Overall Type I Error Rate and Power of Multiple Dunnett's Tests on Rodent Body Weights in Toxicology Studies

Body weight data are routinely collected in in vivo general toxicology studies, including 2-year carcinogenicity studies, to help assess the overall health of animals. The effect of the compound on body weight is statistically evaluated for each sex separately using a linear trend test or a many-to-one test by Dunnett. These tests are performed either in the framework of a one-factor analysis of variance (ANOVA) or a repeated measures ANOVA. The one-factor ANOVA with Dunnett's test at each time point is a common practice in industry. Although each individual test is conducted at the 0.05 significance level, one wonders about the overall type I error rate and power for performing many individual Dunnett's tests. A simulation study is conducted to answer this question for general toxicology studies of durations 1 month, 3 months, and 2 years. These results provide guidance to managing multiplicity of body weight analysis of general toxicology studies.

在体内一般毒理学研究（包括2年致癌性研究）中，体重数据通常会被收集，以帮助评估动物的整体健康状况。使用线性趋势检验或邓尼特的多对一检验，分别对每种性别统计评估化合物对体重的影响。这些检验要么在单因素方差分析（ANOVA）框架内进行，要么在重复测量方差分析框架内进行。在每个时间点进行带有邓尼特检验的单因素方差分析是行业内的常见做法。尽管每个单独的检验都是在0.05的显著性水平下进行的，但人们想知道进行多次单独的邓尼特检验时总体的第一类错误率和功效。针对为期1个月、3个月和2年的一般毒理学研究进行了一项模拟研究以回答这个问题。这些结果为管理一般毒理学研究中体重分析的多重性提供了指导。