Observational studies are often used to understand relationships between exposures and outcomes. They do not, however, allow conclusions about causal relationships to be drawn unless statistical techniques are used to account for the imbalance of confounders across exposure groups. Propensity score and balance weighting (PSBW) are useful techniques that aim to reduce the imbalances between exposure groups by weighting the groups to look alike on the observed confounders. Despite the plethora of available methods to estimate PSBW, there is little guidance on what one defines as adequate balance, and unbiased and robust estimation of the causal treatment effect is not guaranteed unless several conditions hold. Accurate inference requires that 1. the treatment allocation mechanism is known, 2. the relationship between the baseline covariates and the outcome is known, 3. adequate balance of baseline covariates is achieved post-weighting, 4. a proper set of covariates to control for confounding bias is known, and 5. a large enough sample size is available. In this article, we use simulated data of various sizes to investigate the influence of these five factors on statistical inference. Our findings provide evidence that the maximum Kolmogorov- Smirnov statistic is the proper statistical measure to assess balance on the baseline covariates, in contrast to the mean standardised mean difference used in many applications, and 0.1 is a suitable threshold to consider as acceptable balance. Finally, we recommend that 60-80 observations, per confounder per treatment group, are required to obtain a reliable and unbiased estimation of the causal treatment effect.
Causal mediation analysis is used to evaluate direct and indirect causal effects of a treatment on an outcome of interest through an intermediate variable or a mediator.It is difficult to identify the direct and indirect causal effects because the mediator cannot be randomly assigned in many real applications. In this article, we consider a causal model including latent confounders between the mediator and the outcome. We present sufficient conditions for identifying the direct and indirect effects and propose an approach for estimating them. The performance of the proposed approach is evaluat…
When drawing causal inferences about the effects of multiple treatments on clustered survival outcomes using observational data, we need to address implications of the multilevel data structure, multiple treatments, censoring and unmeasured confounding for causal analyses. Few off-the-shelf causal inference tools are available to simultaneously tackle these issues. We develop a flexible random-intercept accelerated failure time model, in which we use Bayesian additive regression trees to capture arbitrarily complex relationships between censored survival times and pre-treatment covariates and …
Causal inference is widely used in various fields, such as biology, psychology and economics, etc. In observational studies, we need to balance the covariates before estimating causal effect. This study extends the one-dimensional entropy balancing method to multiple dimensions to balance the covariates. Both parametric and nonparametric methods are proposed to estimate the causal effect of multivariate continuous treatments and theoretical properties of the two estimations are provided. Furthermore, the simulation results show that the proposed method is better than other methods in various c…
In semicompeting risks problems, nonterminal time-to-event outcomes such as time to hospital readmission are subject to truncation by death. These settings are often modeled with illness-death models for the hazards of the terminal and nonterminal events, but evaluating causal treatment effects with hazard models is problematic due to conditioning on survival (a post-treatment outcome) that is embedded in the definition of a hazard. Extending an existing survivor average causal effect (SACE) estimand, we frame the evaluation of treatment effects in the context of semicompeting risks with princ…
The development of high-throughput sequencing and targeted therapies has led to the emergence of personalized medicine: a patient's molecular profile or the presence of a specific biomarker of drug response will correspond to a treatment recommendation made either by a physician or by a treatment assignment algorithm. The growing number of such algorithms raises the question of how to quantify their clinical impact knowing that a personalized medicine strategy will inherently include different versions of treatment. We thus specify an appropriate causal framework with multiple versions of trea…
In causal mediation studies that decompose an average treatment effect into a natural indirect effect (NIE) and a natural direct effect (NDE), examples of post-treatment confounding are abundant. Past research has generally considered it infeasible to adjust for a post-treatment confounder of the mediator-outcome relationship due to incomplete information: it is observed under the actual treatment condition while missing under the counterfactual treatment condition. This study proposes a new sensitivity analysis strategy for handling post-treatment confounding and incorporates it into weightin…
Marginal structural models (MSM) with inverse probability weighting (IPW) are used to estimate causal effects of time-varying treatments, but can result in erratic finite-sample performance when there is low overlap in covariate distributions across different treatment patterns. Modifications to IPW which target the average treatment effect (ATE) estimand either introduce bias or rely on unverifiable parametric assumptions and extrapolation. This paper extends an alternate estimand, the average treatment effect on the overlap population (ATO) which is estimated on a sub-population with a reaso…
The average causal effect can often be best understood in the context of its variation. We demonstrate with two sets of four graphs, all of which represent the same average effect but with much different patterns of heterogeneity. As with the famous correlation quartet of Anscombe (1973), these graphs dramatize the way in which real-world variation can be more complex than simple numerical summaries. The graphs also give insight into why the average effect is often much smaller than anticipated.
