Low-dose risk bounds via simultaneous confidence bands

通过同时置信带确定低剂量风险界限

• 批准号: 6771237
• 负责人: WALTER W PIEGORSCH
• 金额: $ 13.82万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6771237
• 关键词: animal data; cancer risk; clinical research; data collection methodology /evaluation; dosage; environmental exposure; environmental toxicology; human data; mathematical model; model design /development; statistics /biometry

DESCRIPTION (provided by applicant): Quantifying environmental and other detrimental risks from exposure to hazardous agents is an important component in the process of risk evaluation and assessment. The primary goal of this project is to develop and study methods of simultaneous statistical inference for use in low-dose risk extrapolation. Application is directed to environmental and occupational risk assessment studies where human or animal data are used to set benchmark or other safe low-dose levels of a hazardous agent, but where study information is limited to high dose levels of the agent. Methods are emphasized for simultaneous upper confidence limits on predicted risk for proportion endpoints. From the simultaneous bounds, lower confidence limits on the benchmark dose (BMD) associated with a particular risk are calculated. An important feature of the simultaneous construction is that any inferences based on inverting the simultaneous confidence bounds apply automatically to inverse bounds on the BMD. The methodology extends previous results for simultaneous confidence bands to binomial and overdispersed proportion data under a series of link functions that describe the dose-response relationship. Consideration is also given to address model selection bias across the various link functions via computerized model adequacy appraisals. An evaluation phase of the project studies the small-sample operating characteristics of the methodology via Monte Carlo computer calculations. The new methods continue to fill existing gaps in low-dose risk extrapolation, and have application to the important problem of performing low-dose risk assessment with proportion data. World Wide Web software is constructed to allow the methods to be accessible to the widest possible corps of users.

描述（由申请人提供）：量化因接触有害物质而造成的环境和其他有害风险是风险评估和评估过程中的重要组成部分。该项目的主要目标是开发和研究用于低剂量风险外推的同步统计推断方法。应用针对环境和职业风险评估研究，其中使用人类或动物数据来设定危险剂的基准或其他安全低剂量水平，但研究信息仅限于该剂的高剂量水平。强调了比例终点预测风险的同步置信上限方法。根据同时界限，计算与特定风险相关的基准剂量 (BMD) 的置信下限。同时构建的一个重要特征是，任何基于反转同时置信界限的推论都会自动应用于 BMD 的逆界限。 该方法将先前同时置信带的结果扩展到描述剂量反应关系的一系列链接函数下的二项式和过度分散比例数据。还考虑通过计算机化模型充分性评估来解决各种链接功能之间的模型选择偏差。该项目的评估阶段通过蒙特卡罗计算机计算研究该方法的小样本操作特征。新方法继续填补了低剂量风险外推的现有空白，并应用于利用比例数据进行低剂量风险评估的重要问题。万维网软件的构建是为了让尽可能多的用户能够访问这些方法。