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

IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

Print + Online
See all formats and pricing
More options …
Volume 57, Issue 7


Commutability of reference and control materials: an essential factor for assuring the quality of measurements in Laboratory Medicine

Federica Braga
  • Corresponding author
  • Research Centre for Metrological Traceability in Laboratory Medicine (CIRME), University of Milan, Via G.B. Grassi 74, Milano, Italy, Phone: +39 02 39042766
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mauro Panteghini
  • Research Centre for Metrological Traceability in Laboratory Medicine (CIRME), University of Milan, Milano, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2019-03-23 | DOI: https://doi.org/10.1515/cclm-2019-0154


Traceability to a common reference ensures equivalence of results obtained by different assays. Traceability is achieved by an unbroken sequence of calibrations, using reference materials (RMs) that must be commutable. Using non-commutable RMs for calibration will introduce a bias in the calibrated method producing incorrect results for clinical samples (CS). Commutability was defined in 1973 as “the ability of an enzyme material to show inter-assay activity changes comparable to those of the same enzyme in human serum” and later extended as a characteristic of all RMs. However, the concept is still poorly understood and appreciated. Commutability assessment has been covered in CLSI guidelines and requires: (a) selection of 20 CS spanning the relevant concentration range; (b) analysis of both RM and CS with the pair of procedures; (c) data elaboration using regression analysis and calculation if RM fall within the 95% prediction interval defined by CS. This approach has been criticized and to improve it The International Federation of Clinical Chemistry and Laboratory Medicine established a working group that recently finalized recommendations. Commutability is also a requirement for the applicability of external quality assessment (EQA) results in the evaluation of the performance of participating laboratories in terms of standardization of their measurements. Unfortunately, EQA materials are usually not validated for commutability.

Keywords: commutability; standardization; uncertainty


  • 1.

    Panteghini M. Traceability as a unique tool to improve standardization in laboratory medicine. Clin Biochem 2009;42:236–40.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 2.

    Braga F, Panteghini M. Verification of in vitro medical diagnostics (IVD) metrological traceability: responsibilities and strategies. Clin Chim Acta 2014;432:55–61.CrossrefWeb of SciencePubMedGoogle Scholar

  • 3.

    Young IS. The enduring importance and challenge of commutability. Clin Chem 2018;64:421–3.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 4.

    Fasce CF Jr, Rej R, Copeland WH, Vanderlinde RE. A discussion of enzyme reference materials: applications and specifications. Clin Chem 1973;19:5–9.PubMedGoogle Scholar

  • 5.

    Rej R, Jenny RW, Bretaudiere JP. Quality control in clinical chemistry: characterization of reference materials. Talanta 1984;31:851–62.CrossrefPubMedGoogle Scholar

  • 6.

    JCGM 200:2012. International vocabulary of metrology – basic and general concepts and associated terms (VIM 3), 3rd ed. 2008 version with minor corrections. Sevres, France, 2012.Google Scholar

  • 7.

    Franzini C, Ceriotti F. Impact of reference materials on accuracy in clinical chemistry. Clin Biochem 1998;31:449–57.CrossrefPubMedGoogle Scholar

  • 8.

    Panteghini M, Ceriotti F, Schumann G, Siekmann L. Establishing a reference system in clinical enzymology. Clin Chem Lab Med 2001;39:795–800.PubMedGoogle Scholar

  • 9.

    Dati F, Panteghini M, Apple FS, Christenson RH, Mair J, Wu AH. Proposals from the IFCC Committee on Standardization of Markers of Cardiac Damage (C-SMCD): strategies and concepts on standardization of cardiac marker assays. Scand J Clin Lab Invest Suppl 1999;230:113–23.PubMedGoogle Scholar

  • 10.

    Infusino I, Frusciante E, Ferrero CA, Panteghini M. Commutability of two JCTLM-listed secondary reference materials for two commercial lithium assays. Clin Chim Acta 2012;414:152–3.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 11.

    Zegers I, Keller T, Schreiber W, Sheldon J, Albertini R, Blirup-Jensen S, et al. Characterization of the new serum protein reference material ERM-DA470k/IFCC: value assignment by immunoassay. Clin Chem 2010;56:1880–8.Web of SciencePubMedCrossrefGoogle Scholar

  • 12.

