Tracing a roadmap for vitamin B12 testing using the health technology assessment approach

Abstract

Abstract:In our hospital, we are currently working to manage the appropriateness of vitamin B 12 (B12) testing. Unfortunately, the classic evidence-based approach is unhelpful in this process and meta-analyzing data on the accuracy of this marker for cobalamin deficiency detection is misleading due to the lack of reference diagnostic methods. The approach currently proposed by the Health Technology Assessment (HTA) enables us to tackle the issue of B12 requests as a "healthcare" problem by considering the position of stakeholders involved in ordering, performing, interpreting the test, and receiving its results. Clinical expectations, methodological issues, and ethical aspects concerning the performance of the test can aid us in providing more guidance on the use of this marker. By building such structured information, hemodialysis patients and pregnant women have emerged as those groups preferentially requiring B12 testing, as it may potentially improve the clinical outcome. To avoid misinterpretation of B12 results more care should be taken in considering its biochemical and biological features, as well as the analytical issues. Spurious values obtained by current automated immunoassays may reflect suboptimal pre-analytical steps as well as known interfering conditions. Furthermore, the harmonization of results by available methods is still a farreaching goal and the approach to interpret an individual's results should be improved. Tracing a roadmap for B12 testing by exploiting the HTA model to balance the stakeholders' claims and maximizing the patient's outcome may help to manage the marker demand.

Tackling serum folate test in European countries within the health technology assessment paradigm: request appropriateness, assays and health outcomes

“…To improve harmonization of assays, some commercial folate methods have recently undergone recalibration to the NIBSC 03/178 International Standard in order to fulfil the European Union Directive on in vitro diagnostic medical devices that asks diagnostic manufacturers to ensure traceability of their analytical systems to recognized higher-order references [79]. However, tracing back the calibration of commercial assays to a new reference material can modify results and actually alter their relation to existing reference intervals and decision limits, invalidating the clinical decisionmaking criteria currently used [80][81][82]. In fact, we have recently experienced this problem when Roche Diagnostics has replaced the Folate III assay code 04476433190 (which was home-made calibrated) by the Folate III assay code 07559992190 (traceable to NIBSC 03/178 material).…”

Folate and vitamin B12 assays after recalibration to the WHO International Standard 03/178: making the interpretation as simple as possible, but not simpler

“…The recent alignment of serum folate and vitamin B12 (B12) assays to the WHO International Standard (IS) code 03/178 has produced a significant shift in the average vitamin measured values and triggered studies on the reevaluation of reference intervals (RI) for both biomarkers [1][2][3][4]. This also yielded the opportunity to update recommendations about the cost-effective application of both tests and the interpretation of marker concentrations in serum [5,6]. Authoritative guidelines, which define the risk for vitamin deficiency according to B12 and folate testing, indeed reported as interpretative criteria, RI estimated by using assays not traceable to the WHO IS 03/178 [7].…”

“…For both tests, cost-effectiveness is maximized when the request is applied to subjects at risk for deficiency and when the deficiency itself may represent a life-threatening condition or invalidate the treatment effect (e.g. in pregnant women or hemodialysis patients) [5,6]. On the contrary, tests should not be ordered to monitor or evaluate the effect of vitamin supplementation.…”

“…On the contrary, tests should not be ordered to monitor or evaluate the effect of vitamin supplementation. By applying these indications for an appropriate testing strategy, it was demonstrated an ~50% saving in laboratory costs, without compromising the patient safety [5,6].…”

“…In general, for serum B12 the capability of the test to rule out the deficiency at the individual level is low when a single threshold value, such as the lower reference limit (LRL), is adopted. Multiple thresholds have been validated by clinical studies establishing the relationship between marker concentrations, the probability of deficiency and the need for supplementation [5]. Accordingly, the establishment of RI is not helpful for interpreting B12 concentrations in serum.…”