Disentangled Counterfactual Recurrent Networks for Treatment Effect Inference over Time

Choosing the best treatment-plan for each individual patient requires accurate forecasts of their outcome trajectories as a function of the treatment, over time. While large observational data sets constitute rich sources of information to learn from, they also contain biases as treatments are rarely assigned randomly in practice. To provide accurate and unbiased forecasts, we introduce the Disentangled Counterfactual Recurrent Network (DCRN), a novel sequence-to-sequence architecture that estimates treatment outcomes over time by learning representations of patient histories that are disentangled into three separate latent factors: a treatment factor, influencing only treatment selection; an outcome factor, influencing only the outcome; and a confounding factor, influencing both. With an architecture that is completely inspired by the causal structure of treatment influence over time, we advance forecast accuracy and disease understanding, as our architecture allows for practitioners to infer which patient features influence which part in a patient's trajectory, contrasting other approaches in this domain. We demonstrate that DCRN outperforms current state-of-the-art methods in forecasting treatment responses, on both real and simulated data.

The Medkit-Learn(ing) Environment: Medical Decision Modelling through Simulation

Understanding decision-making in clinical environments is of paramount importance if we are to bring the strengths of machine learning to ultimately improve patient outcomes. Several factors including the availability of public data, the intrinsically offline nature of the problem, and the complexity of human decision making, has meant that the mainstream development of algorithms is often geared towards optimal performance in tasks that do not necessarily translate well into the medical regime; often overlooking more niche issues commonly associated with the area. We therefore present a new benchmarking suite designed specifically for medical sequential decision making: the Medkit-Learn(ing) Environment, a publicly available Python package providing simple and easy access to high-fidelity synthetic medical data. While providing a standardised way to compare algorithms in a realistic medical setting we employ a generating process that disentangles the policy and environment dynamics to allow for a range of customisations, thus enabling systematic evaluation of algorithms' robustness against specific challenges prevalent in healthcare.

Model-Attentive Ensemble Learning for Sequence Modeling

Medical time-series datasets have unique characteristics that make prediction tasks challenging. Most notably, patient trajectories often contain longitudinal variations in their input-output relationships, generally referred to as temporal conditional shift. Designing sequence models capable of adapting to such time-varying distributions remains a prevailing problem. To address this we present Model-Attentive Ensemble learning for Sequence modeling (MAES). MAES is a mixture of time-series experts which leverages an attention-based gating mechanism to specialize the experts on different sequence dynamics and adaptively weight their predictions. We demonstrate that MAES significantly out-performs popular sequence models on datasets subject to temporal shift.

Selecting Treatment Effects Models for Domain Adaptation Using Causal Knowledge

Selecting causal inference models for estimating individualized treatment effects (ITE) from observational data presents a unique challenge since the counterfactual outcomes are never observed. The problem is challenged further in the unsupervised domain adaptation (UDA) setting where we only have access to labeled samples in the source domain, but desire selecting a model that achieves good performance on a target domain for which only unlabeled samples are available. Existing techniques for UDA model selection are designed for the predictive setting. These methods examine discriminative density ratios between the input covariates in the source and target domain and do not factor in the model's predictions in the target domain. Because of this, two models with identical performance on the source domain would receive the same risk score by existing methods, but in reality, have significantly different performance in the test domain. We leverage the invariance of causal structures across domains to propose a novel model selection metric specifically designed for ITE methods under the UDA setting. In particular, we propose selecting models whose predictions of interventions' effects satisfy known causal structures in the target domain. Experimentally, our method selects ITE models that are more robust to covariate shifts on several healthcare datasets, including estimating the effect of ventilation in COVID-19 patients from different geographic locations.

Learning Matching Representations for Individualized Organ Transplantation Allocation

Organ transplantation is often the last resort for treating end-stage illness, but the probability of a successful transplantation depends greatly on compatibility between donors and recipients. Current medical practice relies on coarse rules for donor-recipient matching, but is short of domain knowledge regarding the complex factors underlying organ compatibility. In this paper, we formulate the problem of learning data-driven rules for organ matching using observational data for organ allocations and transplant outcomes. This problem departs from the standard supervised learning setup in that it involves matching the two feature spaces (i.e., donors and recipients), and requires estimating transplant outcomes under counterfactual matches not observed in the data. To address these problems, we propose a model based on representation learning to predict donor-recipient compatibility; our model learns representations that cluster donor features, and applies donor-invariant transformations to recipient features to predict outcomes for a given donor-recipient feature instance. Experiments on semi-synthetic and real-world datasets show that our model outperforms state-of-art allocation methods and policies executed by human experts.

