Serum 25-hydroxyvitamin D measurement in a large population survey with statistical harmonization of assay variation to an international standard.

CONTEXT

An automated application of Immunodiagnostic Systems Limited (IDS) OCTEIA 25-hydroxyvitamin D [25(OH)D] enzyme immunoassay was developed for analyses of 25(OH)D in more than 7000 participants of the 1958 cohort. Variation between 25(OH)D assays hampers between-study comparisons and the definition of relevant cutoffs for hypovitaminosis D.

OBJECTIVE

The objective of the study was to evaluate the importance of assay variation on the estimated prevalence of hypovitaminosis D and assess the use of statistical harmonization to overcome the observed differences.

DESIGN

Agreement analyses were performed between two commercial 25(OH)D assays (IDS enzyme immunoassay and Diasorin RIA), with validation using performance data from Vitamin D External Quality Assessment Scheme (DEQAS).

SETTING

The study was conducted in England, Scotland, and Wales.

PARTICIPANTS

Members of the 1958 British birth cohort participated in the study.

MAIN OUTCOME MEASURES

25(OH)D was measured both by IDS and Diasorin RIA in 781 samples. Additional quality control data were obtained through participation in DEQAS (five distributions throughout the survey).

RESULTS

Average 25(OH)D concentrations by IDS were -15.7 and -13.7 nmol/liter lower, compared with Diasorin or DEQAS mean, respectively (both P < 0.0001). Graphical examination demonstrated a dose-related bias between IDS with Diasorin and DEQAS mean, but log transformation removed the bias. After using the log difference between the measurements as an adjustment factor, there were no differences in average 25(OH)D concentrations (P >or= 0.21 for comparison of IDS with Diasorin or DEQAS) and estimates for hypovitaminosis D obtained by IDS were similar to Diasorin.

CONCLUSIONS

Differences between assays have implications for public health messages about hypovitaminosis D. Harmonization of results with DEQAS enabled the use of previously determined cutoffs for hypovitaminosis D.