Analyses of Animal Carcinogenicity Experiments

This project was supported by NIH grant 1 R29 CA77289 (1998-2003). Hongshik Ahn is the PI, and two graduate research assistants have been working on this research. This research was in collaboration with Ralph Kodell and James Chen and Hojin Moon at the National Center for Toxicological Research, FDA. We are studying the following problems.

• Attribution of tumor lethality in the absence of cause-of-death information: A new statistical approach is developed for estimating the carcinogenic potential of drugs and other chemical substances used by humans. Improved statistical methods are developed for rodent tumorigenicity assays that have interval sacrifices but not cause-of-death or context-of-observation data. Development of a suitable statistical procedure for testing in studies that have only a single terminal sacrifice is investigated. These methods account explicitly for the uncertainty in cause-of-death assignment and could relieve the need for case-by-case assignment of cause of death or context of observation by pathologists. Hence, these methods could result in substantial economic savings.
• Estimation of the lag time between onset of and death from an occult tumor: We developed a method of calculating a representative estimate of the elapsed time between the time to onset of an occult tumor and the time that it causes the death of an animal. By applying this method to the PCR (Project on Caloric Restriction) data, the effect of the caloric restriction is investigated. The difference in the development of a certain disease between the caloric restriction group and the normal diet group is examined. Although the mechanisms of the bodies of the rats and human are different, the results of this study can be used to predict the human dietary effect.
• Trend tests for dose-response analysis: We developed a statistically powerful testing method of evaluating treatment effects at several doses of a test drug in a sequential fashion. The performance of our procedure is evaluated and compared with other existing procedures. The intent of the procedure is to characterize the general shape of the dose-response relationship.