Use of historical controls in time-adjusted trend tests for carcinogenicity

We develop a method for incorporating historical control information into time-adjusted tests for dose effects in carcinogenicity studies. After discretizing the time scale, we use a multinomial distribution to model the number of animals dying with tumor in each interval. Data from past studies are used to estimate the parameters characterizing the prior. A score test derived from the resulting Dirichlet-multinomial generalizes the test of Tarone (1982, Biometrics 38, 215-220) and reduces, in the limit, to the log-rank test in the case of a diffuse prior. The methodology is illustrated with data from a study of the fire retardant 2,2-Bis(bromomethyl)-1,3-propanediol.