Constant risk differences in the analysis of animal tumorigenicity data.

In a typical tumorigenicity study, most tumors are not observable in live animals and only a single (terminal) sacrifice is performed. This paper proposes a nonparametric, survival-adjusted analysis for these data that focuses on tumor incidence and yet does not require data on cause of death or assumptions about the tumor's lethality. The tumor onset/death process is most naturally characterized in terms of the tumor incidence rate and the death rates for tumor-free and tumor-bearing animals. The proposed approach, however, reparameterizes the problem in terms of the incidence rate, the death rate for tumor-free animals, and the difference between the death rates for tumor-free and tumor-bearing animals (i.e., the risk difference). The advantage of this alternative formulation is that a full likelihood analysis is possible with as few as one sacrifice time if the risk difference is assumed to be constant with respect to time. Data from the large ED01 study suggest that reasonable results can be obtained under the assumption of constant risk differences.