General Toxicology, Safety Pharmacology, Reproductive Toxicology, and Juvenile Toxicology Studies

Abstract

This chapter provides a survey of key nonclinical safety assays. For each study type, we discuss the typical study designs employed, including a summary of the type of endpoints collected. We then provide an overview of common statistical approaches in each setting. There are some general themes that are common across the study types (e.g., trend testing). At the same time, the different study types may have features that require special consideration (e.g., cross-over designs for safety pharmacology studies, intra-litter correlation in reproductive toxicology studies). While some of the design aspects of these studies are to some extent “fixed” by precedent across the industry, we do address sample size and power considerations, as this information can be valuable to understanding how statistical results can contribute to the overall interpretation of these studies. Finally, for any discussion of statistical approaches, there are likely to be multiple reasonable approaches. We’ve attempted to cover some of the more common approaches in detail, but we recognize that our treatment is not exhaustive. Where possible, we have provided references for further reading.