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.

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.

scholarly journals Subclinical hypothyroidism: a ‘laboratory-induced’ condition?

2015 ◽  
Vol 173 (4) ◽  
pp. 499-505 ◽  
Author(s):  
Karlien L M Coene ◽  
Ayse Y Demir ◽  
Maarten A C Broeren ◽  
Pauline Verschuure ◽  
Eef G W M Lentjes ◽  
...  
Keyword(s):  
Reference Values ◽  
Subclinical Hypothyroidism ◽  
Analytical Method ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Reference Ranges ◽  
Thyroid Pathology ◽  
Design And Methods

ObjectiveIn current literature and guidelines, there is a tendency to define absolute TSH concentrations at which patient follow-up or even pharmaceutical intervention should be initiated. As TSH concentrations depend on the analytical method/platform used for TSH quantification, absolute cut-off values may pose threats for uniform clinical decision-making. In this study we therefore set out to clarify to what extent the method/platform and the reference values applied for TSH influence the clinical interpretation of thyroid parameters.Design and methodsWe retrospectively analyzed anonymous TSH results from the Dutch external quality assessment program (EQAS) in relation to reference values advised by different manufacturers. We also examined TSH/free thyroxin (fT4) reference ranges and prevalence of thyroid pathology among different Dutch laboratories, including four cases in which a switch in the measuring platform was made.ResultsOur data show that interpretation of thyroid parameters is not only influenced by between-method/platform variation, but is also substantially affected by the variation in TSH/fT4 reference intervals applied in individual laboratories. Additionally, we show that the transition to a novel analytical method/platform can result in a shift in the prevalence of thyroid pathology, especially for subclinical hypothyroidism.ConclusionsSubclinical hypothyroidism can be a ‘laboratory-induced’ condition. This is an undesirable situation in regard to the clinical implications such a diagnosis can have for patients.

Mitotic Index of Invasive Breast Carcinoma

2009 ◽  
Vol 133 (11) ◽  
pp. 1826-1833 ◽  
Author(s):  
John S. Meyer ◽  
Eric Cosatto ◽  
Hans Peter Graf
Keyword(s):  
Breast Carcinoma ◽  
Mitotic Index ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Mitotic Cell ◽  
Standard Errors ◽  
Mitotic Figure ◽  
Binomial Probability ◽  
Breast Carcinomas ◽  
Coefficients Of Variation

Abstract Context.—Mitotic figure counts are related to breast cancer behavior but have not been sufficiently reproducible to be accepted for clinical decision-making. Objective.—To improve reproducibility and accuracy of the mitotic count. Design.—Mitotic index (MI) was defined as the mitotic cell count per 10 high-power fields (HPFs), an area 0.183 mm2. Two to 6 replicate sets of 10 HPFs were counted from 328 invasive breast carcinomas. Standard errors and coefficients of variation for mean MI were compared with expected results predicted by the binomial distribution. Results.—The boundaries for MI that separated the data into equal thirds (tertials) were 1.14 and 5.33. Standard errors and coefficients of variation for MI followed distributions predicted by binomial probability. Mean coefficient of variation was 147% for the low tertial, 72% for the midtertial, and 34.6% for the upper tertial. Conclusions.—Standard errors for MI based on a single count of 10 HPFs are too broad and coefficients of variation too large to be acceptable for clinical use. This is explained as a binomial probability effect, possibly with a contribution from tumor heterogeneity. Errors can be reduced in proportion to the square root of the number of sets of 10 HPFs counted. Tertial cutoffs of MI of the Nottingham system currently used in breast carcinoma grading are too high to be applicable to the population we studied. We recommend validation of cutoffs before they are applied to a particular population of breast carcinomas. Counting 5 sets of 10 HPFs is necessary to accurately rank carcinomas with low MIs.

