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1. Inference for Treatment-Specific Survival Curves Using Machine Learning

   https://doi.org/10.1080/01621459.2023.2205060  

   Westling, Ted; Luedtke, Alex; Gilbert, Peter B; Carone, Marco (April 2024, Journal of the American Statistical Association)

   In the absence of data from a randomized trial, researchers may aim to use observational data to draw causal inference about the effect of a treatment on a time-to-event outcome. In this context, interest often focuses on the treatment-specific survival curves, that is, the survival curves were the population under study to be assigned to receive the treatment or not. Under certain conditions, including that all confounders of the treatment-outcome relationship are observed, the treatment-specific survival curve can be identified with a covariate-adjusted survival curve. In this article, we propose a novel cross-fitted doubly-robust estimator that incorporates data-adaptive (e.g. machine learning) estimators of the conditional survival functions. We establish conditions on the nuisance estimators under which our estimator is consistent and asymptotically linear, both pointwise and uniformly in time. We also propose a novel ensemble learner for combining multiple candidate estimators of the conditional survival estimators. Notably, our methods and results accommodate events occurring in discrete or continuous time, or an arbitrary mix of the two. We investigate the practical performance of our methods using numerical studies and an application to the effect of a surgical treatment to prevent metastases of parotid carcinoma on mortality. 

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2. Semiparametric Inference For Causal Effects In Graphical Models With Hidden Variables

   Bhattacharya, Rohit; Nabi, Razieh; Shpitser, Ilya (October 2022, Journal of machine learning research)

   Identification theory for causal effects in causal models associated with hidden variable directed acyclic graphs (DAGs) is well studied. However, the corresponding algorithms are underused due to the complexity of estimating the identifying functionals they output. In this work, we bridge the gap between identification and estimation of population-level causal effects involving a single treatment and a single outcome. We derive influence function based estimators that exhibit double robustness for the identified effects in a large class of hidden variable DAGs where the treatment satisfies a simple graphical criterion; this class includes models yielding the adjustment and front-door functionals as special cases. We also provide necessary and sufficient conditions under which the statistical model of a hidden variable DAG is nonparametrically saturated and implies no equality constraints on the observed data distribution. Further, we derive an important class of hidden variable DAGs that imply observed data distributions observationally equivalent (up to equality constraints) to fully observed DAGs. In these classes of DAGs, we derive estimators that achieve the semiparametric efficiency bounds for the target of interest where the treatment satisfies our graphical criterion. Finally, we provide a sound and complete identification algorithm that directly yields a weight based estimation strategy for any identifiable effect in hidden variable causal models. 

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3. An Alternative Robust Estimator of Average Treatment Effect in Causal Inference

   https://doi.org/10.1111/biom.12859  

   Liu, Jianxuan; Ma, Yanyuan; Wang, Lan (February 2018, Biometrics)

   Summary The problem of estimating the average treatment effects is important when evaluating the effectiveness of medical treatments or social intervention policies. Most of the existing methods for estimating the average treatment effect rely on some parametric assumptions about the propensity score model or the outcome regression model one way or the other. In reality, both models are prone to misspecification, which can have undue influence on the estimated average treatment effect. We propose an alternative robust approach to estimating the average treatment effect based on observational data in the challenging situation when neither a plausible parametric outcome model nor a reliable parametric propensity score model is available. Our estimator can be considered as a robust extension of the popular class of propensity score weighted estimators. This approach has the advantage of being robust, flexible, data adaptive, and it can handle many covariates simultaneously. Adopting a dimension reduction approach, we estimate the propensity score weights semiparametrically by using a non-parametric link function to relate the treatment assignment indicator to a low-dimensional structure of the covariates which are formed typically by several linear combinations of the covariates. We develop a class of consistent estimators for the average treatment effect and study their theoretical properties. We demonstrate the robust performance of the estimators on simulated data and a real data example of investigating the effect of maternal smoking on babies’ birth weight. 

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4. Sensitivity analysis for unmeasured confounding in coarse Structural Nested Mean Models

   https://doi.org/10.5705/ss.202016.0133  

   Yang S.; Lok J.J. (October 2018, Statistica sinica)

   Coarse Structural Nested Mean Models (SNMMs, Robins (2000)) and G-estimation can be used to estimate the causal effect of a time-varying treatment from longitudinal observational studies. However, they rely on an untestable assumption of no unmeasured confounding. In the presence of unmeasured confounders, the unobserved potential outcomes are not missing at random, and standard G-estimation leads to biased effect estimates. To remedy this, we investigate the sensitivity of G-estimators of coarse SNMMs to unmeasured confounding, assuming a nonidentifiable bias function which quantifies the impact of unmeasured confounding on the average potential outcome. We present adjusted G-estimators of coarse SNMM parameters and prove their consistency, under the bias modeling for unmeasured confounding. We apply this to a sensitivity analysis for the effect of the ART initiation time on the mean CD4 count at year 2 after infection in HIV-positive patients, based on the prospective Acute and Early Disease Research Program. 

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5. Debiased inference for a covariate-adjusted regression function

   https://doi.org/10.1093/jrsssb/qkae041  

   Takatsu, Kenta; Westling, Ted (May 2024, Journal of the Royal Statistical Society Series B: Statistical Methodology)

   In this article, we study nonparametric inference for a covariate-adjusted regression function. This parameter captures the average association between a continuous exposure and an outcome after adjusting for other covariates. Under certain causal conditions, it also corresponds to the average outcome had all units been assigned to a specific exposure level, known as the causal dose–response curve. We propose a debiased local linear estimator of the covariate-adjusted regression function and demonstrate that our estimator converges pointwise to a mean-zero normal limit distribution. We use this result to construct asymptotically valid confidence intervals for function values and differences thereof. In addition, we use approximation results for the distribution of the supremum of an empirical process to construct asymptotically valid uniform confidence bands. Our methods do not require undersmoothing, permit the use of data-adaptive estimators of nuisance functions, and our estimator attains the optimal rate of convergence for a twice differentiable regression function. We illustrate the practical performance of our estimator using numerical studies and an analysis of the effect of air pollution exposure on cardiovascular mortality. 

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