Analysis of Animal Carcinogenicity Data
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Animal carcinogenicity experiments are employed to test the carcinogenic potential of drugs and other chemical substances used by humans. Such bioassays are conducted in animals at doses that are generally well above human exposure levels, in order to detect carcinogenicity with relatively small numbers of animals. Animals are divided into several groups by randomization and treated with a test compound at different dose levels. A typical carcinogenicity study involves a control and 2 to 3 dose groups of 50 or more animals, usually rats or mice. Typically, a chemical is administered at a constant daily dose rate for a major portion of the lifetime of the test animal, for example, for 2 years. Sometimes, scheduled interim sacrifices are performed during the experiment. At the end of the study, all surviving animals are sacrificed and subjected to necropsy. For each animal in a given dose group, the age at death and the presence or absence of specific tumor types are recorded. Groups of animals are compared with respect to tumor development.
KeywordsDose Group Trend Test Occult Tumor Nonparametric Maximum Likelihood Fatal Tumor
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- Dinse, G. E. (1993). Evaluating constraints that allow survival-adjusted incidence analyses in single-sacrifice studies. Biometrics 49, 399407Google Scholar
- Gart, J. J. (1975). Letter to the editor. British Journal of Cancer 31, 696697.Google Scholar
- Gart, J. J., Chu, K. C., and Tarone, R. E. (1979). Statistical issues in interpretation of chronic bioassay tests for carcinogenicity. Journal of the National Cancer Institute 62, 957–974.Google Scholar
- Hoel, D. G., and Walburg, H. E. (1972). Statistical analysis of survival experiments. Journal of the National Cancer Institute 49, 361–372.Google Scholar
- Lindsey, J. C., and Ryan, L. M. (1994). A comparison of continuous-and discrete-time three-state models for rodent tumorigenicity experiments. Environmental Health Perspectives 102, (Suppl. 1) 9–17.Google Scholar
- McKnight, B. and Crowley, J. (1984). Tests for differences in tumor incidence based on animal carcinogenesis experiments. Journal of the American Statistical Association 79 639–648.Google Scholar
- Peto, R., Pike, M. C., Day, N. E., Gray, R. G., Lee, P. N., Parish, S., Peto, J. Richards, S., and Wahrendorf, J. (1980). Guidelines for simple, sensitive significance tests for carcinogenic effects in long-term animal experiments. IARC Monographs Supplement 2 311–426. Annex to: Long-term and Short-term Screening Assays for Carcinogens: a Critical Appraisal.Google Scholar
- Portier, C., Hedges, J., and Hoel, D. G. (1986). Age-specific models of mortality and tumor onset for historical control animals in the national toxicology program’s carcinogenicity experiments. Cancer Research 46, 4372–4378.Google Scholar
- Portier, C. J., and Dinse, G. E. (1987). Semiparametric analysis of tumor incidence rates in survival/sacrifice experiments. Biometrics 43, 107114.Google Scholar