Assessing the harmonization of current total vitamin B12 measurement methods: relevance and implications
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Abstract
Objectives
The UK National Institute for Health and Care Excellence has recommended thresholds for total vitamin B12 (B12) assays with interchangeable results for identifying B12 deficiency. We assessed the agreement between B12 methods, to evaluate whether the thresholds may be assumed applicable to all assays.
Methods
A total of 19 External Quality Assessment (EQA) exercises (1,791 determinations) based on human subjects-pool materials and 97 serum samples were retrieved to characterize the agreement between Alinity and Architect (Abbott Diagnostics), Access DXi (Beckman Coulter Diagnostics), Atellica and ADVIA Centaur (Siemens Healthcare Solution) compared to Cobas (Roche Diagnostics), considered as comparator because its calibrator traceability to the World Health Organisation (WHO) International Standard (IS) code 03/178. Ordinary least squares and Bland-Altman were used for this purpose.
Results
Abbott and Beckman methods overestimated and underestimated, respectively, B12 concentrations vs. Roche and the other methods. We reported similar systematic or proportional error patterns between EQA and serum samples. Only Beckman was affected by both errors. Due to the wide Limit of Agreement Interval, we cannot confidently conclude on the agreement between Roche and the other methods. However, the inter-method bias was well lower than the desirable goal of 9.4 % for Abbott Architect and also lower for Siemens ADVIA Centaur.
Conclusions
The recommended thresholds for serum total B12 should not be assumed applicable to all assays, due to the poor agreement among the currently available methods, a limitation that persists despite the release of the WHO IS 03/178.
Acknowledgments
The authors thank Fabio Pasotti, Duilio Brugnoni working on B12 EQA program of the Italian Regional Coordination Center for Laboratory Medicine (Lombardy).
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Research ethics: The study was approved by the National Research Ethics Committee (Ref 11/H/1302/5).
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Informed consent: Not applicable.
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Author contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. S. Ferraro, conceptualization (lead) and writing original draft (equal); B.M. Cesana formal analysis (lead) and writing original draft (equal); S. daMolin, resources (equal); S. Buoro, resources (lead); N Jassam resources (equal); JH Barth resources (equal); S. Marcovina: reviewing and editing (lead); M.Tosi reviewing and editing (supporting); GV Zuccotti reviewing and editing (supporting).
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Use of Large Language Models, AI and Machine Learning Tools: Not applicable.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: None declared.
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Data availability: The raw data can be obtained on request from the corresponding author.
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Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0939).
© 2025 Walter de Gruyter GmbH, Berlin/Boston
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