Cheng Ju

Cheng Ju, David Benkeser, Mark J. van der Laan

Many estimators of the average effect of a treatment on an outcome require estimation of the propensity score, the outcome regression, or both. It is often beneficial to utilize flexible techniques such as semiparametric regression or machine learning to estimate these quantities. However, optimal estimation of these regressions does not necessarily lead to optimal estimation of the average treatment effect, particularly in settings with strong instrumental variables. A recent proposal addressed these issues via the outcome-adaptive lasso, a penalized regression technique for estimating the propensity score that seeks to minimize the impact of instrumental variables on treatment effect estimators. However, a notable limitation of this approach is that its application is restricted to parametric models. We propose a more flexible alternative that we call the outcome highly adaptive lasso. We discuss large sample theory for this estimator and propose closed form confidence intervals based on the proposed estimator. We show via simulation that our method offers benefits over several popular approaches.

Cheng Ju, James Li, Bram Wasti et al.

Graph-based semi-supervised learning is a fundamental machine learning problem, and has been well studied. Most studies focus on homogeneous networks (e.g. citation network, friend network). In the present paper, we propose the Heterogeneous Embedding Label Propagation (HELP) algorithm, a graph-based semi-supervised deep learning algorithm, for graphs that are characterized by heterogeneous node types. Empirically, we demonstrate the effectiveness of this method in domain classification tasks with Facebook user-domain interaction graph, and compare the performance of the proposed HELP algorithm with the state of the art algorithms. We show that the HELP algorithm improves the predictive performance across multiple tasks, together with semantically meaningful embedding that are discriminative for downstream classification or regression tasks.

Cheng Ju, Antoine Chambaz, Mark J. van der Laan

We wish to infer the value of a parameter at a law from which we sample independent observations. The parameter is smooth and we can define two variation-independent features of the law, its $Q$- and $G$-components, such that estimating them consistently at a fast enough product of rates allows to build a confidence interval (CI) with a given asymptotic level from a plain targeted minimum loss estimator (TMLE). Say that the above product is not fast enough and the algorithm for the $G$-component is fine-tuned by a real-valued $h$. A plain TMLE with an $h$ chosen by cross-validation would typically not yield a CI. We construct a collaborative TMLE (C-TMLE) and show under mild conditions that, if there exists an oracle $h$ that makes a bulky remainder term asymptotically Gaussian, then the C-TMLE yields a CI. We illustrate our findings with the inference of the average treatment effect. We conduct a simulation study where the $G$-component is estimated by the LASSO and $h$ is the bound on the coefficients' norms. It sheds light on small sample properties, in the face of low- to high-dimensional baseline covariates, and possibly positivity violation.

Cheng Ju, Joshua Schwab, Mark J. van der Laan

The positivity assumption, or the experimental treatment assignment (ETA) assumption, is important for identifiability in causal inference. Even if the positivity assumption holds, practical violations of this assumption may jeopardize the finite sample performance of the causal estimator. One of the consequences of practical violations of the positivity assumption is extreme values in the estimated propensity score (PS). A common practice to address this issue is truncating the PS estimate when constructing PS-based estimators. In this study, we propose a novel adaptive truncation method, Positivity-C-TMLE, based on the collaborative targeted maximum likelihood estimation (C-TMLE) methodology. We demonstrate the outstanding performance of our novel approach in a variety of simulations by comparing it with other commonly studied estimators. Results show that by adaptively truncating the estimated PS with a more targeted objective function, the Positivity-C-TMLE estimator achieves the best performance for both point estimation and confidence interval coverage among all estimators considered.

Cheng Ju, Richard Wyss, Jessica M. Franklin et al.

Propensity score (PS) based estimators are increasingly used for causal inference in observational studies. However, model selection for PS estimation in high-dimensional data has received little attention. In these settings, PS models have traditionally been selected based on the goodness-of-fit for the treatment mechanism itself, without consideration of the causal parameter of interest. Collaborative minimum loss-based estimation (C-TMLE) is a novel methodology for causal inference that takes into account information on the causal parameter of interest when selecting a PS model. This "collaborative learning" considers variable associations with both treatment and outcome when selecting a PS model in order to minimize a bias-variance trade off in the estimated treatment effect. In this study, we introduce a novel approach for collaborative model selection when using the LASSO estimator for PS estimation in high-dimensional covariate settings. To demonstrate the importance of selecting the PS model collaboratively, we designed quasi-experiments based on a real electronic healthcare database, where only the potential outcomes were manually generated, and the treatment and baseline covariates remained unchanged. Results showed that the C-TMLE algorithm outperformed other competing estimators for both point estimation and confidence interval coverage. In addition, the PS model selected by C-TMLE could be applied to other PS-based estimators, which also resulted in substantive improvement for both point estimation and confidence interval coverage. We illustrate the discussed concepts through an empirical example comparing the effects of non-selective nonsteroidal anti-inflammatory drugs with selective COX-2 inhibitors on gastrointestinal complications in a population of Medicare beneficiaries.

Cheng Ju, Mary Combs, Samuel D Lendle et al.

The optimal learner for prediction modeling varies depending on the underlying data-generating distribution. Super Learner (SL) is a generic ensemble learning algorithm that uses cross-validation to select among a "library" of candidate prediction models. The SL is not restricted to a single prediction model, but uses the strengths of a variety of learning algorithms to adapt to different databases. While the SL has been shown to perform well in a number of settings, it has not been thoroughly evaluated in large electronic healthcare databases that are common in pharmacoepidemiology and comparative effectiveness research. In this study, we applied and evaluated the performance of the SL in its ability to predict treatment assignment using three electronic healthcare databases. We considered a library of algorithms that consisted of both nonparametric and parametric models. We also considered a novel strategy for prediction modeling that combines the SL with the high-dimensional propensity score (hdPS) variable selection algorithm. Predictive performance was assessed using three metrics: the negative log-likelihood, area under the curve (AUC), and time complexity. Results showed that the best individual algorithm, in terms of predictive performance, varied across datasets. The SL was able to adapt to the given dataset and optimize predictive performance relative to any individual learner. Combining the SL with the hdPS was the most consistent prediction method and may be promising for PS estimation and prediction modeling in electronic healthcare databases.