Robust two-stage approach to repeated measurements analysis of chronic ozone exposure in rats |
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Authors: | Email author" target="_blank">Beow?Yong?YeapEmail author Paul?J?Catalano Louise?M?Ryan Marie?Davidian |
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Institution: | 1.Department of Medicine,Massachusetts General Hospital,Boston;2.Departments of Biostatistics,Haryard School of Public Health and Dana-Farber Cancer Institute,Boston;3.Department of Statistics,North Carolina State University,Raleigh |
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Abstract: | A robust two-stage approach is used to reanalyze the repeated measurements from an experiment of airway responsiveness in
rats randomized to long-term exposure at four ozone doses. The concentration-response data generated for each rat may be represented
as a hierarchical nonlinear model encompasing the sources of variation within and between individual profile for each rat,
the conditional modeling approach can assess the adequacy of an assumed mean model, a fundamental advantage not intrinsic
to marginal techniques. The two-stage population inference is based on the estimated individual parameters, thus maintaining
an intuitive appeal to the toxicologists who traditionally have fitted a separate curve for each animal and then applied ANOVA
to the summary statistics. However, we formally adjust the standard errors for the extra variability due to the initial estimation
of the individual parameters and also allow for their within-rat correlation. The robust two-stage method appropriately down
weights the a berrant responses arising sporadically within individualsand, more importantly, the rats which may be outlying
relative to the usual population variation. The true effect of chronic ozone exposure, including a significant gender interaction,
may be masked by a few rats which exert undue influence on the population estimates in a nonrobust analysis. |
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