A Method-bridging Study for Serum 25-hydroxyvitamin D to Standardize Historical Radioimmunoassay Data to Liquid...

Serum concentrations of 25-hydroxyvitamin D (25OHD) were measured for the National Health and Nutrition Examination Survey (NHANES) over the 1988-2006 period using a radioimmunoassay (RIA). In 2010, the Centers for Disease Control and Prevention (CDC) reissued RIA-harmonized 25OHD for NHANES 2004 and 2006, and advised users to adjust the original RIA data from 1988-1994 by using an equation. Beginning with NHANES 2007-2008, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method measured 25OHD.

A method comparison (bridging) study was designed to convert original RIA 25OHD to LC–MS/MS-equivalents. This report compares the predictive ability of a competitor regression model (Model 2) to the equations that CDC publicly released in 2015 (Model 1). The models differ by time period variable and use of transformations.

The two models provided similar adjusted R(2) (Model 1: 88.9%, Model 2: 90.4%) and root mean square error of prediction (plus or minus 9 to 10 nanomoles per liter [nmol/L]). Applying these models to NHANES 1988–2006 RIA 25OHD, the Pearson correlation of LC–MS/MS-equivalent concentrations was 0.99; the median difference between models was 0 nmol/L (interquartile range: –2.8 to 1 nmol/L). In contrast to declining RIA-harmonized 25OHD, both models showed little change in LC–MS/MS-predicted 25OHD over the 1988–2006 period. For 2001–2006, both models predicted similar prevalences of 25OHD less than 30 nmol/L, which were lower than the prevalence estimates based on RIA-harmonized data. Mean weighted LC–MS/MS-equivalent concentrations based on either model were about 3 nmol/L lower for the 1988–1994 survey and about 3 nmol/L higher for the 2001–2006 surveys, effectively smoothing out temporal trends observed using the harmonized RIA data.

Given minimal differences between models, final selection was based on public availability of the regression data. The bridging equations provide a way to use the previous RIA results to obtain LC–MS/MS-equivalent concentrations and evaluate temporal trends in vitamin D status.