Sources of variability in rodent carcinogenicity studies.

A number of factors may influence tumor rates in rodent carcinogenicity studies, including the animal room environment, genetic differences, food consumption/weight gain, survival/age of the animals, identification of gross lesions, pathology sampling procedures and preparation of the histology slides, and histopathologic diagnosis. The relative importance of these factors is evaluated, making use of laboratory animal carcinogenicity data from the National Toxicology Program and from other sources. An investigator must be aware of these potentially confounding factors, so that appropriate measures can be taken to reduce or eliminate their impact on the interpretation of study results. Certain potential sources of within-study variability can be controlled by appropriate experimental design and by proper conduct according to standard operating procedures. The effect of certain factors influencing tumor prevalence may be magnified when variability from study to study is considered, and thus it may be difficult to formulate a biologically meaningful statistical analysis that uses historical control data in a formal testing framework.