论文标题
评估具有严重程度等级的组织学发现，分析毒理学研究
Evaluation of histological findings with severity grade, to analyze toxicology in-vivo studies
论文作者
论文摘要
体内毒理学研究的特征是多个主要终点，尺度较大。尽管指南和出版物为正态分布的终点（例如器官重）和比例（例如肿瘤率）提供了各种统计检验，但对于分级的组织病理学发现，例如0， +， +，++，+++，几乎没有方法。这代表了统计分析的基本矛盾，因为这些分级发现有时显示出对潜在毒性作用的高预测值。在这里，我们比较讨论不同的方法，尤其是从i）设计的设计的观点，ii）毒理学家的解释性。建议在所有分数级别的组合中执行同时测试，例如（0，+）vs（++，+++）。相应的R代码通过数据示例提供。
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.
