Abstract
Objectives
The US Centers for Medicare & Medicaid Services proposed in 2019 that glycated hemoglobin A1c (HbA1c) be a CLIA′88 regulated analyte. People who commented expressed concerns that the proposed acceptance limit (AL, HbA1c in NGSP unit) ±10% for proficiency testing (PT) would be unable to maintain already improved analytical performance and guarantee the clinical utility of HbA1c testing. Assessing impact of various ALs on PT performance is needed to provide scientific evidence for adopting an appropriate AL.
Methods
Ten patient EDTA-whole blood specimens were distributed to 318 and 336 laboratories in the 2018 and 2019 PT events organized by Shanghai Center for Clinical Laboratory (SCCL). HbA1c concentrations were measured by participants using various methodologies commonly used in the USA and China. Targets were determined using secondary reference measurement procedures (SRM) at SCCL. “Failed Results” were those outside the SRM-defined target ± AL (5% through 10%). Laboratories with Failed Results ≥2 out of five samples per PT event obtained Event Unsatisfactory Status.
Results
HbA1c target values ranged 33.3 mmol/mol (5.2 NGSP%) −102.2 mmol/mol (11.5 NGSP%) for 2018 event, and 33.3 mmol/mol (5.2 NGSP%) −84.7 mmol/mol (9.9 NGSP%) for 2019 event. Overall Laboratory Event Unsatisfactory Rates were 11.3–12.2%, 4.8–5.3%, 0.9–3.1%, 0.6–2.2%, 0.6–1.4% and 0.6–1.4%, at AL of ±5, ±6, ±7, ±8, ±9 and ±10%, respectively.
Conclusions
The AL (in NGSP unit) of ±6% or ±7% for PT evaluation of HbA1c results would be appropriate, with satisfactory event scores for about 95% of participant laboratories in a PT event.
Funding source: Shanghai Natural Science Foundation
Award Identifier / Grant number: (19ZR1445600)
Funding source: National Key Research and Development Program of China
Award Identifier / Grant number: (2019YFF0216500)
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Research funding: Yi Ju is supported by Shanghai Natural Science Foundation (19ZR1445600) and National Key Research and Development Program of China (2019YFF0216500).
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Author contributions: Y.J. contributed inception of the study, analysis of the data and preparation of the manuscript. Z.C. contributed to the design of the study, interpretation of data, literature search, preparation and revision of the manuscript. Q.L. performed data analysis. L. T. implemented PT activities. Y.O. collected and processed data of PT participant laboratories. X.Y. prepared PT materials and samples. W.L. performed IFCC SRM analysis. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Not applicable.
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Ethical approval: Not applicable.
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Disclaimer: Use of trade names and commercial sources is for identification only and does not constitute endorsement by the Wadsworth Center of the New York State Department of Health, and the Upstate Medical University.
References
1. World Health Organization. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus: abbreviated report of a WHO consultation. Available from: http://www.who.int/diabetes/publications/report-hba1c_2011.pdf?ua=1 [accessed October 2020].Search in Google Scholar
2. American Diabetes Association. Standards of medical care in diabetes - 2017. Diabetes Care 2017;40(1 Suppl):S1–132.10.2337/dci17-0007Search in Google Scholar PubMed
3. International Expert Committee. International Expert Committee report on the role of the A1c assay in the diagnosis of diabetes. Diabetes Care 2009;32:1327–34.10.2337/dc09-9033Search in Google Scholar PubMed PubMed Central
4. Little, RR, Rohlfing, CL, Wiedmeyer, HM, Myers, GL, Sacks, DB, Goldstein, DE, NGSP Steering Committee. The national glycohemoglobin standardization program: a five-year progress report. Clin Chem 2001;47:1985–92.Search in Google Scholar
5. Little, RR, Rohlfing, C, Sacks, DB. The national glycohemoglobin standardization program: over 20 years of improving hemoglobin A1c measurement. Clin Chem 2019;65:839–48. https://doi.org/10.1373/clinchem.2018.296962.Search in Google Scholar PubMed PubMed Central
