Home Is the combination of trueness and precision in one expression meaningful? On the use of total error and uncertainty in clinical chemistry
Article
Licensed
Unlicensed Requires Authentication

Is the combination of trueness and precision in one expression meaningful? On the use of total error and uncertainty in clinical chemistry

  • Anders Kallner EMAIL logo
Published/Copyright: January 19, 2016
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 54 Issue 8

Abstract

The performance of all measurement procedures used in routine clinical laboratories shall be verified; a minimum is to verify the precision and trueness of the results. This is well established and adequate recommendations and procedures are available. Conveying this information in a form that is adequate and understandable for the practical end-user in the health care sector is still a much debated issue. By tradition, since several decades, the “total error” (TE) is presented, a quantity that is the linear sum of an imprecision and bias. Since any combination of the two can yield the same TE it may not be very helpful in finding and correcting a root-cause for an unacceptable value. Also, an acceptable TE may hide an unacceptable level of its constituents. An alternative is the measurement uncertainty (MU), which is recommended by accreditation and standardizing bodies The MU separates the imprecision and bias and expresses an interval around a best estimate within which the true value is expected with a certain probability. We describe the reporting the best estimate of a measurement result and describe how the uncertainty of the result, can be calculated, using simple custom-made software.

Keywords: bias elimination; recalibration; schematic calculation; simulation
Corresponding author: Anders Kallner, Department of Clinical chemistry, Karolinska University hospital, Stockholm Sweden, E-mail:

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Directive 98/79/EC of the European parliament and of the council of 27 October 1998 on in vitro diagnostic medical devices. Official Journal of the European Communities 7.12.98. Available at: http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:31998L0079&from=EN. Accessed: Oct 2015.Search in Google Scholar

2. Medical laboratories – Requirements for quality and competence EN/ISO 15189. 2011-09-22 3.Search in Google Scholar

3. CLSI. User verification of performance for precision and trueness approved guideline-third edition. CLSI document EP15-A3 (ISBN 1-56238-000-0).Search in Google Scholar

4. CLSI. Establishment of precision of quantitative measurement procedures; approved guideline-third edition. CLSI document EP5-A3 (ISBN 1-56238-000-0).Search in Google Scholar

5. JCGM 200:2012 International vocabulary of metrology – Basic and general concepts and associated terms (VIM) 3rd edition 2008 version with minor corrections. Available at: www.bipm.org. Accessed: Oct 2015.Search in Google Scholar

6. Guideline of the German medical association on quality assurance in medical laboratory examinations – Rili-BAEK (unauthorized translation). J Lab Med 2015;39:26–69.10.1515/labmed-2014-0046Search in Google Scholar

7. Westgard JO, Carey RN, Wold S. Criteria for judging precision and accuracy in method development and evaluation. Clin Chem 1974;20:825–33.10.1093/clinchem/20.7.825Search in Google Scholar

8. CLSI Clinical and Laboratory Standards Institute (CLSI). CLSI document EP21 DRAFT EP21-A3 2015.Search in Google Scholar

9. Westgard JO. Useful measures and models for analytical quality management in medical laboratories. Clin Chem Lab Med 2016;54:223–33.10.1515/cclm-2015-0710Search in Google Scholar PubMed

10. CLSI. How to construct and interpret an error grid for diagnostic assays; draft guideline. CLSI document EP27 (ISBN 1-56238-000-0).Search in Google Scholar

11. Cox DJ, Clarke WL, Gonder-Frederick L, Pohl S, Hoover C, Snyder A, et al. Accuracy of perceiving blood glucose in IDDM. Diabetes Care 1985;8:529–36.10.2337/diacare.8.6.529Search in Google Scholar PubMed

12. Joan L, Parkes JL, Slatin SL, Pardo S, Ginsberg BH. A new consensus error grid to evaluate the clinical significance of inaccuracies in the measurement of blood glucose. Diabetes Care 2000;23:1143–8.10.2337/diacare.23.8.1143Search in Google Scholar PubMed

13. Levey AS, Coresh J, Greene T, Stevens LA, Zhang Y, Hendriksen S, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006;145:247–54.10.7326/0003-4819-145-4-200608150-00004Search in Google Scholar PubMed

