Vitamin D Biomarker Analytical

Transcription

1 Vitamin D Biomarker Analytical Issues innhanes Clifford Johnson, Director Centers for Disease Control and Prevention National Center for Health Statistics

2 Presentation Objectives Provide brief background on NHANES and Vitamin D biomarker data Discuss NHANES serum 25(OH)D assay challenges and recent data advisory note Discuss recent Roundtable meeting Discuss next steps by NCHS and federal partners relative to Vitamin D biomarker

3 What is NHANES? National Health and Nutrition Examination Survey Conducted by the National Center for Health Statistics (NCHS) of the CDC To assess the health and nutritional status of a nationally representative sample of US population Data used for a variety of research and programmatic purposes

4 What is the Vitamin D status of the US Population? The principal biomarker of vitamin D status is serum 25-hydroxyvitamin D or 25(OH)D. 25(OH)D data collected in many National Health and Nutrition Examination (NHANES) Surveys. 25(OH)D data: NHANES III ( ); NHANES and 2007and beyond

5 NHANES: Serum 25OHD Samples Survey NHANES III ( ) Ages 12+ Sample 18,158 a NHANES 2000 (not on public use file) NHANES ,188 a 7,807 a,b NHANES ,294 a NHANES ,402 b a Looker et al., 2007 NIH conference; b Pfeiffer, Roundtable handouts, 2009

6 NHANES: Serum 25OHD Assays Laboratory: National Center for Environmental Health (NCEH), CDC Methods: DiaSorin RIA (25OHD OHD 3 ) and LC-MS/MS 2007 and after

7 Initial 25(OH)D Assay Concerns (Looker et al., 2008) vs : Reformulation (introduction of antibody to improve binding) of Diasorin RIA assay kit shifts in assay results between these two time periods : Likely affected by drifts in the assay performance (method bias and imprecision) over time Adjusted for assay drifts to compare time trends in 25(OH)D and identify contributing factors Looker et al. Am J Clin Nutr 2008;88:

8 Review of 2004 QC performance DiaSorin RIA assay was performing on the high side of the QC limits during 2004, particularly for the high pool Late 2003 new lot number for standards, tracer, other reagents Late 2004 new lot number of tracer, antiserum Conclusion: Conduct a 150 sample crossover study for QC shift Vitamin D Quality Control 60 HS NH9907 HS9907 HS0303c NH0102 MS0102 MS0302 MS0302c 20 LS0301 NH0101 LS0101 LS0301c /21/2003 5/1/2003 8/9/ /17/2003 2/25/2004 6/4/2004 9/12/ /21/ assay shift

9 ±Adjustment Affects Conclusions Adjustments for assay differences: Looker et al. (2008): Overall mean 25(OH)D lower in than in Assay changes accounted for much of the difference No adjustment for assay differences: Ginde et al. (2009): Marked decrease in 25(OH)D in compared to Growing epidemic of vitamin D insufficiency Saintonge 2009: Vitamin D deficiency is increasing from to 2006 Implementation of national fortification and public health strategy

10 NCHS Analytic Note (2009) Published data : Effect of drifts in assay comparability for the serum 25(OH)D data collected in this time period may not be fully accounted for Additional drifts in assay comparability for the results Cautions users when assessing time trends (especially using 2-year data sets)

11 Review of 2006 QC performance DiaSorin RIA assay was performing on the low side of the QC limits during 2006, particularly for the high pool Early 2006 new lot number for tracer, antiserum and other reagents End date? Stopped using 0301/0302/0303 series QC in Spring 2006; new 05470/05471/05472 series QC (characterized during Spring 2006) performed on the same level from Spring 2006 through Spring Vitamin D Quality Control HS0303c HS05472a MS0302c MS05471a LS0301c LS05470a 0 2/15/2005 5/26/2005 9/3/ /12/2005 3/22/2006 6/30/ /8/2006 1/16/ assay shift

12 25OHD (nmol/l) NHANES weighted means track well with trends seen in QC data NH (males) 70 (females) NH NH NH NH NH NH NH For methods comparison only and not for publication. Not adjusted for reformulation or assay shifts 7. Options

13 Multi-year estimates of 25OHD (nmol/l) Survey years Public data n Mean Percentile Percent 5th 50th 95th <37.5 < Y 7, (58-61) (13-19) 77 (73-80) Y 7, (59-66) (10-18) 71 (66-76) Y 7, (53-57) (17-24) 83 (80-85) Y 15, (59-63) (12-17) 74 (71-77) * Y 14, (57-61) (14-20) 77 (74-80) * Y 22, (58-61) (15-19) 77 (74-79) * N 26, * Odd QC years cancel out 7. Options

14 Roundtable (July 27-28, 2009) Jointly sponsored by National Center for Health Statistics (CDC) and the Office of Dietary Supplements (NIH) Discuss 25(OH)D assay challenges and options for resolving them Biochemists, clinical laboratorians and biostatisticians

15 Roundtable Discussions Laboratory QC data Options for harmonization across Diasorinbased surveys ( and ) Plans for NHANES and beyond

16 NHANES 25(OH)D: Next Steps Today: Data Advisory posted on website Near term: Explore adjustment procedures to account for assay drift and reformulation and update data advisory Longer term: Utilize NIST standard reference material to bridge past and future 25(OH)D data collected in NHANES

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