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。 具体研究工作包括：(1)研究表明背景肿瘤 在目前的研究中，F344大鼠的发病率比那些进行的研究高得多 十年前。肿瘤发病率的增加伴随着肿瘤发病率的下降 生存和体重增加。造成这些问题的因素 肿瘤率的上升包括在当前的尸检中检查更多的组织 研究、组织病理学诊断的变化、基因漂移和饮食 各种因素。(2)发展了一种方法，以允许生存调整 分析肿瘤发病率，同时避免需要进行 关于肿瘤致命性或死亡原因的假设。如果约束为 放在描述潜在肿瘤发病/死亡的转移率上 过程中，分析是可行的，只有一个牺牲时间(例如 终极杀戮)。最有希望的限制是规定了 有和没有动物的死亡率之间的恒定差异 感兴趣的肿瘤。(3)的一些统计性质 计算机测量精子参数，如速度。 对这些数据的分析因有多个来自 同样的动物，给出了动物体内精子的嵌套结构 治疗。与该项目相关的未来研究包括检查 最大耐受量与啮齿动物致癌性的关系 用计算机模拟比较现有的方法与事故 基于死亡率之间的恒定差异的分析 无肿瘤和有肿瘤的动物。

This project is concerned with statistical methodology issues in the design, analysis, and interpretation of laboratory animal experiments. Specific research efforts include: (1) It was shown that background tumor rates in F344 rats a much higher in current studies than in those conducted a decade ago. The increased tumor rates are accompanied by decreased survival and increased body weights. Factors responsible for these increasing tumor rates include more tissue examined at necropsy in current studies, changes in histopathology diagnosis genetic drift, and dietary factors. (2) Methodology was developed to permit a survival-adjusted analysis of tumor incidence rates while avoiding the need to make assumptions about tumor lethality or cause of death. If constraints are placed on the transition rates describing the underlying tumor onset/death process, the analysis is feasible with only one sacrifice time (e.g., the terminal kill). The most promising restriction was the one that specified a constant difference between the death rates for animals with and without the tumor of interest. (3) Some of the statistical properties of computerized measurements sperm parameters such as velocity were examined. The analysis of such data complicated by having multiple sperm from the same animal, giving the nested structure of sperm within animal within treatment. Future research related to this project includes examining the relationship between maximum tolerated dose and rodent carcinogenicity, and comparing by computer's simulation existing methods with the incidence analysis based on constant differences between the death rates for tumor-free and tumor-bearing animals.