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Background Interest in the application of machine learning (ML) to the design, conduct, and analysis of clinical trials has grown, but the evidence base for such applications has not been surveyed. This manuscript reviews the proceedings of a multi-stakeholder conference to discuss the current and future state of ML for clinical research. Key areas of clinical trial methodology in which ML holds particular promise and priority areas for further investigation are presented alongside a narrative review of evidence supporting the use of ML across the clinical trial spectrum. Results Conference attendees included stakeholders, such as biomedical and ML researchers, representatives from the US Food and Drug Administration (FDA), artificial intelligence technology and data analytics companies, non-profit organizations, patient advocacy groups, and pharmaceutical companies. ML contributions to clinical research were highlighted in the pre-trial phase, cohort selection and participant management, and data collection and analysis. A particular focus was paid to the operational and philosophical barriers to ML in clinical research. Peer-reviewed evidence was noted to be lacking in several areas. Conclusions ML holds great promise for improving the efficiency and quality of clinical research, but substantial barriers remain, the surmounting of which will require addressing significant gaps in evidence.

The biomedical field offers many learning tasks that share unique challenges: large amounts of unpaired data, and a high cost to generate labels. In this work, we develop a method to address these issues with semi-supervised learning in regression tasks (e.g., translation from source to target). Our model uses adversarial signals to learn from unpaired datapoints, and imposes a cycle-loss reconstruction error penalty to regularize mappings in either direction against one another. We first evaluate our method on synthetic experiments, demonstrating two primary advantages of the system: 1) distribution matching via the adversarial loss and 2) regularization towards invertible mappings via the cycle loss. We then show a regularization effect and improved performance when paired data is supplemented by additional unpaired data on two real biomedical regression tasks: estimating the physiological effect of medical treatments, and extrapolating gene expression (transcriptomics) signals. Our proposed technique is a promising initial step towards more robust use of adversarial signals in semi-supervised regression, and could be useful for other tasks (e.g., causal inference or modality translation) in the biomedical field.

The ability to determine patient acuity (or severity of illness) has immediate practical use for clinicians. We evaluate the use of multivariate timeseries modeling with the multi-task Gaussian process (GP) models using noisy, incomplete, sparse, heterogeneous and unevenly-sampled clinical data, including both physiological signals and clinical notes. The learned multi-task GP (MTGP) hyperparameters are then used to assess and forecast patient acuity. Experiments were conducted with two real clinical data sets acquired from ICU patients: firstly, estimating cerebrovascular pressure reactivity, an important indicator of secondary damage for traumatic brain injury patients, by learning the interactions between intracranial pressure and mean arterial blood pressure signals, and secondly, mortality prediction using clinical progress notes. In both cases, MTGPs provided improved results: an MTGP model provided better results than single-task GP models for signal interpolation and forecasting (0.91 vs 0.69 RMSE), and the use of MTGP hyperparameters obtained improved results when used as additional classification features (0.812 vs 0.788 AUC)., Intel Science and Technology Center for Big Data, National Institutes of Health. (U.S.). National Library of Medicine (Biomedical Informatics Research Training Grant NIH/NLM 2T15 LM007092-22), National Institute of Biomedical Imaging and Bioengineering (U.S.) (R01 Grant EB001659), Singapore. Agency for Science, Technology and Research (Graduate Scholarship)

Background: Datathons facilitate collaboration between clinicians, statisticians, and data scientists in order to answer important clinical questions. Previous datathons have resulted in numerous publications of interest to the critical care community and serve as a viable model for interdisciplinary collaboration. Objective: We report on an open-source software called Chatto that was created by members of our group, in the context of the second international Critical Care Datathon, held in September 2015. Methods: Datathon participants formed teams to discuss potential research questions and the methods required to address them. They were provided with the Chatto suite of tools to facilitate their teamwork. Each multidisciplinary team spent the next 2 days with clinicians working alongside data scientists to write code, extract and analyze data, and reformulate their queries in real time as needed. All projects were then presented on the last day of the datathon to a panel of judges that consisted of clinicians and scientists. Results: Use of Chatto was particularly effective in the datathon setting, enabling teams to reduce the time spent configuring their research environments to just a few minutes—a process that would normally take hours to days. Chatto continued to serve as a useful research tool after the conclusion of the datathon. Conclusions: This suite of tools fulfills two purposes: (1) facilitation of interdisciplinary teamwork through archiving and version control of datasets, analytical code, and team discussions, and (2) advancement of research reproducibility by functioning postpublication as an online environment in which independent investigators can rerun or modify analyses with relative ease. With the introduction of Chatto, we hope to solve a variety of challenges presented by collaborative data mining projects while improving research reproducibility.

