Covariate selection for estimating the causal effect of control plans by using causal diagrams

Summary. Consider a case where cause–effect relationships between variables can be described by a causal path diagram and the corresponding linear structural equation model. The paper proposes a graphical selection criterion for covariates to estimate the causal effect of a control plan. For designing the control plan, it is essential to determine both covariates that are used for control and covariates that are used for identification. The selection of covariates used for control is only constrained by the requirement that the covariates be non-descendants of a treatment variable. However, the selection of covariates used for identification is dependent on the selection of covariates used for control and is not unique. In the paper, the difference between covariates that are used for identification is evaluated on the basis of the asymptotic variance of the estimated causal effect of an effective control plan. Furthermore, the results can be also described in terms of a graph structure.     

Criteria for surrogate end points based on causal distributions

Summary.  When a treatment has a positive average causal effect (ACE) on an intermediate variable or surrogate end point which in turn has a positive ACE on a true end point, the treatment may have a negative ACE on the true end point due to the presence of unobserved confounders, which is called the surrogate paradox. A criterion for surrogate end points based on ACEs has recently been proposed to avoid the surrogate paradox. For a continuous or ordinal discrete end point, the distributional causal effect (DCE) may be a more appropriate measure for a causal effect than the ACE. We discuss criteria for surrogate end points based on DCEs. We show that commonly used models, such as generalized linear models and Cox's proportional hazard models, can make the sign of the DCE of the treatment on the true end point determinable by the sign of the DCE of the treatment on the surrogate even if the models include unobserved confounders. Furthermore, for a general distribution without any assumption of parametric models, we give a sufficient condition for a distributionally consistent surrogate and prove that it is almost necessary.     

Signed directed acyclic graphs for causal inference

Summary.  Formal rules governing signed edges on causal directed acyclic graphs are described and it is shown how these rules can be useful in reasoning about causality. Specifically, the notions of a monotonic effect, a weak monotonic effect and a signed edge are introduced. Results are developed relating these monotonic effects and signed edges to the sign of the causal effect of an intervention in the presence of intermediate variables. The incorporation of signed edges in the directed acyclic graph causal framework furthermore allows for the development of rules governing the relationship between monotonic effects and the sign of the covariance between two variables. It is shown that when certain assumptions about monotonic effects can be made then these results can be used to draw conclusions about the presence of causal effects even when data are missing on confounding variables.     

Using information on realized effects to determine prospective causal effects

The potential outcomes approach to causal inference postulates that each individual has a number of possibly latent outcomes, each of which would be observed under a different treatment. For any individual, some of these outcomes will be unobservable or counterfactual. Information about post-treatment characteristics sometimes allows statements about what would have happened if an individual or group with these characteristics had received a different treatment. These are statements about the realized effects of the treatment. Determining the likely effect of an intervention before making a decision involves inference about effects in populations defined only by characteristics observed before decisions about treatment are made. Information on realized effects can tighten bounds on these prospectively defined measures of the intervention effect. We derive formulae for the bounds and their sampling variances and illustrate these points with data from a hypothetical study of the efficacy of screening mammography.     

A Bayesian nonparametric causal model

Typically, in the practice of causal inference from observational studies, a parametric model is assumed for the joint population density of potential outcomes and treatment assignments, and possibly this is accompanied by the assumption of no hidden bias. However, both assumptions are questionable for real data, the accuracy of causal inference is compromised when the data violates either assumption, and the parametric assumption precludes capturing a more general range of density shapes (e.g., heavier tail behavior and possible multi-modalities). We introduce a flexible, Bayesian nonparametric causal model to provide more accurate causal inferences. The model makes use of a stick-breaking prior, which has the flexibility to capture any multi-modalities, skewness and heavier tail behavior in this joint population density, while accounting for hidden bias. We prove the asymptotic consistency of the posterior distribution of the model, and illustrate our causal model through the analysis of small and large observational data sets.     

Did the Military Interventions in the Mexican Drug War Increase Violence?

