NTP Database Summarization And Evaluation

该项目的目标是总结、评估和解释NTP啮齿动物致癌性数据库和其他大型数据库中包含的数据。最近，NIEHS共同主办了一次会议，审查关于特定研究中是否存在低剂量内分泌干扰物影响的数据。所有受邀发言者同意在会议前向统计小组提供原始数据，该小组被要求重新评估作者的实验设计、数据分析和对实验结果的解释。哈斯曼博士担任了这个小组的主席，最近发表了一篇总结他们的评估的论文。本文讨论的统计学原理和问题并不是内分泌干扰物研究所特有的，应该为其他类型的实验室调查提供关于适当的实验设计和统计分析的重要指导方针。对大型数据库的评估提供了一个独特的机会来检查使用类似研究方案进行的一系列实验。Peddada博士在国际(经济合作与发展组织(OECD))子宫营养生物检测验证计划第二阶段的设计和分析中发挥了关键作用。这一生物测定旨在鉴定被怀疑为雌激素激动剂或拮抗剂的化合物的体内活性，并帮助确定阳性化合物的优先顺序，以便进一步测试。两个模型系统，未成熟的雌性大鼠和成年的去卵巢大鼠正在进行测试和比较。对来自19个参与实验室的数据进行了评估，这些实验室使用了七种不同的化学物质，以及盲法和非盲法。尽管研究结果的最后总结和解释仍在进行中，但实验室之间以及实验室内部对所评价的大多数化学品的盲法和非盲法议定书似乎普遍达成了良好的一致意见。在另一个正在进行的项目中，NIEHS主任要求我们评估现有的转基因小鼠生物测试文献，并就NTP应如何利用这些动物模型评估潜在致癌物提出具体建议。这项汇编工作已接近完成，不久将开始对数据库进行统计分析。

The goal of this project is to summarize, evaluate, and interpret data contained in the NTP rodent carcinogenicity database and other large databases. Recently, the NIEHS co-sponsored a meeting to examine data addressing the presence or absence of low-dose effects of endocrine disruptors in specific studies. All invited speakers agreed to provide their raw data in advance of the meeting to a Statistics Subpanel, that was asked to re-evaluate the authors' experimental design, data analysis, and interpretation of experimental results. Dr. Haseman chaired this subpanel, and a paper summarizing their evaluation was recently published. The statistical principles and issues that are discussed in this paper are not unique to endocrine disruptor studies, and should provide important guidelines regarding appropriate experimental design and statistical analysis for other types of laboratory investigations. Evaluations of large databases provide a unique opportunity to examine a series of experiments conducted with similar study protocols. Dr. Peddada is playing a key role in the design and analysis of the second phase of an international (Organization for Economic Co-operation and Development (OECD)) validation program for the uterotrophic bioassay. This bioassay is intended to identify the in vivo activity of compounds that are suspected agonists or antagonists of estrogen, and to assist the prioritization of positive compounds for further testing. Two model systems, the immature female rat and the adult ovariectomized rat, are being tested and compared. Data from nineteen participating laboratories using seven different chemicals ,and both a blinded and unblinded protocol were evaluated. Although the final summarization and interpretation of study results are still ongoing, there seemed to be generally good agreement among laboratories and also within laboratories between blinded and unblinded protocols for most of the chemicals evaluated. In another ongoing project, we have been asked by the Director of the NIEHS to evaluate the available literature on transgenic mouse bioassays and make specific recommendations as to how the NTP should make use of these animal models in the evaluation of potential carcinogens. This compilation is nearing completion and the statistical analysis of the database will soon begin.