EXPERIMENTAL DESIGN AND DATA ANALYSIS METHODOLOGY FOR ANIMAL EXPERIMENTS

这个项目关注的是统计方法问题 实验动物实验的设计、分析和解释， 特别是由以下机构进行的长期啮齿动物致癌性研究 国家毒理学计划(NTP)。一项调查使用的数据来自 确定体重/肿瘤发病率的NTP饮食限制研究 关联，并说明这些关联如何减少 检测致癌效应的生物测定法的灵敏度。肿瘤 发病率和体重的相关性也被证明可以解释许多 在一些NTP中观察到与化学相关的肿瘤发生率下降 学习。利用NTP历史控制数据，建立了数学模型 作为以下因素的函数来预测控制特定部位的肿瘤率 死亡年龄和一岁时的体重。所获得的知识 通过这项研究将对未来NTP生物检测的设计产生影响。 另一项调查发展了新的统计方法 恒定风险差(CRD)模型在中国肿瘤发病分析中的应用 动物实验。这种方法的一个重要优点是它 专注于肿瘤的发病分布，但不需要临时 牺牲、死因数据或死亡假设。CRD 对几项NTP研究进行了分析，并取得了良好的效果 相对于标准分析。未来的研究将处理 越来越多地使用非癌症终点和机械数据。

This project is concerned with statistical methodology issues in the design, analysis, and interpretation of laboratory animal experiments, especially the long term rodent carcinogenicity studies carried out by the National Toxicology Program (NTP). One investigation used data from the NTP dietary restriction study to confirm body weight/ tumor incidence associations and to illustrate how these associations may reduce the sensitivity of the bioassay for detecting carcinogenic effects. Tumor incidence/body weight correlations were also shown to explain many of the chemically-related decreased tumor incidences observed in some NTP studies. Using NTP historical control data, mathematical models were developed to predict control site-specific tumor rates as a function of age at death and body weight at one year of age. The knowledge gained through this research will influence the design of future NTP bioassays. Another investigation developed new statistical methodology based on the constant risk difference (CRD) model to analyze tumor incidence data from animal experiments. One important advantage of this approach is that it focuses on the tumor onset distribution and yet does not require interim sacrifices, cause-of-death data, or lethality assumptions. The CRD analysis was applied to several NTP studies and it performed well relative to the standard analyses. Future research will deal increasingly with non-cancer endpoints and with mechanistic data.