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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.

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1437-4331
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Volume 53, Issue 9

Issues

Using the likelihood ratio to evaluate allowable total error – an example with glycated hemoglobin (HbA1c)

Arne Åsberg / Ingrid Hov Odsæter
  • Corresponding author
  • Department of Clinical Chemistry, Trondheim University Hospital, Trondheim, Norway
  • Faculty of Medicine, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Sven Magnus Carlsen
  • Department of Cancer Research and Molecular Medicine, Unit for Applied Clinical Research, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
  • Department of Endocrinology, Trondheim University Hospital, Trondheim, Norway
  • Other articles by this author:
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/ Gustav Mikkelsen
Published Online: 2015-04-18 | DOI: https://doi.org/10.1515/cclm-2014-1125

Abstract

Background: Allowable total error is derived in many ways, often from data on biological variation in normal individuals. We present a new principle for evaluating allowable total error: What are the diagnostic consequences of allowable total errors in terms of errors in likelihood ratio (LR)? Glycated hemoglobin A1c in blood (HbA1c) in diagnosing diabetes mellitus is used as an example. Allowable total error for HbA1c is 3.0% derived from data on biological variation compared to 6.0% as defined by National Glycohemoglobin Standardization Program (NGSP).

Methods: We estimated a function for LR of HbA1c in diagnosing diabetes mellitus using logistic regression with a clinical database (n=572) where diabetes status was defined by WHO criteria. Then we estimated errors in LR that correspond to errors in the measurement of HbA1c.

Results: Measuring HbA1c 3% too low at HbA1c of 6.5 percentage points (the suggested diagnostic limit) gives a LR of 0.36 times the correct LR, while measuring HbA1c 3% too high gives a LR of 2.77 times the correct LR. The corresponding errors in LR for allowable total error of 6% are 0.13 and 7.69 times the correct LR, respectively.

Conclusions: These principles of evaluating allowable total error can be applied to any diagnostically used analyte where the distribution of the analyte’s concentration is known in patients with and without the disease in a clinically relevant population. In the example used, the allowable total error of 6% leads to very erroneous LRs, suggesting that the NGSP limits of ±6% are too liberal.

Keywords: assessment; healthcare quality; diagnostic errors; hemoglobin A; glycosylated; logistic regression

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About the article

Corresponding author: Ingrid Hov Odsæter, Department of Clinical Chemistry, Trondheim University Hospital, 7006 Trondheim, Norway; and Faculty of Medicine, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway, E-mail:


Received: 2014-11-17

Accepted: 2015-03-12

Published Online: 2015-04-18

Published in Print: 2015-08-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 53, Issue 9, Pages 1459–1464, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2014-1125.

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