Statistical Methods in Risk Science

先进的统计方法越来越多地用于风险的定量表征，为支持风险决策的发展提供了重要的证据。目前的研究计划侧重于当前感兴趣的六个方法学问题，这些问题将通过创新统计技术的发展和应用来解决。* * * 1。环境疾病负担（EBD）评估环境因素对人类疾病的影响，有助于确定减少环境健康风险的优先事项。以前开发的用于描述EBD特征的统计方法将扩展到包括生活质量的降低，并使用最近与职业铅暴露相关的神经系统疾病风险荟萃分析的数据进行说明。****2。氡在家庭中的危害。氡气是导致肺癌的重要原因，它自然存在于地壳的岩石和土壤中，并通过地基上的微小裂缝和裂缝进入房屋。为了指导进一步的氡缓解工作，将根据加拿大和国际上新的流行病学和监测数据，制定住宅氡肺癌风险的最新估计。****3。动物和人类肿瘤部位的一致性。国际癌症研究机构（IARC）最近完成了对109种致癌物质数据更新的审查，包括：药物；生物制剂;砷、金属、纤维和粉尘；辐射;个人习惯和室内燃烧；以及化学制剂及相关职业。这些数据将用于评估由这些药物引起的动物和人类肿瘤类型之间的一致性程度****4。动物和人类癌症的生物学机制。上述(3)所述的国际癌症研究机构数据也将用于比较致癌物剂在动物和人类中的作用机制。****使用药代动力学模型进行组织剂量测定。将探索在剂量-反应模型中使用药代动力学模型预测的组织浓度，期望组织剂量可能比饮食或环境浓度产生更准确的风险指标。****6。艾姆斯沙门氏菌试验的最佳实验设计。由于最近在毒性测试中使用体外数据的趋势，将开发最佳实验设计，以估计剂量-反应曲线上的起点（包括传统的基准剂量和最近提出的信号-噪声交叉剂量），用于为Ames沙门氏菌测定制定暴露指南。****总的来说，这项工作将扩大可用于定量风险评估的技术套件，从而有助于更好地评估风险和健全的基于风险的决策。******

Advanced statistical methods are increasingly used in the quantitative characterization of risk, providing important evidence to support the development of risk decisions. The present research program focuses on six methodological issues of current interest, which will be addressed through the development and application of innovative statistical techniques. ***1. Environmental burden of disease (EBD). Estimation of the contribution of environmental agents to human disease is importing for establishing priorities for environmental health risk reduction. Statistical methods developed previously to characterize the EBD will be extended to incorporate reduction in quality of life, and illustrated using data from a recent meta-analysis of the risks of neurological disease associated with occupational exposure to lead.****2. Risks of radon in homes. Radon gas, an important cause of lung cancer, is naturally present in rocks and soils in the earth's crust, and enters homes through tiny cracks and fissures in the foundation. In order to guide further radon mitigation efforts, updated estimates of residential radon lung cancer risks will be developed based on new epidemiological and monitoring data from Canada and internationally.****3. Concordance between animal and human tumour sites. The International Agency for Research on Cancer (IARC) has recently completed a review an update of data on 109 cancer causing agents, including: pharmaceuticals; biological agents; arsenic, metals, fibres and dusts; radiation; personal habits and indoor combustions; and chemical agents and related occupations. These data will be used to evaluate the degree of concordance between tumour types seen in animals and humans that are caused by these agents****4. Biological mechanisms of cancer in animals and humans. The IARC data described in (3) above will also be used to compare the mechanisms by which carcinogenic agents operate in animals and humans.****5. Use of pharmacokinetic models for tissue dosimetry. The use of tissue concentrations predicted by pharmacokinetic models in dose-response modelling will be explored, with the expectation that tissue doses may lead to more accurate indicators of risk than dietary or ambient concentrations.****6. Optimal experimental designs for the Ames Salmonella assay. Because of the recent trend towards the use of in vitro data in toxicity testing, optimal experimental designs to estimate a point of departure on the dose-response curve (including both the traditional benchmark dose and the recently proposed signal-to-noise crossover dose) used in setting exposure guidelines for the Ames Salmonella assay will be developed.****Collectively, this work will expand the suite of techniques available for quantitative risk assessment, thereby contributing to better assessments of risk and sound risk-based decision making.******