Incorporation of historical controls using semiparametric mixed models

The analysis of animal carcinogenicity data is complicated by various stati stical issues. A topic of recent debate is how to control for the effect of the animals' body weight on the outcome of interest, the onset of tumours. We propose a method which incorporates historical information from the con trol 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 mod el allows the relationship between weight and onset of the tumour to vary f rom one experiment to another.