A zlog-based algorithm and tool for plausibility checks of reference intervals
-
Sandra Klawitter
,
Georg Hoffmann
Abstract
Objectives
Laboratory information systems typically contain hundreds or even thousands of reference limits stratified by sex and age. Since under these conditions a manual plausibility check is hardly feasible, we have developed a simple algorithm that facilitates this check. An open-source R tool is available as a Shiny application at github.com/SandraKla/Zlog_AdRI.
Methods
Based on the zlog standardization, we can possibly detect critical jumps at the transitions between age groups, regardless of the analytical method or the measuring unit. Its advantage compared to the standard z-value is that means and standard deviations are calculated from the reference limits rather than from the underlying data itself. The purpose of the tool is illustrated by the example of reference intervals of children and adolescents from the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER).
Results
The Shiny application identifies the zlog values, lists them in a colored table format and plots them additionally with the specified reference intervals. The algorithm detected several strong and rapid changes in reference intervals from the neonatal period to puberty. Remarkable jumps with absolute zlog values of more than five were seen for 29 out of 192 reference limits (15.1%). This might be attenuated by introducing shorter time periods or mathematical functions of reference limits over age.
Conclusions
Age-partitioned reference intervals will remain the standard in laboratory routine for the foreseeable future, and as such, algorithmic approaches like our zlog approach in the presented Shiny application will remain valuable tools for testing their plausibility on a wide scale.
-
Research funding: None declared.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Authors state no conflict of interest.
-
Informed consent: Not applicable.
-
Ethical approval: Not applicable.
References
1. Cadamuro, J, Hillarp, A, Unger, A, von Meyer, A, Bauca, J, Plekhanova, O, et al.. Presentation and formatting of laboratory results: a narrative review on behalf of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group “postanalytical phase” (WG-POST). Crit Rev Clin Lab Sci 2021;58:329–53. https://doi.org/10.1080/10408363.2020.1867051.Search in Google Scholar PubMed
2. CLSI. Defining, establishing, and verifying reference intervals in the clinical laboratory; Approved Guideline—Third Edition. CLSI document C28-A3c. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.Search in Google Scholar
3. Zierk, J, Arzideh, F, Rechenauer, T, Haeckel, R, Rascher, W, Metzler, M, et al.. Age- and sex-specific dynamics in 22 hematologic and biochemical analytes from birth to adolescence. Clin Chem 2015;61:964–73. https://doi.org/10.1373/clinchem.2015.239731.Search in Google Scholar PubMed
4. Palm, J, Hoffmann, G, Klawonn, F, Tutarel, O, Palm, H, Holdenrieder, S, et al.. Continuous, complete and comparable NT-proBNP reference ranges in healthy children. Clin Chem Lab Med 2020;58:1509–151. https://doi.org/10.1515/cclm-2019-1185.Search in Google Scholar PubMed
5. Asgari, S, Higgins, V, McCudden, C, Adeli, K. Continuous reference intervals for 38 biochemical markers in healthy children and adolscents: comparison to traditionally partitioned reference intervals. Clin Biochem 2019;73:82–9. https://doi.org/10.1016/j.clinbiochem.2019.08.010.Search in Google Scholar PubMed
6. Hoffmann, G, Klawonn, F, Lichtinghagen, R, Orth, M. The zlog value as a basis for the standardization of laboratory results. J Lab Med 2017;41:23–31. https://doi.org/10.1515/labmed-2017-0135.Search in Google Scholar
7. Colantonio, D, Kyriakopoulou, L, Chan, M, Daly, C, Brinc, D, Venner, A, et al.. Closing the gaps in pediatric laboratory reference intervals: a CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children. Clin Chem 2012;58:854–68. https://doi.org/10.1373/clinchem.2011.177741.Search in Google Scholar PubMed
8. Gibb, S. zlog: z(log) Transformation for Laboratory Measurements. R package version 1.0.0. CRAN; 2021.10.32614/CRAN.package.zlogSearch in Google Scholar
9. Hoffmann, G, Lichtinghagen, R, Wosniok, W. Simple estimation of reference intervals from routine laboratory data. J Lab Med 2016;39: English translation pp. 000010151520150104.10.1515/labmed-2015-0104Search in Google Scholar
10. Haeckel, R, Wosniok, W, Postma, T. Quantity quotient reporting. Comparison of various models. Clin Chem Lab Med 2015;53:1921–6. https://doi.org/10.1515/cclm-2015-0101.Search in Google Scholar PubMed
