EXPERIMENTAL DESIGN AND DATA ANALYSIS METHODOLOGY FOR ANIMAL EXPERIMENTS

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。 一项研究评价了最大耐受剂量与 剂量（MTD）和检测啮齿动物致癌性的研究灵敏度 216种啮齿动物致癌物。大约三分之二的致癌物质 即使没有最高剂量也能检测到，剩余的近80% 啮齿类致癌物在数值上（但不显著）升高 相同部位特异性肿瘤在较低剂量下， 表明在啮齿类动物中MTD时观察到的大多数致癌作用 也有研究（发生率降低）在较低剂量（1/2 MTD，1/4 MTD）。 在另一项调查中， 进行了计算机模拟以评估操作特性 比较隐匿性肿瘤发病率的各种趋势检验。 在88种不同的情况下生成数据，以模拟 广泛的现实动物致癌实验。 以各种 实验条件和假设的潜在剂量反应模型， 始终表现最好的过程（即，下操作 最大的力量，最大的力量，最大的力量。 基于风险差异的调整测试，这是一个不 需要关于死亡原因或肿瘤致死率的信息。 未来 研究工作包括评估影响 肿瘤发病率，特别强调与身体 体重和多重笼养的影响。 未来的研究还将 越来越多地指向非癌症终点。

This project is concerned with statistical methodology issues in the design, analysis, and interpretation of laboratory animal experiments. One investigation evaluated the relationship between maximum tolerated dose (MTD) and study sensitivity for detecting rodent carcinogenicity for 216 rodent carcinogens. Approximately 2/3 of these carcinogens would have been detected even without the top dose, Nearly 80% of the remaining rodent carcinogens had numerically (but not significantly) elevated rates of the same site-specific tumors at lower doses, This evaluation indicates that most carcinogenic effects observed at the MTD in rodent studies are also present (with reduced incidence) at the lower doses (1/2 MTD, 1/4 MTD) typically employed. In another investigation, a large computer simulation was conducted to assess the operating characteristics of various trend tests for comparing incidence rates of occult tumors. Data were generated under 88 different scenarios in order to simulate a wide range of realistic animal carcinogenic experiments. Under a variety of experimental conditions and assumed underlying dose-response models, the procedure that consistently performed best (i.e., operated at the correct level of significance and had greatest power) was the survival- adjusted test based on risk differences, a procedure that does not require information on cause of death or tumor lethality. Future research efforts include an evaluation of the various factors affecting tumor incidence, with particular emphasis on associations with body weight and the effect of multiple caging. Future research will also be increasingly directed toward non-cancer endpoints.