Learning $\mathbf{\mathit{Matching}}$ Representations for Individualized Organ Transplantation Allocation

Organ transplantation is often the last resort for treating end-stage illness, but the probability of a successful transplantation depends greatly on compatibility between donors and recipients. Current medical practice relies on coarse rules for donor-recipient matching, but is short of domain knowledge regarding the complex factors underlying organ compatibility. In this paper, we formulate the problem of learning data-driven rules for organ matching using observational data for organ allocations and transplant outcomes. This problem departs from the standard supervised learning setup in that it involves matching the two feature spaces (i.e., donors and recipients), and requires estimating transplant outcomes under counterfactual matches not observed in the data. To address these problems, we propose a model based on representation learning to predict donor-recipient compatibility; our model learns representations that cluster donor features, and applies donor-invariant transformations to recipient features to predict outcomes for a given donor-recipient feature instance. Experiments on semi-synthetic and real-world datasets show that our model outperforms state-of-art allocation methods and policies executed by human experts.

Strictly Batch Imitation Learning by Energy-based Distribution Matching

Consider learning a policy purely on the basis of demonstrated behavior---that is, with no access to reinforcement signals, no knowledge of transition dynamics, and no further interaction with the environment. This *strictly batch imitation learning* problem arises wherever live experimentation is costly, such as in healthcare. One solution is simply to retrofit existing algorithms for apprenticeship learning to work in the offline setting. But such an approach bargains heavily on model estimation or off-policy evaluation, and can be indirect and inefficient. We argue that a good solution should be able to explicitly parameterize a policy (i.e. respecting action conditionals), implicitly account for rollout dynamics (i.e. respecting state marginals), and---crucially---operate in an entirely offline fashion. To meet this challenge, we propose a novel technique by *energy-based distribution matching* (EDM): By identifying parameterizations of the (discriminative) model of a policy with the (generative) energy function for state distributions, EDM provides a simple and effective solution that equivalently minimizes a divergence between the occupancy measures of the demonstrator and the imitator. Through experiments with application to control tasks and healthcare settings, we illustrate consistent performance gains over existing algorithms for strictly batch imitation learning.

Estimating the Effects of Continuous-valued Interventions using Generative Adversarial Networks

While much attention has been given to the problem of estimating the effect of discrete interventions from observational data, relatively little work has been done in the setting of continuous-valued interventions, such as treatments associated with a dosage parameter. In this paper, we tackle this problem by building on a modification of the generative adversarial networks (GANs) framework. Our model, SCIGAN, is flexible and capable of simultaneously estimating counterfactual outcomes for several different continuous interventions. The key idea is to use a significantly modified GAN model to learn to generate counterfactual outcomes, which can then be used to learn an inference model, using standard supervised methods, capable of estimating these counterfactuals for a new sample. To address the challenges presented by shifting to continuous interventions, we propose a novel architecture for our discriminator - we build a hierarchical discriminator that leverages the structure of the continuous intervention setting. Moreover, we provide theoretical results to support our use of the GAN framework and of the hierarchical discriminator. In the experiments section, we introduce a new semi-synthetic data simulation for use in the continuous intervention setting and demonstrate improvements over the existing benchmark models.

Estimating Counterfactual Treatment Outcomes over Time Through Adversarially Balanced Representations

Identifying when to give treatments to patients and how to select among multiple treatments over time are important medical problems with a few existing solutions. In this paper, we introduce the Counterfactual Recurrent Network (CRN), a novel sequence-to-sequence model that leverages the increasingly available patient observational data to estimate treatment effects over time and answer such medical questions. To handle the bias from time-varying confounders, covariates affecting the treatment assignment policy in the observational data, CRN uses domain adversarial training to build balancing representations of the patient history. At each timestep, CRN constructs a treatment invariant representation which removes the association between patient history and treatment assignments and thus can be reliably used for making counterfactual predictions. On a simulated model of tumour growth, with varying degree of time-dependent confounding, we show how our model achieves lower error in estimating counterfactuals and in choosing the correct treatment and timing of treatment than current state-of-the-art methods.

Time Series Deconfounder: Estimating Treatment Effects over Time in the Presence of Hidden Confounders

The estimation of treatment effects is a pervasive problem in medicine. Existing methods for estimating treatment effects from longitudinal observational data assume that there are no hidden confounders. This assumption is not testable in practice and, if it does not hold, leads to biased estimates. In this paper, we develop the Time Series Deconfounder, a method that leverages the assignment of multiple treatments over time to enable the estimation of treatment effects even in the presence of hidden confounders. The Time Series Deconfounder uses a novel recurrent neural network architecture with multitask output to build a factor model over time and infer substitute confounders that render the assigned treatments conditionally independent. Then it performs causal inference using the substitute confounders. We provide a theoretical analysis for obtaining unbiased causal effects of time-varying exposures using the Time Series Deconfounder. Using simulations we show the effectiveness of our method in deconfounding the estimation of treatment responses in longitudinal data.