Randomized experiments are the gold standard for estimating the causal effects of an intervention. In the simplest setting, each experimental unit is randomly assigned to receive treatment or control, and then the outcomes in each treatment arm are compared. In many settings, however, randomized experiments need to be executed over several time periods such that treatment assignment happens at each time period. In such temporal experiments, it has been observed that the effects of an intervention on a given unit may be large when the unit is first exposed to it, but then it often attenuates, o…
Background/aims: While randomized controlled trials are the gold standard for measuring causal effects, robust conclusions about causal relationships can be obtained using data from observational studies if proper statistical techniques are used to account for the imbalance of pretreatment confounders across groups. Propensity score (PS) and balance weighting are useful techniques that aim to reduce the observed imbalances between treatment groups by weighting the groups to be as similar as possible with respect to observed confounders. Methods: We have created CoBWeb, a free and easy-to-use w…
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 the potential impact of treatment switching in a re-analysis evaluating the treatment effect of NucleosideReverse Transc…
Suppose that a sequence of treatments are assigned to influence an outcome of interest that occurs after the last treatment. Between treatments there exist time-dependent covariates that may be posttreatment variables of the earlier treatments and confounders of the subsequent treatments. In this article, we develop a parametric approach to inference of the causal effect of the treatment sequence on the outcome called the sequential causal effect. We construct a point parametrization for the conditional distribution of an outcome given all treatments and time-dependent covariates, in which the…
CIMTx provides efficient and unified functions to implement modern methods for causal inferences with multiple treatments using observational data with a focus on binary outcomes. The methods include regression adjustment, inverse probability of treatment weighting, Bayesian additive regression trees, regression adjustment with multivariate spline of the generalized propensity score, vector matching and targeted maximum likelihood estimation. In addition, CIMTx illustrates ways in which users can simulate data adhering to the complex data structures in the multiple treatment setting. Furthermo…
One of the main tasks of causal inference is estimating well-defined causal parameters. One of the main causal parameters is the average causal effect (ACE) - the expected value of the individual level causal effects in the target population. For binary treatments, the individual level causal effect is defined as contrast between potential outcomes. For continuous outcomes, however, there are many such contrasts in finite samples, thus hampering their use as a useful summary of the causal relationship. Here, we proposed a generalized version of the ACE, where individual level causal effects ar…
The propensity score is a common tool for estimating the causal effect of a binary treatment in observational data. In this setting, matching, subclassification, imputation, or inverse probability weighting on the propensity score can reduce the initial covariate bias between the treatment and control groups. With more than two treatment options, however, estimation of causal effects requires additional assumptions and techniques, the implementations of which have varied across disciplines. This paper reviews current methods, and it identifies and contrasts the treatment effects that each one …
Cause-effect relationships are typically evaluated by comparing outcome responses to binary treatment values, representing two arms of a hypothetical randomized controlled trial. However, in certain applications, treatments of interest are continuous and multidimensional. For example, understanding the causal relationship between severity of radiation therapy, summarized by a multidimensional vector of radiation exposure values and post-treatment side effects is a problem of clinical interest in radiation oncology. An appropriate strategy for making interpretable causal conclusions is to reduc…
Randomized clinical trials (RCTs) are ideal for estimating causal effects, because the distributions of background covariates are similar in expectation across treatment groups. When estimating causal effects using observational data, matching is a commonly used method to replicate the covariate balance achieved in a RCT. Matching algorithms have a rich history dating back to the mid-1900s, but have been used mostly to estimate causal effects between two treatment groups. When there are more than two treatments, estimating causal effects requires additional assumptions and techniques. We propo…
Consider a situation with two treatments, the first of which is randomized but the second is not, and the multifactor version of this. Interest is in treatment effects, defined using standard factorial notation. We define estimators for the treatment effects and explore their properties when there is information about the nonrandomized treatment assignment and when there is no information on the assignment of the nonrandomized treatment. We show when and how hidden treatments can bias estimators and inflate their sampling variances.