    Infusino I, Braga F, Valente C, Panteghini M. Commutability of the ERM-DA470k reference material for two assays measuring serum albumin using immunochemical principles. Clin Chem Lab Med 2011;49:1383–4.PubMedWeb of ScienceGoogle Scholar

  • 13.

    Braga F, Infusino I, Frusciante E, Ceriotti F, Panteghini M. Trueness evaluation and verification of interassay agreement of 11 serum IgA measuring systems: implications for medical decisions. Clin Chem 2019;65:473–83.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 14.

    Infusino I, Valente C, Dolci A, Panteghini M. Standardization of ceruloplasmin measurements is still an issue despite the availability of a common reference material. Anal Bioanal Chem 2010;397:521–5.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 15.

    Zegers I, Beetham R, Keller T, Sheldon J, Bullock D, MacKenzie F, et al. The importance of commutability of reference materials used as calibrators: the example of ceruloplasmin. Clin Chem 2013;59:1322–9.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 16.

    Thienpont LM, Van Uytfanghe K, Beastall G, Faix JD, Ieiri T, Miller WG, et al. IFCC Working Group on Standardization of Thyroid Function Tests. Report of the IFCC Working Group for Standardization of Thyroid Function Tests; Part 1: Thyroid-stimulating hormone. Clin Chem 2010;56:902–11.CrossrefWeb of ScienceGoogle Scholar

  • 17.

    Miller WG, Myers GL, Rej R. Why commutability matters. Clin Chem 2006;52:553–4.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 18.

    Miller WG, Myers GL. Commutability still matters. Clin Chem 2013;59:1291–3.Web of SciencePubMedCrossrefGoogle Scholar

  • 19.

    ISO 15194:2009. In vitro diagnostic medical devices – measurement of quantities in samples of biological origin – Requirements for certified reference materials and content of supporting documentation. 2nd ed. Geneva, Switzerland: ISO, 2009.Google Scholar

  • 20.

    ISO 17034:2016. General requirements for the competence of reference material producers. Geneva, Switzerland: ISO, 2016.Google Scholar

  • 21.

    Panteghini M, Myers GL, Miller GW, Greenberg N. The importance of metrological traceability on the validity of creatinine measurement as an index of renal function. Clin Chem Lab Med 2006;44:1187–92.Google Scholar

  • 22.

    Deprez L, Toussaint B, Zegers I, Schimmel H, Grote-Koska D, Klauke R, et al. Commutability assessment of candidate reference materials for pancreatic α-amylase. Clin Chem 2018;64:1193–202.CrossrefWeb of SciencePubMedGoogle Scholar

  • 23.

    Andreasson U, Kuhlmann J, Pannee J, Umek RM, Stoops E, Vanderstichele H, et al. Commutability of the certified reference materials for the standardization of β-amyloid 1–42 assay in human cerebrospinal fluid: lessons for tau and β-amyloid 1–40 measurements. Clin Chem Lab Med 2018;56:2058–66.CrossrefWeb of SciencePubMedGoogle Scholar

  • 24.

    CLSI. Characterization and qualification of commutable reference materials for laboratory medicine; Approved guideline. Document EP30-A (formerly C53-A). Wayne, PA: Clinical and Laboratory Standards Institute, 2010.Google Scholar

  • 25.

    CLSI. Evaluation of commutability of processed samples: approved guideline – 3rd ed. Document EP14-A3. Wayne, PA: Clinical and Laboratory Standards Institute, 2014.Google Scholar

  • 26.

    Miller WG, Schimmel H, Rej R, Greenberg N, Ceriotti F, Burns C, et al. for the IFCC Working Group on Commutability. IFCC working group recommendations for assessing commutability. Part 1: General experimental design. Clin Chem 2018;64:447–54.CrossrefGoogle Scholar

  • 27.

    Nilsson G, Budd JR, Greenberg N, Delatour V, Rej R, Panteghini M, et al. IFCC working group recommendations for assessing commutability. Part 2: Using the difference in bias between a reference material and clinical samples. Clin Chem 2018;64:455–64.CrossrefWeb of ScienceGoogle Scholar

  • 28.

