EXPERIMENTAL DESIGN AND DATA ANALYSIS METHODOLOGY

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， 特别是由以下机构进行的长期啮齿动物致癌性研究 国家毒理学计划(NTP)。NTP啮齿动物的利用 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病率 其他因素；(2)评估发生频率和影响因素 NTP研究中与化学相关的肿瘤减少；以及(3)进行 鼻腔致癌物在非鼻咽癌患者中的频率评价 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。 这一地区的另一项调查评估了 暴露于氯丹的小鼠。我们发现，这两种治疗的比例 患肝癌的小鼠，以及平均每只小鼠的肝肿瘤数量 经氯丹处理的小鼠，在氯丹暴露后显著下降 停下来了。此外，接受治疗的小鼠经历中毒的比例 与肝细胞的时间发育密切相关的变化 肿瘤，随着毒性的严重程度开始增加，然后 肿瘤最大负荷点后下降。有没有可能 暴露诱导的肿瘤在停止治疗后可能会消退 对NTP的设计、分析和解释有很大影响 学习。

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.