Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

12 Issues per year


IMPACT FACTOR 2016: 3.432

CiteScore 2016: 2.21

SCImago Journal Rank (SJR) 2016: 1.000
Source Normalized Impact per Paper (SNIP) 2016: 1.112

Online
ISSN
1437-4331
See all formats and pricing
More options …
Volume 53, Issue 8

Issues

Permissible limits for uncertainty of measurement in laboratory medicine

Rainer Haeckel / Werner Wosniok / Ebrhard Gurr / Burkhard Peil
Published Online: 2015-01-23 | DOI: https://doi.org/10.1515/cclm-2014-0874

Abstract

The international standard ISO 15189 requires that medical laboratories estimate the uncertainty of their quantitative test results obtained from patients’ specimens. The standard does not provide details how and within which limits the measurement uncertainty should be determined. The most common concept for establishing permissible uncertainty limits is to relate them on biological variation defining the rate of false positive results or to base the limits on the state-of-the-art. The state-of-the-art is usually derived from data provided by a group of selected medical laboratories. The approach on biological variation should be preferred because of its transparency and scientific base. Hitherto, all recommendations were based on a linear relationship between biological and analytical variation leading to limits which are sometimes too stringent or too permissive for routine testing in laboratory medicine. In contrast, the present proposal is based on a non-linear relationship between biological and analytical variation leading to more realistic limits. The proposed algorithms can be applied to all measurands and consider any quantity to be assured. The suggested approach tries to provide the above mentioned details and is a compromise between the biological variation concept, the GUM uncertainty model and the technical state-of-the-art.

Keywords: measurement uncertainty; permissible bias; permissible imprecision

References

  • 1.

    International Standard Medical laboratories – Requirements for quality and competence, ISO 15189-2012(E),1–39.Google Scholar

  • 2.

    International Organisation for Standardisation. ISO/IEC Guide 98-3:2008 Uncertainty of measurement. Part 3: guide to the expression of uncertainty in measurement (GUM:1995). Genf, ISBN 92-67-10188-9.Google Scholar

  • 3.

    Lillo R, Salinas M, Lopez-Carrigos M, Naranjo-Santana Y, Gutierrez M, Marin MD, et al. Reducing preanalytical laboratory sampling errors through educational and technological interventions. Clin Lab 2012;38:911–7.Web of ScienceGoogle Scholar

  • 4.

    Gurr E, Arzideh F, Brandhorst G. Gröning A, Haeckel R, Hoff T, et al. Exemplary standard operating procedure pre-examination. J Lab Med 2011;35:55–60.Google Scholar

  • 5.

    Clinical and Laboratory Standards Institute. Expression of measurement uncertainty in laboratory medicine; approved guideline, vol. 32. CLSI document C51-A. Wayne, PA: CLSI, 2012.Google Scholar

  • 6.

    Richtlinie der Bundesaerztekammer zur Qualitätssicherung laboratoriumsmedizinischer Untersuchungen. Dt Aerzteblatt 2008;105:C301–13. Available from: http://www.aerzteblatt.de/plus1308.

  • 7.

    Clinical Laboratory Standard Institute C24A3. Statistical quality control for quantitative measurement procedures: principles and definitions. Wayne, PA: CLSI, 2006.Google Scholar

  • 8.

    Haeckel R, Wosniok W. A new concept to derive permissible limits for analytical imprecision and bias considering diagnostic requirements and technical state-of-the-art. Clin Chem Lab Med 2011;49:623–35.Web of SciencePubMedGoogle Scholar

  • 9.

    Oosterhuis WP. Gross overestimation of total allowable error based on biological variation. Clin Chem 2011;57:1334–6.CrossrefWeb of SciencePubMedGoogle Scholar

  • 10.

    Fraser CG. Biological variation: from principles to practice. Washington DC: AACC Press, 2001:1–151.Google Scholar

  • 11.

    Haeckel R, Wosniok W. Observed, unknown distributions of clinical chemical quantities should be considered to be log-normal: a proposal. Clin Chem Lab Med 2010;48:1393–6.Web of ScienceGoogle Scholar

  • 12.

