Evaluation of Clinical Pathology Data

TLDR

In vivo toxicology studies collect and interpret in‑life, clinical pathology, and anatomic pathology parameters, and understanding the inherent variability and physiologic factors of each analyte is essential for accurate interpretation. The article demonstrates how hemolysis and hepatotoxicity examples illustrate relationships among clinical, anatomic, and other data sets. The authors evaluate clinical pathology parameters integratively with concurrent clinical signs and anatomic pathology to assess test‑article–related changes and infer underlying pathophysiology. In rats, hemolysis data sets correlated tightly, whereas liver injury biomarkers often conflicted with other data sets.

Abstract

During the conduct of in vivo toxicology studies, in-life, clinical pathology, and anatomic pathology parameters are collected and interpreted. These sets of parameters are evaluated in an integrative manner to determine the overall toxicity of a test article. For clinical pathology parameters, the inherent variability and physiologic factors affecting each analyte must be understood prior to interpretation. Changes in clinical pathology parameters that are considered to be test article–related are then assessed with respect to changes in the concurrent data sets such as clinical signs and anatomic pathology to determine the underlying pathophysiology. In this article, examples of hemolysis and hepatotoxicity are used to demonstrate the relationships among the various parameters and data sets. Whereas there was tight correlation of all data sets in the example of hemolysis in rats, the examples of altered enzymes and other biomarkers indicating liver injury and dysfunction were more often discordant with other data sets.