To estimate causal effects, analysts performing observational studies in health settings utilize several strategies to mitigate bias due to confounding by indication. There are two broad classes of approaches for these purposes: use of confounders and instrumental variables (IVs). Because such approaches are largely characterized by untestable assumptions, analysts must operate under an indefinite paradigm that these methods will work imperfectly. In this tutorial, we formalize a set of general principles and heuristics for estimating causal effects in the two approaches when the assumptions are potentially violated. This crucially requires reframing the process of observational studies as hypothesizing potential scenarios where the estimates from one approach are less inconsistent than the other. While most of our discussion of methodology centers around the linear setting, we touch upon complexities in non-linear settings and flexible procedures such as target minimum loss-based estimation (TMLE) and double machine learning (DML). To demonstrate the application of our principles, we investigate the use of donepezil off-label for mild cognitive impairment (MCI). We compare and contrast results from confounder and IV methods, traditional and flexible, within our analysis and to a similar observational study and clinical trial.
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Estimates of individual treatment effects from networked observational data are attracting increasing attention these days. One major challenge in network scenarios is the violation of the stable unit treatment value assumption (SUTVA), which assumes that the treatment assignment of a unit does not influence others' outcomes. In network data, due to interference, the outcome of a unit is influenced not only by its treatment (i.e., direct effects) but also by others' treatments (i.e., spillover effects). Furthermore, the influences from other units are always heterogeneous (e.g., friends with similar interests affect a person differently than friends with different interests). In this paper, we focus on the problem of estimating individual treatment effects (both direct and spillover effects) under heterogeneous interference. To address this issue, we propose a novel Dual Weighting Regression (DWR) algorithm by simultaneously learning attention weights that capture the heterogeneous interference and sample weights to eliminate the complex confounding bias in networks. We formulate the entire learning process as a bi-level optimization problem. In theory, we present generalization error bounds for individual treatment effect estimation. Extensive experiments on four benchmark datasets demonstrate that the proposed DWR algorithm outperforms state-of-the-art methods for estimating individual treatment effects under heterogeneous interference.
Causal discovery (CD) from time-varying data is important in neuroscience, medicine, and machine learning. Techniques for CD include randomized experiments which are generally unbiased but expensive. It also includes algorithms like regression, matching, and Granger causality, which are only correct under strong assumptions made by human designers. However, as we found in other areas of machine learning, humans are usually not quite right and human expertise is usually outperformed by data-driven approaches. Here we test if we can improve causal discovery in a data-driven way. We take a perturbable system with a large number of causal components (transistors), the MOS 6502 processor, acquire the causal ground truth, and learn the causal discovery procedure represented as a neural network. We find that this procedure far outperforms human-designed causal discovery procedures, such as Mutual Information, LiNGAM, and Granger Causality both on MOS 6502 processor and the NetSim dataset which simulates functional magnetic resonance imaging (fMRI) results. We argue that the causality field should consider, where possible, a supervised approach, where CD procedures are learned from large datasets with known causal relations instead of being designed by a human specialist. Our findings promise a new approach toward improving CD in neural and medical data and for the broader machine learning community.
In this paper, we consider recent progress in estimating the average treatment effect when extreme inverse probability weights are present and focus on methods that account for a possible violation of the positivity assumption. These methods aim at estimating the treatment effect on the subpopulation of patients for whom there is a clinical equipoise. We propose a systematic approach to determine their related causal estimands and develop new insights into the properties of the weights targeting such a subpopulation. Then, we examine the roles of overlap weights, matching weights, Shannon's entropy weights, and beta weights. This helps us characterize and compare their underlying estimators, analytically and via simulations, in terms of the accuracy, precision, and root mean squared error. Moreover, we study the asymptotic behaviors of their augmented estimators (that mimic doubly robust estimators), which lead to improved estimations when either the propensity or the regression models are correctly specified. Based on the analytical and simulation results, we conclude that overall overlap weights are preferable to matching weights, especially when there is moderate or extreme violations of the positivity assumption. Finally, we illustrate the methods using a real data example marked by extreme inverse probability weights.
Semi-competing risks refers to the survival analysis setting where the occurrence of a non-terminal event is subject to whether a terminal event has occurred, but not vice versa. Semi-competing risks arise in a broad range of clinical contexts, with a novel example being the pregnancy condition preeclampsia, which can only occur before the `terminal' event of giving birth. Models that acknowledge semi-competing risks enable investigation of relationships between covariates and the joint timing of the outcomes, but methods for model selection and prediction of semi-competing risks in high dimensions are lacking. Instead, researchers commonly analyze only a single or composite outcome, losing valuable information and limiting clinical utility -- in the obstetric setting, this means ignoring valuable insight into timing of delivery after preeclampsia has onset. To address this gap we propose a novel penalized estimation framework for frailty-based illness-death multi-state modeling of semi-competing risks. Our approach combines non-convex and structured fusion penalization, inducing global sparsity as well as parsimony across submodels. We perform estimation and model selection via a pathwise routine for non-convex optimization, and prove the first statistical error bound results in this setting. We present a simulation study investigating estimation error and model selection performance, and a comprehensive application of the method to joint risk modeling of preeclampsia and timing of delivery using pregnancy data from an electronic health record.
