Evaluating Constraints That Allow Survival-Adjusted Incidence Analyses in Single-Sacrifice Studies

Ideally, analyses of tumor incidence data from long-term animal experiments should allow the incidence rates to vary with age, without restricting tumor lethality, without requiring data on cause of death, and without assuming independence of competing risks. This article focuses on nonparametric methods that not only satisfy these conditions, but also accommodate studies having just one sacrifice time, by constraining the effects of age on one of the three functions used to characterize the likelihood. Several constrained analyses were evaluated using data on over 18,000 mice from the ED01study. Of the five constraints considered, only the assumption of constant differences between the death rates for animals with and without the tumor of interest produced reasonable results across a wide range of tumor lethalities.