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Alternative Methods for Analyzing Clustered Binary Data in Ophthalmological Studies

 


A. Russell Localio, J. Richard Landis, Susan L. Weaver, Tonya J. Sharp
Center for Biostatistics and Epidemiology, Penn State University
1993, Presented at the Biometrics Society Spring Meetings.

Abstract
This paper describes modeling alternatives for binary data in ophthalmology, where clustering (correlation) of eyes within subject is a well-recognized issue, to determine how long after fatal accident donor corneas can be transplanted safely. Rabbits were sacrificed, and corneas of one eye were examined microscopically to determine the rate of cell death (under 7 per 1,000). Rabbits (and remaining eyes) were either refrigerated or not, and cell death rate was determined at 6 and 24 hours. Modeling the effect of refrigeration and time on cell viability was performed using: (1) logistic regression (LR) (SAS CATMOD) with no consideration of clustering of cells within eye, or the correlation of eyes within rabbit, (2) exact LR using LogXact, (3) LR using SUDAAN and considering the clustering of cells within eye, (4) LR using SUDAAN and considering the two stages of clustering, cell within eye and eye within rabbit, (5) GEE with a logistic link and binomial error that accounts for clustering of cells within eye, and (6) cells within rabbit, (7) GEE with log link and Poisson error term that conditions on eye and accounts for correlation of eyes within rabbit, (8) conditional LR that conditions on rabbit (STATA), and (9) exact conditional LR (Log-Xact). Methods are compared both in terms of interpretation of parameters and standard errors, and computing requirements for samples of 3,000 observations per eye and a total of 130,000 data points.