25-Hydroxyvitamin D testing: challenging the performance of current automated immunoassays

Farrell, C.; Soldo, Joshua; Williams, Paul F.; Herrmann, Markus

doi:10.1515/cclm-2012-0522

Cited by 50 publications

(58 citation statements)

References 3 publications

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“…Only the SIEMENS Centaur assay appears to not achieve satisfactory performance (2,11) . If read uncritically one may conclude that latest generation assays are fi t for purpose.…”

Section: Markus Herrmannmentioning

confidence: 99%

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The measurement of 25-hydroxy vitamin D – an analytical challenge

Herrmann

2012

Clinical Chemistry and Laboratory Medicine (CCLM)

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Over the last decade requests for the measurement of 25-hydroxy vitamin D (25-OHD) have risen exponentially. For example, statistics from the Australian government provides evidence for a 100-fold increase between 2000 and 2010 (1) . This burst of vitamin D requests has several causes including an increased awareness of the medical community and the general population to the high prevalence of vitamin D defi ciency and its relevance for osteoporosis, cardiovascular disease, malignancies, infectious and autoimmune disease. The massively increased demand for 25-OHD testing has important implications for healthcare systems and clinical laboratories. Whereas healthcare systems worldwide face an explosion of costs for 25-OHD testing, laboratories have to adopt methods that can cope with the elevated workload. External quality control programs show that most laboratories use automated immunoassays. Diagnostic manufacturers have identifi ed 25-OHD as a highly profi table and strategic test, which has lead to the commercialization of new automated immunoassays during recent years. However, it has to be acknowledged that 25-OHD is a challenging analyte to accurately measure in human blood (2) . Analytical diffi culties are related to its lipohilic nature, strong affi nity to vitamin D binding protein (VDBP) and association with human serum albumin, as well as the presence of very low to high levels of 25-OH vitamin D 3 (25-OHD 3 ) and/or 25-OH vitamin D 2 (25-OHD 2 ), multiple 25-OHD metabolites (e.g., 24,25-dihydroxy vitamin D 3 ), C3-epimer of 25-OHD 3 and 25-OHD 2 (25-OHD 3 -epi and 25-OHD 2 -epi), and other sources of assay interference, such as heterophilic antibodies. Therefore, 25-OH vitamin D immunoassays are required to detect 25-OHD 2 and 25-OHD 3 in an equimolar fashion and report a total 25-OHD result.Previous automated immunoassay comparison studies have demonstrated signifi cant analytical limitations for some of these assays (2, 3) . External quality assurance programs, such as DEQAS, or the Quality Assurance Program of the Royal Australian College of Pathologists, also show a wide spread of reported results for the same sample, which in some cases vary from defi cient ( < 25 nmol/L) to suffi cient ( > 75 nmol/L). Analytical problems of 25-OHD immunoassays have also been noted by clinicians who often question the laboratory about results that do not correspond to the clinical picture of their patients. The apparent issues of automated immunoassays have resulted in the worldwide withdrawal of the Roche 25-OHD 3 assay in 2010 and to the modifi cation of the assay conditions of several other commercial immunoassays, such as SIEMENS Centaur, Abbott ARCHITECT and DiaSorin LIAISON. Regulatory bodies, such as the FDA have also become aware of analytical issues with some of the recently launched assays. For example, the FDA has imposed certain conditions on some of the recently cleared 510(k) assays, such as limiting the measuring range of the Abbott ARCHITECT assay from 13 ng/mL (32.5 nmol/ < L) to 96 ng/mL (240...

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“…Only the SIEMENS Centaur assay appears to not achieve satisfactory performance (2,11) . If read uncritically one may conclude that latest generation assays are fi t for purpose.…”

Section: Markus Herrmannmentioning

confidence: 99%

“…How these aspects affect assay performance is nicely shown in the study Farrell et al where automated 25-OHD immunoassays were specifi cally challenged with high and low samples as well as samples containing 25-OHD 2 and heterophilic antibodies (11) .…”

Section: Markus Herrmannmentioning

confidence: 99%

The measurement of 25-hydroxy vitamin D – an analytical challenge

Herrmann

2012

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…This study adds to a growing literature [9][10][11][12][13][14][15][16][17][22][23][24][25][26][27][28] [13,15,23]. In the accuracy performance testing using Labquality reference serum panel, both Roche and Abbott displayed a similar bias at higher 25(OH)D concentrations as with study serum samples.…”

