Software tools for Analysis of Animal Carcinogenicity Experiments

This project was supported in part by NIH grant R29 CA77289 (PI: Hongshik Ahn, 1998-2003) and the Tobacco Settlement Funds approved by the Texas State Legislature (Hojin Moon and J. Jack Lee). This research has been conducted in collaboration with Hojin Moon and Ralph Kodell at the National Center for Toxicological Research, FDA, and J. Jack Lee and Rumiana Nikolova at M. D. Anderson Cancer Center. Hojin Moon initiated the development of these software tools.

• Web-based simulator for calculating sample size and power in animal carcinogenicity studies ( software site ): We have developed a new Web-based sample size and power simulator for animal carcinogenicity studies to detect a dose-related trend in tumor incidence following exposure to a putative carcinogen. It is applicable for studies of occult tumors for which the time to tumor onset is not directly observable. The development of this statistical tool was motivated by a lung cancer prevention study developed at M. D. Anderson Cancer Center. The particular goal was to evaluate the carcinogenic potential of the tobacco carcinogen NNK, a byproduct of tobacco smoke. This tool was applied to provide sufficient power to detect a dose-related trend of the occurrence of lung adenomas and adenocarcinomas. Monte Carlo simulation is introduced in this tool to simulate experiments of rodent bioassays because no closed-form solution is available. The estimation of sample size and power is conducted by the Peto test. The design parameters can be entered through the World Wide Web and pass to a core C program via Extensible Markup Language interface. Upon the completion of simulation, the results are sent back through the Web or by an e-mail.
• A computational tool for testing dose-related trend using an age-adjusted bootstrap-based Poly-k test ( Downloadable tool ): We developed a computational tool for testing dose-related trend and/or pairwise difference in the incidence of an occult tumor via our age-adjusted Poly-k test and the original Poly-k test. This tool is applicable to rodent tumorigenicity assays that have a single terminal sacrifice. This tool takes input information simply from a user's screen and reports testing results back to the screen through user-interface. The computational tool is implemented in C/C++ and is applied to analyze real data sets. This software will provide a great benefit to FDA and pharmaceutical industry by furnishing a user-friendly software tool for statistical analysis of tumorigenicity data from animal bioassays.