <19 years) upon informed consent. Biomarker concentrations were retrospectively compared between four major ethnic groups (i.e. Black, Caucasian, East Asian, and South Asian, determined by parental ethnicity). Retrospective results were verified prospectively using an additional 500 healthy pediatric samples with equal sample size across ethnicities. Ethnic-specific differences were assessed based on statistical significance and biological and analytical variations. Appropriate age-, sex-, and ethnic-specific RIs were calculated.ResultsEthnic-specific differences were not observed for 34 biomarkers examined in the retrospective analysis, while 18 demonstrated statistically significant ethnic differences. Among these, seven analytes demonstrated ethnic-specific differences in the prospective analysis: vitamin D, amylase, ferritin, follicle-stimulating hormone (FSH), immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM). Analysis of select NHANES data confirmed CALIPER findings.ConclusionsThis is the first comprehensive Canadian pediatric study examining ethnic-specific differences in common biomarkers. While the majority of biomarkers did not require ethnic partitioning, ethnic-specific RIs were established for seven biomarkers showing marked differences. Further studies in other populations are needed to confirm our findings.

Paediatric reference intervals for 17 Roche cobas 8000 e602 immunoassays in the CALIPER cohort of healthy children and adolescents

2019 ◽  
Vol 57 (12) ◽  
pp. 1968-1979 ◽  
Author(s):  
Mary Kathryn Bohn ◽  
Victoria Higgins ◽  
Shervin Asgari ◽  
Felix Leung ◽  
Barry Hoffman ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Reference Values ◽  
Laboratory Tests ◽  
Clinical Decision Making ◽  
Reference Intervals ◽  
Healthy Children ◽  
Serum Samples ◽  
Clinical Laboratories ◽  
Age And Sex ◽  
Roche Cobas

Abstract Background The diagnostic utility of laboratory tests in paediatric medicine relies heavily on the availability of appropriate reference intervals (RIs). The Canadian Laboratory Initiative on Paediatric Reference Intervals (CALIPER) has established a comprehensive database of covariate-stratified RIs for many paediatric laboratory tests using a large, healthy reference population. Several automated analysers in widespread use in clinical laboratories have already been studied. Here, we extend the testing to Roche immunoassays and report, for the first time, comprehensive paediatric RIs for 17 endocrine and special chemistry markers. Methods A total of 741 healthy children and adolescents (1 day to <19 years) were recruited and serum samples were analysed for 17 immunoassays on the Roche cobas 8000 e602 Immunoassay Analyzer. Age and sex-specific RIs were established and corresponding 90% confidence intervals (CIs) were calculated in accordance with Clinical and Laboratory Standards Institute guidelines. Results Reference values for all analytes measured required age partitioning, particularly during early life and throughout adolescence. Of the 17 analytes measured, eight required sex partitioning, including ferritin, thyroid stimulating hormone (TSH), total triiodothyronine (TT3) and all fertility/sex hormones, except prolactin. Conclusions This is the first study to determine accurate paediatric RIs for Roche immunoassays. RIs were generally similar to those previously published by CALIPER on other analytical platforms, highlighting the reproducibility of age- and sex-specific trends in reference values observed across the paediatric age range. The RIs established in this study will improve the accuracy of test result interpretation and clinical decision-making in clinical laboratories utilising Roche immunoassays.

High-resolution pediatric reference intervals for 15 biochemical analytes described using fractional polynomials

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jakob Zierk ◽  
Hannsjörg Baum ◽  
Alexander Bertram ◽  
Martin Boeker ◽  
Armin Buchwald ◽  
...  
Keyword(s):  
Information Systems ◽  
Laboratory Test ◽  
Clinical Decision Making ◽  
Age Groups ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Test Results ◽  
Laboratory Test Results ◽  
Glutamyl Transferase ◽  
Laboratory Information Systems

Abstract Objectives Assessment of children’s laboratory test results requires consideration of the extensive changes that occur during physiological development and result in pronounced sex- and age-specific dynamics in many biochemical analytes. Pediatric reference intervals have to account for these dynamics, but ethical and practical challenges limit the availability of appropriate pediatric reference intervals that cover children from birth to adulthood. We have therefore initiated the multi-center data-driven PEDREF project (Next-Generation Pediatric Reference Intervals) to create pediatric reference intervals using data from laboratory information systems. Methods We analyzed laboratory test results from 638,683 patients (217,883–982,548 samples per analyte, a median of 603,745 test results per analyte, and 10,298,067 test results in total) performed during patient care in 13 German centers. Test results from children with repeat measurements were discarded, and we estimated the distribution of physiological test results using a validated statistical approach (kosmic). Results We report continuous pediatric reference intervals and percentile charts for alanine transaminase, aspartate transaminase, lactate dehydrogenase, alkaline phosphatase, γ-glutamyl-transferase, total protein, albumin, creatinine, urea, sodium, potassium, calcium, chloride, anorganic phosphate, and magnesium. Reference intervals are provided as tables and fractional polynomial functions (i.e., mathematical equations) that can be integrated into laboratory information systems. Additionally, Z-scores and percentiles enable the normalization of test results by age and sex to facilitate their interpretation across age groups. Conclusions The provided reference intervals and percentile charts enable precise assessment of laboratory test results in children from birth to adulthood. Our findings highlight the pronounced dynamics in many biochemical analytes in neonates, which require particular consideration in reference intervals to support clinical decision making most effectively.