Estimating causal effects of continuous-time dynamic treatments with unmeasured confounders
Key Laboratory of Advanced Theory and Application in Statistics and Data Science -MOE, School of Statistics, East China Normal University（华东师范大学统计学院统计学与数据科学前沿理论及应用教育部重点实验室）
We apply causal forests to a dataset derived from the National Study of Learning Mindsets, and consider resulting practical and conceptual challenges. In particular, we discuss how causal forests use estimated propensity scores to be more robust to confounding, and how they handle data with clustered errors.
We develop a Bayesian nonparametric (BNP) approach to evaluate the causal effect of treatment in a randomized trial where a nonterminal event may be censored by a terminal event, but not vice versa (i.e., semi-competing risks). Based on the idea of principal stratification, we define a novel estimand for the causal effect of treatment on the nonterminal event. We introduce identification assumptions, indexed by a sensitivity parameter, and show how to draw inference using our BNP approach. We conduct simulation studies and illustrate our methodology using data from a brain cancer trial.
In causal estimation problems, the parameter of interest is often only partially identified, implying that the parameter cannot be recovered exactly, even with infinite data. Here, we study Bayesian inference for partially identified treatment effects in multi-treatment causal inference problems with unobserved confounding. In principle, inferring the partially identified treatment effects is natural under the Bayesian paradigm, but the results can be highly sensitive to parameterization and prior specification, often in surprising ways. It is thus essential to understand which aspects of the …
Researchers are often interested in analyzing conditional treatment effects. One variant of this is "causal moderation," which implies that intervention upon a third (moderator) variable would alter the treatment effect. This study considers the conditions under which causal moderation can be identified and presents a generalized framework for estimating causal moderation effects given randomized treatments and non-randomized moderators. As part of the estimation process, it allows researchers to implement their preferred method of covariate adjustment, including parametric and non-parametric …
Causal effects are commonly defined as comparisons of the potential outcomes under treatment and control, but this definition is threatened by the possibility that the treatment or control condition is not well-defined, existing instead in more than one version. A simple, widely applicable analysis is proposed to address the possibility that the treatment or control condition exists in two versions with two different treatment effects. This analysis loses no power in the main comparison of treatment and control, provides additional information about version effects, and controls the family-wis…
The micro-randomized trial (MRT) is a sequential randomized experimental design to empirically evaluate the effectiveness of mobile health (mHealth) intervention components that may be delivered at hundreds or thousands of decision points. MRTs have motivated a new class of causal estimands, termed "causal excursion effects", for which semiparametric inference can be conducted via a weighted, centered least squares criterion (Boruvka et al., 2018). Existing methods assume between-subject independence and non-interference. Deviations from these assumptions often occur. In this paper, causal exc…
Randomized controlled trials are the gold standard for measuring causal effects. However, they are often not always feasible, and causal treatment effects must be estimated from observational data. Observational studies do not allow robust conclusions about causal relationships unless statistical techniques account for the imbalance of pretreatment confounders across groups while key assumptions hold. Propensity score and balance weighting (PSBW) are useful techniques that aim to reduce the imbalances between treatment groups by weighting the groups to look alike on the observed confounders. T…
Causal inference in observational studies can be challenging when confounders are subject to missingness. Generally, the identification of causal effects is not guaranteed even under restrictive parametric model assumptions when confounders are missing not at random. To address this, We propose a general framework to establish the identification of causal effects when confounders are subject to treatment-independent missingness, which means that the missing data mechanism is independent of the treatment, given the outcome and possibly missing confounders. We give special consideration to commo…