6. Little, RR, Rohlfing, CL. Sacks DB for the national glycohemoglobin standardization program (NGSP) steering committee. Status of hemoglobin A1c measurement and goals for improvement: from chaos to order for improving diabetes care. Clin Chem 2011;57:205–14. https://doi.org/10.1373/clinchem.2010.148841.Search in Google Scholar PubMed
7. Clinical laboratory improvement amendments of 1988 (CLIA) proficiency testing regulations related to analytes and acceptable performance - a proposed rule by the Centers for Medicare & Medicaid Services on 02/04/2019. Available from: https://www.federalregister.gov/documents/2019/02/04/2018-28363/clinical-laboratory-improvement-amendments-of-1988-clia-proficiency-testing-regulations-related-to [accessed October 2020].Search in Google Scholar
8. Liu, WB, Yu, Y, Tang, LP, Wang, MJ, Ou, YZ, Yu, XX, et al.. IFCC second reference measurement procedure for 4 HbA1c determination systems. Lab Med 2019;34:443–6.Search in Google Scholar
9. Lenters-Westra, E, English, E. Evaluating new HbA1c methods for adoption by the IFCC and NGSP reference networks using international quality targets. Clin Chem Lab Med 2017;55:1426–34. https://doi.org/10.1515/cclm-2017-0109.Search in Google Scholar PubMed
10. ISO 13528:2015(en) Statistical methods for use in proficiency testing by interlaboratory comparison. Available from: https://www.iso.org/obp/ui/#iso:std:iso:13528:ed-2:v2:en [accessed October 2020].Search in Google Scholar
11. US Department of Health and Human Services. Clinical laboratory improvement amendments of 1988 (CLIA) proficiency testing regulations related to analytes and acceptable performance 2019. Available from: https://www.govinfo.gov/content/pkg/FR-2019-02-04/pdf/2018-28363.pdf [accessed October 2020].Search in Google Scholar
12. International Federation of Clinical Chemistry and Laboratory Medicine. Approved laboratories of the IFCC Network laboratories for HbA1c. Available from: http://information.ifcchba1c.org/sustainable-implementation/reference-laboratories/list-reference-laboratories.aspx [accessed October 2020].Search in Google Scholar
13. Weykamp, C, John, G, Gillery, P, English, E, Ji, L, Lenters-Westra, E, et al.. IFCC task force on implementation of HbA1c standardization. Investigation of 2 models to set and evaluate quality targets for HbA1c: biological variation and sigma-metrics. Clin Chem 2015;61:752–9. https://doi.org/10.1373/clinchem.2014.235333.Search in Google Scholar PubMed PubMed Central
14. 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. https://doi.org/10.1515/cclm-2018-0861.Search in Google Scholar PubMed
15. 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
16. Delatour, V, Clouet-Foraison, N, Jaisson, S, Kaiser, P, Gillery, P. Beware of noncommutability of external quality assessment materials for hemoglobin A1c. Clin Chem 2020;66:390–1. https://doi.org/10.1093/clinchem/hvz024.Search in Google Scholar PubMed
17. AACC provides input on CLIA proficiency testing requirements. Available from: https://www.aacc.org/health-and-science-policy/advocacy/comment-letters/2019/aacc-provides-input-on-clia-pt-requirements [accessed October 2020].Search in Google Scholar
18. American College of physicians. Available from: https://www.acponline.org/acp_policy/letters/acp_comment_letter_clia_proposed_rule_2019.pdf [accessed October 2020].Search in Google Scholar
19. Klonoff, DC, Aron, D, Cohen, RM, Home, P, John, WG, Little, RR, et al.. The need for accuracy in hemoglobin A1c proficiency testing: why the proposed CLIA Rule of 2019 is a step backward. J Diabetes Sci Technol 2019;13:424–7. https://doi.org/10.1177/1932296819841699.Search in Google Scholar PubMed PubMed Central
20. Paxton, A. Idea to ease PT standard for HbA1c stirs alarm. CAP Today; 2019. Available from: https://www.captodayonline.com/idea-to-ease-pt-standard-for-hba1c-stirs-alarm/ [accessed October 2020].Search in Google Scholar
21. Åsberg, A, Odsæter, IH, Carlsen, SM, Mikkelsen, G. Using the likelihood ratio to evaluate allowable total error--An example with glycated hemoglobin (HbA1c). Clin Chem Lab Med 2015;53:1459–64. https://doi.org/10.1515/cclm-2014-1125.Search in Google Scholar PubMed
22. Cao, ZT, Botelho, JC, Rej, R, Vesper, H. Accuracy-based proficiency testing for testosterone measurements with immunoassays and liquid chromatography-mass spectrometry. Clin Chim Acta 2017;469:31–6. https://doi.org/10.1016/j.cca.2017.03.010.Search in Google Scholar PubMed PubMed Central
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