Omitted variable bias can affect treatment effect estimates obtained from observational data due to the lack of random assignment to treatment groups. Sensitivity analyses adjust these estimates to quantify the impact of potential omitted variables. This paper presents methods of sensitivity analysis to adjust interval estimates of treatment effect---both the point estimate and standard error---obtained using multiple linear regression. Central to our approach is what we term benchmarking, the use of data to establish reference points for speculation about omitted confounders. The method adapts to treatment effects that may differ by subgroup, to scenarios involving omission of multiple variables, and to combinations of covariance adjustment with propensity score stratification. We illustrate it using data from an influential study of health outcomes of patients admitted to critical care.
In the causal adjustment setting, variable selection techniques based on either the outcome or treatment allocation model can result in the omission of confounders or the inclusion of spurious variables in the propensity score. We propose a variable selection method based on a penalized likelihood which considers the response and treatment assignment models simultaneously. The proposed method facilitates confounder selection in high-dimensional settings. We show that under some conditions our method attains the oracle property. The selected variables are used to form a double robust regression…
In the causal adjustment setting, variable selection techniques based on one of either the outcome or treatment allocation model can result in the omission of confounders, which leads to bias, or the inclusion of spurious variables, which leads to variance inflation, in the propensity score. We propose a variable selection method based on a penalized objective function which considers the outcome and treatment assignment models simultaneously. The proposed method facilitates confounder selection in high-dimensional settings. We show that under regularity conditions our method attains the oracl…
Interventional effects have been proposed as a solution to the unidentifiability of natural (in)direct effects under mediator-outcome confounders affected by the exposure. Such confounders are an intrinsic characteristic of studies with time-varying exposures and mediators, yet the generalization of the interventional effect framework to the time-varying case has received little attention in the literature. We present an identification result for interventional effects in a general longitudinal data structure that allows flexibility in the specification of treatment-outcome, treatment-mediator…
Instrumental variables have been widely used to estimate the causal effect of a treatment on an outcome. Existing confidence intervals for causal effects based on instrumental variables assume that all of the putative instrumental variables are valid; a valid instrumental variable is a variable that affects the outcome only by affecting the treatment and is not related to unmeasured confounders. However, in practice, some of the putative instrumental variables are likely to be invalid. This paper presents a simple and general approach to construct a confidence interval that is robust to possib…
Instrumental variables have been widely used to estimate the causal effect of a treatment on an outcome. Existing confidence intervals for causal effects based on instrumental variables assume that all of the putative instrumental variables are valid; a valid instrumental variable is a variable that affects the outcome only by affecting the treatment and is not related to unmeasured confounders. However, in practice, some of the putative instrumental variables are likely to be invalid. This paper presents two tools to conduct valid inference and tests in the presence of invalid instruments. Fi…
Unlike parametric regression, machine learning (ML) methods do not generally require precise knowledge of the true data generating mechanisms. As such, numerous authors have advocated for ML methods to estimate causal effects. Unfortunately, ML algorithms can perform worse than parametric regression. We demonstrate the performance of ML-based single- and double-robust estimators. We use 100 Monte Carlo samples with sample sizes of 200, 1200, and 5000 to investigate bias and confidence interval coverage under several scenarios. In a simple confounding scenario, confounders were related to the t…
Conventional methods in causal effect inferencetypically rely on specifying a valid set of control variables. When this set is unknown or misspecified, inferences will be erroneous. We propose a method for inferring average causal effects when all potential confounders are observed, but thecontrol variables are unknown. When the data-generating process belongs to the class of acyclical linear structural causal models, we prove that themethod yields asymptotically valid confidence intervals. Our results build upon a smooth characterization of linear directed acyclic graphs. We verify the capabi…
We consider the problem of selecting confounders for adjustment from a potentially large set of covariates, when estimating a causal effect. Recently, the high-dimensional Propensity Score (hdPS) method was developed for this task; hdPS ranks potential confounders by estimating an importance score for each variable and selects the top few variables. However, this ranking procedure is limited: it requires all variables to be binary. We propose an extension of the hdPS to general types of response and confounder variables. We further develop a group importance score, allowing us to rank groups o…
For observational studies, we study the sensitivity of causal inference when treatment assignments may depend on unobserved confounders. We develop a loss minimization approach for estimating bounds on the conditional average treatment effect (CATE) when unobserved confounders have a bounded effect on the odds ratio of treatment selection. Our approach is scalable and allows flexible use of model classes in estimation, including nonparametric and black-box machine learning methods. Based on these bounds for the CATE, we propose a sensitivity analysis for the average treatment effect (ATE). Our…
