Overcoming ecologic bias using the two-phase study design.

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.