A Multivariate Method for Measurement Error Correction Using Pairs of Concentration Biomarkers
Department of Adventist Health Study-2, Loma Linda University, Loma Linda, CA 92350, USA. Annals of Epidemiology
(Impact Factor: 2).
02/2007; 17(1):64-73. DOI: 10.1016/j.annepidem.2006.08.002
Measurement error is a pervasive problem in behavioral epidemiology, and available methods of correction all have generally untenable assumptions. We propose a multivariate method with more realistic assumptions.
The method uses two concentration biomarkers for each nutritional variable of interest and structural equation modeling. This produces corrected estimates of the effects on an outcome variable of changing the true exposure variables by one standard deviation, a standardized regression calibration. However, hypothesis testing in original units is preserved. The main assumptions are that certain error correlations between dietary estimates and biomarkers or between biomarkers be close to zero.
Two illustrative models used simulated data with the covariance structure of a real data set. The corrections produced often were very substantial. A sensitivity analysis allowed error correlations to depart from zero over a modest range. Root mean square biases show the advantage of the corrected approach. Relatively large calibration studies are needed for adequate precision.
As long as concentration biomarkers are selected carefully, error-corrected multivariate hypothesis testing and standardized effect estimation is possible. With the deviations from assumptions that were tested, the corrected method usually produces much less biased results than an uncorrected analysis.
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ABSTRACT: Dietary biomarkers are objective measures of food or nutrient intake and can be related to endpoints in epidemiological studies, used in the validation of dietary assessment instruments and used to check of compliance during intervention studies. Alkylresorcinols (AR), phenolic lipids present exclusively in the outer parts of wheat and rye grains, have been suggested as biomarkers of whole grain wheat and
The overall aim with this thesis was to evaluate AR as specific biomarkers of whole grain wheat and rye intake. This was conducted by developing a rapid GC-MS method for the analysis of AR in plasma and by studying AR pharmacokinetics, dose-response, reproducibility and relative validity in human intervention studies
under controlled intake conditions. Factors affecting plasma AR concentrations were investigated in free-living Danish women.
The method developed proved suitable for the analysis of relatively small sample volumes (50- 200μL). The results showed that AR in fasting plasma samples can be used as short-term concentration biomarkers, reflecting the intake range normally found in the Nordic countries in a dose-dependent manner. One or two repeated measurements of AR were found to adequately describe a subject’s average plasma
AR concentration at regular and constant intake. In free-living Danish women, rye bread was identified as the major factor affecting plasma AR concentration and there was no evidence of non-dietary factors or other foods having an effect. In conclusion, our results support that AR can be used as biomarkers in intervention
studies on whole grain wheat and rye and probably also in epidemiological endpoint- and validation studies.
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