Estimating what would be an individual's potential response to varying levels of exposure to a treatment is of high practical relevance for several important fields, such as healthcare, economics and public policy. However, existing methods for learning to estimate counterfactual outcomes from observational data are either focused on estimating average dose-response curves, or limited to settings with only two treatments that do not have an associated dosage parameter. Here, we present a novel machine-learning approach towards learning counterfactual representations for estimating individual dose-response curves for any number of treatments with continuous dosage parameters with neural networks. Building on the established potential outcomes framework, we introduce performance metrics, model selection criteria, model architectures, and open benchmarks for estimating individual dose-response curves. Our experiments show that the methods developed in this work set a new state-of-the-art in estimating individual dose-response.
In contrast to existing methods, we present the first doubly-robust, non-linear machine-learning approach to learn to estimate individual dose-response curves for multiple available treatments with a continuous dosage parameter from observational data. We address treatment assignment bias using several known regularisation schemes for counterfactual inference. To facilitate future research in this important area, we introduce new performance metrics, model selection criteria, and open benchmarks. We believe this work could be particularly important for applications in precision medicine, where the current state-of-the-art of estimating the average dose response across the entire population does not take into account individual differences, even though large differences in dose-response between individuals are well-documented for many diseases @cite_31 @cite_10 @cite_34 .
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Treatment effects can be estimated from observational data as the difference in potential outcomes. In this paper, we address the challenge of estimating the potential outcome when treatment-dose levels can vary continuously over time. Further, the outcome variable may not be measured at a regular frequency. Our proposed solution represents the treatment response curves using linear time-invariant dynamical systems---this provides a flexible means for modeling response over time to highly variable dose curves. Moreover, for multivariate data, the proposed method: uncovers shared structure in treatment response and the baseline across multiple markers; and, flexibly models challenging correlation structure both across and within signals over time. For this, we build upon the framework of multiple-output Gaussian Processes. On simulated and a challenging clinical dataset, we show significant gains in accuracy over state-of-the-art models. We present an adversarial domain adaptation based deep learning approach for automatic tumor segmentation from T2-weighted MRI. Our approach is composed of two steps: (i) a tumor-aware unsupervised cross-domain adaptation (CT to MRI), followed by (ii) semi-supervised tumor segmentation using Unet trained with synthesized and limited number of original MRIs. We introduced a novel target specific loss, called tumor-aware loss, for unsupervised cross-domain adaptation that helps to preserve tumors on synthesized MRIs produced from CT images. In comparison, state-of-the art adversarial networks trained without our tumor-aware loss produced MRIs with ill-preserved or missing tumors. All networks were trained using labeled CT images from 377 patients with non-small cell lung cancer obtained from the Cancer Imaging Archive and unlabeled T2w MRIs from a completely unrelated cohort of 6 patients with pre-treatment and 36 on-treatment scans. Next, we combined 6 labeled pre-treatment MRI scans with the synthesized MRIs to boost tumor segmentation accuracy through semi-supervised learning. Semi-supervised training of cycle-GAN produced a segmentation accuracy of 0.66 computed using Dice Score Coefficient (DSC). Our method trained with only synthesized MRIs produced an accuracy of 0.74 while the same method trained in semi-supervised setting produced the best accuracy of 0.80 on test. Our results show that tumor-aware adversarial domain adaptation helps to achieve reasonably accurate cancer segmentation from limited MRI data by leveraging large CT datasets. Predicated on the increasing abundance of electronic health records, we investigate the problem of inferring individualized treatment effects using observational data. Stemming from the potential outcomes model, we propose a novel multi-task learning framework in which factual and counterfactual outcomes are modeled as the outputs of a function in a vector-valued reproducing kernel Hilbert space (vvRKHS). We develop a nonparametric Bayesian method for learning the treatment effects using a multi-task Gaussian process (GP) with a linear coregionalization kernel as a prior over the vvRKHS. The Bayesian approach allows us to compute individualized measures of confidence in our estimates via pointwise credible intervals, which are crucial for realizing the full potential of precision medicine. The impact of selection bias is alleviated via a risk-based empirical Bayes method for adapting the multi-task GP prior, which jointly minimizes the empirical error in factual outcomes and the uncertainty in (unobserved) counterfactual outcomes. We conduct experiments on observational datasets for an interventional social program applied to premature infants, and a left ventricular assist device applied to cardiac patients wait-listed for a heart transplant. In both experiments, we show that our method significantly outperforms the state-of-the-art. We present new statistical analyses of data arising from a clinical trial designed to compare two-stage dynamic treatment regimes (DTRs) for advanced prostate cancer. The trial protocol mandated that patients be initially randomized among four chemotherapies, and that those who responded poorly be re-randomized to one of the remaining candidate therapies. The primary aim was to compare the DTRs’ overall success rates, with success defined by the occurrence of successful responses in each of two consecutive courses of the patient’s therapy. Of the 150 study participants, 47 did not complete their therapy as per the algorithm. However, 35 of them did so for reasons that precluded further chemotherapy, that is, toxicity and or progressive disease. Consequently, rather than comparing the overall success rates of the DTRs in the unrealistic event that these patients had remained on their assigned chemotherapies, we conducted an analysis that compared viable switch rules defined by the per-protocol rules but with the additional provision that patients who developed toxicity or progressive disease switch to a non-prespecified therapeutic or palliative strategy. This modification involved consideration of bivariate per-course outcomes encoding both efficacy and toxicity. We used numerical scores elicited from the trial’s principal investigator to quantify the clinical desirability of each bivariate per-course outcome, and defined one endpoint as their average over all courses of treatment. Two other simpler sets of scores as well as log survival time were also used as endpoints. Estimation of each DTR-specific mean score was conducted using inverse probability weighted methods that assumed that missingness in the 12 remaining dropouts was informative but explainable in that it only depended on past recorded data. We conducted additional worst- and best-case analyses to evaluate sensitivity of our findings to extreme departures from the explainable dropout assumption.