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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 / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

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Volume 57, Issue 10


Extra-analytical sources of uncertainty: which ones really matter?

Andrea PadoanORCID iD: https://orcid.org/0000-0003-1284-7885
  • Corresponding author
  • Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
  • Department of Medicine – DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy, Phone: +390498212801, Fax: +390498211981
  • orcid.org/0000-0003-1284-7885
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Laura SciacovelliORCID iD: https://orcid.org/0000-0003-3156-1399 / Rui Zhou
  • Department of Laboratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, Beijing, P.R. China
  • Beijing Center for Clinical Laboratories, Beijing, P.R. China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mario PlebaniORCID iD: https://orcid.org/0000-0002-0270-1711
Published Online: 2019-05-23 | DOI: https://doi.org/10.1515/cclm-2019-0197


Since the endorsement by ISO15189:2012 of measurement uncertainty (MU) for the estimation of error in measurement procedures, the debate has been ongoing with questions concerning which method should be used for estimating MU and the benefits of using MU over other error methods. However, only limited attention has been given to extra-analytical sources of uncertainty and, currently, a clear standpoint is still missing. This opinion paper aims to evaluate whether extra-analytical variables could be included in MU. Considering coagulation tests as an example, the possible sources of preanalytical variations are evaluated by using a fishbone diagram. After excluding preanalytical errors, additional sources of uncertainty are divided into amenable to standardization/harmonization and/or possible random sources, which are not standardizable nor harmonizable. Finally, sources of uncertainty are evaluated for a possible inclusion into MU. In addition, postanalytical uncertainty is discussed, particularly considering the laboratory results calculated through a mathematical equation, derived from one or more quantities affected by their specific uncertainty.

Keywords: extra-analytical; harmonization; measurement uncertainty; postanalytical; preanalytical; standardization


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About the article

Received: 2019-02-20

Accepted: 2019-04-23

Published Online: 2019-05-23

Published in Print: 2019-09-25

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

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

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.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 57, Issue 10, Pages 1488–1493, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2019-0197.

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