With growing concerns that big data will only augment the problem of unreliable research, the Laboratory of Computational Physiology at the Massachusetts Institute of Technology organized the Critical Data Conference in January 2014. Thought leaders from academia, government, and industry across disciplines--including clinical medicine, computer science, public health, informatics, biomedical research, health technology, statistics, and epidemiology--gathered and discussed the pitfalls and challenges of big data in health care. The key message from the conference is that the value of large amounts of data hinges on the ability of researchers to share data, methodologies, and findings in an open setting. If empirical value is to be from the analysis of retrospective data, groups must continuously work together on similar problems to create more effective peer review. This will lead to improvement in methodology and quality, with each iteration of analysis resulting in more reliability.

The ability to predict psychiatric readmission would facilitate the development of interventions to reduce this risk, a major driver of psychiatric health-care costs. The symptoms or characteristics of illness course necessary to develop reliable predictors are not available in coded billing data, but may be present in narrative electronic health record (EHR) discharge summaries. We identified a cohort of individuals admitted to a psychiatric inpatient unit between 1994 and 2012 with a principal diagnosis of major depressive disorder, and extracted inpatient psychiatric discharge narrative notes. Using these data, we trained a 75-topic Latent Dirichlet Allocation (LDA) model, a form of natural language processing, which identifies groups of words associated with topics discussed in a document collection. The cohort was randomly split to derive a training (70%) and testing (30%) data set, and we trained separate support vector machine models for baseline clinical features alone, baseline features plus common individual words and the above plus topics identified from the 75-topic LDA model. Of 4687 patients with inpatient discharge summaries, 470 were readmitted within 30 days. The 75-topic LDA model included topics linked to psychiatric symptoms (suicide, severe depression, anxiety, trauma, eating/weight and panic) and major depressive disorder comorbidities (infection, postpartum, brain tumor, diarrhea and pulmonary disease). By including LDA topics, prediction of readmission, as measured by area under receiver-operating characteristic curves in the testing data set, was improved from baseline (area under the curve 0.618) to baseline+1000 words (0.682) to baseline+75 topics (0.784). Inclusion of topics derived from narrative notes allows more accurate discrimination of individuals at high risk for psychiatric readmission in this cohort. Topic modeling and related approaches offer the potential to improve prediction using EHRs, if generalizability can be established

Accurate knowledge of a patient's disease state and trajectory is critical in a clinical setting. Modern electronic healthcare records contain an increasingly large amount of data, and the ability to automatically identify the factors that influence patient outcomes stand to greatly improve the efficiency and quality of care. We examined the use of latent variable models (viz. Latent Dirichlet Allocation) to decompose free-text hospital notes into meaningful features, and the predictive power of these features for patient mortality. We considered three prediction regimes: (1) baseline prediction, (2) dynamic (time-varying) outcome prediction, and (3) retrospective outcome prediction. In each, our prediction task differs from the familiar time-varying situation whereby data accumulates; since fewer patients have long ICU stays, as we move forward in time fewer patients are available and the prediction task becomes increasingly difficult. We found that latent topic-derived features were effective in determining patient mortality under three timelines: in-hospital, 30 day post-discharge, and 1 year post-discharge mortality. Our results demonstrated that the latent topic features important in predicting hospital mortality are very different from those that are important in post-discharge mortality. In general, latent topic features were more predictive than structured features, and a combination of the two performed best. The time-varying models that combined latent topic features and baseline features had AUCs that reached 0.85, 0.80, and 0.77 for in-hospital, 30 day post-discharge and 1 year post-discharge mortality respectively. Our results agreed with other work suggesting that the first 24 hours of patient information are often the most predictive of hospital mortality. Retrospective models that used a combination of latent topic features and structured features achieved AUCs of 0.96, 0.82, and 0.81 for in-hospital, 30 day, and 1-year mortality prediction. Our work, Intel Corporation. Science and Technology Center for Big Data, National Library of Medicine (U.S.) (Biomedical Informatics Research Training Grant NIH/NLM 2T15 LM007092-22)