We analyze publicly available data to estimate the causal effects of military interventions on the homicide rates in certain problematic regions in Mexico. We use the Rubin causal model to compare the post-intervention homicide rate in each intervened region to the hypothetical homicide rate for that same year had the military intervention not taken place. Because the effect of a military intervention is not confined to the municipality subject to the intervention, a nonstandard definition of units is necessary to estimate the causal effect of the intervention under the standard no-interference assumption of stable-unit treatment value assumption (SUTVA). Donor pools are created for each missing potential outcome under no intervention, thereby allowing for the estimation of unit-level causal effects. A multiple imputation approach accounts for uncertainty about the missing potential outcomes.     

Effects of correlated covariates on the asymptotic efficiency of matching and inverse probability weighting estimators for causal inference

In observational studies, the overall aim when fitting a model for the propensity score is to reduce bias for an estimator of the causal effect. To make the assumption of an unconfounded treatment plausible researchers might include many, possibly correlated, covariates in the propensity score model. In this paper, we study how the asymptotic efficiency of matching and inverse probability weighting estimators for average causal effects change when the covariates are correlated. We investigate the case with multivariate normal covariates, a logistic model for the propensity score and linear models for the potential outcomes and show results under different model assumptions. We show that the correlation can both increase and decrease the large sample variances of the estimators, and that the correlation affects the asymptotic efficiency of the estimators differently, both with regard to direction and magnitude. Moreover, the strength of the confounding towards the outcome and the treatment plays an important role.     

MODEL SELECTION FOR PENALIZED SPLINE SMOOTHING USING AKAIKE INFORMATION CRITERIA

Two different forms of Akaike's information criterion (AIC) are compared for selecting the smooth terms in penalized spline additive mixed models. The conditional AIC (cAIC) has been used traditionally as a criterion for both estimating penalty parameters and selecting covariates in smoothing, and is based on the conditional likelihood given the smooth mean and on the effective degrees of freedom for a model fit. By comparison, the marginal AIC (mAIC) is based on the marginal likelihood from the mixed‐model formulation of penalized splines which has recently become popular for estimating smoothing parameters. To the best of the authors' knowledge, the use of mAIC for selecting covariates for smoothing in additive models is new. In the competing models considered for selection, covariates may have a nonlinear effect on the response, with the possibility of group‐specific curves. Simulations are used to compare the performance of cAIC and mAIC in model selection settings that have correlated and hierarchical smooth terms. In moderately large samples, both formulations of AIC perform extremely well at detecting the function that generated the data. The mAIC does better for simple functions, whereas the cAIC is more sensitive to detecting a true model that has complex and hierarchical terms.     

Comparison of causal effect estimators under exposure misclassification

Over the past decades, various principles for causal effect estimation have been proposed, all differing in terms of how they adjust for measured confounders: either via traditional regression adjustment, by adjusting for the expected exposure given those confounders (e.g., the propensity score), or by inversely weighting each subject's data by the likelihood of the observed exposure, given those confounders. When the exposure is measured with error, this raises the question whether these different estimation strategies might be differently affected and whether one of them is to be preferred for that reason. In this article, we investigate this by comparing inverse probability of treatment weighted (IPTW) estimators and doubly robust estimators for the exposure effect in linear marginal structural mean models (MSM) with G-estimators, propensity score (PS) adjusted estimators and ordinary least squares (OLS) estimators for the exposure effect in linear regression models. We find analytically that these estimators are equally affected when exposure misclassification is independent of the confounders, but not otherwise. Simulation studies reveal similar results for time-varying exposures and when the model of interest includes a logistic link.     

The Effect of Treatment Compliance in a Placebo-controlled Trial: Regression with Unpaired Data

The causal effect of a treatment is estimated at different levels of treatment compliance, in a placebo-controlled trial on the reduction of blood pressure. The structural nested mean model makes no direct assumptions on selected treatment compliance levels and placebo prognosis but relies on the randomization assumption and a parametric form for causal effects. It can be seen as a regression model for unpaired data, where pre- and post-randomization covariables are treated differently. The causal parameters are found as solutions to estimating equations involving estimated placebo response and treatment compliance based on base-line covariates for all subjects. Our example considers a linear effect of the percentage of prescribed dose taken on achieved diastolic blood pressure reduction. We propose an exploration of structural model checks. In the example, this reveals an interaction between the causal effect of active dose taken and the base-line body weight of the patient.     

