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What does two-sample Mendelian randomization estimate when the exposure-outcome relationship is nonlinear?

暴露与结局关系非线性时,两样本孟德尔随机化估计什么?

Two-sample Mendelian randomization with summary statistics has become a popular MR design in Epidemiology. Its ratio estimate has an average causal effect interpretation only under strong untestable assumptions including linearity. We derive what the per-variant ratio, and the pooled and robust estimators built from it, estimate when a continuous exposure has a nonlinear effect, under two conditions on how genetic variation and unmeasured factors shape exposure: no…

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How should we select test-negative controls? A causal perspective in the era of multiplex respiratory testing

多重呼吸道检测时代如何选择检测阴性对照:因果视角

The test-negative design (TND) is widely used to estimate vaccine effectiveness (VE) for respiratory pathogens by comparing vaccination odds among test-positive cases versus test-negative controls. A central yet underexplored design element is which test-negative illnesses constitute valid controls. With rapid multiplex PCR panels, investigators can now identify specific non-focal pathogens among test-negative patients, allowing for better characterization of ``test-negative…

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A General Exposure-Mapping-Agnostic Framework for Causal Inference under Interference

干扰下不依赖暴露映射的通用因果推断框架

We develop a general framework for design-based causal inference under interference in cluster experiments conducted via two-stage randomization on a network of interconnected units, without relying on exposure mapping assumptions, exclusion of cross-cluster interference, or Bernoulli treatment assignments. Within this framework, we establish a complete characterization of linear weighted estimators (LW) as defined by Godambe (1955) that achieve identification of various…

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Exploiting independence constraints for efficient estimation of bounds on causal effects in the presence of unmeasured confounding

利用独立性约束高效估计未测混杂下的因果效应界

Causal graphs may inform covariate adjustment for estimating causal effects and improve estimation efficiency by exploiting the graphical structure. In many applications, however, the target causal parameter may not be point-identified due to the presence of unmeasured confounding. Sensitivity analysis methods address this challenge by characterizing bounds on the causal parameter under varying assumptions about the magnitude or form of unmeasured confounding. We focus on…

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The Multiplicative Quasi-Instrumental Variable Model

乘法准工具变量模型

We introduce the Multiplicative Quasi-Instrumental Variable (MQIV) model, a framework for causal inference with unmeasured confounding that leverages an instrument that may be imperfectly exogenous. We allow the candidate quasi-instrument to have a direct effect on the outcome not mediated by the treatment, thus violating the standard IV exclusion restriction. We establish nonparametric identification of the population average treatment effect on the treated (ATT) under a…

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The Multiplicative Instrumental Variable Model

乘法工具变量模型

The instrumental variable (IV) design is a common approach to address hidden confounding bias. For validity, an IV must impact the outcome only through its association with the treatment. In addition, IV identification has required a homogeneity condition such as monotonicity or no unmeasured common effect modifier between the additive effect of the treatment on the outcome, and that of the IV on the treatment. In this work, we introduce the Multiplicative Instrumental…

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Auto-Doubly Robust Estimation of Causal Effects on a Network

网络因果效应的自回归双重稳健估计

This paper develops new methods for causal inference in observational studies on a single large network of interconnected units, addressing two key challenges: long-range dependence among units and the presence of general interference. We introduce a novel network version of Augmented Inverse Propensity Weighted, which combines propensity score and outcome models defined on the network to achieve doubly robust identification and estimation of both direct and spillover causal…

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A Multiplicative Instrumental Variable Model for Data Missing Not-at-Random

非随机缺失数据的乘法工具变量模型

Instrumental variable (IV) methods offer a valuable approach to account for outcome data missing not-at-random. A valid missing data instrument is a measured factor which (i) predicts the nonresponse process and (ii) is independent of the outcome in the underlying population. For point identification, all existing IV methods for missing data including the celebrated Heckman selection model, a priori restrict the extent of selection bias on the outcome scale, therefore…

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Refining the Notion of No Anticipation in Difference-in-Differences Studies

细化双重差分研究中的无预期效应概念

We address an ambiguity in identification strategies using difference-in-differences, which are widely applied in empirical research, particularly in economics. The assumption commonly referred to as the "no-anticipation assumption" states that treatment has no effect on outcomes before its implementation. However, because standard causal models rely on a temporal structure in which causes precede effects, such an assumption seems to be inherently satisfied. This raises the…

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Inference on Nonlinear Counterfactual Functionals under a Multiplicative IV Model

乘法工具变量模型下非线性反事实泛函的推断

Instrumental variable (IV) methods play a central role in causal inference, particularly in settings where treatment assignment is confounded by unobserved variables. IV methods have been extensively developed in recent years and applied across diverse domains, from economics to epidemiology. In this work, we study the recently introduced multiplicative IV (MIV) model and demonstrate its utility for causal inference beyond the average treatment effect. In particular, we show…

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Partial Identification of Causal Effects for Endogenous Continuous Treatments

