Baseline Assessment of 25-Hydroxyvitamin D Assay Performance: A Vitamin D Standardization Program (VDSP) Interlaboratory Comparison Study

Abstract

The Vitamin D Standardization Program (VDSP) coordinated an interlaboratory study to assess the comparability of measurements of total 25-hydroxyvitamin D [25(OH)D] in human serum, which is the primary marker of vitamin D status. A set of 50 individual donor samples were analyzed by 15 different laboratories representing national nutrition surveys, assay manufacturers, and clinical and/or research laboratories to provide results for total 25(OH)D using both immunoassays (IAs) and LC tandem MS (MS/MS). The results were evaluated relative to bias compared with the target values assigned based on a combination of measurements at Ghent University (Belgium) and the U.S. National Institute of Standards and Technology using reference measurement procedures for the determination of 25(OH)D2 and 25(OH)D3. CV and mean bias for each laboratory and assay platform were assessed and compared with previously established VDSP performance criteria, namely CV ≤ 10% and mean bias ≤ 5%. Nearly all LC-MS/MS results achieved VDSP criteria, whereas only 50% of IAs met the criterion for a ≤10% CV and only three of eight IAs achieved the ≤5% bias. These results establish a benchmark for the evaluation of 25(OH)D assay performance and standardization activities in the future.

Antenatal vitamin D exposure and childhood eczema, food allergy, asthma and allergic rhinitis at 2 and 5 years of age in the atopic disease‐specific Cork BASELINE Birth Cohort Study

“…While some studies have published relationships between maternal vitamin D intake and infant atopic outcomes, evaluation of the biomarker of exposure, 25(OH)D, is preferable to an estimate of dietary intake. A further consideration is the considerable variability between different analytical methods used to quantify serum 25(OH)D concentrations . It has been suggested that commercial assays produce more unreliable estimates at the higher and lower ends of the distribution of 25(OH)D concentrations, due to higher limits of detection and cross‐reactivity with downstream metabolites .…”

“…A further consideration is the considerable variability between different analytical methods used to quantify serum 25(OH)D concentrations . It has been suggested that commercial assays produce more unreliable estimates at the higher and lower ends of the distribution of 25(OH)D concentrations, due to higher limits of detection and cross‐reactivity with downstream metabolites . Particular attention should be given to chromatographically resolving minor circulating vitamin D metabolites known to interfere with 25(OH)D assays, especially in paediatric populations .…”

Vitamin D Measurement, the Debates Continue, New Analytes Have Emerged, Developments Have Variable Outcomes

“…In the last 10 years, much progress has been made to reduce bias and enable comparability between laboratories through the Vitamin D standardisation programme (VDSP) [22]. Recently, 15 clinical and research laboratories participated in an inter-laboratory comparison study coordinated by the VDSP; nearly all LC-MS/MS results achieved VDSP criteria (CV ≤ 10% and mean bias ≤ 5% against NIST RMP/Ghent University), whereas only 50% of immunoassays met the criterion for a ≤ 10% CV and only three of eight immunoassays achieved the ≤ 5% bias [23]. It is now widely accepted that a standardised measurement of 25(OH)D is a LC-MS/MS method that is aligned to NIST RMP, with quality assurance certified by DEQAS.…”

The (Sun)Light and Dark of 25-Hydroxyvitamin D Testing

“…In 2011, a study was undertaken by the VDSP to determine the baseline of 25OHD assay performance with both immunoassays and LC-MS/MS assays in different laboratory environments (61). The study consisted of each laboratory running 50 patient samples that had 25OHD3, 25OHD2, and 3-epi-25OHD3 concentrations assigned by reference measurement procedures at NIST and at Ghent University on their current 25OHD assay, and the results were compared.…”

“…They found that 6 out of 8 LC-MS/MS assays passed the VDSCP criteria of ≤10% CV and bias of ≤5%. However, only 4 out of 8 immunoassays passed the ≤10% CV criterion, and only 3 out of 8 passed the ≤5% bias requirement (61). Another VDSCP interlaboratory study is currently underway to see if this performance has improved (62).…”