You are here:
Use of Severity Grades to Characterize Histopathologic Changes
Citation:
Schafer, K., J. Eighmy, J. Fikes, W. Halpern, R. Hukkanen, G. Long, E. Meseck, D. Patrick, M. Thibodeau, C. Wood, AND S. Francke. Use of Severity Grades to Characterize Histopathologic Changes. TOXICOLOGIC PATHOLOGY. Society of Toxicology, RESTON, VA, 46(3):256-265, (2018).
Impact/Purpose:
Interpretation of histopathologic effects in nonclinical toxicity studies is a fundamental part of the risk assessment process for chemicals, foods, and pharmaceuticals. The severity grade is an important part of the diagnosis for many treatment-related findings, as it indicates the extent of an effect by categorizing histopathologic features into semi-quantitative descriptive grading scales. This information adds relevant context to observed findings and comprises an important element of the pathology report. A Working Group of the STP Scientific and Regulatory Policy Committee (SRPC) was formed to review current issues and considerations related to severity grading in nonclinical study reports. The ultimate goal of this Working Group was to improve communication by the study pathologist and increase consistency in the assignment and interpretation of severity grades. The scope of this “points to consider” article applies specifically to approaches for assessing and recording the severity of histopathology changes in toxicity studies submitted for review by regulatory agencies.
Description:
The severity grade is an important component of a histopathologic diagnosis in a nonclinical toxicity study that helps distinguish treatment-related effects from background findings and aids in determining adverse dose levels during hazard characterization. Severity grades should be assigned based only on the extent (i.e., amount and complexity) of the morphologic change in the examined tissue section(s) and be clearly defined in the pathology report for critical lesions impacting study interpretation. However, the level of detail provided and criteria by which severity grades are assigned can vary, which can lead to inappropriate comparisons and confusion when evaluating pathology results. To help address this issue, a Working Group of the Society of Toxicologic Pathology’s Scientific and Regulatory Policy Committee was formed to provide a “points to consider” article on the assignment and application of pathology severity grades. Overall, the Working Group supports greater transparency and consistency in the reporting of grading scales and provides recommendations to improve selection of diagnoses requiring more detailed severity criteria. This information should enhance the overall understanding by toxicologic pathologists, toxicologists, and regulatory reviewers of pathology findings and thereby improve effective communication in regulatory submissions.