Analytical Goals for Quantities Used to Assess Thyrometabolic Status

1989 ◽  
Vol 26 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Margaret C K Browning
Keyword(s):  
Reference Values ◽  
Clinical Decision Making ◽  
Extreme Values ◽  
State Of The Art ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Confidence Limits ◽  
Analytical Goals ◽  
Coefficients Of Variation ◽  
Variation Data

Analytical goals for imprecision derived from data on intra-individual variation for total T4, free T4, total T3, free T3 and thyrotropin (TSH) are coefficients of variation (CV) ⩽ 2·5, 4·7, 5·2, 3·9 and 8·1%, respectively. If total T4 is used to monitor replacement therapy with thyroxine, a more stringent goal of CV ⩽ 1·;4% is appropriate. For those analytes for which biological variation data are not available, analytical goals may be derived either from reference intervals or from the ‘state of the art’ as judged from the performance of a stated proportion of laboratories participating in an interlaboratory quality assessment scheme. Analytical goals for imprecision for reverse T3 and thyroxine-binding globulin derived from reference values are CV ⩽ 10·;7 and 7·;2%, respectively. The goal for inaccuracy is that there should be none. Statements regarding the detection limit of an assay should be replaced with information about the range of concentrations over which specified goals for imprecision are met. If goals are not achieved at concentrations which are used for clinical decision making the 95% confidence limits of the extreme values of the ‘working range’ should be calculated using the relevant imprecision. Improved analytical performance will result in better between-laboratory comparability and eventually allow the use of universally applicable reference values.

Immunochemical methods for measurement of transferrin in serum: effects of analytical errors and inappropriate reference intervals on diagnostic utility.

1985 ◽  
Vol 31 (10) ◽  
pp. 1601-1605 ◽  
Author(s):  
Z L Bandi ◽  
I Schoen ◽  
D E Bee
Keyword(s):  
Serum Proteins ◽  
Reference Interval ◽  
Reference Intervals ◽  
Confidence Limits ◽  
Serum Samples ◽  
Normal Reference ◽  
Two Samples ◽  
Reference Preparation ◽  
Immunochemical Methods ◽  
Analytical Errors

Abstract We estimated analytical errors of the Calbiochem, Kallestad, Hyland, Meloy, Helena, and Beckman immunochemical methods for serum transferrin. Intermethod biases were determined by analysis of the "Reference Preparation for Serum Proteins" of the College of American Pathologists and by analysis of 106 patients' serum samples. We judged the acceptability of errors by comparing confidence limits for total errors with 1/4 of the normal reference intervals. The transferrin status of each patient's sample was interpreted by comparing the result of each method with the normal reference interval claimed by the corresponding manufacturer. We found that the combined effects of medically unacceptable analytical errors and inappropriate normal intervals caused results of the tested methods not to be interchangeable. The Calbiochem method identified 61 serum samples (57%) as having abnormally high transferrin concentrations. In contrast, for the same specimen, with the Meloy method we found abnormally high transferrin concentrations for only two samples (1.8%).

Pediatric reference value distributions and covariate-stratified reference intervals for 29 endocrine and special chemistry biomarkers on the Beckman Coulter Immunoassay Systems: a CALIPER study of healthy community children

2016 ◽  
Vol 54 (4) ◽  
Author(s):  
Kimiya Karbasy ◽  
Danny C.C. Lin ◽  
Alexandra Stoianov ◽  
Man Khun Chan ◽  
Victoria Bevilacqua ◽  
...  
Keyword(s):  
Pediatric Population ◽  
Reference Value ◽  
Reference Interval ◽  
Reference Intervals ◽  
Healthy Children ◽  
Serum Samples ◽  
Laboratory Assessment ◽  
Research Initiative ◽  
Closing The Gaps ◽  
Gender Based

AbstractThe CALIPER program is a national research initiative aimed at closing the gaps in pediatric reference intervals. CALIPER previously reported reference intervals for endocrine and special chemistry markers on Abbott immunoassays. We now report new pediatric reference intervals for immunoassays on the Beckman Coulter Immunoassay Systems and assess platform-specific differences in reference values.A total of 711 healthy children and adolescents from birth to <19 years of age were recruited from the community. Serum samples were collected for measurement of 29 biomarkers on the Beckman Coulter Immunoassay Systems. Statistically relevant age and/or gender-based partitions were determined, outliers removed, and reference intervals calculated in accordance with Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines.Complex profiles were observed for all 29 analytes, necessitating unique age and/or sex-specific partitions. Overall, changes in analyte concentrations observed over the course of development were similar to trends previously reported, and are consistent with biochemical and physiological changes that occur during childhood. Marked differences were observed for some assays including progesterone, luteinizing hormone and follicle-stimulating hormone where reference intervals were higher than those reported on Abbott immunoassays and parathyroid hormone where intervals were lower.This study highlights the importance of determining reference intervals specific for each analytical platform. The CALIPER Pediatric Reference Interval database will enable accurate diagnosis and laboratory assessment of children monitored by Beckman Coulter Immunoassay Systems in health care institutions worldwide. These reference intervals must however be validated by individual labs for the local pediatric population as recommended by CLSI.

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