A Three-State Multiplicative Model for Rodent Tumorigenicity Experiments

Abstract

SUMMARY A three-state illness-death model provides a useful way to represent data from rodent tumorigenicity experiments. Some of the earliest proposals use fully parametric models based on, for example, Weibull distributional assumptions. Recently, nonparametric versions of this model have been proposed, but these generally require large data sets with frequent interim sacrifices to yield stable estimates. As a compromise between these extremes, others have considered semiparametric models. In this paper, we develop a model that assumes a multiplicative relationship between death rates with and without tumour and a piecewise exponential model for the base-line transition rates. The model can be fitted with information from a single sacrifice. An EM algorithm provides a useful way to fit the model, since the likelihood corresponds to that from a standard piecewise exponential survival model when time to tumour onset is known. We discuss the relationship between the piecewise exponential model and other recent proposals and illustrate the method with data from two carcinogenicity studies.