    Budd JR, Weykamp C, Rej R, MacKenzie F, Ceriotti F, Greenberg N, et al. for the IFCC Working Group on Commutability. IFCC working group recommendations for assessing commutability. Part 3: Using the calibration effectiveness of a reference material. Clin Chem 2018;64:465–74.Web of ScienceCrossrefGoogle Scholar

  • 29.

    Sandberg S, Fraser CG, Horvath AR, Jansen R, Jones G,Oosterhuis W, et al. Defining analytical performance specifications: Consensus Statement from the 1st Strategic Conference of the European Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem Lab Med 2015;53:833–5.PubMedWeb of ScienceGoogle Scholar

  • 30.

    Panteghini M. Application of traceability concepts to analytical quality control may reconcile total error with uncertainty of measurement. Clin Chem Lab Med 2010;48:7–10.PubMedWeb of ScienceGoogle Scholar

  • 31.

    Braga F, Pasqualetti S, Panteghini M. The role of external quality assessment in the verification of in vitro medical diagnostics in the traceability era. Clin Biochem 2018;57:23–8.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 32.

    Miller WG, Jones GR, Horowitz GL, Weykamp C. Proficiency testing/external quality assessment: current challenges and future directions. Clin Chem 2011;57:1670–80.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 33.

    CLSI. Preparation and validation of commutable frozen human serum pools as secondary reference materials for cholesterol measurement procedures: approved guideline. Document C37-A. Wayne, PA: Clinical and Laboratory Standards Institute, 1999.Google Scholar

  • 34.

    James D, Ames D, Lopez B, Still R, Simpson W, Twomey P. External quality assessment: best practice. J Clin Pathol 2014;67:651–5.CrossrefWeb of SciencePubMedGoogle Scholar

  • 35.

    Jones GRD, Albarede S, Kesseler D, MacKenzie F, Mammen J, Pedersen M, et al. EFLM Task Finish Group – Analytical Performance Specifications for EQAS (TFG-APSEQA). Analytical performance specifications for external quality assessment – definitions and descriptions. Clin Chem Lab Med 2017;55:949–55.PubMedGoogle Scholar

  • 36.

    Stepman HC, Tiikkainen U, Stöckl D, Vesper HW, Edwards SH, Laitinen H, et al. Measurements for 8 common analytes in native sera identify inadequate standardization among 6 routine laboratory assays. Clin Chem 2014;60:855–63.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 37.

    Weykamp C, Secchiero S, Plebani M, Thelen M, Cobbaert C, Thomas A, et al. Analytical performance of 17 general chemistry analytes across countries and across manufacturers in the INPUtS project of EQA organizers in Italy, the Netherlands, Portugal, United Kingdom and Spain. Clin Chem Lab Med 2017;55:203–11.Web of SciencePubMedGoogle Scholar

  • 38.

    Kristensen GB, Rustad P, Berg JP, Aakre KM. Analytical bias exceeding desirable quality goal in 4 out of 5 common immunoassays: results of a native single serum sample external quality assessment program for cobalamin, folate, ferritin, thyroid-stimulating hormone, and free T4 analyses. Clin Chem 2016;62:1255–63.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 39.

    Ferraro S, Braga F, Panteghini M. Laboratory medicine in the new healthcare environment. Clin Chem Lab Med 2016;54:523–33.PubMedWeb of ScienceGoogle Scholar

  • 40.

    Braga F, Infusino I, Panteghini M. Performance criteria for combined uncertainty budget in the implementation of metrological traceability. Clin Chem Lab Med 2015;53:905–12.Web of SciencePubMedGoogle Scholar

  • 41.

    Hage-Sleiman M, Capdevila L, Bailleul S, Lefevre G. High-sensitivity cardiac troponin-I analytical imprecisions evaluated by internal quality control or imprecision profile. Clin Chem Lab Med 2019;57:e49–51.Web of ScienceCrossrefPubMedGoogle Scholar

About the article

Received: 2019-02-08

Accepted: 2019-02-25

Published Online: 2019-03-23

Published in Print: 2019-06-26

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 7, Pages 967–973, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2019-0154.

Export Citation

©2019 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

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.

Simona Ferraro and Mauro Panteghini
The American Journal of Clinical Nutrition, 2019, Volume 110, Number 3, Page 780

Comments (0)

Please log in or register to comment.
Log in