Chapter 14 - Clinical Pathology

Abstract

Clinical pathology, traditionally comprising clinical chemistry, coagulation, hematology, and urinalysis evaluations, is established as an integral part of the preclinical safety assessment of test articles (new chemical entities, exploratory novel medicines, xenobiotics), especially in short- and medium-term toxicity studies. Results of these evaluations provide information regarding the overall health status of animals, as well as general metabolic, adaptive, or toxic processes and target organs associated with exposure to test articles. Clinical pathology evaluations therefore assist in establishing toxicological dose–response relationships in the preclinical safety assessment of a test article. The importance and relevance of these findings may be used for dose selection in chronic studies, and extrapolation to humans for risk assessment and management. The objective of this chapter is to provide guidance on the principles of clinical pathology testing and interpretation in the species used in toxicology studies. The application of clinical pathology testing in preclinical safety assessment, and the areas of development for novel biomarker implementation within the laboratory to expand testing capability and improve its contribution to the identification of more sensitive, early signals of drug- induced target organ toxicity or pathophysiology, are discussed. Finally, the importance of interpretation of clinical pathology and integration of the findings with other study data in the evaluation of overall safety or risk assessment is highlighted.