Benjamin A. Goldstein

Feier Chang, Jay Krishnan, Jillian H Hurst et al.

To identify patients who are hospitalized because of COVID-19 as opposed to those who were admitted for other indications, we compared the performance of different computable phenotype definitions for COVID-19 hospitalizations that use different types of data from the electronic health records (EHR), including structured EHR data elements, provider notes, or a combination of both data types. And conduct a retrospective data analysis utilizing chart review-based validation. Participants are 586 hospitalized individuals who tested positive for SARS-CoV-2 during January 2022. We used natural language processing to incorporate data from provider notes and LASSO regression and Random Forests to fit classification algorithms that incorporated structured EHR data elements, provider notes, or a combination of structured data and provider notes. Results: Based on a chart review, 38% of 586 patients were determined to be hospitalized for reasons other than COVID-19 despite having tested positive for SARS-CoV-2. A classification algorithm that used provider notes had significantly better discrimination than one that used structured EHR data elements (AUROC: 0.894 vs 0.841, p < 0.001), and performed similarly to a model that combined provider notes with structured data elements (AUROC: 0.894 vs 0.893). Assessments of hospital outcome metrics significantly differed based on whether the population included all hospitalized patients who tested positive for SARS-CoV-2 versus those who were determined to have been hospitalized due to COVID-19. This work demonstrates the utility of natural language processing approaches to derive information related to patient hospitalizations in cases where there may be multiple conditions that could serve as the primary indication for hospitalization.

Yilin Ning, Victor Volovici, Marcus Eng Hock Ong et al.

A prediction model is most useful if it generalizes beyond the development data with external validations, but to what extent should it generalize remains unclear. In practice, prediction models are externally validated using data from very different settings, including populations from other health systems or countries, with predictably poor results. This may not be a fair reflection of the performance of the model which was designed for a specific target population or setting, and may be stretching the expected model generalizability. To address this, we suggest to externally validate a model using new data from the target population to ensure clear implications of validation performance on model reliability, whereas model generalizability to broader settings should be carefully investigated during model development instead of explored post-hoc. Based on this perspective, we propose a roadmap that facilitates the development and application of reliable, fair, and trustworthy artificial intelligence prediction models.

Minghui Sun, Matthew M. Engelhard, Benjamin A. Goldstein

Risk assessments for a pediatric population are often conducted across multiple stages. For example, clinicians may evaluate risks prenatally, at birth, and during Well-Child visits. Although predictions made at later stages typically achieve higher precision, it is clinically desirable to make reliable risk assessments as early as possible. Therefore, this study focuses on improving prediction performance in early-stage risk assessments. Our solution, \textbf{Borrowing From the Future (BFF)}, is a contrastive multi-modal framework that treats each time window as a distinct modality. In BFF, a model is trained on all available data throughout the time while performing a risk assessment using up-to-date information. This contrastive framework allows the model to ``borrow'' informative signals from later stages (e.g., Well-Child visits) to implicitly supervise the learning at earlier stages (e.g., prenatal/birth stages). We validate BFF on two real-world pediatric outcome prediction tasks, demonstrating consistent improvements in early risk assessments. The code is available at https://github.com/scotsun/bff.

