Schafer Kenneth A, Eighmy John, Fikes James D, Halpern Wendy G, Hukkanen Renee R, Long Gerald G, Meseck Emily K, Patrick Daniel J, Thibodeau Michael S, Wood Charles E, Francke Sabine
1 Vet Path Services, Inc., Mason, Ohio, USA.
2 Covance Laboratories, Inc., Madison, Wisconsin, USA.
Toxicol Pathol. 2018 Apr;46(3):256-265. doi: 10.1177/0192623318761348. Epub 2018 Mar 12.
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.
严重程度分级是非临床毒性研究中组织病理学诊断的重要组成部分，有助于区分与治疗相关的效应和背景发现，并有助于在危害特征描述过程中确定不良剂量水平。严重程度分级应仅基于所检查组织切片中形态学变化的程度（即数量和复杂性）来指定，并应在影响研究解释的关键病变的病理报告中明确界定。然而，所提供的细节水平和指定严重程度分级的标准可能会有所不同，这在评估病理结果时可能导致不恰当的比较和混淆。为帮助解决这一问题，毒理病理学会科学与监管政策委员会成立了一个工作组，以提供一篇关于病理严重程度分级的指定和应用的“需考虑要点”文章。总体而言，工作组支持在分级量表报告中提高透明度和一致性，并提供建议以改进对需要更详细严重程度标准的诊断的选择。这些信息应增强毒理病理学家、毒理学家和监管评审人员对病理结果的整体理解，从而改善监管申报中的有效沟通。
