NTP DATABASE SUMMARIZATION AND EVALUATION

该项目的目标是总结、评估和解释国家毒理学计划啮齿动物致癌性数据库和其他大型数据库中包含的数据。随着国家毒理学规划致癌性数据库越来越多地向一般科学界开放，那些可能不完全了解其所包含的复杂信息的人无意中滥用该数据库的机会也在增加。我们证明了先前发表的NTP数据库评估夸大了统计学上显著的肿瘤下降趋势的频率，导致这些错误的因素包括未能调整生存差异，评估不适当的肿瘤组合，未能达到报告的显著性水平（p<0.01），重复计算化学物质的部位特异性降低肿瘤发生率，以及使用科学上不充分的研究。在另一个项目中，作为ICCVAM（替代方法验证机构间协调委员会）倡议的一部分，我们评估了来自青蛙胚胎畸形试验-非洲爪（FETAX）结果的大型数据库。我们发现，在某些情况下，报告的畸形率在实验室间存在显著差异，这似乎与研究者之间的诊断差异有关。基于这些结果，就如何改进FETAX方案以减少这种可变性并促进该试验的未来验证提出了具体建议。

The goal of this project is to summarize, evaluate, and interpret data contained in the NTP rodent carcinogenicity database and other large databases. As the NTP carcinogenicity database becomes increasingly accessible to the general scientific community, there is increased opportunity for inadvertent misuse of the database by those who may not have a complete understanding of the complex information it contains. We demonstrated that a previously published evaluation of the NTP database exaggerated the frequencies of statistically significant decreasing tumor trends, The factors contributing to these errors included failure to adjust for survival differences, evaluating improper tumor combinations, failure to achieve the reported (p<0.01) level of significance, double counting a chemical's site-specific decreased tumor incidence, and using scientifically inadequate studies. In another project, we evaluated the large database of results from the Frog Embryo Teratogenesis Assay - Xenopus (FETAX), as part of an ICCVAM (Interagency Coordinating Committee on the Validation of Alternative Methods) initiative, We found that in some cases there was significant inter-laboratory variability in the reported malformation rates that appeared to be related to diagnostic differences among investigators, Based on these results, specific recommendations were made as to how the FETAX protocols could be improved to reduce this variability and facilitate any future validation of this assay.