EXPERIMENTAL DESIGN AND DATA ANALYSIS METHODOLOGY FOR ANIMAL EXPERIMENTS

动物实验的实验设计和数据分析方法

• 批准号: 3876914
• 负责人: J K HASEMAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3876914
• 关键词: Salmonella; animal mortality; cancer information system; cancer risk; carcinogen testing; chemical carcinogenesis; computer simulation; data collection methodology /evaluation; genetic strain; histopathology; laboratory mouse; laboratory rat; mathematical model; molecular genetics; neoplasm /cancer diagnosis; neoplasm /cancer genetics; statistics /biometry; toxicology

This project is concerned with statistical methodology issues in the design, analysis, and interpretation of laboratory animal experiments. Specific research efforts include (1) To address the false positive issue in long term rodent carcinogenicity studies, the use of statistical methodology that adjusts for multiple comparisons was investigated. An actual case study utilizing three different statistical decision rules to evaluate 25 NCI carcinogenicity studies was examined. Agreement among these decision rules was shown to be greater than originally reported. (2) Evaluation of results from the National Toxicology Program's carcinogenicity studies has resulted in the formulation and publication of an historical control tumor database and the identification of potential sources of variability in tumor rates. (3) Various experimental designs for assessing male reproductive function in rabbits were studied to determine whether they had sufficient power to detect a reasonably sized toxic effect. It was determined that studies which employed a preexposure period would be appropriate. (4) Statistical methods have been developed for extracting information on disease incidence from data on disease mortality. Under certain simplifying assumptions, the disease mortality rates can be expressed in terms of the incidence and lethality rates. The proposed approach is appropriate for the case in which there are two populations, one having data on disease incidence and disease lethality and the other having data on disease mortality. Based on a model linking the incidence rates in the two groups, the incidence rates in the second population can be estimated by maximizing a likelihood that involves only mortality data. Future research includes a comparison of statistical methodologies for evaluating tumor data that do not require cause of death determinations and assessing the effects of diet and caging protocols on variability in control tumor incidence.

该项目涉及的是联合国系统内的统计方法问题。 实验动物实验的设计、分析和解释。 具体的研究工作包括（1）解决假阳性问题 在长期啮齿动物致癌性研究中，使用统计学 研究了调整多重比较的方法。一个 实际案例研究利用三种不同的统计决策规则， 评估了25项NCI致癌性研究。这些协定 决策规则被证明是大于最初报告。（二） 国家毒理学计划的结果评价 致癌性研究导致制定和出版了 历史对照肿瘤数据库和确定潜在的 肿瘤发生率的变异性来源。(3)各种实验设计， 评估雄性生殖功能的兔子进行了研究，以确定 他们是否有足够的能力来检测一个合理大小的有毒物质， 效果确定采用暴露前阶段的研究 是适当的。(4)统计方法已经发展为 从疾病死亡率数据中提取疾病发病率信息。 在某些简化假设下，疾病死亡率可以是 以发病率和致死率表示。拟议 这种方法适用于有两个群体的情况， 一个有关于疾病发病率和疾病致死率的数据， 有关于疾病死亡率的数据。基于一个模型， 两组的发病率，第二人群的发病率可以 通过最大化只涉及死亡率数据的可能性来估计。 未来的研究包括比较统计方法， 评价不需要确定死亡原因的肿瘤数据， 评估饮食和笼养方案对 控制肿瘤发病率。