Vitamin D Assay Standardisation and the Deficiency Threshold: How Method Choice Moves the Diagnosis

Abstract

Despite two decades of standardisation effort through the Vitamin D Standardization Program (VDSP), clinically meaningful
differences between 25-hydroxyvitamin D assay platforms persist, and these differences are large enough, relative to the narrow
band separating commonly used deficiency and insufficiency thresholds, to change which diagnostic category an individual
patient's result falls into depending on which platform measured it. We systematically reviewed method comparison studies
published since VDSP standardisation efforts began, quantifying inter-platform bias at the specific concentrations corresponding
to the 20 ng/mL and 30 ng/mL thresholds most widely used to define deficiency and insufficiency. Inter-platform bias at these
thresholds ranged from -15% to +12% across the platforms reviewed even among assays certified as VDSP-traceable, sufficient to
reclassify a meaningful proportion of patients near either threshold. We discuss what this means for a laboratory reporting a
categorical deficiency classification rather than a numeric result alone, and for interpreting a patient's vitamin D trend across a
platform change.