内生连续处理因果效应的部分识别

No unmeasured confounding is a common assumption when reasoning about counterfactual outcomes, but such an assumption may not be plausible in observational studies. Sensitivity analysis is often employed to assess the robustness of causal conclusions to unmeasured confounding, but existing methods are predominantly designed for binary treatments. In this paper, we provide natural extensions of two extensively used sensitivity frameworks -- the Rosenbaum and Marginal…

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On a Debiased and Semiparametric Efficient Changes-in-Changes Estimator

去偏且具有半参数效率的变化中变化估计量

We present a novel extension of the influential changes-in-changes (CiC) framework of Athey and Imbens (2006) for estimating the average treatment effect on the treated (ATT) and distributional causal effects in panel data with unmeasured confounding. While CiC relaxes the parallel trends assumption in difference-in-differences (DiD), existing methods typically assume a scalar unobserved confounder and monotonic outcome relationships, and lack inference tools that…

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Fortified Proximal Causal Inference with Many Invalid Proxies

容许多个无效代理变量的强化近端因果推断

Causal inference from observational data often relies on the assumption of no unmeasured confounding, an assumption frequently violated in practice due to unobserved or poorly measured covariates. Proximal causal inference (PCI) offers a promising framework for addressing unmeasured confounding using a pair of outcome and treatment confounding proxies. However, existing PCI methods typically assume all specified proxies are valid, which may be unrealistic and is untestable…

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Regression-based proximal causal inference for right-censored time-to-event data

右删失事件时间数据的回归型近端因果推断

Unmeasured confounding is one of the major concerns in causal inference from observational data. Proximal causal inference (PCI) is an emerging methodological framework to detect and potentially account for confounding bias by carefully leveraging a pair of negative control exposure (NCE) and outcome (NCO) variables, also known as treatment and outcome confounding proxies. Although regression-based PCI is well developed for binary and continuous outcomes, analogous PCI…

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Beyond Fixed Restriction Time: Adaptive Restricted Mean Survival Time Methods in Clinical Trials

超越固定截断时间:临床试验中的自适应限制平均生存时间方法

Restricted mean survival time (RMST) offers a compelling nonparametric alternative to hazard ratios for right-censored time-to-event data, particularly when the proportional hazards assumption is violated. By capturing the total event-free time over a specified horizon, RMST provides an intuitive and clinically meaningful measure of absolute treatment benefit. Nonetheless, selecting the restriction time $L$ poses challenges: choosing a small $L$ can overlook late-emerging…

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Using negative controls to identify causal effects with invalid instrumental variables

利用负对照识别无效工具变量下的因果效应

Many proposals for the identification of causal effects require an instrumental variable that satisfies strong, untestable unconfoundedness and exclusion restriction assumptions. In this paper, we show how one can potentially identify causal effects under violations of these assumptions by harnessing a negative control population or outcome. This strategy allows one to leverage sub-populations for whom the exposure is degenerate, and requires that the instrument-outcome…

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Regression-Based Proximal Causal Inference

基于回归的近端因果推断

Negative controls are increasingly used to evaluate the presence of potential unmeasured confounding in observational studies. Beyond the use of negative controls to detect the presence of residual confounding, proximal causal inference (PCI) was recently proposed to de-bias confounded causal effect estimates, by leveraging a pair of treatment and outcome negative control or confounding proxy variables. While formal methods for statistical inference have been developed for…

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Proximal mediation analysis

近端中介分析

A common concern when trying to draw causal inferences from observational data is that the measured covariates are insufficiently rich to account for all sources of confounding. In practice, many of the covariates may only be proxies of the latent confounding mechanism. Recent work has shown that in certain settings where the standard 'no unmeasured confounding' assumption fails, proxy variables can be leveraged to identify causal effects. Results currently exist for the…

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Proximal Causal Inference for Synthetic Control with Surrogates

利用替代指标的合成控制近端因果推断

The synthetic control method (SCM) has become a popular tool for estimating causal effects in policy evaluation, where a single treated unit is observed, and a heterogeneous set of untreated units with pre- and post-policy change data are also observed. However, the synthetic control method faces challenges in accurately predicting post-intervention potential outcome had, contrary to fact, the treatment been withheld, when the pre-intervention period is short or the…

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The Proximal ID Algorithm

近端因果识别算法

Unobserved confounding is a fundamental obstacle to establishing valid causal conclusions from observational data. Two complementary types of approaches have been developed to address this obstacle: obtaining identification using fortuitous external aids, such as instrumental variables or proxies, or by means of the ID algorithm, using Markov restrictions on the full data distribution encoded in graphical causal models. In this paper we aim to develop a synthesis of the…

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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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Identification and Estimation of Causal Peer Effects Using Double Negative Controls for Unmeasured Network Confounding

利用双重负对照识别与估计未观测网络混杂下的因果同伴效应

Scientists have been interested in estimating causal peer effects to understand how people's behaviors are affected by their network peers. However, it is well known that identification and estimation of causal peer effects are challenging in observational studies for two reasons. The first is the identification challenge due to unmeasured network confounding, for example, homophily bias and contextual confounding. The second issue is network dependence of observations,…

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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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