Matching estimators for average treatment effects are widely used in the binary treatment setting, in which missing potential outcomes are imputed as the average of observed outcomes of all matches for each unit. With more than two treatment groups, however, estimation using matching requires additional techniques. In this paper, we propose a nearest-neighbors matching estimator for use with multiple, nominal treatments, and use simulations to show that this method is precise and has coverage levels that are close to nominal. In addition, we implement the proposed inference methods to examine …
Intercurrent events (ICEs) and missing values are inevitable in clinical trials of any size and duration, making it difficult to assess the treatment effect for all patients in randomized clinical trials. Defining the appropriate estimand that is relevant to the clinical research question is the first step in analyzing data. The tripartite estimands, which evaluate the treatment differences in the proportion of patients with ICEs due to adverse events, the proportion of patients with ICEs due to lack of efficacy, and the primary efficacy outcome for those who can adhere to study treatment unde…
In most nonrandomized observational studies, differences between treatment groups may arise not only due to the treatment but also because of the effect of confounders. Therefore, causal inference regarding the treatment effect is not as straightforward as in a randomized trial. To adjust for confounding due to measured covariates, a variety of methods based on the potential outcomes framework are used to estimate average treatment effects. One of the key assumptions is treatment positivity, which states that the probability of treatment is bounded away from zero and one for any possible combi…
Amazon（亚马逊）；Massachusetts Institute of Technology（麻省理工学院）
We extend the definition of the marginal causal effect to the continuous treatment setting and develop a novel characterization of causal bias in the framework of structural causal models. We prove that our derived bias expression is zero if, and only if, the causal effect is identifiable via covariate adjustment. We show that under some restrictions on the structural equations, the causal bias can be estimated efficiently and allows for causal regularization of predictive probabilistic models. We demonstrate the effectiveness of our method for causal bias quantification in various settings wh…
In non-network settings, encouragement designs have been widely used to analyze causal effects of a treatment, policy, or intervention on an outcome of interest when randomizing the treatment was considered impractical or when compliance to treatment cannot be perfectly enforced. Unfortunately, such questions related to treatment compliance have received less attention in network settings and the most well-studied experimental design in networks, the two-stage randomization design, requires perfect compliance with treatment. The paper proposes a new experimental design called peer encouragemen…
Clinical studies sometimes encounter truncation by death, rendering outcomes undefined. Statistical analysis based solely on observed survivors may give biased results because the characteristics of survivors differ between treatment groups. By principal stratification, the survivor average causal effect was proposed as a causal estimand defined in always-survivors. However, this estimand is not identifiable when there is unmeasured confounding between the treatment assignment and survival or outcome process. In this paper, we consider the comparison between an aggressive treatment and a conse…
Didi Chuxing（滴滴出行）；University of North Carolina at Chapel Hill（北卡罗来纳大学教堂山分校）
Uplift modeling is a rapidly growing approach that utilizes causal inference and machine learning methods to directly estimate the heterogeneous treatment effects, which has been widely applied to various online marketplaces to assist large-scale decision-making in recent years. The existing popular models, like causal forest (CF), are limited to either discrete treatments or posing parametric assumptions on the outcome-treatment relationship that may suffer model misspecification. However, continuous treatments (e.g., price, duration) often arise in marketplaces. To alleviate these restrictio…
Estimating causal effects with propensity scores relies upon the availability of treated and untreated units observed at each value of the estimated propensity score. In settings with strong confounding, limited so-called "overlap" in propensity score distributions can undermine the empirical basis for estimating causal effects and yield erratic finite-sample performance of existing estimators. We propose a Bayesian procedure designed to estimate causal effects in settings where there is limited overlap in propensity score distributions. Our method relies on the posterior predictive treatment …
