Efficient designs for animal: Carcinogenicity experiments

In a typical carcinogenicity study, animals, usually rats or mice, are divided into a control and two to three dose groups of 50 or more by randomization. A chemical is administered at a constant daily dose rate for a major portion of the lifetime of the test animals, for example, two years. In general, such an experiment is expensive and time consuming. In this paper, we propose an efficient design with reduced sample size and/or shortened study duration. An equal number of animals per dose group is considered in this study. A power study of the age-adjusted trend test for the tumor incidence rate for single-sacrifice experiments proposed by Kodell et al. (Drug Information Journal, 1997) is conducted. A Monte Carlo simulation study is performed to compare the performance of the trend test for the standard design and various reduced designs. Based on the Kodell et al. test, the 21-month study duration with sample size 50 per group is recommended as the best reduced design over the traditional 2-year study design with the same sample size.