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An Instrumental Variable Approach to Account for Informative Treatment Switching in Real-world Evidence

真实世界证据中信息性治疗切换的工具变量方法

Reproducible and generalizable assessment of treatment decisions requires principled handling of subsequent treatment switching that may inform expected outcomes and shift across cohorts and over time. To effectively account for informative treatment switching, we propose an instrumental variable approach that characterizes the poorly documented expected outcomes at switching as unmeasured confounding. After establishing the baseline treatment as a viable instrumental…

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Efficient Inference for Incremental Causal Effects of Time to Treatment

处理启动时间增量因果效应的有效推断

We consider continuous time to treatment initiation. This can commonly occur in preventive medicine, such as disease screening and vaccination; it can also occur with non-fatal health conditions such as HIV infection without the onset of AIDS. While traditional causal inference focused on `when to treat' and its effects, we consider the incremental causal effect when the intensity of time to treatment initiation is intervened upon. We derive the efficient influence function…

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Causal Identification for Complex Functional Longitudinal Studies

复杂函数型纵向研究的因果识别

Real-time monitoring in modern medical research introduces functional longitudinal data, characterized by continuous-time measurements of outcomes, treatments, and confounders. This complexity leads to uncountably infinite treatment-confounder feedbacks, which traditional causal inference methodologies cannot handle. Inspired by the coarsened data framework, we adopt stochastic process theory, measure theory, and net convergence to propose a nonparametric causal…

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Incremental Causal Effect for Time to Treatment Initialization

治疗启动时间的增量因果效应

We consider time to treatment initialization. This can commonly occur in preventive medicine, such as disease screening and vaccination; it can also occur with non-fatal health conditions such as HIV infection without the onset of AIDS; or in tech industry where items wait to be reviewed manually as abusive or not, etc. While traditional causal inference focused on `when to treat' and its effects, including their possible dependence on subject characteristics, we consider…

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A Liberating Framework from Truncation and Censoring, with Application to Learning Treatment Effects

摆脱截断与删失限制的学习框架及其处理效应应用

Time-to-event outcomes are often subject to left truncation and right censoring. While many survival analysis methods have been developed to handle truncation and censoring, majority of the past works require strong independence assumptions. We relax these stringent assumptions through leveraging covariate information together with orthogonal learning, and develop a liberating framework from left truncation and right censoring so that desirable properties like double…

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A Robust Instrumental Variable Method Accounting for Treatment Switching in Open-Label Randomized Controlled Trials

处理开放标签随机对照试验中治疗转换的稳健工具变量方法

In a randomized controlled trial, treatment switching (also called contamination or crossover) occurs when a patient initially assigned to one treatment arm changes to another arm during the course of follow-up. Overlooking treatment switching might substantially bias the evaluation of treatment efficacy or safety. To account for treatment switching, instrumental variable (IV) methods by leveraging the initial randomized assignment as an IV serve as natural adjustment…

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Proximal Causal Inference for Complex Longitudinal Studies

复杂纵向研究中的近端因果推断

A standard assumption for causal inference about the joint effects of time-varying treatment is that one has measured sufficient covariates to ensure that within covariate strata, subjects are exchangeable across observed treatment values, also known as "sequential randomization assumption (SRA)". SRA is often criticized as it requires one to accurately measure all confounders. Realistically, measured covariates can rarely capture all confounders with certainty. Often…

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Proximal Causal Inference for Marginal Counterfactual Survival Curves

边际反事实生存曲线的近端因果推断

Contrasting marginal counterfactual survival curves across treatment arms is an effective and popular approach for inferring the causal effect of an intervention on a right-censored time-to-event outcome. A key challenge to drawing such inferences in observational settings is the possible existence of unmeasured confounding, which may invalidate most commonly used methods that assume no hidden confounding bias. In this paper, rather than making the standard no unmeasured…

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Minimax Kernel Machine Learning for a Class of Doubly Robust Functionals with Application to Proximal Causal Inference

双重稳健泛函的极小极大核学习及近端因果推断应用

Robins et al. (2008) introduced a class of influence functions (IFs) which could be used to obtain doubly robust moment functions for the corresponding parameters. However, that class does not include the IF of parameters for which the nuisance functions are solutions to integral equations. Such parameters are particularly important in the field of causal inference, specifically in the recently proposed proximal causal inference framework of Tchetgen Tchetgen et al. (2020),…

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A New Causal Approach to Account for Treatment Switching in Randomized Experiments under a Structural Cumulative Survival Model

结构累积生存模型下处理随机试验治疗转换的因果方法

Treatment switching in a randomized controlled trial is said to occur when a patient randomized to one treatment arm switches to another treatment arm during follow-up. This can occur at the point of disease progression, whereby patients in the control arm may be offered the experimental treatment. It is widely known that failure to account for treatment switching can seriously dilute the estimated effect of treatment on overall survival. In this paper, we aim to account for…

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