EXPERIMENTAL DESIGN AND DATA ANALYSIS METHODOLOGY FOR ANIMAL EXPERIMENTS

本项目涉及统计方法问题 参与实验室的设计、分析和解释 动物实验，特别强调两年 致癌性研究。 实验设计问题包括 检查肿瘤发病率变化的潜在来源。 实验室间差异和时间相关趋势被发现， 是可变性的重要来源。 未来的研究计划 包括重新评估早期NCI肿瘤诊断， 目前的NTP研究，以确定具体的因素负责 这种可变性。 数据分析领域的研究已经 重点是制定统计程序， 不需要死亡原因信息的肿瘤数据，或 多次临时杀人 特别有希望的是一个程序， 根据以下因素对无肿瘤死亡的动物的贡献进行加权 肿瘤发病分布的假设形式。 所得 程序是Cochran-Armitage趋势的简单修改 测试，并可能最终导致一个重要的进展， 肿瘤数据的统计学评价。 的评估 毒性、遗传毒性和致癌性之间的关系 在实验室啮齿类动物中， 阳性致癌性研究的比例（10-15%） 可能导致死亡的靶器官毒性类型 所有观察到的致癌作用。 此外，没有明显的 在“仅高剂量”之间观察到致突变性差异 致癌物质和所有致癌物质。

This project is concerned with statistical methodology issues involved in the design, analysis, and interpretation of laboratory animal experiments, with particular emphasis on two-year carcinogenicity studies. Experimental design issues include examining potential sources of variability in tumor incidence. Inter-laboratory differences and time-related trends were found to be significant sources of variability. Future research plans include a re-evaluation of tumor diagnoses from early NCI and current NTP studies, to identify the specific factors responsible for this variability. Research in the area of data analysis has focused on the development of statistical procedures for evaluating tumor data that do not require cause of death information or numerous interim kills. Particularly promising is a procedure that weights the contribution of animals that die tumor-free based upon a hypothesized form of the tumor onset distribution. The resulting procedure is a simple modification of the Cochran-Armitage trend test and may ultimately result in an important advance in the statistical evaluation of tumor data. An evaluation of the relationship between toxicity, genotoxicity, and carcinogenicity in laboratory rodents indicated that only a relatively small proportion (10-15%) of positive carcinogenicity studies exhibited the types of target organ toxicity that could have been the cause of all observed carcinogenic effects. Furthermore, no apparent difference in mutagenicity was observed between "high dose only" carcinogens and the entire set of carcinogens.