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American Journal of Epidemiology Advance Access published online on February 12, 2008

American Journal of Epidemiology, doi:10.1093/aje/kwm386
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Practice of Epidemiology

Overcoming Ecologic Bias using the Two-Phase Study Design

Jon Wakefield1 and Sebastien J.-P. A. Haneuse2

1 Departments of Statistics and Biostatistics, University of Washington, Seattle, WA
2 Center for Health Studies, Group Health Cooperative of Puget Sound, Seattle, WA

Correspondence to Dr. Jon Wakefield, Box 357232, Department of Biostatistics, University of Washington, Seattle, WA 98195-7232 (e-mail: jonno{at}u.washington.edu).

Received for publication February 1, 2007. Accepted for publication December 7, 2007.

Ecologic (aggregate) data are widely available and widely utilized in epidemiologic studies. However, ecologic bias, which arises because aggregate data cannot characterize within-group variability in exposure and confounder variables, can only be removed by supplementing ecologic data with individual-level data. Here the authors describe the two-phase study design as a framework for achieving this objective. In phase 1, outcomes are stratified by any combination of area, confounders, and error-prone (or discretized) versions of exposures of interest. Phase 2 data, sampled within each phase 1 stratum, provide accurate measures of exposure and possibly of additional confounders. The phase 1 aggregate-level data provide a high level of statistical power and a cross-classification by which individuals may be efficiently sampled in phase 2. The phase 2 individual-level data then provide a control for ecologic bias by characterizing the within-area variability in exposures and confounders. In this paper, the authors illustrate the two-phase study design by estimating the association between infant mortality and birth weight in several regions of North Carolina for 2000–2004, controlling for gender and race. This example shows that the two-phase design removes ecologic bias and produces gains in efficiency over the use of case-control data alone. The authors discuss the advantages and disadvantages of the approach.

bias (epidemiology); case-control studies; confounding factors (epidemiology); data interpretation, statistical; research design; sampling studies


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