Correlation and efficiency of propensity score-based estimators for average causal effects

Propensity score-based estimators are commonly used to estimate causal effects in evaluation research. To reduce bias in observational studies, researchers might be tempted to include many, perhaps correlated, covariates when estimating the propensity score model. Taking into account that the propensity score is estimated, this study investigates how the efficiency of matching, inverse probability weighting, and doubly robust estimators change under the case of correlated covariates. Propositions regarding the large sample variances under certain assumptions on the data-generating process are given. The propositions are supplemented by several numerical large sample and finite sample results from a wide range of models. The results show that the covariate correlations may increase or decrease the variances of the estimators. There are several factors that influence how correlation affects the variance of the estimators, including the choice of estimator, the strength of the confounding toward outcome and treatment, and whether a constant or non-constant causal effect is present.     

Is regression adjustment supported by the Neyman model for causal inference?

This paper examines both theoretically and empirically whether the common practice of using OLS multivariate regression models to estimate average treatment effects (ATEs) under experimental designs is justified by the Neyman model for causal inference. Using data from eight large U.S. social policy experiments, the paper finds that estimated standard errors and significance levels for ATE estimators are similar under the OLS and Neyman models when baseline covariates are included in the models, even though theory suggests that this may not have been the case. This occurs primarily because treatment effects do not appear to vary substantially across study subjects.     

Is Early Smoking a Causal Risk Factor for Later Cognitive Impairment? A 20-year Prospective Study with Time-varying Propensity Score Matching Based on Random Intercept and Slope

Although epidemiological studies support an association between smoking and cognitive impairment, existing data do not answer the question of whether this association is causal or arises from covariates. In this paper, we investigate smoking status, assessed from adolescence to adulthood, and subsequent cognitive problems in a large representative sample of youths. To analyze this data, we propose a method for causal effects using full matching based on the subject-specific random intercept and slope of the propensity scores. The findings suggest that earlier smoking is not a causal factor for later cognitive problem (odds ratio = 1.64, 95% CI: 0.97–2.80, p = 0.06).     

Estimating a Marginal Causal Odds Ratio Subject to Confounding

Odds ratios are frequently used to describe the relationship between a binary treatment or exposure and a binary outcome. An odds ratio can be interpreted as a causal effect or a measure of association, depending on whether it involves potential outcomes or the actual outcome. An odds ratio can also be characterized as marginal versus conditional, depending on whether it involves conditioning on covariates. This article proposes a method for estimating a marginal causal odds ratio subject to confounding. The proposed method is based on a logistic regression model relating the outcome to the treatment indicator and potential confounders. Simulation results show that the proposed method performs reasonably well in moderate-sized samples and may even offer an efficiency gain over the direct method based on the sample odds ratio in the absence of confounding. The method is illustrated with a real example concerning coronary heart disease.     

Defining causal mediation with a longitudinal mediator and a survival outcome

In the context of causal mediation analysis, prevailing notions of direct and indirect effects are based on nested counterfactuals. These can be problematic regarding interpretation and identifiability especially when the mediator is a time-dependent process and the outcome is survival or, more generally, a time-to-event outcome. We propose and discuss an alternative definition of mediated effects that does not suffer from these problems, and is more transparent than the current alternatives. Our proposal is based on the extended graphical approach of Robins and Richardson (in: Shrout (ed) Causality and psychopathology: finding the determinants of disorders and their cures, Oxford University Press, Oxford, 2011), where treatment is decomposed into different components, or aspects, along different causal paths corresponding to real world mechanisms. This is an interesting alternative motivation for any causal mediation setting, but especially for survival outcomes. We give assumptions allowing identifiability of such alternative mediated effects leading to the familiar mediation g-formula (Robins in Math Model 7:1393, 1986); this implies that a number of available methods of estimation can be applied.

