Time Trend in Historical Controls for Tumour Incidences in Long-Term Animal Studies

Abstract

In the analysis of neoplastic lesions in long-term animal studies it is often desirable to incorporate historical evidence provided by the control groups. A model by Dempster and co-workers is used for this and is extended to include a time trend term. A full Bayesian analysis is performed, based on multidimensional numerical integration. A data set (liver tumours in male mice) is then presented and analysed which shows a pronounced increase in tumour incidence over time. Although Dempster's model includes an error term to deal with the between-study variation, it does not include a term which handles possible time trends (shifts) in the incidence of lesions. Historical control data collected over several years at Ciba-Geigy do, however, show such shifts for liver tumours in mice