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JNCI Monographs 1999 1999(26):43-48;
© 1999 by Oxford University Press
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Journal of the National Cancer Institute Monographs, No. 26, 43-48, 1999
© 1999 Oxford University Press

II. GENE CHARACTERIZATION PANEL

Multistage Sampling for Disease Family Registries

Kimberly D. Siegmund, Alice S. Whittemore, Duncan C. Thomas

Affiliations of authors: K. D. Siegmund, D. C. Thomas,Department of Preventive Medicine, University of Southern California, Los Angeles; A. S. Whittemore, Department of Health Research and Policy, Stanford University School of Medicine, CA.

Correspondence to: Kimberly D. Siegmund, Ph.D., Department of Preventive Medicine, University of Southern California, 1540 Alcazar St., Suite 220, Los Angeles, CA 90089-9011 (e-mail: kims{at}rcf.usc.edu).

BACKGROUND: The objectives of a family-based disease registry range from characterizing measured genetic factors and gene-environment interaction effects to detecting novel susceptibility genes. Gathering complete information on exposure and disease status in all family members for a sample of affected subjects (probands) to address these diverse objectives would be prohibitively expensive. METHODS: Multistage sampling can be used to design an efficient family-based disease registry. At each stage, the probands are classified on the basis of previously collected data, and a subsample is selected for more detailed observation. The design can be optimized to minimize the variance of any of the model parameter estimates, subject to a constraint on the total sample size. RESULTS: We describe the basic statistical theory and its application to a four-stage sampling scheme proposed for the Cooperative Family Registry for Epidemiologic Studies of Colorectal Cancer at the University of Southern California.


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