    Haeckel R, Haeckel H. The determination of glucose concentration in 20 microliter capillary blood, liquor and urine by the hexokinase method with the endpoint analyzer 5030 (Eppendorf). Z Klin Chem Klin Biochem 1972;10:453–61.Google Scholar

  • 13.

    Haeckel R, Mathias D. A two-point method for the determination of urea with the Gemsaec analyzer. Z Klin Chem Klin Biochem 1974;12:515–20.Google Scholar

  • 14.

    Permissible imprecision (pCVA) and combined uncertainty (pU%) for a particular measurand (xi). Available from: http:www.dgkl.de. Accessed 10 December, 2014.

  • 15.

    Richtlinie der Bundesärztekammer zur Qualitätssicherung quantitativer laboratoriumsmedizinischer Untersuchungen. Dt Aerzteblatt 2003;100:B2775–8. Available from: www.aerzteblatt.de/plus1308.

  • 16.

    Mina A, Favaloro EJ, Koutts J. A practical approach to instrument selection, evaluation, basic financial management and implementation in pathology and research. Clin Chem Lab Med 2008;46:1223–9.Web of SciencePubMedGoogle Scholar

  • 17.

    Krouwer JS. Setting performance goals and evaluating total analytical error for diagnostic assays. Clin Chem 2002;48:919–27.PubMedGoogle Scholar

  • 18.

    Westgard JO. Update on measurement uncertainty: new CLSI C51A guidance. Available from: www.westgard.com/clsi-c51.htm. Accessed 24 February, 2012.

  • 19.

    Klee GG. Tolerance limits for short-term analytical bias and analytical imprecision derived from clinical assay specificity. Clin Chem 1993;39:1514–8.PubMedGoogle Scholar

  • 20.

    Macdonald R. Quality assessment of quantitative analytical results in laboratory medicine by root mean square of measurement deviation. J Lab Med 2000;30:111–7.Google Scholar

  • 21.

    White GH. Basics of estimating measurement uncertainty. Clin Biochem Rev 2008;29:S53–60.Google Scholar

  • 22.

    Geilenkeuser WJ. Precision and accuracy in internal quality control of German laboratories – a survey performed by DGKL. J Lab Med 2005;29:11–6.Google Scholar

  • 23.

    Haeckel R, Wosniok W, Kratochvila J, Carobene A. A pragmatic approach for permissible limits in external assessment schemes with a compromise between biological variation and the state of the art. Clin Chem Lab Med 2012;50:833–9.PubMedWeb of ScienceGoogle Scholar

  • 24.

    Froslie KF, Godang K, Bollerslev J, Henriksen T, Roislien J, Veierod MB, et al. Correction of unexpected increasing trend in glucose measurements during 7 years recruitment to a cohort study. Clin Biochem 2011;44:1483–6.Web of ScienceGoogle Scholar

  • 25.

    Magnusson B, Ellison SL. Treatment of uncorrected measurement bias in uncertainty estimation for chemical measurements. Anal Bioanal Chem 2008;390:201–13.Web of SciencePubMedCrossrefGoogle Scholar

  • 26.

    Coucke W, van Blerk M, Libeer JC, van Campenhout C, Albert A. A new statistical method for evaluating long-term analytical performance of laboratories applied to an external quality assessment scheme for flow cytometry. Clin Chem Lab Med 2010;48:645–50.Web of SciencePubMedGoogle Scholar

  • 27.

    Arzideh F, Wosniok W, Gurr E, Hinsch W, Schumann G, Weinstock N, et al. A plea for intra-laboratory decision limits. Part 2. A bimodal deductive concept for determining decision limits from intra-laboratory data bases demonstrated by catalytic activity concentrations of enzymes. Clin Chem Lab Med 2007;45:1043–57.Web of ScienceGoogle Scholar

  • 28.

    Arzideh F, Wosniok W, Haeckel R. Reference limits of plasma and serum creatinine concentrations from intra-laboratory data bases of several German and Italian medical centres. Comparison between direct and indirect procedures. Clin Chem Acta 411;2010:215–21.Google Scholar

  • 29.

