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IJE Advance Access originally published online on December 4, 2006
International Journal of Epidemiology 2006 35(6):1570-1578; doi:10.1093/ije/dyl233
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Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2006; all rights reserved.

Methodology

Regression dilution methods for meta-analysis: assessing long-term variability in plasma fibrinogen among 27 247 adults in 15 prospective studies

The Fibrinogen Studies Collaboration*

* Corresponding author. Angela Wood, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge CB2 8RN, UK. E-mail: amw79{at}medschl.cam.ac.uk


   Abstract

Background Within-person variability in measured values of a risk factor can bias its association with disease. The extent of this regression dilution bias for plasma fibrinogen was investigated using repeat measurement data collected at varying time intervals on 27 247 adults in 15 prospective studies.

Methods Regression dilution ratios (RDRs) were estimated from a linear regression of repeat measurements on baseline values in each study and for each time interval, and pooled allowing for within- and between-study heterogeneity. RDRs were estimated both without and with adjustment for confounders, and factors were investigated that might influence the RDRs.

Results The unadjusted overall RDR was 0.51 (95% CI: 0.47, 0.55), which decreased to 0.46 (95% CI: 0.42, 0.49) after adjustment for age, sex and measured values of other established vascular risk factors. The RDR did not vary materially by assay method, age, sex or smoking status, but decreased at higher levels of baseline fibrinogen.

Conclusion It is appropriate to use an RDR of 0.5 to correct approximately for regression dilution bias in plasma fibrinogen values; however, this correction factor may produce somewhat conservative hazard ratios in adjusted analyses, at higher fibrinogen concentrations and in follow-up beyond a decade. More generally, the methods described in this report have widespread applicability to quantifying regression dilution bias in repeatability data from multiple prospective studies.


Keywords Regression dilution bias, correction methods, measurement error, long-term variability, plasma fibrinogen, meta-analysis

Accepted 26 September 2006


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Associations of Plasma Fibrinogen Levels with Established Cardiovascular Disease Risk Factors, Inflammatory Markers, and Other Characteristics: Individual Participant Meta-Analysis of 154,211 Adults in 31 Prospective Studies: The Fibrinogen Studies Collaboration
Am. J. Epidemiol., October 15, 2007; 166(8): 867 - 879.
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