14. Strategies to set global analytical quality specifications in laboratory medicine. In: Petersen PH, Fraser CG, Kallner A, Kenny D, editors. Scand J Clin Lab Invest 1999;59:475–583.10.1080/00365519950185184Search in Google Scholar

15. 1st EFLM Strategic Conference/“Defining analytical performance goals – 15 years after the Stockholm Conference”. In: Gillery P, Lackner KJ, Lippi G, Melichar B, Schlattmann P, Tate JR, et al. editors. Clin Chem Lab Med 2015;53:829–958.Search in Google Scholar

16. JCGM 100:2008. Evaluation of measurement data – Guide to the expression of uncertainty in measurement, with minor corrections (GUM). Available at: www.bipm.org. Accessed: Oct 2015.Search in Google Scholar

17. CLSI. Measurement procedure comparison and average bias estimation using patient samples; draft guideline–third edition. CLSI document EP09 (ISBN 1-56238-000-0).Search in Google Scholar

18. Kallner A. Comprehensive method comparisons: Getting more from the data. Accred Qual Assur 2014;19:451–7.10.1007/s00769-014-1089-9Search in Google Scholar

19. Magnusson B, Ellison SL. Treatment of uncorrected measurement bias in uncertainty estimation for chemical measurements. Anal Bioanal Chem 2008;390:201–13.10.1007/s00216-007-1693-1Search in Google Scholar PubMed

20. Krouwer JS. How to improve total error modeling by accounting for error sources beyond imprecision and bias. Clin Chem 2001;47:1329–30.10.1093/clinchem/47.7.1329Search in Google Scholar

21. Kragten J. Calculating standard deviations and confidence intervals with a universally applicable spreadsheet technique. Analyst 1994;119:2161–6.10.1039/an9941902161Search in Google Scholar

22. EURACHEM/CITAC Guide CG 4 Quantifying uncertainty in analytical measurement. QUAM 2000. Appendix E. Available at: www.citac.cc/QUAM2000-1.pdf. Accessed: Oct 2015.Search in Google Scholar

23. Farrance I, Frenkel R. Uncertainty in measurement: a review of Monte Carlo simulation using Microsoft Excel for the calculation of uncertainties through functional relationships, including uncertainties in empirically derived constants. Clin Biochem Rev 2014;35:37–61.Search in Google Scholar

24. Kallner A. Microsoft Excel 2010 offers an improved random number generator allowing efficient simulation in chemical laboratory studies. Clin Chim Acta 2015;438:210–1.10.1016/j.cca.2014.08.036Search in Google Scholar PubMed

Received: 2015-10-7
Accepted: 2015-12-1
Published Online: 2016-1-19
Published in Print: 2016-8-1

©2016 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. Laboratory analytical quality – the process continues
  4. Measurement uncertainty – a revised understanding of its calculation and use
  5. Review
  6. Substrate-zymography: a still worthwhile method for gelatinases analysis in biological samples
  7. Opinion Papers
  8. Is the combination of trueness and precision in one expression meaningful? On the use of total error and uncertainty in clinical chemistry
  9. The problem with total error models in establishing performance specifications and a simple remedy
  10. Measurement uncertainty for clinical laboratories – a revision of the concept
  11. Uncertainty in measurement and total error – are they so incompatible?
  12. General Clinical Chemistry and Laboratory Medicine
  13. Using the hazard ratio to evaluate allowable total error in predictive measurands
  14. Performance of electrolyte measurements assessed by a trueness verification program
  15. Analytical interference by monoclonal immunoglobulins on the direct bilirubin AU Beckman Coulter assay: the benefit of unsuspected diagnosis from spurious results
  16. Preliminary probe of quality indicators and quality specification in total testing process in 5753 laboratories in China
  17. Analytical and clinical evaluation of the new Fujirebio Lumipulse®G non-competitive assay for 25(OH)-vitamin D and three immunoassays for 25(OH)D in healthy subjects, osteoporotic patients, third trimester pregnant women, healthy African subjects, hemodialyzed and intensive care patients
  18. Patient-performed extraction of faecal calprotectin
  19. Comparison of the clinical utility of the Elia CTD Screen to indirect immunofluorescence on Hep-2 cells
  20. Reference Values and Biological Variations
  21. Sex-related differences in the association of ghrelin levels with obesity in adolescents
  22. Gestation specific reference intervals for thyroid function tests in pregnancy
  23. Cancer Diagnostics
  24. SOX17 promoter methylation in plasma circulating tumor DNA of patients with non-small cell lung cancer
  25. Dopamine concentration in blood platelets is elevated in patients with head and neck paragangliomas
  26. Letters to the Editor
  27. Cancer dynamics and the success of cancer screening programs
  28. Mother’s instinct – a rare case of multiple test interferences due to heterophile antibodies
  29. Sigma metric or defects per million opportunities (DPMO): the performance of clinical laboratories should be evaluated by the Sigma metrics at decimal level with DPMOs
  30. A national survey of preanalytical handling of oral glucose tolerance tests in pregnancy
  31. Updating pregnancy diabetes guidelines: is (y)our laboratory ready?
  32. Low serum bilirubin values are associated with pulmonary embolism in a case-control study
  33. Effect of Hb H on HbA1c measurements as measured by IFCC reference method and affinity HPLC
  34. Adipocytes in venipunctures cause falsely elevated S-100B serum values
  35. Earlier detection of sepsis by Candida parapsilosis using three-dimensional cytographic anomalies on the Mindray BC-6800 hematological analyzer
  36. Theranos phenomenon – part 4: Theranos at an International Conference
https://doi.org/10.1515/cclm-2015-0975
Keywords for this article
bias elimination; recalibration; schematic calculation; simulation

