No Arabic abstract
Instrumental variable methods have been widely used to identify causal effects in the presence of unmeasured confounding. A key identification condition known as the exclusion restriction states that the instrument cannot have a direct effect on the outcome which is not mediated by the exposure in view. In the health and social sciences, such an assumption is often not credible. To address this concern, we consider identification conditions of the population average treatment effect with an invalid instrumental variable which does not satisfy the exclusion restriction, and derive the efficient influence function targeting the identifying functional under a nonparametric observed data model. We propose a novel multiply robust locally efficient estimator of the average treatment effect that is consistent in the union of multiple parametric nuisance models, as well as a multiply debiased machine learning estimator for which the nuisance parameters are estimated using generic machine learning methods, that effectively exploit various forms of linear or nonlinear structured sparsity in the nuisance parameter space. When one cannot be confident that any of these machine learners is consistent at sufficiently fast rates to ensure $surd{n}$-consistency for the average treatment effect, we introduce a new criteria for selective machine learning which leverages the multiple robustness property in order to ensure small bias. The proposed methods are illustrated through extensive simulations and a data analysis evaluating the causal effect of 401(k) participation on savings.
The primary analysis of randomized screening trials for cancer typically adheres to the intention-to-screen principle, measuring cancer-specific mortality reductions between screening and control arms. These mortality reductions result from a combination of the screening regimen, screening technology and the effect of the early, screening-induced, treatment. This motivates addressing these different aspects separately. Here we are interested in the causal effect of early versus delayed treatments on cancer mortality among the screening-detectable subgroup, which under certain assumptions is estimable from conventional randomized screening trial using instrumental variable type methods. To define the causal effect of interest, we formulate a simplified structural multi-state model for screening trials, based on a hypothetical intervention trial where screening detected individuals would be randomized into early versus delayed treatments. The cancer-specific mortality reductions after screening detection are quantified by a cause-specific hazard ratio. For this, we propose two estimators, based on an estimating equation and a likelihood expression. The methods extend existing instrumental variable methods for time-to-event and competing risks outcomes to time-dependent intermediate variables. Using the multi-state model as the basis of a data generating mechanism, we investigate the performance of the new estimators through simulation studies. In addition, we illustrate the proposed method in the context of CT screening for lung cancer using the US National Lung Screening Trial (NLST) data.
We consider the estimation of the average treatment effect in the treated as a function of baseline covariates, where there is a valid (conditional) instrument. We describe two doubly robust (DR) estimators: a locally efficient g-estimator, and a targeted minimum loss-based estimator (TMLE). These two DR estimators can be viewed as generalisations of the two-stage least squares (TSLS) method to semi-parametric models that make weaker assumptions. We exploit recent theoretical results that extend to the g-estimator the use of data-adaptive fits for the nuisance parameters. A simulation study is used to compare standard TSLS with the two DR estimators finite-sample performance, (1) when fitted using parametric nuisance models, and (2) using data-adaptive nuisance fits, obtained from the Super Learner, an ensemble machine learning method. Data-adaptive DR estimators have lower bias and improved coverage, when compared to incorrectly specified parametric DR estimators and TSLS. When the parametric model for the treatment effect curve is correctly specified, the g-estimator outperforms all others, but when this model is misspecified, TMLE performs best, while TSLS can result in large biases and zero coverage. Finally, we illustrate the methods by reanalysing the COPERS (COping with persistent Pain, Effectiveness Research in Self-management) trial to make inference about the causal effect of treatment actually received, and the extent to which this is modified by depression at baseline.
Instrumental variables are widely used to deal with unmeasured confounding in observational studies and imperfect randomized controlled trials. In these studies, researchers often target the so-called local average treatment effect as it is identifiable under mild conditions. In this paper, we consider estimation of the local average treatment effect under the binary instrumental variable model. We discuss the challenges for causal estimation with a binary outcome, and show that surprisingly, it can be more difficult than the case with a continuous outcome. We propose novel modeling and estimating procedures that improve upon existing proposals in terms of model congeniality, interpretability, robustness or efficiency. Our approach is illustrated via simulation studies and a real data analysis.
Consider the problem of estimating the local average treatment effect with an instrument variable, where the instrument unconfoundedness holds after adjusting for a set of measured covariates. Several unknown functions of the covariates need to be estimated through regression models, such as instrument propensity score and treatment and outcome regression models. We develop a computationally tractable method in high-dimensional settings where the numbers of regression terms are close to or larger than the sample size. Our method exploits regularized calibrated estimation, which involves Lasso penalties but carefully chosen loss functions for estimating coefficient vectors in these regression models, and then employs a doubly robust estimator for the treatment parameter through augmented inverse probability weighting. We provide rigorous theoretical analysis to show that the resulting Wald confidence intervals are valid for the treatment parameter under suitable sparsity conditions if the instrument propensity score model is correctly specified, but the treatment and outcome regression models may be misspecified. For existing high-dimensional methods, valid confidence intervals are obtained for the treatment parameter if all three models are correctly specified. We evaluate the proposed methods via extensive simulation studies and an empirical application to estimate the returns to education.
Estimating dynamic treatment regimes (DTRs) from retrospective observational data is challenging as some degree of unmeasured confounding is often expected. In this work, we develop a framework of estimating properly defined optimal DTRs with a time-varying instrumental variable (IV) when unmeasured covariates confound the treatment and outcome, rendering the potential outcome distributions only partially identified. We derive a novel Bellman equation under partial identification, use it to define a generic class of estimands (termed IV-optimal DTRs), and study the associated estimation problem. We then extend the IV-optimality framework to tackle the policy improvement problem, delivering IV-improved DTRs that are guaranteed to perform no worse and potentially better than a pre-specified baseline DTR. Importantly, our IV-improvement framework opens up the possibility of strictly improving upon DTRs that are optimal under the no unmeasured confounding assumption (NUCA). We demonstrate via extensive simulations the superior performance of IV-optimal and IV-improved DTRs over the DTRs that are optimal only under the NUCA. In a real data example, we embed retrospective observational registry data into a natural, two-stage experiment with noncompliance using a time-varying IV and estimate useful IV-optimal DTRs that assign mothers to high-level or low-level neonatal intensive care units based on their prognostic variables.