No Arabic abstract
We focus on the problem of generalizing a causal effect estimated on a randomized controlled trial (RCT) to a target population described by a set of covariates from observational data. Available methods such as inverse propensity weighting are not designed to handle missing values, which are however common in both data sources. In addition to coupling the assumptions for causal effect identifiability and for the missing values mechanism and to defining appropriate estimation strategies, one difficulty is to consider the specific structure of the data with two sources and treatment and outcome only available in the RCT. We propose and compare three multiple imputation strategies (separate imputation, joint imputation with fixed effect, joint imputation without source information), as well as a technique that uses estimators that can handle missing values directly without imputing them. These methods are assessed in an extensive simulation study, showing the empirical superiority of fixed effect multiple imputation followed with any complete data generalizing estimators. This work is motivated by the analysis of a large registry of over 20,000 major trauma patients and a RCT studying the effect of tranexamic acid administration on mortality. The analysis illustrates how the missing values handling can impact the conclusion about the effect generalized from the RCT to the target population.
Support vector machine (SVM) is one of the most popular classification algorithms in the machine learning literature. We demonstrate that SVM can be used to balance covariates and estimate average causal effects under the unconfoundedness assumption. Specifically, we adapt the SVM classifier as a kernel-based weighting procedure that minimizes the maximum mean discrepancy between the treatment and control groups while simultaneously maximizing effective sample size. We also show that SVM is a continuous relaxation of the quadratic integer program for computing the largest balanced subset, establishing its direct relation to the cardinality matching method. Another important feature of SVM is that the regularization parameter controls the trade-off between covariate balance and effective sample size. As a result, the existing SVM path algorithm can be used to compute the balance-sample size frontier. We characterize the bias of causal effect estimation arising from this trade-off, connecting the proposed SVM procedure to the existing kernel balancing methods. Finally, we conduct simulation and empirical studies to evaluate the performance of the proposed methodology and find that SVM is competitive with the state-of-the-art covariate balancing methods.
Analyses of environmental phenomena often are concerned with understanding unlikely events such as floods, heatwaves, droughts or high concentrations of pollutants. Yet the majority of the causal inference literature has focused on modelling means, rather than (possibly high) quantiles. We define a general estimator of the population quantile treatment (or exposure) effects (QTE) -- the weighted QTE (WQTE) -- of which the population QTE is a special case, along with a general class of balancing weights incorporating the propensity score. Asymptotic properties of the proposed WQTE estimators are derived. We further propose and compare propensity score regression and two weighted methods based on these balancing weights to understand the causal effect of an exposure on quantiles, allowing for the exposure to be binary, discrete or continuous. Finite sample behavior of the three estimators is studied in simulation. The proposed methods are applied to data taken from the Bavarian Danube catchment area to estimate the 95% QTE of phosphorus on copper concentration in the river.
While a randomized controlled trial (RCT) readily measures the average treatment effect (ATE), this measure may need to be generalized to the target population to account for a sampling bias in the RCTs population. Identifying this target population treatment effect needs covariates in both sets to capture all treatment effect modifiers that are shifted between the two sets. Standard estimators then use either weighting (IPSW), outcome modeling (G-formula), or combine the two in doubly robust approaches (AIPSW). However such covariates are often not available in both sets. Therefore, after completing existing proofs on the complete case consistency of those three estimators, we compute the expected bias induced by a missing covariate, assuming a Gaussian distribution and a semi-parametric linear model. This enables sensitivity analysis for each missing covariate pattern, giving the sign of the expected bias. We also show that there is no gain in imputing a partially-unobserved covariate. Finally we study the replacement of a missing covariate by a proxy. We illustrate all these results on simulations, as well as semi-synthetic benchmarks using data from the Tennessee Student/Teacher Achievement Ratio (STAR), and with a real-world example from critical care medicine.
Estimating causal effects for survival outcomes in the high-dimensional setting is an extremely important topic for many biomedical applications as well as areas of social sciences. We propose a new orthogonal score method for treatment effect estimation and inference that results in asymptotically valid confidence intervals assuming only good estimation properties of the hazard outcome model and the conditional probability of treatment. This guarantee allows us to provide valid inference for the conditional treatment effect under the high-dimensional additive hazards model under considerably more generality than existing approaches. In addition, we develop a new Hazards Difference (HDi), estimator. We showcase that our approach has double-robustness properties in high dimensions: with cross-fitting, the HDi estimate is consistent under a wide variety of treatment assignment models; the HDi estimate is also consistent when the hazards model is misspecified and instead the true data generating mechanism follows a partially linear additive hazards model. We further develop a novel sparsity doubly robust result, where either the outcome or the treatment model can be a fully dense high-dimensional model. We apply our methods to study the treatment effect of radical prostatectomy versus conservative management for prostate cancer patients using the SEER-Medicare Linked Data.
With a large number of baseline covariates, we propose a new semi-parametric modeling strategy for heterogeneous treatment effect estimation and individualized treatment selection, which are two major goals in personalized medicine. We achieve the first goal through estimating a covariate-specific treatment effect (CSTE) curve modeled as an unknown function of a weighted linear combination of all baseline covariates. The weight or the coefficient for each covariate is estimated by fitting a sparse semi-parametric logistic single-index coefficient model. The CSTE curve is estimated by a spline-backfitted kernel procedure, which enables us to further construct a simultaneous confidence band (SCB) for the CSTE curve under a desired confidence level. Based on the SCB, we find the subgroups of patients that benefit from each treatment, so that we can make individualized treatment selection. The innovations of the proposed method are three-fold. First, the proposed method can quantify variability associated with the estimated optimal individualized treatment rule with high-dimensional covariates. Second, the proposed method is very flexible to depict both local and global associations between the treatment and baseline covariates in the presence of high-dimensional covariates, and thus it enjoys flexibility while achieving dimensionality reduction. Third, the SCB achieves the nominal confidence level asymptotically, and it provides a uniform inferential tool in making individualized treatment decisions.