    Haeckel R, Schneider B. Detection of drift effects before calculating the standard deviation as a measure of analytical imprecision. J Clin Chem Clin Biochem 1983;21:491–7.Google Scholar

  • 30.

    Tonks DB. A study of the accuracy and precision of clinical chemistry determinations in 170 Canadian laboratories. Clin Chem 1963;9:217–31.Google Scholar

  • 31.

    Cotlove E, Harris EK, Williams GZ. Biological and analytic components of variation in long-term studies of serum constituents in normal subjects. Clin Chem 1970;16:1028–32.PubMedGoogle Scholar

  • 32.

    Stöckl D, Baadenhuijsen H, Fraser CG, Libeer JC, Hylthof Petersen P, Ricos C. Desirable routine analytical goals for quantities assayed in serum. Eur J Clin Chem Clin Biochem 1995;33:157–69.PubMedGoogle Scholar

  • 33.

    Braga F, Panteghini M. Standardization and analytical goals for glycated hemoglobin measurement. Clin Chem Lab Med 2013;51:1719–26.Web of SciencePubMedGoogle Scholar

  • 34.

    Niederau CM, Reinauer H. Evaluating a new, fully automated HPLC-ion exchange system (Merck-Hitachi L-9100) for determination of glycated hemoglobin. J Lab Med 1993;17:388–94.Google Scholar

  • 35.

    Ricos C et al. Available from: www.westgard.com. Biological variation database. The 2014 update.

  • 36.

    Klee G. A conceptual model for establishing tolerance limits for analytic bias and imprecision based on variations in population test distributions. Clin Chem Acta 1997;260:175–88.CrossrefGoogle Scholar

  • 37.

    Haeckel R, Wosniok W. Benefits of combining bias and imprecision in quality assurance of clinical chemistry procedures. J Lab Med 2007;31:87–9.Google Scholar

  • 38.

    Hylthoft Petersen P, Klee P. Influence of analytical bias and imprecision on the number of false positive results using Guideline-Driven Medical Decision Limits. Clin Chim Acta 2014;430:1–8.CrossrefWeb of ScienceGoogle Scholar

  • 39.

    Klee GG. Establishment of outcome-related analytic performance goals. Clin Chem 2010;56:714–22.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 40.

    Boyd JC. Cautions in the adoption of common reference intervals. Clin Chem 2008;54:238–9.CrossrefPubMedGoogle Scholar

  • 41.

    Aitchison J, Brown JA. The lognormal distribution. Cambridge: Cambridge University Press, 1969:1–176.Google Scholar

  • 42.

    Moore DS, McCabe GP. Introduction to the practice of statistics. New York: W. H. Freeman and Company, 1999:1–825.Google Scholar

  • 43.

    Thomas L. Clinical laboratory diagnostics. Frankfurt, Germany: TH-Books GmbH, 1998.Google Scholar

  • 44.

    Gressner AM, Arndt T. Lexikon der Medizinischen Laboratoriumsdiagnostik. Heidelberg: Springer Medizin Verlag, 2007:1–1411.Google Scholar

  • 45.

    Rustad P, Felding P, Lahti A, Hyltoft Petersen P. Descriptive analytical data and consequences for calculation of common reference intervals in the Nordic reference interval project 2000. Scand J Clin Lab Invest 2004;64:343–70.Google Scholar

About the article

Corresponding author: Rainer Haeckel, Bremer Zentrum für Laboratoriumsmedizin, Klinikum Bremen Mitte, 28305 Bremen, Germany, Phone: +49 412 273448, E-mail:


Received: 2014-09-01

Accepted: 2014-11-13

Published Online: 2015-01-23

Published in Print: 2015-07-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 53, Issue 8, Pages 1161–1171, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2014-0874.

Export Citation

©2015 by De Gruyter. Copyright Clearance Center

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Plebani Mario, Sciacovelli Laura, Bernardi Daniela, Aita Ada, Antonelli Giorgia, and Padoan Andrea
Clinical Biochemistry, 2018
[2]
Rainer Haeckel, Eberhard Gurr, Torsten Hoff, and on behalf of the working group Guid
LaboratoriumsMedizin, 2016, Volume 40, Number 4

Comments (0)

Please log in or register to comment.
Log in