Section: Discussionmentioning

confidence: 65%

“…Furthermore, LC-MS/ MS assays require specialized equipment and expertise. However, the development of automated assays for 25(OH) has proved to be problematic [12]. Vitamin D is difficult to measure, for a number of reasons.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the National Institute of Standards and Technology (NIST) and the University of Ghent have released standard reference materials (SRMs) in an attempt to improve the performance of currently available 25(OH)D assays. Nevertheless, discrepancies between the results of immunological assays and reference LC-MS/MS methods persist [11][12][13][14][15]. Unacceptable levels of assay bias have been demonstrated in samples from a number of patient groups at risk of vitamin D deficiency, including pregnant women, haemodialysis patients and patients in intensive care units [16,17].…”

Section: -Hydroxy Vitamin D (25(oh)d) Is the Predominant Circulatinmentioning

confidence: 99%

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Analytical and clinical performance of the new Fujirebio 25-OH vitamin D assay, a comparison with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and three other automated assays

Saleh

Müller

Eckardstein

2016

Clinical Chemistry and Laboratory Medicine (CCLM)

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Results: Intra-and inter-day imprecision of the Fujirebio 25(OH)D assay was < 5%. Fujirebio 25(OH)D assay showed the highest correlation among the assays tested with the LC-MS/MS method (R = 0.986). The mean relative bias obtained was -15.6% (Fujirebio), -12.7% (Beckman), -2.1% (Abbott) and 9.7% (Roche) as compared to LC-MS/ MS. Comparison with the Labquality certified reference serum panel yielded a mean bias of -11.8% (Fujirebio), -14.1% (Beckman), 4.4% (Abbott) and 3.2% (Roche), respectively. Compared to LC-MS/MS, the sensitivity of different methods in detecting vitamin D insufficiency ( < 50 nmol/L) varied from 100% for the Fujirebio assay to 72.7% for Roche, and specificity ranged from 94.4% for Roche to 87.6% for Beckman.

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Automated Competitive Protein‐Binding Assay for Total 25‐OH Vitamin D, Multicenter Evaluation and Practical Performance

Wielders

Carter²,

Eberl

et al. 2014

Clinical Laboratory Analysis

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Background:The Roche Elecsys Vitamin D Total competitive protein-binding assay uses recombinant vitamin D binding protein for measuring 25-hydroxyvitamin D (25-OHD), which is different from commonly used antibody assays. Methods: The assay, standardized against LC-MS/MS, was tested at four sites. Evaluation included precision; between-laboratory variability; functional sensitivity; correlation to LC-MS/MS, HPLC, and immunoassays; as well as robustness, traceability, and EQAS performance. Results: Precision testing showed within-run coefficient of variations (CVs) of ࣘ7%, within-laboratory CVs of <9.5%, between-laboratory precision CVs of ࣘ10.1%, and a functional sensitivity below 9.8 nmol/l (at CV 12.9%). The assay showed equivalent 25-OHD levels for matched serum and plasma samples, good reagent lot-to-lot consistency in pooled sera over time, and good agreement with HPLC (relative bias −8.8%). Comparison with LC-MS/MS methods yielded relative biases of −15.4, −13.5, −10.2, and 3.2%. Comparison against immunoassays showed a relative bias of 14.5% (DiaSorin Liaison) and −58.2% (IDS-iSYS). The overall mean results in 2 years DE-QAS was 102% of the ALTM. In a certified reference patient panel, the average bias was <4% for the sum of 25-OHD2 and 25-OHD3. Conclusion: The Elecsys Vitamin D Total assay demonstrated good overall performance and is, according to present standards, very suitable for automated measurement of 25-OHD.

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25-Hydroxyvitamin D testing: challenging the performance of current automated immunoassays

Abstract: The latest generation of 25-OHD immunoassays has improved performance compared to previous assays. However, some immunoassays can still give discrepant results and this is most apparent when immunoassays are evaluated with a range of samples that challenge their analytical performance.

Cited by 50 publications

References 3 publications

The measurement of 25-hydroxy vitamin D – an analytical challenge

The measurement of 25-hydroxy vitamin D – an analytical challenge

Analytical and clinical performance of the new Fujirebio 25-OH vitamin D assay, a comparison with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and three other automated assays

Automated Competitive Protein‐Binding Assay for Total 25‐OH Vitamin D, Multicenter Evaluation and Practical Performance

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