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. Laboratory analytical quality – the process continues
  4. Measurement uncertainty – a revised understanding of its calculation and use
  5. Review
  6. Substrate-zymography: a still worthwhile method for gelatinases analysis in biological samples
  7. Opinion Papers
  8. Is the combination of trueness and precision in one expression meaningful? On the use of total error and uncertainty in clinical chemistry
  9. The problem with total error models in establishing performance specifications and a simple remedy
  10. Measurement uncertainty for clinical laboratories – a revision of the concept
  11. Uncertainty in measurement and total error – are they so incompatible?
  12. General Clinical Chemistry and Laboratory Medicine
  13. Using the hazard ratio to evaluate allowable total error in predictive measurands
  14. Performance of electrolyte measurements assessed by a trueness verification program
  15. Analytical interference by monoclonal immunoglobulins on the direct bilirubin AU Beckman Coulter assay: the benefit of unsuspected diagnosis from spurious results
  16. Preliminary probe of quality indicators and quality specification in total testing process in 5753 laboratories in China
  17. Analytical and clinical evaluation of the new Fujirebio Lumipulse®G non-competitive assay for 25(OH)-vitamin D and three immunoassays for 25(OH)D in healthy subjects, osteoporotic patients, third trimester pregnant women, healthy African subjects, hemodialyzed and intensive care patients
  18. Patient-performed extraction of faecal calprotectin
  19. Comparison of the clinical utility of the Elia CTD Screen to indirect immunofluorescence on Hep-2 cells
  20. Reference Values and Biological Variations
  21. Sex-related differences in the association of ghrelin levels with obesity in adolescents
  22. Gestation specific reference intervals for thyroid function tests in pregnancy
  23. Cancer Diagnostics
  24. SOX17 promoter methylation in plasma circulating tumor DNA of patients with non-small cell lung cancer
  25. Dopamine concentration in blood platelets is elevated in patients with head and neck paragangliomas
  26. Letters to the Editor
  27. Cancer dynamics and the success of cancer screening programs
  28. Mother’s instinct – a rare case of multiple test interferences due to heterophile antibodies
  29. Sigma metric or defects per million opportunities (DPMO): the performance of clinical laboratories should be evaluated by the Sigma metrics at decimal level with DPMOs
  30. A national survey of preanalytical handling of oral glucose tolerance tests in pregnancy
  31. Updating pregnancy diabetes guidelines: is (y)our laboratory ready?
  32. Low serum bilirubin values are associated with pulmonary embolism in a case-control study
  33. Effect of Hb H on HbA1c measurements as measured by IFCC reference method and affinity HPLC
  34. Adipocytes in venipunctures cause falsely elevated S-100B serum values
  35. Earlier detection of sepsis by Candida parapsilosis using three-dimensional cytographic anomalies on the Mindray BC-6800 hematological analyzer
  36. Theranos phenomenon – part 4: Theranos at an International Conference
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 7.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2015-0975/html
Scroll to top button