Before the transition of AVs to urban roads and subsequently unprecedented changes in traffic conditions, evaluation of transportation policies and futuristic road design related to pedestrian crossing behavior is of vital importance. Recent studies analyzed the non-causal impact of various variables on pedestrian waiting time in the presence of AVs. However, we mainly investigate the causal effect of traffic density on pedestrian waiting time. We develop a Double/Debiased Machine Learning (DML) model in which the impact of confounders variable influencing both a policy and an outcome of inter…
We consider the problem of constructing bounds on the average treatment effect (ATE) when unmeasured confounders exist but have bounded influence. Specifically, we assume that omitted confounders could not change the odds of treatment for any unit by more than a fixed factor. We derive the sharp partial identification bounds implied by this assumption by leveraging distributionally robust optimization, and we propose estimators of these bounds with several novel robustness properties. The first is double sharpness: our estimators consistently estimate the sharp ATE bounds when one of two nuisa…
Instrumental variable methods are widely used for inferring the causal effect in the presence of unmeasured confounders. Existing instrumental variable methods for nonlinear outcome models require stringent identifiability conditions. This paper considers a flexible semi-parametric potential outcome model that allows for possibly invalid instruments. We propose new identifiability conditions to identify the causal parameters when the majority of the instrumental variables are valid. We devise a novel inference procedure for a new average structural function and the conditional average treatmen…
Causal mediation analysis has historically been limited in two important ways: (i) a focus has traditionally been placed on binary treatments and static interventions, and (ii) direct and indirect effect decompositions have been pursued that are only identifiable in the absence of intermediate confounders affected by treatment. We present a theoretical study of an (in)direct effect decomposition of the population intervention effect, defined by stochastic interventions jointly applied to the treatment and mediators. In contrast to existing proposals, our causal effects can be evaluated regardl…
Negative control variables are increasingly used to adjust for unmeasured confounding bias in causal inference using observational data. They are typically identified by subject matter knowledge and there is currently a severe lack of data-driven methods to find negative controls. In this paper, we present a statistical test for discovering negative controls of a special type -- disconnected negative controls -- that can serve as surrogates of the unmeasured confounder, and we incorporate that test into the Data-driven Automated Negative Control Estimation (DANCE) algorithm. DANCE first uses t…
The strata-specific treatment effect or so-called blip for a randomly drawn strata of confounders defines a random variable and a corresponding cumulative distribution function. However, the CDF is not pathwise differentiable, necessitating a kernel smoothing approach to estimate it at a given point or perhaps many points. Assuming the CDF is continuous, we derive the efficient influence curve of the kernel smoothed version of the blip CDF and a CV-TMLE estimator. The estimator is asymptotically efficient under two conditions, one of which involves a second order remainder term which, in this …
Weighting methods are popular tools for estimating causal effects; assessing their robustness under unobserved confounding is important in practice. In the following paper, we introduce a new set of sensitivity models called "variance-based sensitivity models". Variance-based sensitivity models characterize the bias from omitting a confounder by bounding the distributional differences that arise in the weights from omitting a confounder, with several notable innovations over existing approaches. First, the variance-based sensitivity models can be parameterized with respect to a simple $R^2$ pa…
Inverse Probability Weighting-based Mediation Analysis for Microbiome Data
The University of Texas at San Antonio（德克萨斯大学圣安东尼奥分校）；The University of Texas MD Anderson Cancer Center（德克萨斯大学安德森癌症中心）；BeOne Medicines（博生医药）；Texas A&M University（德克萨斯农工大学）；University of Toronto（多伦多大学）；Columbia University（哥伦比亚大学）
Estimation of causal parameters from observational data requires complete confounder adjustment, as well as positivity of the propensity score for each treatment arm. There is often a trade-off between these two assumptions: confounding bias may be reduced through adjustment for a large number of pre-treatment covariates, but positivity is less likely in analyses with irrelevant predictors of treatment such as instrumental variables. Under empirical positivity violations, propensity score weights are highly variable, and doubly robust estimators suffer from high variance and large finite sampl…
Causal inference is known to be very challenging when only observational data are available. Randomized experiments are often costly and impractical and in instrumental variable regression the number of instruments has to exceed the number of causal predictors. It was recently shown in Peters et al. [2016] that causal inference for the full model is possible when data from distinct observational environments are available, exploiting that the conditional distribution of a response variable is invariant under the correct causal model. Two shortcomings of such an approach are the high computatio…
