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Incorporation of historical controls using semiparametric mixed models

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The analysis of animal carcinogenicity data is complicated by various statistical issues. A topic of recent debate is how to control for the effect of the animal's body weight on the outcome of interest, the onset of tumours. We propose a method which incorporates historical information from the control animals in previously conducted experiments. We allow non-linearity in the effects of body weight by modelling the relationship nonparametrically through a penalized spline. A simple extension of the penalized spline model allows the relationship between weight and the onset of tumour to vary from one experiment to another.

Keywords: Body weight; Carcinogenicity; Penalized spline; Phenolphthalein; Rodent bioassay

Document Type: Original Article


Affiliations: 1: Harvard School of Public Health, Boston, USA, 2: Cornell University, Ithaca, USA, 3: Harvard School of Public Health, Boston, and Dana-Farber Cancer Institute, Boston, USA

Publication date: January 1, 2001


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