11. Wright, E, Royston, P. A comparison of statistical methods for age-related reference intervals. J Roy Stat Soc: Ser A (Stat Soc) 2008;160:47–69. https://doi.org/10.1111/1467-985X.00045.Search in Google Scholar
12. Zierk, J, Hirschmann, J, Toddenroth, D, Arzideh, F, Haeckel, R, Bertram, A, et al.. Next-generation reference intervals for pediatric hematology. Clin Chem Lab Med 2019;57:1595–607. https://doi.org/10.1515/cclm-2018-1236.Search in Google Scholar PubMed
13. Yang, Q, Lew, H, Peh, R, Metz, M, Loh, T. An automated and objective method for age partitioning of reference intervals based on continuous centile curves. J Pathol 2016;48:581–5. https://doi.org/10.1016/j.pathol.2016.07.002.Search in Google Scholar PubMed
14. Haeckel, R, Wosniok, W, Streichert, T, Members of the Section Guide Limits of the DGKL. Review of potentials and limitations of indirect approaches for estimating reference limits/intervals of quantitative procedures in laboratory medicine. J Lab Med 2021;45:35–53. https://doi.org/10.1515/labmed-2020-0131.Search in Google Scholar
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2022-0688).
© 2022 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- Standardization and harmonization in laboratory medicine: not only for clinical chemistry measurands
- Mini Review
- The effect of the immunoassay curve fitting routine on bias in troponin
- Opinion Papers
- An overview of the most important preanalytical factors influencing the clinical performance of SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs)
- Time to address quality control processes applied to antibody testing for infectious diseases
- Perspectives
- Definition and application of performance specifications for measurement uncertainty of 23 common laboratory tests: linking theory to daily practice
- The gaps between the new EU legislation on in vitro diagnostics and the on-the-ground reality
- General Clinical Chemistry and Laboratory Medicine
- Second-generation Elecsys cerebrospinal fluid immunoassays aid diagnosis of early Alzheimer’s disease
- Evaluation of the interchangeability between the new fully-automated affinity chrome-mediated immunoassay (ACMIA) and the Quantitative Microsphere System (QMS) with a CE-IVD-certified LC-MS/MS assay for therapeutic drug monitoring of everolimus after solid organ transplantation
- Quantitative detection of anti-PLA2R antibodies targeting different epitopes and its clinical application in primary membranous nephropathy
- Reference Values and Biological Variations
- A zlog-based algorithm and tool for plausibility checks of reference intervals
- Harmonization of indirect reference intervals calculation by the Bhattacharya method
- Red blood cell parameters in early childhood: a prospective cohort study
- Cancer Diagnostics
- Association of circulating free and total oxysterols in breast cancer patients
- Effect of short-term storage of blood samples on gene expression in lung cancer patients
- Infectious Diseases
- Operation Moonshot: rapid translation of a SARS-CoV-2 targeted peptide immunoaffinity liquid chromatography-tandem mass spectrometry test from research into routine clinical use
- Seroprevalence of SARS-CoV-2 antibodies in Italy in newborn dried blood spots
- Positivization time of a COVID-19 rapid antigen self-test predicts SARS-CoV-2 viral load: a proof of concept
- New insights into SARS-CoV-2 Lumipulse G salivary antigen testing: accuracy, safety and short TAT enhance surveillance
- Preanalytical stability of SARS-CoV-2 anti-nucleocapsid antibodies
- Prognostic value of procalcitonin in cancer patients with coronavirus disease 2019
- 24/7 workflow for bloodstream infection diagnostics in microbiology laboratories: the first step to improve clinical management
- Diagnostic performance of machine learning models using cell population data for the detection of sepsis: a comparative study
- Diagnostic value of procalcitonin, hypersensitive C-reactive protein and neutrophil-to-lymphocyte ratio for bloodstream infections in pediatric tumor patients
- Letters to the Editor
- Pseudohyponatremia: interference of hyperglycemia on indirect potentiometry
- Ligand binding assay-related underestimation of 25-hydroxyvitamin D in pregnant women exaggerates the prevalence of vitamin D insufficiency
- Urokinase-type plasminogen activator soluble receptor (suPAR) assay in clinical routine: evaluation one year after its introduction in the high automation corelab of the A. Gemelli hospital
- Is this a true lambda free light chain?
