Abstract
The toxicology and carcinogenicity testing paradigms of the United States industry and associated regulatory agencies currently appear successful based in part, on the continuously increasing life expectancy and the declining age-adjusted cancer rates in the United States. Pharmaceutical carcinogenesis likely has a trivial impact in the population statistics for cancer rates, but individual patient risk must be the focus of pathologists and toxicologists involved in drug development. As our understanding in carcinogenesis increases exponentially and after thousands of rodent cancer tests, significant improvement in the precision of human pharmaceutical carcinogenesis risk assessment should now be possible, and would enable reduction in the substantive false negative and high false positive rates inherent in the current and previous hazard identification paradigms. Significant inertia exists when it comes to any change opportunity for cancer testing paradigms, but reputable pharmaceutical and regulatory toxicologists/pathologists must continuously work to address recognizable flaws. The past and to a degree the current, cancer hazard identification paradigm takes thousands of animals, millions of dollars, and over three years for execution. In the past few years, European, Japanese and American regulatory and pharmaceutical toxicologists/pathologists have launched a major collaborative research effort to design paradigms that would increase the effectiveness and efficiency of the process. This effort attempts to determine the appropriate use of chronic and special toxicology tests to identify the pharmaceutical-associated cancer risk factors. Pharmaceutical agent carcinogenesis has been generally recognized to act through hormonal modulation, immunosuppression, genetic toxicity, and chronic toxicity mechanisms, none of which require life time cancer bioassays for identification. In this current issue, toxicology/pathology scientists from Merck present data specifically addressing this challenge in “An Evaluation of Chronic 6- and 12-Month Rat Toxicology Studies as Predictors of 2-Year Tumor Outcome” (M. V. Reddy, F. D. Sistare, J. S. Christensen, J. G. DeLuca, G. K. Wollenberg, and J. J. DeGeorge). This article presents data supporting a new pharmaceutical testing paradigm that might enhance efficiency in predicting cancer hazard without compromising effectiveness.