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Scientific and Regulatory Policy Committee Points to Consider: 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. Scientific and Regulatory Policy Committee Points to Consider: Use of Severity Grades to Characterize Histopathologic Changes. Annual Meeting of the American College of Veterinary Pathologists, Vancouver, British Columbia, CANADA, November 04 - 08, 2017.
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 (or score) 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 evaluating adversity during hazard characterization. Severity grades ideally should be assigned based only on the extent and magnitude 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. The Working Group supports greater transparency and consistency in the reporting of grading scales and provides recommendations to improve selection of endpoints that may need more detailed criteria for accurate characterization. This information should enhance the overall understanding by toxicologists and regulatory reviewers of pathology findings and thereby improve effective communication in regulatory submissions. This presentation will cover summary “points to consider” for the assignment of grading scales, effective communication of grading criteria in reporting documents, and the interpretation of grades by reviewers.