Abstract
Background
With the worldwide increase of diabetes mellitus prevalence, ensuring that HbA1c assays are accurate is essential. External quality assessment (EQA) programs enable laboratories to verify that analytical methods perform according to the manufacturers’ specifications. However, assessing trueness requires commutable materials, a property that is rarely characterized for EQA materials.
Methods
The difference in bias approach was used to assess commutability of 26 processed quality control materials for 17 of the most frequently used HbA1c assays. Involved assays included immuno-assays, enzymatic assays, affinity, ion-exchange HPLC boronate affinity HPLC and capillary electrophoresis. The measurements were performed at manufacturers or expert laboratories. Assay trueness was additionally assessed against the IFCC reference measurement procedure using fresh clinical specimens that were distributed to 450 medical laboratories.
Results
Commutability of processed EQA materials was highly heterogeneous and globally insufficient to rigorously assess the trueness of HbA1c assays. Using fresh clinical specimens, mean bias was −0.13 mmol/mol for low HbA1c (34 mmol/mol), between +1.0 and +1.3 mmol/mol for intermediate HbA1c (49 and 58 mmol/mol) and +1.2 mmol/mol for elevated HbA1c (90 mmol/mol).
Conclusions
This study demonstrates that due to insufficient commutability, most processed EQA materials are unsuitable to assess trueness of HbA1c assays and agreement between the different assays. These materials can only provide information on comparability of individual laboratory results with its peers and on assay precision. Using fresh whole blood samples, this study additionally shows that most HbA1c assays are fairly accurate and meet the total allowable error quality target of 5 mmol/mol.
Acknowledgments
We thank EQA providers and manufacturers of quality control materials having shared the materials which commutability was assessed in this study.
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.
References
1. World Health Organization. Global report on diabetes. 2016.Search in Google Scholar
2. Bunn HF. Nonenzymatic glycosylation of protein: relevance to diabetes. Am J Med 1981;70:325–30.10.1016/0002-9343(81)90769-5Search in Google Scholar
3. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvasular complications of type 2 diabetes (UKPDS 35): prospective observational study. Br Med J 2000;321:405–12.10.1136/bmj.321.7258.405Search in Google Scholar
4. The Diabetes Control and Complications Trial Research Group (DCCT). The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial. Diabetes 1995;44:968–83.10.2337/diab.44.8.968Search in Google Scholar
5. Peterson KP, Pavlovich JG, Goldstein D, Little R, England J, Peterson CM, et al. What is hemoglobin A1c? An analysis of glycated hemoglobins by electrospray ionization mass spectrometry. Clin Chem 1998;44:1951–8.10.1093/clinchem/44.9.1951Search in Google Scholar
6. American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care 2017;40 (Suppl. 1):S11–24.10.2337/dc17-S005Search in Google Scholar
7. Gillery P. A history of HbA1c through Clinical Chemistry and Laboratory Medicine. Clin Chem Lab Med 2013;51:65–74.10.1515/cclm-2012-0548Search in Google Scholar
8. Miller WG, Jones GR, Horowitz GL, Weykamp C. Proficiency testing/external quality assessment: current challenges and future directions. Clin Chem 2011;57:1670–80.10.1373/clinchem.2011.168641Search in Google Scholar
9. Miller WG. Specimen materials, target values and commutability for external quality assessment (proficiency testing) schemes. Clin Chim Acta 2003;327:25–37.10.1016/S0009-8981(02)00370-4Search in Google Scholar
10. Miller WG, Myers GL. Commutability still matters. Clin Chem 2013;59:1291–3.10.1373/clinchem.2013.208785Search in Google Scholar PubMed
11. Vesper HW, Miller WG, Myers GL. Reference materials and commutability. Clin Biochem Rev 2007;28:139–47.Search in Google Scholar
12. Delatour V, Liu Q, Vesper HW. Commutability assessment of external quality assessment materials with the difference in bias approach: are acceptance criteria based on medical requirements too strict? Clin Chem 2016;62:1670–1.10.1373/clinchem.2016.261008Search in Google Scholar PubMed PubMed Central
