Cost effective measures to standardize serum 25(OH)D values from completed studies

Abstract

RMP reference measurement procedure VDSP Vitamin D Standardization Program 25-Hydroxyvitamin D [25(OH)D] assay variation is thwarting attempts to develop evidenced-based criteria for defining clinical states of vitamin D status, i.e., deficiency, insufficiency, sufficiency, and toxicity. Since 1968 when 25(OH)D was discovered through 2016, some 60,000 papers have been published with only a handful based on standardized 25(OH)D measurements [1]. This lack of standardized 25(OH)D measurements makes it difficult if not impossible to conduct meta analyses of the relationship of 25(OH)D to vitamin D clinical states in order to develop 25(OH)D cut-points. The challenge for the vitamin D field is to select key studies among those completed studies and, where stored samples exist, standardize the 25(OH)D measurements by calibrating the old values to values which are traceable to the Reference Measurement Procedures (RMPs) of the National Institute for Standards and Technology (NIST), Ghent University, and the Centers for Disease Control and Prevention (CDC). This is referred to as Retrospective Standardization. To accomplish retrospective standardization, the Vitamin D Standardization Program (VDSP) has developed two options for conducting calibration studies [2]. Option 1 has three steps: [1] Use results from the measurement of 40-50 single donor serum samples with RMP target values to develop an equation to convert values based on the current assay to the NIST-Ghent-CDC RMPs, [2] re-measure a statistically defined subsample of the stored sera from the completed study and develop an equation to convert past values to the current assay, and [3] merge the two sets of equations to form a single BMaster Equationt hat is used to convert past study 25(OH)D values to the NIST-Ghent University-CDC RMPs. A fourth step in this option might be to send a duplicate set of samples to a certified traceable laboratory for confirmation.Option 2 is similar except for the fact that all new 2(OH)D measurements are made by a laboratory which is certified to be traceable to the RMPs [2]. The traceable laboratory measures a statistically representative sample of all the stored sera and then, using regression analysis, a Master Equation is developed to predict NIST-Ghent-CDC traceable laboratory values from the original assay values. The Master Equation is then used to convert all of the old data to NIST-Ghent-CDC traceable values.Developing an affordable modified Option 1 is the goal of Drs. Jakab et al. in a thoughtful paper published recently in Osteoporosis International [3]. The authors propose using values from the analysis of samples distributed as part of the Vitamin D External Quality Assessment Scheme (DEQAS) to standardize the 206 25OHD measurements from the HunMen study by calibrating them to the RMPs.

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) .…”

Vitamin D: Moving Forward to Address Emerging Science

“…Newer more cost-effective methods for standardizing completed studies were recently suggested by Jakab et al [ 44 ]. Those new methods are based using small subsets of DEQAS and CAP ABVD materials to determine an equation to calibrate the original 25(OH)D values to NIST-Ghent-CDC RMP standardized or true values [ 45 ]. Over time, it is hoped that data from key clinical trials and other research studies will be standardized and added to the pool of true results.…”

The need for vitamin D assay standardisation in research

“…To ensure that articles published in PHN can contribute to consensus, and where appropriate to defining adequate and other levels of 25(OH)D, we are proposing to introduce a requirement that all papers published in Public Health Nutrition use standardised 25(OH)D levels that are fit for purpose. The Vitamin D Standardization Program has developed two options for retrospective standardisation of existing measures (6) . This would not apply to papers that have already been submitted and are undergoing review but will be taken into account for new submissions starting in 2021.…”