Incorporation of historical controls using semiparametric mixed models

Abstract

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 animals' 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 onset of the tumour to vary from one experiment to another.