In randomized experiments and observational studies, weighting methods are often used to generalize and transport treatment effect estimates to a target population. Traditional methods construct the weights by separately modeling the treatment assignment and study selection probabilities and then multiplying functions (e.g., inverses) of their estimates. However, these estimated multiplicative weights may not produce adequate covariate balance and can be highly variable, resulting in biased and unstable estimators, especially when there is limited covariate overlap across populations or treatment groups. To address these limitations, we propose a general weighting approach that weights each treatment group towards the target population in a single step. We present a framework and provide a justification for this one-step approach in terms of generic probability distributions. We show a formal connection between our method and inverse probability and inverse odds weighting. By construction, the proposed approach balances covariates and produces stable estimators. We show that our estimator for the target average treatment effect is consistent, asymptotically Normal, multiply robust, and semiparametrically efficient. We demonstrate the performance of this approach using a simulation study and a randomized case study on the effects of physician racial diversity on preventive healthcare utilization among Black men in California.
Commonsense causality reasoning (CCR) aims at identifying plausible causes and effects in natural language descriptions that are deemed reasonable by an average person. Although being of great academic and practical interest, this problem is still shadowed by the lack of a well-posed theoretical framework; existing work usually relies on deep language models wholeheartedly, and is potentially susceptible to confounding co-occurrences. Motivated by classical causal principles, we articulate the central question of CCR and draw parallels between human subjects in observational studies and natural languages to adopt CCR to the potential-outcomes framework, which is the first such attempt for commonsense tasks. We propose a novel framework, ROCK, to Reason O(A)bout Commonsense K(C)ausality, which utilizes temporal signals as incidental supervision, and balances confounding effects using temporal propensities that are analogous to propensity scores. The ROCK implementation is modular and zero-shot, and demonstrates good CCR capabilities on various datasets.
This PhD thesis contains several contributions to the field of statistical causal modeling. Statistical causal models are statistical models embedded with causal assumptions that allow for the inference and reasoning about the behavior of stochastic systems affected by external manipulation (interventions). This thesis contributes to the research areas concerning the estimation of causal effects, causal structure learning, and distributionally robust (out-of-distribution generalizing) prediction methods. We present novel and consistent linear and non-linear causal effects estimators in instrumental variable settings that employ data-dependent mean squared prediction error regularization. Our proposed estimators show, in certain settings, mean squared error improvements compared to both canonical and state-of-the-art estimators. We show that recent research on distributionally robust prediction methods has connections to well-studied estimators from econometrics. This connection leads us to prove that general K-class estimators possess distributional robustness properties. We, furthermore, propose a general framework for distributional robustness with respect to intervention-induced distributions. In this framework, we derive sufficient conditions for the identifiability of distributionally robust prediction methods and present impossibility results that show the necessity of several of these conditions. We present a new structure learning method applicable in additive noise models with directed trees as causal graphs. We prove consistency in a vanishing identifiability setup and provide a method for testing substructure hypotheses with asymptotic family-wise error control that remains valid post-selection. Finally, we present heuristic ideas for learning summary graphs of nonlinear time-series models.
Analyzing observational data from multiple sources can be useful for increasing statistical power to detect a treatment effect; however, practical constraints such as privacy considerations may restrict individual-level information sharing across data sets. This paper develops federated methods that only utilize summary-level information from heterogeneous data sets. Our federated methods provide doubly-robust point estimates of treatment effects as well as variance estimates. We derive the asymptotic distributions of our federated estimators, which are shown to be asymptotically equivalent to the corresponding estimators from the combined, individual-level data. We show that to achieve these properties, federated methods should be adjusted based on conditions such as whether models are correctly specified and stable across heterogeneous data sets.
This paper focuses on the expected difference in borrower's repayment when there is a change in the lender's credit decisions. Classical estimators overlook the confounding effects and hence the estimation error can be magnificent. As such, we propose another approach to construct the estimators such that the error can be greatly reduced. The proposed estimators are shown to be unbiased, consistent, and robust through a combination of theoretical analysis and numerical testing. Moreover, we compare the power of estimating the causal quantities between the classical estimators and the proposed estimators. The comparison is tested across a wide range of models, including linear regression models, tree-based models, and neural network-based models, under different simulated datasets that exhibit different levels of causality, different degrees of nonlinearity, and different distributional properties. Most importantly, we apply our approaches to a large observational dataset provided by a global technology firm that operates in both the e-commerce and the lending business. We find that the relative reduction of estimation error is strikingly substantial if the causal effects are accounted for correctly.
Causal inference is a critical research topic across many domains, such as statistics, computer science, education, public policy and economics, for decades. Nowadays, estimating causal effect from observational data has become an appealing research direction owing to the large amount of available data and low budget requirement, compared with randomized controlled trials. Embraced with the rapidly developed machine learning area, various causal effect estimation methods for observational data have sprung up. In this survey, we provide a comprehensive review of causal inference methods under the potential outcome framework, one of the well known causal inference framework. The methods are divided into two categories depending on whether they require all three assumptions of the potential outcome framework or not. For each category, both the traditional statistical methods and the recent machine learning enhanced methods are discussed and compared. The plausible applications of these methods are also presented, including the applications in advertising, recommendation, medicine and so on. Moreover, the commonly used benchmark datasets as well as the open-source codes are also summarized, which facilitate researchers and practitioners to explore, evaluate and apply the causal inference methods.
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