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Causal Inference Methods for Mediation and Comparisons of Confidence Regions

用于中介和置信区域比较的因果推理方法

基本信息

批准号：
1854934
负责人：
Judith Lok
金额：
$ 15.33万
依托单位：
Trustees of Boston University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2022-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1854934&HistoricalAwards=false
关键词：
Causal Inference Methods Mediation Comparisons

项目摘要

In epidemiology, clinical research, and the social sciences, inferences about the causal effects of treatments and risk factors are used to design more effective interventions. This project focuses on the development of statistical methods for causal inference. The first part of this project will develop a causal inference method for mediation analysis. If a treatment has a beneficial effect on an outcome, it is often of interest to investigate what are the pathways by which it affects the outcome. Direct and indirect effects decompose the effect of a treatment into the part that is mediated by a covariate (the mediator) and the part that is not. For example, in HIV/ AIDS research, it is important to estimate how much of the effect of Antiretroviral Therapy (ART) on mother-to-child-transmission of HIV is mediated by the effect of ART treatment on the HIV viral load in the mother's blood. In medicine, psychology, political science, and economics, differentiating between indirect and direct effects has become increasingly important. Therefore, it is paramount that appropriate statistical methods are developed to estimate direct and indirect effects in a variety of settings, including the setting in which there are post-treatment common causes of the mediator and the outcome. The second part of this project will compare confidence regions. Recently, there has been extensive discussion in the statistical community about a move away from p-values. P-values can lead researchers to conclude that a treatment has a significant effect even if that effect is very small, and clinically irrelevant. Confidence regions are the obvious alternative to p-values, as they provide a range of values of the parameters of interest that are most consistent with the data. While comparisons of p-values have been extensively researched and confidence regions are routinely reported, comparison of confidence regions has received relatively little attention. In this project, confidence regions will be compared based on the notion of asymptotic equivalence. Natural direct and indirect effects use cross-worlds counterfactuals: outcomes under treatment with the mediator "set" to its value without treatment. Cross-worlds counterfactuals can never be observed, as they involve quantities under two different treatments where only one treatment is given to any particular patient or unit. The PI has recently proposed organic direct and indirect effects to avoid the use of cross-worlds counterfactuals. Organic direct and indirect effects also apply when the mediator cannot be "set". For example, the HIV viral load in the mother's blood cannot be set; if it could be set, doctors would set it to zero. In the first part of this project, organic direct and indirect effects will be extended to settings with post-treatment common causes of the mediator and the outcome. It will be shown that, in contrast to natural direct and indirect effects, estimators and confidence intervals can be developed in that setting for organic effects. The second part of this project will compare confidence regions. Most work on the comparison of confidence regions has studied coverage probabilities, confidence interval length, and small sample properties. In this project, confidence regions will be compared for large samples, based on the asymptotic behavior of the Hausdorff distance between the different confidence regions. The Hausdorff distance between partly overlapping intervals is simply the maximum of the difference between the left limits and the right limits of the intervals. The Hausdorff distance has also been defined for non-convex sets and in higher dimensions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在流行病学、临床研究和社会科学中，对治疗的因果效应和风险因素的推断被用来设计更有效的干预措施。这个项目的重点是开发用于因果推断的统计方法。本项目的第一部分将开发一种用于调解分析的因果推理方法。如果一种治疗对结果有好处，调查它通过什么途径影响结果通常是有意义的。直接和间接效应将治疗效果分解为由协变量(中介)调节的部分和非协变量调节的部分。例如，在艾滋病毒/艾滋病研究中，估计抗逆转录病毒疗法(ART)对艾滋病毒母婴传播的影响在多大程度上是通过ART治疗对母亲血液中艾滋病毒病毒载量的影响来实现的，这一点很重要。在医学、心理学、政治学和经济学中，区分间接影响和直接影响变得越来越重要。因此，至关重要的是，必须制定适当的统计方法，以估计各种情况下的直接和间接影响，包括治疗后调解人和结果的共同原因的情况。本项目的第二部分将比较置信度区域。最近，统计界对放弃p值进行了广泛的讨论。P值可能会导致研究人员得出结论，一种治疗具有显著的效果，即使这种效果非常小，而且与临床无关。置信域是p值的明显替代，因为它们提供与数据最一致的感兴趣参数的值范围。虽然p值的比较已经得到了广泛的研究，置信域的比较也经常被报道，但置信域的比较相对较少受到关注。在这个项目中，将基于渐近等价的概念来比较置信域。自然的直接和间接影响使用跨世界的反事实：接受调解人治疗的结果在没有治疗的情况下“设定”为其价值。跨世界的反事实永远不会被观察到，因为它们涉及两种不同治疗下的数量，即只对任何特定的患者或单位给予一种治疗。国际和平研究所最近提出了有机的直接和间接效应，以避免使用跨世界的反事实。当调解人不能被“设定”时，有机的直接和间接影响也适用。例如，母亲血液中的HIV病毒载量不能设置；如果可以设置，医生会将其设置为零。在这个项目的第一部分，有机的直接和间接影响将扩展到治疗后调解人和结果的共同原因的环境中。它将表明，与自然的直接和间接影响相比，可以在有机影响的背景下开发估计器和可信区间。本项目的第二部分将比较置信度区域。大多数关于置信度区域比较的工作都研究了覆盖概率、置信度区间长度和小样本性质。在这个项目中，将根据不同置信域之间Hausdorff距离的渐近行为，对大样本的置信度区域进行比较。部分重叠区间之间的Hausdorff距离就是区间的左限和右限之差的最大值。豪斯道夫距离也被定义为非凸集和更高的维度。这个奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Randomized Trial Evaluating Clinical Impact of RAPid IDentification and Susceptibility Testing for Gram-negative Bacteremia: RAPIDS-GN

评估 RAPid 鉴定和药敏试验对革兰氏阴性菌血症临床影响的随机试验：RAPIDS-GN

DOI：
发表时间：
2021
期刊：
Clinical infectious diseases
影响因子：
11.8
作者：
Banerjee R.;Komarow L.;Virk A.;Rajapakse N.;Schuetz A.;Dylla B.;Earley M.;Lok J.J.;Kohner P.;Ihde S.
通讯作者：
Ihde S.

Evaluating the power of the causal impact method in observational studies of HCV treatment as prevention

评估因果影响法在 HCV 治疗作为预防的观察性研究中的功效

DOI：
10.1515/scid-2020-0005
发表时间：
2021
期刊：
Statistical communications in infectious diseases
影响因子：
0
作者：
Samartsidis P.;Martin N.;De Gruttola V.;De Vocht F.;Hutchinson S.;Lok J.J.;Puenpatom A.;Wang R.;Hickman M.;De Angelis D.
通讯作者：
De Angelis D.

Molecular and Clinical Epidemiology of Carbapenem-Resistant Enterobacteriaceae in the United States: a Prospective Cohort Study

美国耐碳青霉烯类肠杆菌科细菌的分子和临床流行病学：前瞻性队列研究

DOI：
发表时间：
2020
期刊：
Lancet infections disease
影响因子：
0
作者：
David van Duin M.D.;Arias C.A.;Komarow L.;Chen L.;Hanson B.M.;Weston G.;.... Multi-Drug Resistant Organism Network Investigators
通讯作者：
.... Multi-Drug Resistant Organism Network Investigators

Estimation of the cumulative incidence function under multiple dependent and independent censoring mechanisms