HbA1c: EQA in Germany, Belgium and the Netherlands using fresh whole blood samples with target values assigned with the IFCC reference system

Patricia Kaiser 1 , Michael Spannagl 1 , Christel van Campenhout 2 , Yolande Lenga 2 , Carla Siebelder 3  and Cas Weykamp 3
  • 1 INSTAND e.V., Reference Laboratory, Düsseldorf, Germany
  • 2 Scientific Institute of Public Health, Brussels, Belgium
  • 3 ERL, Queen Beatrix Hospital, Winterswijk, The Netherlands
Patricia Kaiser, Michael Spannagl, Christel van Campenhout, Yolande Lenga, Carla Siebelder and Cas Weykamp



External quality assessment/proficiency test (EQA/PT) organizers play an important role in monitoring the performance of HbA1c measurements. With increasing quality of the assays, HbA1c is increasingly used for diagnosis of diabetes and the demands on EQA/PT organizers themselves are rising constantly. EQA organizers in Germany (INSTAND), Belgium (WIV/IPV), and the Netherlands (SKML) organized a program with commutable samples and target values assigned with the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference system. The aim of this project was to confirm the logistic feasibility of organizing synchronically in the three countries, an accuracy-based EQA program with fresh whole blood, to investigate the performance of HbA1c assays within and across countries and manufacturers, and to review the EQA acceptance limits.


Throughout 2015, ten fresh whole blood samples were supplied to the participants. Aggregated results were evaluated according to the IFCC model for quality targets at four levels: overall, per country, per manufacturer, and per country per manufacturer.


Robust results in summer and winter demonstrated the feasibility of organizing an EQA with fresh whole blood samples in three countries. The overall performances, as well as the performance for each country were very similar: results fell within the IFCC criteria. Although substantial differences between results from different manufacturers were present, the performances of laboratories using tests of the same manufacturer were strikingly similar in the three countries, suggesting that the quality of HbA1c assays is for the most part manufacturer- related. The improved design of the EQA program also suggested that acceptance limits for performance can be reduced to approximately 8%.

    • Supplementary material
  • 1.

    American Diabetes Association. Standards of medical care in diabetes. 2011. Diabetes Care 2011;34(Suppl 1):S11–61.

  • 2.

    Sacks DB, Arnold M, Bakris GL, Bruns DE, Horvath AR, Kirkman MS, et al. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2011;57:e1–47.

  • 3.

    Nathan D. On behalf of the Expert Committee. International Expert Committee on the role of A1c assay in the diagnosis of diabetes. Diabetes Care 2009;32:1327–34.

  • 4.

    Mosca A, Paleari R, Carobene A, Weykamp C, Ceriotti F. Performance of glycated hemoglobin (HbA1c) methods evaluated with EQAS studies using fresh blood samples: still space for improvements. Clin Chim Acta 2015;451:305–9.

  • 5.

    EN ISO/IEC 17043, Conformity assessment –General requirements for proficiency testing. International Organization for Standardization (Geneva, Switzerland).

  • 6.

    ISO 13528, Statistical methods for use in proficiency testing by interlaboratory comparisons. International Organization for Standardization (Geneva, Switzerland).

  • 7.

    Jeppson JO, Kobold U, Barr J, Finke A, Hoelzel W, Hoshino T, et al. Approved IFCC reference method for measurement of HbA1c in human blood. Clin Chem Lab Med 2002;40:78–89.

  • 8.

    Kaiser P, Akerboom T, Molnar P, Reinauer H. Modified HPLC-electrospray ionization/mass spectrometry method for HbA1c based on IFCC reference measurement procedure. Clin Chem 2008;54:1018–22.

  • 9.

    Evaluation of measurement data – Guide to the expression of uncertainty in measurement. BIPM Joint Comm Guides Metrol 100:2008.

  • 10.

    Weykamp C, John G, Gillery P, English E, Li Linong, Lenters-Westra E, et al. Investigation of 2 models to set and evaluate quality targets for HbA1c: biological variation and sigma-metrics. Clin Chem 2015;61:752–9.

  • 11.

    Richtlinie der Bundesärztekammer zur Qualitätssicherung laboratoriums-medizinischer Untersuchungen. Dtsch Arztebl 2014;38:A1583–618.

  • 12.

    Mosca A, Weykamp C. Feasibility of an EQAS for HbA1c in Italy using fresh blood samples. Clin Chem Lab Med 2014;52:e151–3.

  • 13.

    Weykamp C, Mosca A, Gillery P, Panteghini M. The analytical goals for hemoglobin A(1c) measurement in IFCC units and national Glycohemoglobin Standardization Program Units are different. Clin Chem 2011;57:1204–6.

  • 14.

    Miller WG, Jones GR, Horowitz GL, Weykamp C. Proficiency testing/external quality assessment: current challenges and future directions. Clin Chem 2011;57:1677–80.

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Clinical Chemistry and Laboratory Medicine ( CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. CCLM welcomes contributions on the progress in fundamental and applied research and cutting-edge clinical laboratory medicine. It is one of the leading journals in the field, with an impact factor of over three. CCLM is the official journal of nine national clinical societies and associated with EFLM.