Analysis of multiple tumor data from a rodent carcinogenicity experiment

Rodent tumorigenicity experiments are conducted to determine the safety of substances for human exposure. The carcinogenicity of a substance is generally determined by statistical tests that compare the effects of treatment on the rate of tumor development at several body sites. The statistical analysis of such studies often includes hypothesis testing of the dose effect at each of the sites. However, the multiplicity of the significance tests may cause an excess overall false positive rate. In consideration of this problem, recent interest has focused on developing methods to test simultaneously for the treatment effect at multiple sites. In this paper, we propose a test that is based on the count of tumor-bearing sites. The test is appropriate regardless of tumor lethality or of treatment-related differences in the underlying mortality. Simulations are given which compare the performance of the proposed test to several other tests including a Bonferroni adjustment of site-specific tests, and the test is illustrated using the data from the large ED01 experiment.