13. Joint Committee for Guides in Metrology (JCGM). JCGM 200: 2012 International vocabulary of metrology – basic and general concepts and associated terms (VIM) – 3rd edition. 2012.Search in Google Scholar
14. Myers GL, Eckfeldt JH, Greenberg N, Levine JB, Miller WG, WiebeDA. CLSI C37-A: National Committee for Clinical Laboratory Standards. Preparation and validation of commutable frozen human serum pools as secondary reference materials for cholesterol measurements procedures; approved guideline. Wayne, PA: NCCLS Document C37-A 1999 NCCLS, 1999.Search in Google Scholar
15. Agence nationale de sécurité du médicament. Annales du contrôle national de qualité des analyses de biologie médicale – 15BIO1 – HbA1c. 2015.Search in Google Scholar
16. Little Randie R, Roberts William L. A review of variant hemoglobins interfering with hemoglobin A1c measurement. J Diabetes Sci Technol 2009;3:446–51.10.1177/193229680900300307Search in Google Scholar PubMed PubMed Central
17. INSTAND e.V. – Ringversuchsprogramm [Internet]. [cited 2019 April 29]. Available from: https://www.instand-ev.de/en/eqas/eqa-program.html.Search in Google Scholar
18. 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;54:1018–22.10.1373/clinchem.2007.100875Search in Google Scholar PubMed
19. Jeppsson J, Kobold U, Barr J, Hoelzel W, Hoshino T, Miedema K, et al. Approved IFCC reference method for the measurement of HbA1c in human blood. Clin Chem Lab Med 2002;35:78–89.10.1515/CCLM.2002.016Search in Google Scholar PubMed
20. Hoelzel W, Weykamp C, Jeppsson J-O, Miedema K, Barr JR, Goodall I, et al. IFCC Reference system for measurement of Hemoglobin A1c in human blood and the National Standardization Schemes in the unites States, Japan, and Sweden: a method-comparison study. Clin Chem 2004;50:166–74.10.1373/clinchem.2003.024802Search in Google Scholar PubMed
21. Miller WG, Schimmel H, Rej R, Greenberg N, Ceriotti F, Burns C, et al. IFCC working group recommendations for assessing commutability. Part 1: general experimental design. Clin Chem 2018;64:447–54.10.1373/clinchem.2017.277525Search in Google Scholar PubMed PubMed Central
22. 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;64:455–64.10.1373/clinchem.2017.277541Search in Google Scholar PubMed PubMed Central
23. Korzun WJ, Nilsson G, Bachmann LM, Myers GL, Sakurabayashi I, Nakajima K, et al. Difference in bias approach for commutability assessment: application to frozen pools of human serum measured by 8 direct methods for HDL and LDL cholesterol. Clin Chem 2015;61:1107–13.10.1373/clinchem.2015.240861Search in Google Scholar PubMed
24. Desirable Biological Variation Database Specifications – Westgard [Internet]. [cited 2019 April 29]. Available from: https://www.westgard.com/biodatabase1.htm.Search in Google Scholar
25. Weykamp C, John G, Gillery P, English E, Ji L, 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;61:752–9.10.1373/clinchem.2014.235333Search in Google Scholar PubMed PubMed Central
26. Little RR, Rohlfing CL. Assessing quality from an accuracy-based HbA1c proficiency survey. Clin Chem Lab Med 2016;54:e75–6.10.1515/cclm-2015-0972Search in Google Scholar PubMed PubMed Central
27. Kaiser P, Spannagl M, Van Campenhout C, Lenga Y, Siebelder C, Weykamp C. HbA1c: EQA in Germany, Belgium and the Netherlands using fresh whole blood samples with target values assigned with the IFCC reference system. Clin Chem Lab Med 2016;54:1769–75.10.1515/cclm-2016-0123Search in Google Scholar PubMed
28. Liu H, Wong L, Yong S, Liu Q, Teo TL, Lee TK, et al. Commutable whole blood reference materials for hemoglobin A1c validated on multiple clinical analyzers. Clin Chem Lab Med 2019;57:648–58.10.1515/cclm-2018-0861Search in Google Scholar PubMed
29. Weykamp C, John WG, English E, Erasmus RT, Sacks DB, on behalf of the EurA1c Trial Group. EurA1c: the European HbA1c trial to investigate the performance of HbA1c assays in 2166 laboratories across 17 countries and 24 manufacturers by use of the IFCC model for quality targets. Clin Chem 2018;64:1183–92.10.1373/clinchem.2018.288795Search in Google Scholar PubMed
30. 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;451:305–9.10.1016/j.cca.2015.10.014Search in Google Scholar PubMed
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2019-0219).
©2019 Walter de Gruyter GmbH, Berlin/Boston
