Low-dose risk bounds via simultaneous confidence bands

描述(由申请人提供)：量化暴露于危险试剂的环境风险和其他有害风险是风险评估和评估过程中的一个重要组成部分。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时统计推断方法。适用于环境和职业风险评估研究，其中人类或动物数据被用来设定危险制剂的基准或其他安全的低剂量水平，但研究信息仅限于该制剂的高剂量水平。重点介绍了比例终点预测风险的同时置信限的确定方法。根据同时的界限，计算出与特定风险相关的基准剂量(BMD)的下限。同时构造的一个重要特征是，任何基于倒置同时置信限的推断都自动适用于BMD的倒界。 该方法在描述剂量-反应关系的一系列链接函数下，将先前关于同时置信带的结果扩展到二项和过度分散的比例数据。还考虑通过计算机化的模型充分性评估来解决不同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洛计算机计算研究了该方法的小样本操作特性。新方法继续填补了低剂量风险外推的现有空白，并应用于使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广泛的用户能够访问这些方法。

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.