Mobile health studies can leverage longitudinal sensor data from smartphones to guide the application of personalized medical interventions. In this paper, we propose that adoption of an instrumental variable approach for randomized trials with imperfect compliance provides a natural framework for personalized causal inference of medication response in mobile health studies. Randomized treatment suggestions can be easily delivered to the study participants via electronic messages popping up on the smart-phone screen. Under quite general assumptions we can identify the causal effect of the actu…
In this paper, we propose a robust method to estimate the average treatment effects in observational studies when the number of potential confounders is possibly much greater than the sample size. We first use a class of penalized M-estimators for the propensity score and outcome models. We then calibrate the initial estimate of the propensity score by balancing a carefully selected subset of covariates that are predictive of the outcome. Finally, the estimated propensity score is used to construct the inverse probability weighting estimator. We prove that the proposed estimator, which has the…
We consider the estimation of heterogeneous treatment effects with arbitrary machine learning methods in the presence of unobserved confounders with the aid of a valid instrument. Such settings arise in A/B tests with an intent-to-treat structure, where the experimenter randomizes over which user will receive a recommendation to take an action, and we are interested in the effect of the downstream action. We develop a statistical learning approach to the estimation of heterogeneous effects, reducing the problem to the minimization of an appropriate loss function that depends on a set of auxili…
Background: Estimations of causal effects from observational data are subject to various sources of bias. One method of adjusting for the residual biases in the estimation of a treatment effect is through negative control outcomes, where the treatment does not affect the outcome. The empirical calibration procedure is a technique that uses negative controls to calibrate p-values. An extension of empirical calibration calibrates the coverage of the 95% confidence interval of a treatment effect estimate by using negative control outcomes as well as positive control outcomes (where treatment affe…
Centre for Big Data Research in Health (CBDRH)（健康大数据研究中心）
Causal inference for observational longitudinal studies often requires the accurate estimation of treatment effects on time-to-event outcomes in the presence of time-dependent patient history and time-dependent covariates. To tackle this longitudinal treatment effect estimation problem, we have developed a time-variant causal survival (TCS) model that uses the potential outcomes framework with an ensemble of recurrent subnetworks to estimate the difference in survival probabilities and its confidence interval over time as a function of time-dependent covariates and treatments. Using simulated …
We develop a new approach for identifying and estimating average causal effects in panel data under a linear factor model with unmeasured confounders. Compared to other methods tackling factor models such as synthetic controls and matrix completion, our method does not require the number of time periods to grow infinitely. Instead, we draw inspiration from the two-way fixed effect model as a special case of the linear factor model, where a simple difference-in-differences transformation identifies the effect. We show that analogous, albeit more complex, transformations exist in the more genera…
When drawing causal inference from observational data, there is always concern about unmeasured confounding. One way to tackle this is to conduct a sensitivity analysis. One widely-used sensitivity analysis framework hypothesizes the existence of a scalar unmeasured confounder U and asks how the causal conclusion would change were U measured and included in the primary analysis. Works along this line often make various parametric assumptions on U, for the sake of mathematical and computational simplicity. In this article, we further this line of research by developing a valid sensitivity analy…
We argue that randomized controlled trials (RCTs) are special even among settings where average treatment effects are identified by a nonparametric unconfoundedness assumption. This claim follows from two results of Robins and Ritov (1997): (1) with at least one continuous covariate control, no estimator of the average treatment effect exists which is uniformly consistent without further assumptions, (2) knowledge of the propensity score yields a uniformly consistent estimator and honest confidence intervals that shrink at parametric rates with increasing sample size, regardless of how complic…
In the comparative interrupted time series design (also called the method of difference-in-differences), the change in outcome in a group exposed to treatment in the periods before and after the exposure is compared to the change in outcome in a control group not exposed to treatment in either period. The standard difference-in-difference estimator for a comparative interrupted time series design will be biased for estimating the causal effect of the treatment if there is an interaction between history in the after period and the groups; for example, there is a historical event besides the sta…
To identify the estimand in missing data problems and observational studies, it is common to base the statistical estimation on the "missing at random" and "no unmeasured confounder" assumptions. However, these assumptions are unverifiable using empirical data and pose serious threats to the validity of the qualitative conclusions of the statistical inference. A sensitivity analysis asks how the conclusions may change if the unverifiable assumptions are violated to a certain degree. In this paper we consider a marginal sensitivity model which is a natural extension of Rosenbaum's sensitivity m…
