Tianhui Zhou

Tianhui Zhou, William E. Carson, Michael Hunter Klein et al.

Observational studies are regarded as economic alternatives to randomized trials, often used in their stead to investigate and determine treatment efficacy. Due to lack of sample size, observational studies commonly combine data from multiple sources or different sites/centers. Despite the benefits of an increased sample size, a naive combination of multicenter data may result in incongruities stemming from center-specific protocols for generating cohorts or reactions towards treatments distinct to a given center, among other things. These issues arise in a variety of other contexts, including capturing a treatment effect related to an individual's unique biological characteristics. Existing methods for estimating heterogeneous treatment effects have not adequately addressed the multicenter context, but rather treat it simply as a means to obtain sufficient sample size. Additionally, previous approaches to estimating treatment effects do not straightforwardly generalize to the multicenter design, especially when required to provide treatment insights for patients from a new, unobserved center. To address these shortcomings, we propose Multiple Domain Causal Networks (MDCN), an approach that simultaneously strengthens the information sharing between similar centers while addressing the selection bias in treatment assignment through learning of a new feature embedding. In empirical evaluations, MDCN is consistently more accurate when estimating the heterogeneous treatment effect in new centers compared to benchmarks that adjust solely based on treatment imbalance or general center differences. Finally, we justify our approach by providing theoretical analyses that demonstrate that MDCN improves on the generalization bound of the new, unobserved target center.

Tianhui Zhou, William E Carson, David Carlson

Traditional causal inference approaches leverage observational study data to estimate the difference in observed and unobserved outcomes for a potential treatment, known as the Conditional Average Treatment Effect (CATE). However, CATE corresponds to the comparison on the first moment alone, and as such may be insufficient in reflecting the full picture of treatment effects. As an alternative, estimating the full potential outcome distributions could provide greater insights. However, existing methods for estimating treatment effect potential outcome distributions often impose restrictive or simplistic assumptions about these distributions. Here, we propose Collaborating Causal Networks (CCN), a novel methodology which goes beyond the estimation of CATE alone by learning the full potential outcome distributions. Estimation of outcome distributions via the CCN framework does not require restrictive assumptions of the underlying data generating process. Additionally, CCN facilitates estimation of the utility of each possible treatment and permits individual-specific variation through utility functions. CCN not only extends outcome estimation beyond traditional risk difference, but also enables a more comprehensive decision-making process through definition of flexible comparisons. Under assumptions commonly made in the causal literature, we show that CCN learns distributions that asymptotically capture the true potential outcome distributions. Furthermore, we propose an adjustment approach that is empirically effective in alleviating sample imbalance between treatment groups in observational data. Finally, we evaluate the performance of CCN in multiple synthetic and semi-synthetic experiments. We demonstrate that CCN learns improved distribution estimates compared to existing Bayesian and deep generative methods as well as improved decisions with respects to a variety of utility functions.

Tianhui Zhou, Yitong Li, Yuan Wu et al.

Effective decision making requires understanding the uncertainty inherent in a prediction. In regression, this uncertainty can be estimated by a variety of methods; however, many of these methods are laborious to tune, generate overconfident uncertainty intervals, or lack sharpness (give imprecise intervals). We address these challenges by proposing a novel method to capture predictive distributions in regression by defining two neural networks with two distinct loss functions. Specifically, one network approximates the cumulative distribution function, and the second network approximates its inverse. We refer to this method as Collaborating Networks (CN). Theoretical analysis demonstrates that a fixed point of the optimization is at the idealized solution, and that the method is asymptotically consistent to the ground truth distribution. Empirically, learning is straightforward and robust. We benchmark CN against several common approaches on two synthetic and six real-world datasets, including forecasting A1c values in diabetic patients from electronic health records, where uncertainty is critical. In the synthetic data, the proposed approach essentially matches ground truth. In the real-world datasets, CN improves results on many performance metrics, including log-likelihood estimates, mean absolute errors, coverage estimates, and prediction interval widths.