Harmonization of Measurement Results of the Alcohol Biomarker Carbohydrate- Deficient Transferrin by Use of the Toolbox of Technical Procedures of the International Consortium for Harmonization of Clinical Laboratory Results C. Weykamp, J. Wielders, A. Helander, R.F. Anton, V. Bianchi, J.-O. Jeppsson, C. Siebelder, J.B. Whitfield, and F. Schellenberg on behalf of the IFCC Working Group on Standardization of Carbohydrate-Deficient Transferrin July © Copyright 2014 by the American Association for Clinical Chemistry

© Copyright 2009 by the American Association for Clinical Chemistry Introduction  What is CDT?  Carbohydrate-deficient transferrin  Alcohol biomarker  Why measured?  Identify chronic alcohol overconsumption (memory of several weeks)  Monitor abstinence during treatment

© Copyright 2009 by the American Association for Clinical Chemistry Introduction  What is Harmonization? Effort to get equivalent (the same) results in a sample for all routine methods when there is no reference measurement procedure of higher metrological order  Why Harmonization? Equivalent results enable effective use of clinical guidelines for disease diagnosis and patient management

© Copyright 2009 by the American Association for Clinical Chemistry Introduction  Aim of this Study Harmonization of results of CDT using the harmonization toolbox of the International Consortium for Harmonization of Clinical Laboratory Results (ICHCLR)  Associated papers in same issue of Clin Chem  Editorial: Zegers I and Schimmel H. To Harmonize and Standardize: Making Measurement Results Comparable. Clin Chem 2014;60:911.  Q&A: Harmonization of Test Results: What Are the Challenges; How Can We Make It Better? Clin Chem 2014;60:923.

© Copyright 2009 by the American Association for Clinical Chemistry Question  Why is harmonization of CDT important?

© Copyright 2009 by the American Association for Clinical Chemistry Materials & Methods: Tools in the Toolbox

© Copyright 2009 by the American Association for Clinical Chemistry Materials & Methods: Table 1. Samples in the Study. For the Assessment part of the study two batches of frozen candidate reference materials (cRMs) and 3 batches of lyophilized candidate reference materials were included. To monitor the success of the harmonization effort one batch of frozen candidate reference material and 27 single donation specimens of patients were included in the study. cRMP, candidate reference method procedure.

© Copyright 2009 by the American Association for Clinical Chemistry Question  Why is commutability of a reference material important?

© Copyright 2009 by the American Association for Clinical Chemistry Results: Table 2. Harmonization Potential. A first requirement for harmonization is that the routine tests to be harmonized have the potential to be harmonized. The results in this table show that the reproducibility, the linearity and the heterogeneity of the respective tests are good enough to allow harmonization.

© Copyright 2009 by the American Association for Clinical Chemistry Results: Fig. 1. Bland–Altman plots for commutability. Commutability of the 3 batches of lyophilized cRMs (Lyo cRM 2, 3, 4) and 1 batch of frozen cRMs (Fro cRM 2) for the routine MPs. CDT concentrations in IFCC CDT units are on the x-axis. Differences in CDT between the respective routine MPs and the cRMP in IFCC CDT units are on the y-axis.

© Copyright 2009 by the American Association for Clinical Chemistry Results Table 3. Targeting reference materials. Successful use of reference materials requires that it is possible to assign reliable target values. The results in table 3 show that it is possible to target the reference materials for CDT with a network of 6 reference laboratories operating the reference method: the targeting is reproducible and the uncertainty is low.

© Copyright 2009 by the American Association for Clinical Chemistry Results  Success of harmonization can be derived from:  The reduction of the intermethod CV in patients (from 8.8 to 3.4%)  The recovery of the target set by the reference method (3.07% is measured whereas the target is 3.09)  The fact that recovery is fine for all routine methods (ranging from 2.97 to 3.13 with a target of 3.09%)  All these parameters indicate success of harmonization.

© Copyright 2009 by the American Association for Clinical Chemistry Results Table 4. Success of harmonization of CDT routine measurement procedures (MPs): inter- method CV and recovery target values after calibration with frozen cRMs.

© Copyright 2009 by the American Association for Clinical Chemistry Question  Why is the Toolbox of the consortium so convenient?

© Copyright 2009 by the American Association for Clinical Chemistry Summary/Conclusions  CDT Results can be harmonized  There is harmonization potential  Reference materials available  Reference method available  Manufacturers expressed intention to harmonize  Success demonstrated  Toolbox of the ICHCLR is efficient  As demonstrated in the process of harmonizing CDT

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