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On Using Summary Statistics From an External Calibration Sample to Correct for Covariate Measurement Error

Guo, Yinga; Little, Roderick J.b; McConnell, Daniel S.c

doi: 10.1097/EDE.0b013e31823a4386

Background: Covariate measurement error is common in epidemiologic studies. Current methods for correcting measurement error with information from external calibration samples are insufficient to provide valid adjusted inferences. We consider the problem of estimating the regression of an outcome Y on covariates X and Z, where Y and Z are observed, X is unobserved, but a variable W that measures X with error is observed. Information about measurement error is provided in an external calibration sample where data on X and W (but not Y and Z) are recorded.

Methods: We describe a method that uses summary statistics from the calibration sample to create multiple imputations of the missing values of X in the regression sample, so that the regression coefficients of Y on X and Z and associated standard errors can be estimated using simple multiple imputation combining rules, yielding valid statistical inferences under the assumption of a multivariate normal distribution.

Results: The proposed method is shown by simulation to provide better inferences than existing methods, namely the naive method, classical calibration, and regression calibration, particularly for correction for bias and achieving nominal confidence levels. We also illustrate our method with an example using linear regression to examine the relation between serum reproductive hormone concentrations and bone mineral density loss in midlife women in the Michigan Bone Health and Metabolism Study.

Conclusions: Existing methods fail to adjust appropriately for bias due to measurement error in the regression setting, particularly when measurement error is substantial. The proposed method corrects this deficiency.

Author Information

From aMerck & Co., Inc., Rahway, NJ; and the Departments of bBiostatistics and cEpidemiology, School of Public Health, University of Michigan, Ann Arbor, MI.

Submitted 6 April 2011; accepted 23 August 2011.

Supported in part with funding from the American Chemistry Council and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The authors reported no other financial interests related to this research.

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Correspondence: Ying Guo, Merck & Co., Inc., 126 East Lincoln Ave, RY34–316, Rahway NJ 07065. E-mail:

© 2012 Lippincott Williams & Wilkins, Inc.