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

• Activity Number: 372
• Type: Contributed
• Date/Time: Tuesday, August 11, 2015 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Lei Shu* and Lanju Zhang and Bo Yang
• Companies: AbbVie and AbbVie and AbbVie
• Keywords: Carcinogenicity study ; Cochran-Armitage test ; Exact statistical test ; Exact Poly-k test ; Exact Peto' test ; Transgenic mouse study

Abstract

Statistical positive trend tests to predict drugs' tumorigenic potential for lifetime carcinogenicity studies, for example, Peto's test, are well accepted in practice. 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 poster, we evaluated three types of exact methods via simulation: exact Cochran-Armitage (C-A) test, exact Peto's test and a proposed conditional exact Poly-k test. Based on an original exact Poly-k test introduced by Rahman that requires extensive computation, we proposed an exact test that modifies the original test by conditioning on observed mortality data. The proposed conditional exact Poly-k test significantly reduces the computational. We show that the Type I error rate and statistical power are very similar for these three exact tests under various mortality rates and tumorigenic patterns.