Personalising laboratory medicine in the ‘real world’: Assessing clinical utility, by clinical indication, of serum total B₁₂ and Active-B₁₂® (holotranscobalamin) in the diagnosis of vitamin B₁₂ deficiency

Abstract

Background: Assessing the pre and post test probability of disease in the context of routine health care is challenging. We wished to study how test performance parameters relating to clinical utility vary by clinical indication in a ‘real world’ setting. Methods: The diagnostic accuracy of serum total B<sub>12</sub> and Active-B<sub>12</sub>® (holotranscobalamin) was evaluated in a primary care population, using serum methylmalonic acid as the reference standard. We used electronic requesting to establish the clinical indication for each request. Routine requests from primary care for serum total B<sub>12</sub> were included if creatinine was also measured and estimated glomerular filtration rate was at least 60 ml/min/1.73m<sup>2</sup>. Results Clinical indications included peripheral neuropathy (n=168), anaemia (n=168), cognitive decline (n=125), suspected dietary deficiency (n=76), other (n=362). For peripheral neuropathy, the area under the receiver operator curve ± 95% confidence interval (AUC±CI) was 0.63 (0.54–0.71)(p=0.002) for total B<sub>12</sub> and 0.68 (0.60–0.77) (p<0.0001) for Active-B<sub>12</sub>®. For anaemia, AUC±CI was 0.56 (0.47–0.66)(p=0.10) for total B<sub>12</sub> and 0.69 (0.59–0.78) (p<0.0001) for Active-B<sub>12</sub>®. For cognitive decline, AUC±CI was 0.54 (0.43–0.65)(p=0.26) for total B<sub>12</sub> and 0.69 (0.58–0.80) (p=0.0002) for Active-B<sub>12</sub>®. The pre-post test change in probability of disease varied by clinical indication. Conclusion Combining diagnostic accuracy studies and electronic testing allows clinical utility to be assessed by clinical indication. Wider application of this would permit more personalised laboratory medicine. In this study, diagnostic performance of total B<sub>12</sub> and Active-B<sub>12</sub>® varied across all indications. Active-B<sub>12</sub>® provided better discrimination, but this may have reflected the cut-offs used.

Vitamin B12 – a scoping review for Nordic Nutrition Recommendations 2023

“…Circulating holoTC represents the active fraction (10–30%) of serum vitamin B 12 , and the test has been shown to provide a somewhat better or an equal discrimination compared to serum vitamin B 12 , also depending upon the decision limits used ( 52 ). Unlike the other biomarkers, HoloTC increases in the postprandial period and is therefore a better indicator of recent intake ( 14 ).…”

Vitamin B12 reference intervals on Beckman, Roche and Siemens analytical platforms

“…Though alternative biochemical markers have been proposed (e.g. active B12 and methyl malonic acid (MMA)), 1 the routine assessment of vitamin B12 status is most widely performed using total vitamin B12 measurement. Vitamin B12 is a complex molecule that exists in serum in multiple forms.…”

Preliminary evaluation of the diagnostic performance of Roche Elecsys® active vitamin B12 versus total vitamin B12 for vitamin B12 deficiency screening

“…AVB12 generally demonstrated better performances in the diagnosis of vitamin B12 deficiency than TVB12. 4,[11][12][13] Until now, only few manufacturers were offering AVB12, limiting its availability. Recently a new AVB12 assay was presented by Roche manufacturer: Roche Elecsys® Active B12 immunoassay.…”