Toxicologic Pathology Forum*: Opinion on Qualitative Severity Descriptors to Express Magnitude of Changes in Clinical Pathology Endpoints in Nonclinical Toxicity Studies.

Abstract

Clinical pathology endpoints are routinely assessed in nonclinical toxicity studies and the magnitude of test article-related changes is frequently expressed using quantitative and/or qualitative severity descriptors. Quantitative descriptors (ie, percent or fold change) are easily calculated to express numerical magnitude of a change but may not adequately convey biological relevance. A specific quantitative magnitude may be associated with vastly different levels of pathophysiologic relevance depending on several factors, including the nature of the endpoint, the animal species/strain, and the magnitude and direction of change. Qualitative descriptors (eg, minimal and mild) offer a succinct way to provide additional context to the pathophysiologic relevance but are more challenging to ascribe to a change. The assignment of qualitative descriptors often requires a subjective, comprehensive, and multifaceted approach using various factors in addition to numerical calculation. Because of the subjectivity involved, the qualitative severity descriptor assigned to a specific change may differ among clinical pathology endpoints, species/strain, contributing scientists, and studies/programs. Quantitative and qualitative severity descriptors may provide complementary information and may be used individually or in combination. This opinion piece primarily explains the process and discusses caveats and various factors taken into consideration by clinical pathologists while ascribing qualitative severity descriptors.