Reconsidering False Positive Rates for a Portfolio of Carcinogenicity Studies

Music City Center 

Hundreds of chemicals have been evaluated for their potential carcinogenicity via two-year rodent studies. Each study includes two rodent species, two sexes, three or more dose groups, and over 40 tumor types. The data are binary, with tumors being either present or not. With over 480 dose-related trend and pairwise tests per study, there are concerns about the overall false positive rate (FPR). While statistical significance is not the only consideration for declaring the carcinogenicity of a chemical, it is an important contributing factor. Previous work has examined FPRs, but the data and methods have changed over time: tumor background rates have shifted, and more sophisticated models are sometimes needed. Newer methods include adjustments for differential survivability among the dose groups. Here, we use simulations to assess a study's FPR using the Poly-3 test. These simulations use current historical controls data and assist in estimating the FPR of a study. This work seeks to emphasize the real-world impact of statistical modeling and enhance confidence in science. This research was supported in part by the Intramural Research Program of the NIH including 75N96022F00055.

False Positive Rate

Simulation

Carcinogenicity

Binary Data 

Health Policy Statistics Section