Statistical Methods In Epidemiology--general

流行病学统计方法——综述

• 批准号: 8734061
• 负责人: Clarice Weinberg
• 金额: $ 5.42万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8734061
• 关键词: American; Antibodies; Archives; Area; Autoimmunity; Biological Assay; Biological Markers; Blood; Chemicals; Cost Savings; Data; Data Analyses; Detection; Dioxins; Dose; Environmental Exposure; Environmental Risk Factor; Epidemiologic Methods; Epidemiology; Event; Exposure to; Failure; Future; Genetic Predisposition to Disease; Human; Immunity; Individual; Journals; Learning; Logistic Models; Measures; Methods; Modeling; National Health and Nutrition Examination Survey; Nuclear; Observational Study; Outcome; Paper; Population; Pregnancy; Price; Publishing; Research Design; Risk; Sampling; Specimen; Statistical Methods; Survival Analysis; Time; Toxic effect; Weight; Work; Xenobiotics; base; case control; cost; design; disorder risk; flexibility; human data; improved; prospective; reproductive; response; tool

This project develops new statistical methods for epidemiology with broad applications and also methods as needed for ongoing projects in epidemiology, particularly those related to reproductive studies. The work this year involved two main projects. (1) One project concerns pooled assessment of expensive-to-assay biomarkers based on human samples. Earlier work had shown that in a case-control setting one can pool together specimens from sets of cases and sets of controls and carry out a set-based analysis. With a slightly modified logistic model that analysis can estimate the individual-level risk parameters and loses almost no power compared to analysis based on individual assays. This means that if an exposure is based on an expensive assay that uses human samples, one can markedly improve efficiency by pooling specimens prior to assay. In recent work, we have extended these methods to apply using outcome-dependent pooling in the context of time-to-event data, e.g. time to pregnancy studies. Although these methods can produce huge cost savings and spare precious samples, the methods impose restrictions that limit the flexibility of models that can be fit. For example, one cannot explore secondary endpoints and one cannot fit nonlinear dose-logit-response models. We are now doing additional work aimed at developing semi-parametric methods for "prospective pooling," which will overcome some of the limitations caused by the need to use outcome-dependent pooling. We are now developing semi-parametric methods for "prospective pooling" in time-to-event settings. Such methods should allow powerful and inexpensive assessments of the effects of environmental exposures on survival and other failure-time outcomes. (2) A second project is developing methods for analysis of outcomes related to environmental exposures where the exposure biomarker is often at a level below the assay limit of detection. Methods developed for survival analysis can be employed and permit confounder adjustment. We are applying this to data from the National Health and Nutrition Examination Survey data relating toxic analytes in blood to the presence of a biomarker, anti-nuclear antibodies, for autoimmunity. We have a paper describing this method under revision for the American Journal of Epidemiology. In future work we hope to extend this work to mixtures of chemicals, making use of existing toxic equivalency factors to create a censored toxicity-weighted average.

该项目开发了具有广泛应用的流行病学的新统计方法，还根据流行病学中正在进行的项目（尤其是与生殖研究相关的项目）所需的方法开发了新的统计方法。 今年的工作涉及两个主要项目。 （1）一个项目涉及基于人类样本的昂贵到公允生物标志物的评估。较早的工作表明，在病例对照设置中，可以将标本从一组情况和一组控件组合在一起，并进行基于设定的分析。 通过一个稍微修改的逻辑模型，分析可以估计单个级别的风险参数，并且与基于个体测定的分析相比，几乎没有功率。 这意味着，如果曝光是基于使用人类样品的昂贵测定法，则可以通过在测定前汇总样品来显着提高效率。在最近的工作中，我们扩展了这些方法，以在事件时间数据的背景下使用结果依赖性池进行应用，例如妊娠研究的时间。尽管这些方法可以节省大量的成本和剩余的宝贵样本，但这些方法施加的限制限制了可以合适的模型的灵活性。 例如，人们无法探索次要终点，并且不能符合非线性剂量 - 差异响应模型。现在，我们正在进行旨在开发“准合并”的半参数方法的其他工作，这将克服由于需要使用结果依赖性的汇总而造成的一些局限性。现在，我们正在开发半参数方法，用于在事件时间设置中“预期合并”。 这样的方法应允许对环境暴露对生存和其他失败时间结果的影响进行强大而廉价的评估。 （2）第二个项目是开发用于分析与环境暴露相关的结果的方法，在这种情况下，暴露生物标志物通常处于低于检测的测定极限的水平。 可以采用用于生存分析的方法并允许调整混杂因素。 我们将其应用于国家健康和营养检查调查数据，将血液中有毒分析物与存在生物标志物抗核抗体的存在有关，以进行自身免疫性。 我们有一篇论文在《美国流行病学杂志》中描述了这种方法。 在未来的工作中，我们希望将这项工作扩展到化学物质的混合物，利用现有的毒性等效因素来审查毒性加权的平均水平。