Total Amylase and Pancreatic Isoamylase in Serum and Urine: Considerations from Data on Biological Variation

1989 ◽  
Vol 26 (4) ◽  
pp. 335-340 ◽  
Author(s):  
Steven T Cummings ◽  
Callum G Fraser
Keyword(s):  
Clinical Decision Making ◽  
Amylase Activity ◽  
Clinical Decision ◽  
Population Based ◽  
Reference Intervals ◽  
Similar Data ◽  
Creatinine Ratio ◽  
Additional Information ◽  
Pancreatic Isoamylase ◽  
Urine Amylase

The analytical, within-subject and between-subject components of variation were estimated for amylase activity and pancreatic isoamylase activity in serum measured using newer analytical methods. Desirable analytical imprecisions based on within-subject variation were CV ≤ 4·4% and CV ≤ 7·0%, respectively. Conventional population-based reference intervals were not useful because of marked individuality; clinical decision-making points should be derived from the desired sensitivity and specificity. Serial results must change more than about 30% and 40% respectively before significance (P ≤ 0·05) can be claimed. Similar data on total amylase and pancreatic isoamylase activities in random and first morning urines showed that the use of conventional reference intervals was appropriate. Very large changes (> 100%) were required before a difference in serial results was significant. Calculation of the urine amylase/creatinine ratio appeared to confer no advantage. Derivation of the ratio of pancreatic isoamylase to total amylase activity in serum or urine was unlikely to provide additional information of value in either diagnosis or monitoring.

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.

Establishment of Reference Intervals for Alkaline Phosphatase in Pakistani Children Using a Data Mining Approach

2019 ◽  
Vol 51 (5) ◽  
pp. 484-490 ◽  
Author(s):  
Sibtain Ahmed ◽  
Jakob Zierk ◽  
Aysha Habib Khan
Keyword(s):  
Data Mining ◽  
Alkaline Phosphatase ◽  
Clinical Decision Making ◽  
Clinical Chemistry ◽  
Age Groups ◽  
Clinical Decision ◽  
German Society ◽  
Reference Intervals ◽  
Photometric Method ◽  
Data Mining Approach

Abstract Objective To establish reference intervals (RIs) for alkaline phosphatase (ALP) levels in Pakistani children using an indirect data mining approach. Methods ALP levels analyzed on a Siemens Advia 1800 analyzer using the International Federation of Clinical Chemistry’s photometric method for both inpatients and outpatients aged 1 to 17 years between January 2013 and December 2017, including patients from intensive care units and specialty units, were retrieved. RIs were calculated using a previously validated indirect algorithm developed by the German Society of Clinical Chemistry and Laboratory Medicine’s Working Group on Guide Limits. Results From a total of 108,845 results, after the exclusion of patients with multiple specimens, RIs were calculated for 24,628 males and 18,083 females with stratification into fine-grained age groups. These RIs demonstrate the complex age- and sex-related ALP dynamics occurring during physiological development. Conclusion The population-specific RIs serve to allow an accurate understanding of the fluctuations in analyte activity with increasing age and to support clinical decision making.

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.

scholarly journals Morphometric evaluation of relevant radiographic parameters of the forefeet of clinically normal donkeys (Equus αsinus)

2018 ◽  
Vol 68 (3) ◽  
pp. 467 ◽  
Author(s):  
E. A. EL-SHAFAEY ◽  
M. G. SALEM ◽  
E. MOSBAH ◽  
A. E. ZAGHLOUL
Keyword(s):  
Digital Imaging ◽  
Clinical Decision Making ◽  
Reference Data ◽  
Clinical Decision ◽  
Repeated Measurements ◽  
Vertical Position ◽  
Clinically Normal ◽  
Radiographic Parameters ◽  
Coefficients Of Variation ◽  
Morphometric Evaluation

This study provides a standard database of morphometric evaluation of the digital bone and hoof parameters of the forefeet of clinically normal donkeys using Digital Imaging and Communications in Medicine (DICOM) software programme, as a means to improve diagnosis and clinical decision-making regarding foot lameness in equine practice. Thirty orthopedically sound donkeys were included in this study. For each donkey forefoot, lateromedial (LM) and dorsopalmar (DP) radiographs were obtained with the foot in a vertical position. A total of 26 digital bone and hoof parameters obtained from the LM and DP radiographs were evaluated through repeated measurements of the same digitalized radiograph by three operators using DICOM software. Data of the morphometric radiographic parameters of the forefeet were statistically analyzed for the frequency distribution and calculation of the intra-assay and interassay coefficients of variation (CVs) of the reproducibility of the measured parameters. Mean ± SD of digital bone and hoof parameters were significantly different among the measurements obtained for the 26 parameters. However, intra-assay and interassay CVs for digital bone and hoof parameters measurements did not differ significantly between the three examiners. In conclusion, morphometric evaluation of the radiographic parameters of the forefeet in clinically normal donkeys, establishes a reference data base correspondingly for the donkey different to those accepted for the horse.

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