- Effect of various blood collection tubes on serum lithium and other electrolytes: our perspective from a tertiary healthcare institute
Articles in the same Issue
- Frontmatter
- Editorial
- Standardization and harmonization in laboratory medicine: not only for clinical chemistry measurands
- Mini Review
- The effect of the immunoassay curve fitting routine on bias in troponin
- Opinion Papers
- An overview of the most important preanalytical factors influencing the clinical performance of SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs)
- Time to address quality control processes applied to antibody testing for infectious diseases
- Perspectives
- Definition and application of performance specifications for measurement uncertainty of 23 common laboratory tests: linking theory to daily practice
- The gaps between the new EU legislation on in vitro diagnostics and the on-the-ground reality
- General Clinical Chemistry and Laboratory Medicine
- Second-generation Elecsys cerebrospinal fluid immunoassays aid diagnosis of early Alzheimer’s disease
- Evaluation of the interchangeability between the new fully-automated affinity chrome-mediated immunoassay (ACMIA) and the Quantitative Microsphere System (QMS) with a CE-IVD-certified LC-MS/MS assay for therapeutic drug monitoring of everolimus after solid organ transplantation
- Quantitative detection of anti-PLA2R antibodies targeting different epitopes and its clinical application in primary membranous nephropathy
- Reference Values and Biological Variations
- A zlog-based algorithm and tool for plausibility checks of reference intervals
- Harmonization of indirect reference intervals calculation by the Bhattacharya method
- Red blood cell parameters in early childhood: a prospective cohort study
- Cancer Diagnostics
- Association of circulating free and total oxysterols in breast cancer patients
- Effect of short-term storage of blood samples on gene expression in lung cancer patients
- Infectious Diseases
- Operation Moonshot: rapid translation of a SARS-CoV-2 targeted peptide immunoaffinity liquid chromatography-tandem mass spectrometry test from research into routine clinical use
- Seroprevalence of SARS-CoV-2 antibodies in Italy in newborn dried blood spots
- Positivization time of a COVID-19 rapid antigen self-test predicts SARS-CoV-2 viral load: a proof of concept
- New insights into SARS-CoV-2 Lumipulse G salivary antigen testing: accuracy, safety and short TAT enhance surveillance
- Preanalytical stability of SARS-CoV-2 anti-nucleocapsid antibodies
- Prognostic value of procalcitonin in cancer patients with coronavirus disease 2019
- 24/7 workflow for bloodstream infection diagnostics in microbiology laboratories: the first step to improve clinical management
- Diagnostic performance of machine learning models using cell population data for the detection of sepsis: a comparative study
- Diagnostic value of procalcitonin, hypersensitive C-reactive protein and neutrophil-to-lymphocyte ratio for bloodstream infections in pediatric tumor patients
- Letters to the Editor
- Pseudohyponatremia: interference of hyperglycemia on indirect potentiometry
- Ligand binding assay-related underestimation of 25-hydroxyvitamin D in pregnant women exaggerates the prevalence of vitamin D insufficiency
- Urokinase-type plasminogen activator soluble receptor (suPAR) assay in clinical routine: evaluation one year after its introduction in the high automation corelab of the A. Gemelli hospital
- Is this a true lambda free light chain?
- Effect of various blood collection tubes on serum lithium and other electrolytes: our perspective from a tertiary healthcare institute
