Statistical Methods in Evidence-based Risk Assessment

循证风险评估中的统计方法

• 批准号: RGPIN-2022-05034
• 负责人: Krewski, Daniel
• 金额: $ 1.31万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=753399
• 关键词: Statistical; Methods; Evidence; based; Risk

The major research theme underlying the proposal is value-of-information (VOI) analysis. In preliminary work, a new Bayesian framework for VOI analysis has been developed, allowing trade-offs between the cost, uncertainty, and timeliness of data collected in support of risk assessment. An important component of this new framework is the explicit characterization of the cost of delay in acquiring information on critical population health risks, which can result in a significant public health burden, pending identification and elimination or reduction of those risks. The framework considers two risk decision making paradigms: a benefit-risk decision maker (BRDM), who seeks to minimize the total social cost associated with the risk issue of concern (with adverse population health impacts valued in economic terms), and a target-risk decision maker (TRDM), who seeks to ensure risk is below a pre-determined level. Initial applications of the VOI framework in testing large numbers of chemicals to which humans are exposed suggests that the use of so-called new approach methodologies (NAMs) based on high-throughput in vitro screening (HTS) tests will provide a greater return on investment (ROI) than traditional animal-based toxicity tests, which, although subject to less uncertainty, are much more expensive and time-consuming to conduct. Two additional research themes will also be pursued as part of this proposal. First, novel points of departure (PoD's) on the exposure-response curve will be examined as the basis for establishing human exposure guidelines, specifically the signal-to-noise crossover dose (SNCD) corresponding to the point where the biological signal cannot be statistically distinguished from the background response rate. Second, optimal experimental designs for estimating the SNCD will be developed in order to obtain the best possible human exposure guidelines. Collectively, this research will greatly strengthen evidence-based risk assessment practices through the application of VOI analyses to identify the most informative sources of data to support human health risk assessment; by developing improved human exposure guidelines through the use of more refined exposure-response analyses; and by developing optimal experimental designs to maximize the statistical information about the shape of the exposure-response curve.

该提案的主要研究主题是信息价值（VOI）分析。在初步工作中，一个新的贝叶斯框架VOI分析已经开发出来，允许权衡成本，不确定性和及时性的数据收集，以支持风险评估。这一新框架的一个重要组成部分是明确说明在查明和消除或减少重大人口健康风险之前，拖延获取有关这些风险的信息可能造成重大公共卫生负担的代价。该框架考虑了两种风险决策模式：一种是效益-风险决策者（BRDM），他寻求最大限度地减少与所关注的风险问题相关的总社会成本（从经济角度评估对人口健康的不利影响），另一种是目标-风险决策者（TRDM），他寻求确保风险低于预定水平。VOI框架在测试人类接触的大量化学品中的初步应用表明，使用基于高通量体外筛选（HTS）测试的所谓新方法（NAM）将提供比传统的基于动物的毒性测试更高的投资回报率（ROI），尽管不确定性较小，但进行起来要昂贵得多，耗时得多。另外两个研究主题也将作为这项建议的一部分。首先，将检查暴露-反应曲线上的新的出发点（PoD），作为建立人体暴露指南的基础，特别是与生物信号无法在统计学上与背景反应率区分开的点相对应的信噪比交叉剂量（SNCD）。第二，将开发用于估计SNCD的最佳实验设计，以获得尽可能好的人类接触准则。总的来说，这项研究将大大加强循证风险评估的做法，通过应用VOI分析，以确定最翔实的数据来源，以支持人类健康风险评估;通过开发改进的人类接触准则，通过使用更精细的安全性-响应分析;并通过开发最佳的实验设计，以最大限度地提高安全性-响应曲线的形状的统计信息。