Exact Statistical Tests on Comparing Tumor Incidence Trend in Transgenic Mouse Carcinogenicity Studies

Abstract

ABSTRACTStatistical positive trend tests to predict drugs' tumorigenic potential for long-term carcinogenicity studies, for example, Peto's test, are well accepted in practice and by regulatory agencies. Recently, short-term transgenic mouse studies become widely used as an alternative to lifetime mouse carcinogenicity studies. In general, the tumor incidence rates in a short-term study are much lower than those for a traditional long-term study, so exact positive trend test should be used. However, little is discussed about exact statistical trend tests for transgenic mouse studies. In this article, we evaluated three types of exact methods for testing tumor trend via simulation: exact Cochran-Armitage (C-A) test, exact Peto's test, and a proposed conditional exact Poly-k test. We show, via a simulations study, that the Type I error rate and statistical power are very similar for these three exact tests under various mortality rates and tumorigenic patterns. Overall, we recommend using exact C-A test to compare tumor incidence trend for short-term transgenic mouse studies. When survival adjustment is needed, the proposed conditional exact Poly-k test can be used as an alternative.