Using Epidemiological Studies to Check the Consistency of the Cancer Risks Predicted by High-Dose Animal Experiments: A Methodological Review

Epidemiological studies have been cited in the literature as evidence both for and against the human cancer risks predicted by high‐exposure rodent studies. However, there has been little overall consistency in the ways that these animal‐to‐human comparisons have been made. This review examines some examples of these types of comparisons and describes the methods and techniques used by different investigators. Eleven “key decision areas” that need to be addressed are identified and recommendations for consistent, logical, and statistically appropriate approaches that might be taken to standardize the process are provided. In general, it is suggested that investigators provide the most useful information when they use logical, transparent, and statistically valid comparisons to pursue limited and focused objectives, such as directly testing the validity of an existing regulatory guidance value. Other recommendations include selecting biologically plausible extrapolative models that fit the data and drawing conclusions that are consistent with the study results and objectives.