Vitamin D: how to decide when you need it, regardless of laboratory results

When the laboratory changes, the decision may change. If a patient’s result is close to the threshold for reimbursement, a difference in methodology between laboratories may lead to a different classification of the same biological condition. In other words, a patient might be deemed eligible for reimbursement by one laboratory but not by another, even though nothing has changed from a clinical point of view. This is precisely the main implication of our work, carried out in collaboration with Professor Massimo Locatelli’s team. When a therapeutic or administrative decision depends on the strict application of a threshold value, analytical variability can lead to inconsistencies in access to care.

Note 96 is an outdated tool. These observations do not call into question the guiding principles of Note 96. The aim of promoting appropriate prescribing, avoiding unnecessary treatments and ensuring the sustainability of the National Health Service remains fully valid and serves as a fundamental reference point for clinical practice. However, new evidence suggests that biochemical thresholds cannot be regarded as absolute and self-sufficient criteria when laboratory data exhibit such significant methodological variability. Rather than replacing Note 96, we need to support its evolution in the light of current knowledge, emphasising clinical judgement and taking into account the inherent limitations of analytical methods.

The value of clinical judgement. Measuring 25-hydroxyvitamin D levels remains an essential tool in patient assessment, but it cannot be interpreted in isolation. Age, skeletal health, fracture risk, sun exposure, malabsorption conditions, drug therapies, metabolic comorbidities such as obesity or prediabetes, and the overall clinical context are equally important factors in treatment decisions. This is the same approach advocated by the recent international consensus published in *Endocrine Reviews*, according to which laboratory results constitute one element of clinical assessment and not its sole determinant.

Standardisation as a priority. The study also highlights another strategic need: to press ahead resolutely with the standardisation of vitamin D assay methods. Today, most measurements are carried out using automated immunometric assays, which are essential for coping with the high volumes of work in clinical laboratories. However, the differences that still exist between platforms demonstrate that the harmonisation process is not yet complete. Reducing variability means increasing the reliability of laboratory data, ensuring greater equity in clinical decision-making and also strengthening regulatory decisions. This is an objective that requires a shared commitment between laboratories, diagnostic system manufacturers, scientific societies and regulatory authorities.

Towards more personalised medicine. Modern medicine is gradually moving away from decision-making models based solely on threshold values, favouring an integrated approach that combines biological data, individual characteristics and clinical judgement. Vitamin D should be no exception. The evidence currently available does not suggest prescribing more vitamin D, nor does it suggest prescribing less. Rather, it suggests prescribing it more effectively, using laboratory data as a tool to support clinical decision-making rather than as an automatic administrative procedure. Note 96 should help to promote a more appropriate use of supplementation. Today, new scientific evidence indicates that this approach can take a further step forward: complementing biochemical criteria with a full understanding of the quality and limitations of laboratory data, thereby restoring clinical judgement to its rightful central role. For when a figure can vary depending on the method used to measure it, it is the doctor – and not the laboratory – who must continue to guide the therapeutic decision.

* Professor of Endocrinology and Metabolism, Head of the Endocrinology Department at the IRCCS San Raffaele Hospital in Milan,
Vita-Salute San Raffaele University in Milan