EXPERIMENTAL DESIGN AND DATA ANALYSIS METHODOLOGY

该项目涉及的是联合国系统内的统计方法问题。 实验室动物实验的设计、分析和解释， 特别是长期啮齿动物致癌性研究， 国家毒理学计划（NTP）。 利用NTP啮齿动物 致癌性数据库，我们（1）开发了数学模型来预测 根据年龄、体重和体重控制大鼠和小鼠的肿瘤发生率， 其他因素;（2）评估的频率和因素负责 NTP研究中化学相关的肿瘤减少;和（3）进行 NTP中鼻腔致癌物频率的评价 数据库通过这项研究获得的知识将增加我们的 了解长期啮齿动物研究的价值和局限性。 该领域的另一项研究评价了 暴露于三氯甲烷的老鼠 我们发现，接受治疗的比例 小鼠肝癌，和平均数量的肝肿瘤， 处理的小鼠，在暴露于氯霉素后显著降低， 停止. 此外，接受治疗的小鼠中出现毒性反应的比例 与肝细胞的时间发展密切相关 肿瘤，毒性的严重程度最初增加，然后 在最大肿瘤负荷点之后降低。 的可能性 化疗诱导的肿瘤在治疗停止后可能会消退， 对NTP的设计、分析和解释有很大影响 问题研究

This project is concerned with statistical methodology issues in the design, analysis, and interpretation of laboratory animal experiments, especially the long term rodent carcinogenicity studies carried out by the National Toxicology Program (NTP). Making use of the NTP rodent carcinogenicity database, we (1) developed mathematical models to predict control tumor incidence in rats and mice based on age, body weight, and other factors; (2) evaluated the frequency of and factors responsible for chemically-related tumor decreases in NTP studies; and (3) carried out an evaluation of the frequency of nasal cavity carcinogens in the NTP database. The knowledge gained through this research will increase our understanding of the value and limitations of long term rodent studies. Another investigation in this area evaluated hepatocarcinogenicity among mice exposed to chlordane. We found that both the proportion of treated mice with liver carcinomas, and the average number of liver tumors per treated mouse, decreased significantly after chlordane exposure was stopped. In addition, the proportion of treated mice experiencing toxic changes closely paralleled the temporal development of hepatocellular neoplasia, with the severity of toxicity increasing initially and then decreasing after the point of maximum tumor burden. The possibility that exposure-induced tumors might regress after treatment is stopped could have a large impact on the design, analysis, and interpretation of NTP studies.