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Application of the SUDAAN Software Package to Clustered Data Problems: Pharmaceutical Research

Gayle S. Bieler and Rick L. Williams, Research Triangle Institute
Presented to the US Food and Drug Administration, February and June,1996,
at the 1996 Joint Statistical Meetings, and to the New Jersey Chapter of the ASA.

Abstract
In the pharmaceutical sciences, researchers often encounter data which are observed in clusters. Individual responses may represent multiple outcomes from the same patient (such as sets of teeth, pairs of eyes, or longitudinal outcomes on the same individual) or from multiple patients within a larger cluster, such as a physician clinic or an animal litter. Intracluster correlation, or the potential for clustermates to respond similarly, poses special problems for statistical analysis. This occurs because experimental units from the same cluster are not statistically independent. Failure to account for the cluster effect in the statistical analysis can result in underestimated standard errors and false-positive test results. In addition, cross-over clinical trials will not yield the associated increase in statistical power if the design is ignored in the analysis. This workshop will cover the statistical theory used in SUDAAN to fit marginal or population-averaged models using generalized estimating equations (GEE) with robust variance estimates which fully account for intracluster correlation. Attendees should be familiar with pharmaceutical research as well as fitting regression models.