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。 一项调查评估了最大耐受量与 检测鼠类致癌性的剂量(MTD)和研究敏感性 216种啮齿动物致癌物质。大约三分之二的这些致癌物会有 即使没有最大剂量也被检测到，剩下的近80% 啮齿动物致癌物的比率在数字上(但不是很明显)升高。 在更低的剂量下，相同部位的肿瘤，这项评估 表明在啮齿动物的MTD观察到的大多数致癌作用 也有低剂量(1/2)的研究(发病率降低)。 MTD、1/4 MTD)通常采用。在另一项调查中，一家大型 进行了计算机模拟以评估其运行特性 用于比较隐匿性肿瘤发病率的各种趋势测试。 数据是在88种不同的场景下生成的，以便模拟 广泛的现实动物致癌实验。在一个变种之下 实验条件和假定的潜在剂量-反应模型， 始终执行最好的程序(即，在 意义的正确程度和具有最大的力量)是生存- 根据风险差异进行调整的测试，这是一个不 要求提供有关死亡原因或肿瘤致命性的信息。未来 研究工作包括对各种影响因素的评估 肿瘤发病率，特别强调与身体的关系 重量和多笼的效果。未来的研究也将是 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.