     

Estimating the causal effects in randomized trials for survival data with a cure fraction and non compliance

We consider causal inference in randomized studies for survival data with a cure fraction and all-or-none treatment non compliance. To describe the causal effects, we consider the complier average causal effect (CACE) and the complier effect on survival probability beyond time t (CESP), where CACE and CESP are defined as the difference of cure rate and non cured subjects’ survival probability between treatment and control groups within the complier class. These estimands depend on the distributions of survival times in treatment and control groups. Given covariates and latent compliance type, we model these distributions with transformation promotion time cure model whose parameters are estimated by maximum likelihood. Both the infinite dimensional parameter in the model and the mixture structure of the problem create some computational difficulties which are overcome by an expectation-maximization (EM) algorithm. We show the estimators are consistent and asymptotically normal. Some simulation studies are conducted to assess the finite-sample performance of the proposed approach. We also illustrate our method by analyzing a real data from the Healthy Insurance Plan of Greater New York.     

Estimating percentile-specific treatment effects in counterfactual models: a case-study of micronutrient supplementation, birth weight and infant mortality

Summary.  Clinical trials of micronutrient supplementation are aimed at reducing the risk of infant mortality by increasing birth weight. Because infant mortality is greatest among the low birth weight (LBW) infants (2500 g or under), an effective intervention increases the birth weight among the smallest babies. The paper defines population and counterfactual parameters for estimating the treatment effects on birth weight and on survival as functions of the percentiles of the birth weight distribution. We use a Bayesian approach with data augmentation to approximate the posterior distributions of the parameters, taking into account uncertainty that is associated with the imputation of the counterfactuals. This approach is particularly suitable for exploring the sensitivity of the results to unverifiable modelling assumptions and other prior beliefs. We estimate that the average causal effect of the treatment on birth weight is 72 g (95% posterior regions 33–110 g) and that this causal effect is largest among the LBW infants. Posterior inferences about average causal effects of the treatment on birth weight are robust to modelling assumptions. However, inferences about causal effects for babies at the tails of the birth weight distribution can be highly sensitive to the unverifiable assumption about the correl-ation between the observed and the counterfactuals birth weights. Among the LBW infants who have a large causal effect of the treatment on birth weight, we estimate that a baby receiving the treatment has 5% less chance of death than if the same baby had received the control. Among the LBW infants, we found weak evidence supporting an additional beneficial effect of the treatment on mortality independent of birth weight.     

Matching Using Sufficient Dimension Reduction for Causal Inference

ABSTRACT

To estimate causal treatment effects, we propose a new matching approach based on the reduced covariates obtained from sufficient dimension reduction. Compared with the original covariates and the propensity score, which are commonly used for matching in the literature, the reduced covariates are nonparametrically estimable and are effective in imputing the missing potential outcomes, under a mild assumption on the low-dimensional structure of the data. Under the ignorability assumption, the consistency of the proposed approach requires a weaker common support condition. In addition, researchers are allowed to employ different reduced covariates to find matched subjects for different treatment groups. We develop relevant asymptotic results and conduct simulation studies as well as real data analysis to illustrate the usefulness of the proposed approach.     

Accommodating stochastic departures from percentile invariance in causal models

Summary.  Consider a clinical trial in which participants are randomized to a single-dose treatment or a placebo control and assume that the adherence level is accurately recorded. If the treatment is effective, then good adherers in the treatment group should do better than poor ad- herers because they received more drug; the treatment group data follow a dose–response curve. But, good adherers to the placebo often do better than poor adherers, so the observed adherence–response in the treatment group cannot be completely attributed to the treatment. Efron and Feldman proposed an adjustment to the observed adherence–response in the treatment group by using the adherence–response in the control group. It relies on a percentile invariance assumption under which each participant's adherence percentile within their assigned treatment group does not depend on the assigned group (active drug or placebo). The Efron and Feldman approach is valid under percentile invariance, but not necessarily under departures from it. We propose an analysis based on a generalization of percentile invariance that allows adherence percentiles to be stochastically permuted across treatment groups, using a broad class of stochastic permutation models. We show that approximate maximum likelihood estimates of the underlying dose–response curve perform well when the stochastic permutation process is correctly specified and are quite robust to model misspecification.