SOURCES OF VARIABILITY IN TUMOR INCIDENCE IN LONG TERM RODENT STUDIES

肿瘤发病率的三个变异性来源是 调查过了。为了评估随机变化的影响，我们 评价了几种统计方法的运行特点 比较肿瘤发病率的程序。我们发现那些 使用预定重要性级别的技术(例如， P&lt；0.01)对于所有比较，可能产生不可接受的高错误 积极的比率。我们得出的结论是，韦斯特福尔得出的一个程序 如果使用得当，索珀似乎提供了一种合理的平衡 在控制总体假阳性率和维持 检测致癌效应的能力。调查其影响 体重差异对肿瘤发病率的影响，我们评估了数据 来自NTP饮食限制研究。我们的调查显示 注重于实现类似目标的饮食限制策略 剂量组和对照组的体重可能会产生假 如果需要更多的食物限制，结果是积极的 对于对照组，而不是给药的动物。我们还发现， 对给药和控制动物的食物限制可能会产生虚假的 如果由此产生的体重实质上是 剂量组和对照组不同。另一种方法 人们正在研究减轻体重，包括饮食 修改和要求饲养员提供更轻的动物。最后， 我们评估了肝螺杆菌感染对 肝脏肿瘤的发病率。对照B6C3F1雄性小鼠9只 感染肝螺杆菌的NTP研究显示增加 (P&lt；0.05)26人的肝脏肿瘤发病率与对照组相比 未感染的生物检测。肝细胞癌发病率的增加 肿瘤主要见于表现出H. 肝病相关性肝炎。我们的结论是，对 B6C3F1小鼠肝脏的致癌作用可能是 不清楚是否存在肝炎性肝炎。

Three sources of variability in tumor incidence were investigated. To assess the impact of random variability, we evaluated the operating characteristics of several statistical procedures for comparing tumor incidences. We found that those techniques that use pre-determined levels of significance (e.g., p<0.01) for all comparisons may produce unacceptably high false positive rates. We concluded that a procedure derived by Westfall and Soper, if used properly, seems to provide a reasonable balance between controlling the overall false positive rate and maintaining power for detecting carcinogenic effects. To investigate the impact of body weight differences on tumor incidence, we evaluated data from the NTP Dietary Restriction Study. Our investigation suggests that a dietary restriction strategy that focuses on achieving similar body weights in dosed and control groups may produce false positive outcomes if substantially more food restriction is required for control groups than for dosed animals. We also found that equal food restriction to dosed and control animals may produce false negative outcomes if the resulting body weights are substantially different in dosed and control groups. Alternative methods of reducing body weight are being studied, including dietary modifiation and requiring lighter animals from the breeder. Finally, we evaluated the impact Helicobacter hepaticus infection on the incidence of liver neoplasms. Control B6C3F1 male mice from nine NTP studies infected with Helicobacter hepaticus showed increased (p<0.05) liver tumor incidences compared with controls from 26 uninfected bioassays. The increased incidences of hepatocellular neoplasms were seen primarily in those males exhibiting H. hepaticus associated hepatitis. We concluded that interpretation of carcinogenic effects in the liver of B6C3F1 mice may be confounded if there is H. hepaticus associated hepatitis.