The Vitamin D Standardization Program (VDSP) Manual for Retrospective Laboratory Standardization of Serum 25-Hydroxyvitamin D Data

Abstract

Low concentrations of total 25-hydroxyvitamin D [25(OH)D], the principal biological measure of vitamin D status, have been associated with clinical and public health outcomes. The determination of levels under which there is an increase in the risk of disease, as well as comparisons across populations, have been difficult to establish due the large assay variability in measuring 25(OH)D. Accordingly, the Vitamin D Standardization Program (VDSP) includes the retrospective standardization of existing 25(OH)D values collected by epidemiological and clinical studies, as well as clinical trials, as one of its main objectives. We introduce methodology developed by the VDSP that can be used to standardize the measurement of time-stable analytes, including 25(OH)D, in samples that have been banked and maintained appropriately. Sample size estimation formulae are first applied to calculate the required number of banked blood samples to be reanalyzed using either of two approaches. In the first approach, existing samples are remeasured using the current measurement procedure, and an equation relating "old" to "current" measurements is obtained. A second set of sera, usually 40-50 single-donor serum samples, are measured with the current measurement procedure and an assay traceable to a reference measurement procedure and/or certified reference materials, which yields a second calibration equation. These two equations are combined to produce standardized levels from the original old values. This approach is necessary when study restrictions prevent serum samples from being shipped to an external laboratory and is illustrated with samples from the Canadian Health Measures Survey. When serum samples are permitted to be shared with other laboratories, or the study investigators can carry out the measurements with a traceable assay, a single calibration equation method is used. Existing samples are selected and remeasured using the available traceable assay. We outline the statistical theory supporting the VDSP protocol and provide implementation examples. The methods proposed are generalizable to any instance in which banked specimens have been properly prepared and stored and the analyte of interest is stable under those conditions.

Consensus statement from 2nd International Conference on Controversies in Vitamin D

“…Prospective standardization is the process whereby the initial measurements for a study are standardized using VDSP guidelines. Retrospective standardization of previously measured study samples is possible when appropriately stored serum samples are available [25][26][27]. In the discussion above, data from the Canadian Health Measures Surveys, the three German national surveys and the meta-analysis data cited by Cashman et al were all retrospectively standardized.…”

25-Hydroxyvitamin D assay standardisation and vitamin D guidelines paralysis

“…Virtually all of those, where serum total 25(OH)D was measured, reported only 1922 1929 1934 1939 1944 1949 1954 1959 1964 1969 1974 1979 1984 1989 1994 1999 2004 2009 unstandardised data. As a result, we recommend that the vitamin D field needs to work with researchers, journal editors and research funding agencies around the world to identify and promote keys studies for retrospective standardisation using methods and procedures developed by the VDSP (73,92) . At that point, the retrospectively standardised data could be re-analysed and published in meta-analyses based solely on standardised results (93) .…”

An evaluation of total 25-hydroxyvitamin D assay standardization: Where are we today?

“…However, assay variation has made it difficult or even impossible to compare or pool data from the many studies. For the purpose of being able to compare existing studies where 25(OH)D was measured on non-standardized assay, VDSP provides a manual for retrospectively standardizing laboratory results of 25(OH) [7]. It has become clear that interpretation of data from large cohort-based studies is highly dependent and influenced by the assay used and whether there has been a re-standardization of results.…”

“…Therefore, in 2010 the Vitamin D Standardization Program (VDSP) was founded with the focus of promoting standardized measurements of serum total 25(OH)D around the world [5,6]. VDSP developed tools and methods to standardize the measurements prospectively as well as retrospectively so also 25(OH)D measurements performed in past studies could be standardized [7].…”