Currently available risk prediction methods are limited in their ability to deal with complex, heterogeneous, and longitudinal data such as that available in primary care records, or in their ability to deal with multiple competing risks. This paper develops a novel deep learning approach that is able to successfully address current limitations of standard statistical approaches such as landmarking and joint modeling. Our approach, which we call Dynamic-DeepHit, flexibly incorporates the available longitudinal data comprising various repeated measurements (rather than only the last available measurements) in order to issue dynamically updated survival predictions for one or multiple competing risk(s). Dynamic-DeepHit learns the time-to-event distributions without the need to make any assumptions about the underlying stochastic models for the longitudinal and the time-to-event processes. Thus, unlike existing works in statistics, our method is able to learn data-driven associations between the longitudinal data and the various associated risks without underlying model specifications. We demonstrate the power of our approach by applying it to a real-world longitudinal dataset from the U.K. Cystic Fibrosis Registry, which includes a heterogeneous cohort of 5883 adult patients with annual follow-ups between 2009 to 2015. The results show that Dynamic-DeepHit provides a drastic improvement in discriminating individual risks of different forms of failures due to cystic fibrosis. Furthermore, our analysis utilizes post-processing statistics that provide clinical insight by measuring the influence of each covariate on risk predictions and the temporal importance of longitudinal measurements, thereby enabling us to identify covariates that are influential for different competing risks.

Missing data is a ubiquitous problem. It is especially challenging in medical settings because many streams of measurements are collected at different-and often irregular-times. Accurate estimation of the missing measurements is critical for many reasons, including diagnosis, prognosis, and treatment. Existing methods address this estimation problem by interpolating within data streams or imputing across data streams (both of which ignore important information) or ignoring the temporal aspect of the data and imposing strong assumptions about the nature of the data-generating process and/or the pattern of missing data (both of which are especially problematic for medical data). We propose a new approach, based on a novel deep learning architecture that we call a Multi-directional Recurrent Neural Network that interpolates within data streams and imputes across data streams. We demonstrate the power of our approach by applying it to five real-world medical datasets. We show that it provides dramatically improved estimation of missing measurements in comparison to 11 state-of-the-art benchmarks (including Spline and Cubic Interpolations, MICE, MissForest, matrix completion, and several RNN methods); typical improvements in Root Mean Squared Error are between 35%-50%. Additional experiments based on the same five datasets demonstrate that the improvements provided by our method are extremely robust.

The medical and machine learning communities are relying on the promise of artificial intelligence (AI) to transform medicine through enabling more accurate decisions and personalized treatment. However, progress is slow. Legal and ethical issues around unconsented patient data and privacy is one of the limiting factors in data sharing, resulting in a significant barrier in accessing routinely collected electronic health records (EHR) by the machine learning community. We propose a novel framework for generating synthetic data that closely approximates the joint distribution of variables in an original EHR dataset, providing a readily accessible, legally and ethically appropriate solution to support more open data sharing, enabling the development of AI solutions. In order to address issues around lack of clarity in defining sufficient anonymization, we created a quantifiable, mathematical definition for "identifiability". We used a conditional generative adversarial networks (GAN) framework to generate synthetic data while minimize patient identifiability that is defined based on the probability of re-identification given the combination of all data on any individual patient. We compared models fitted to our synthetically generated data to those fitted to the real data across four independent datasets to evaluate similarity in model performance, while assessing the extent to which original observations can be identified from the synthetic data. Our model, ADS-GAN, consistently outperformed state-of-the-art methods, and demonstrated reliability in the joint distributions. We propose that this method could be used to develop datasets that can be made publicly available while considerably lowering the risk of breaching patient confidentiality.

Privacy concerns often arise as the key bottleneck for the sharing of data between consumers and data holders, particularly for sensitive data such as Electronic Health Records (EHR). This impedes the application of data analytics and ML-based innovations with tremendous potential. One promising approach for such privacy concerns is to instead use synthetic data. We propose a generative modeling framework, EHR-Safe, for generating highly realistic and privacy-preserving synthetic EHR data. EHR-Safe is based on a two-stage model that consists of sequential encoder-decoder networks and generative adversarial networks. Our innovations focus on the key challenging aspects of real-world EHR data: heterogeneity, sparsity, coexistence of numerical and categorical features with distinct characteristics, and time-varying features with highly-varying sequence lengths. Under numerous evaluations, we demonstrate that the fidelity of EHR-Safe is almost-identical with real data (<3% accuracy difference for the models trained on them) while yielding almost-ideal performance in practical privacy metrics.

With the advent of electronic health records, more data are continuously collected for individual patients, and more data are available for review from past patients. Despite this, it has not yet been possible to successfully use this data to systematically build clinical decision support systems that can produce personalized clinical recommendations to assist clinicians in providing individualized healthcare. In this paper, we present a novel approach, discovery engine (DE), that discovers which patient characteristics are most relevant for predicting the correct diagnosis and/or recommending the best treatment regimen for each patient. We demonstrate the performance of DE in two clinical settings: diagnosis of breast cancer as well as a personalized recommendation for a specific chemotherapy regimen for breast cancer patients. For each distinct clinical recommendation, different patient features are relevant; DE can discover these different relevant features and use them to recommend personalized clinical decisions. The DE approach achieves a 16.6% improvement over existing state-of-the-art recommendation algorithms regarding kappa coefficients for recommending the personalized chemotherapy regimens. For diagnostic predictions, the DE approach achieves a 2.18% and 4.20% improvement over existing state-of-the-art prediction algorithms regarding prediction error rate and false positive rate, respectively. We also demonstrate that the performance of our approach is robust against missing information and that the relevant features discovered by DE are confirmed by clinical references.

Risk prediction is crucial in many areas of medical practice, such as cardiac transplantation, but existing clinical risk-scoring methods have suboptimal performance. We develop a novel risk prediction algorithm and test its performance on the database of all patients who were registered for cardiac transplantation in the United States during 1985-2015. We develop a new, interpretable, methodology (ToPs: Trees of Predictors) built on the principle that specific predictive (survival) models should be used for specific clusters within the patient population. ToPs discovers these specific clusters and the specific predictive model that performs best for each cluster. In comparison with existing clinical risk scoring methods and state-of-the-art machine learning methods, our method provides significant improvements in survival predictions, both post- and pre-cardiac transplantation. For instance: in terms of 3-month survival post-transplantation, our method achieves AUC of 0.660; the best clinical risk scoring method (RSS) achieves 0.587. In terms of 3-year survival/mortality predictions post-transplantation (in comparison to RSS), holding specificity at 80.0%, our algorithm correctly predicts survival for 2,442 (14.0%) more patients (of 17,441 who actually survived); holding sensitivity at 80.0%, our algorithm correctly predicts mortality for 694 (13.0%) more patients (of 5,339 who did not survive). ToPs achieves similar improvements for other time horizons and for predictions pre-transplantation. ToPs discovers the most relevant features (covariates), uses available features to best advantage, and can adapt to changes in clinical practice. We show that, in comparison with existing clinical risk-scoring methods and other machine learning methods, ToPs significantly improves survival predictions both post- and pre-cardiac transplantation. ToPs provides a more accurate, personalized approach to survival prediction that can benefit patients, clinicians, and policymakers in making clinical decisions and setting clinical policy. Because survival prediction is widely used in clinical decision-making across diseases and clinical specialties, the implications of our methods are far-reaching.