采用严重程度等级评价组织学结果，以分析体内毒理学研究
Evaluation of histological findings with severity grade, to analyze toxicology in-vivo studies
摘要：
体内毒理学研究的特点是具有不同尺度的多个主要终点。尽管指南和出版物提供了正态分布终点（如器官重量）和比例（如肿瘤发生率）的各种统计检验，但很少有方法可用于分级组织病理学结果，如0，+，++，+。这代表了统计分析的一个基本矛盾，因为这些分级结果有时显示出潜在毒性作用的高预测值。在这里，我们讨论了不同的方法比较，特别是从i）非常小的样本量的设计和ii）毒理学家的解释性的观点。推荐一种新的方法，其中对分数水平的所有类组合进行同时测试，例如（0，+）vs（++，+）。相应的R代码以数据示例的方式提供。
英文摘要：
In-vivo toxicological studies are characterized by multiple primary endpoints with quite different scales. Whereas guidelines and publications provide various statistical tests for normally distributed endpoints (such as organ weights) and proportions (such as tumor rates), few approaches are available for graded histopathological findings, such as 0, +, ++, +++. This represents a basic contradiction of the statistical analysis because these graded findings sometimes show a high predictive value for potential toxic effects. Here we discuss different methods comparatively, especially from the viewpoints of i) designs for very small sample sizes and ii) interpretability by toxicologists. A new approach is recommended where a simultaneous test is performed over all class combinations of score levels, such as (0, +) vs (++, +++). Corresponding R code is provided by way of a data example.
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