Journal Article

Two-Stage Case-Control Studies: Precision of Parameter Estimates and Considerations in Selecting Sample Size

James A. Hanley, Ilona Csizmadi and Jean-Paul Collet

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 162, issue 12, pages 1225-1234
Published in print December 2005 | ISSN: 0002-9262
Published online November 2005 | e-ISSN: 1476-6256 | DOI: http://dx.doi.org/10.1093/aje/kwi340
Two-Stage Case-Control Studies: Precision of Parameter Estimates and Considerations in Selecting Sample Size

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A two-stage case-control design, in which exposure and outcome are determined for a large sample but covariates are measured on only a subsample, may be much less expensive than a one-stage design of comparable power. However, the methods available to plan the sizes of the stage 1 and stage 2 samples, or to project the precision/power provided by a given configuration, are limited to the case of a binary exposure and a single binary confounder. The authors propose a rearrangement of the components in the variance of the estimator of the log-odds ratio. This formulation makes it possible to plan sample sizes/precision by including variance inflation factors to deal with several confounding factors. A practical variance bound is derived for two-stage case-control studies, where confounding variables are binary, while an empirical investigation is used to anticipate the additional sample size requirements when these variables are quantitative. Two methods are suggested for sample size planning based on a quantitative, rather than binary, exposure.

Keywords: case-control studies; confounding factors (epidemiology); efficiency; multivariate analysis; sample size; two-stage sampling; variance inflation factor; HRT, hormone replacement therapy; ln, natural logarithm; MI, myocardial infarction; or, empirical odds ratio: estimate of the odds ratio parameter OR; V, vasectomy

Journal Article.  6140 words.  Illustrated.

Subjects: Public Health and Epidemiology

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