Minghui Sun, Benjamin A. Goldstein, Matthew M. Engelhard

Learning representations unaffected by superficial characteristics is important to ensure that shifts in these characteristics at test time do not compromise downstream prediction performance. For instance, in healthcare applications, we might like to learn features that contain information about pathology yet are unaffected by race, sex, and other sources of physiologic variability, thereby ensuring predictions are equitable and generalizable across all demographics. Here we propose Contrastive LEarning with Anti-contrastive Regularization (CLEAR), an intuitive and easy-to-implement framework that effectively separates essential (i.e., task-relevant) characteristics from superficial (i.e., task-irrelevant) characteristics during training, leading to better performance when superficial characteristics shift at test time. We begin by supposing that data representations can be semantically separated into task-relevant content features, which contain information relevant to downstream tasks, and task-irrelevant style features, which encompass superficial attributes that are irrelevant to these tasks, yet may degrade performance due to associations with content present in training data that do not generalize. We then prove that our anti-contrastive penalty, which we call Pair-Switching (PS), minimizes the Mutual Information between the style attributes and content labels. Finally, we instantiate CLEAR in the latent space of a Variational Auto-Encoder (VAE), then perform experiments to quantitatively and qualitatively evaluate the resulting CLEAR-VAE over several image datasets. Our results show that CLEAR-VAE allows us to: (a) swap and interpolate content and style between any pair of samples, and (b) improve downstream classification performance in the presence of previously unseen combinations of content and style. Our code will be made publicly available.

Raymond M. Xiong, Panyu Chen, Tianze Dong et al.

Electronic health records (EHRs) are central to modern healthcare delivery and research; yet, many researchers lack the database expertise necessary to write complex SQL queries or generate effective visualizations, limiting efficient data use and scientific discovery. To address this barrier, we introduce CELEC, a large language model (LLM)-powered framework for automated EHR data extraction and analytics. CELEC translates natural language queries into SQL using a prompting strategy that integrates schema information, few-shot demonstrations, and chain-of-thought reasoning, which together improve accuracy and robustness. On a subset of the EHRSQL benchmark, CELEC achieves execution accuracy comparable to prior systems while maintaining low latency, cost efficiency, and strict privacy by exposing only database metadata to the LLM. CELEC also adheres to strict privacy protocols: the LLM accesses only database metadata (e.g., table and column names), while all query execution occurs securely within the institutional environment, ensuring that no patient-level data is ever transmitted to or shared with the LLM. Ablation studies confirm that each component of the SQL generation pipeline, particularly the few-shot demonstrations, plays a critical role in performance. By lowering technical barriers and enabling medical researchers to query EHR databases directly, CELEC streamlines research workflows and accelerates biomedical discovery.

Mengying Yan, Ziye Tian, Siqi Li et al.

Clinical decision support tools built on electronic health records often experience performance drift due to temporal population shifts, particularly when changes in the clinical environment initially affect only a subset of patients, resulting in a transition to mixed populations. Such case-mix changes commonly arise following system-level operational updates or the emergence of new diseases, such as COVID-19. We propose TRACER (Transfer Learning-based Real-time Adaptation for Clinical Evolving Risk), a framework that identifies encounter-level transition membership and adapts predictive models using transfer learning without full retraining. In simulation studies, TRACER outperformed static models trained on historical or contemporary data. In a real-world application predicting hospital admission following emergency department visits across the COVID-19 transition, TRACER improved both discrimination and calibration. TRACER provides a scalable approach for maintaining robust predictive performance under evolving and heterogeneous clinical conditions.

Yilin Ning, Marcus Eng Hock Ong, Bibhas Chakraborty et al.

Interpretable machine learning has been focusing on explaining final models that optimize performance. The current state-of-the-art is the Shapley additive explanations (SHAP) that locally explains variable impact on individual predictions, and it is recently extended for a global assessment across the dataset. Recently, Dong and Rudin proposed to extend the investigation to models from the same class as the final model that are "good enough", and identified a previous overclaim of variable importance based on a single model. However, this method does not directly integrate with existing Shapley-based interpretations. We close this gap by proposing a Shapley variable importance cloud that pools information across good models to avoid biased assessments in SHAP analyses of final models, and communicate the findings via novel visualizations. We demonstrate the additional insights gain compared to conventional explanations and Dong and Rudin's method using criminal justice and electronic medical records data.

Han Yuan, Feng Xie, Marcus Eng Hock Ong et al.

Background: Medical decision-making impacts both individual and public health. Clinical scores are commonly used among a wide variety of decision-making models for determining the degree of disease deterioration at the bedside. AutoScore was proposed as a useful clinical score generator based on machine learning and a generalized linear model. Its current framework, however, still leaves room for improvement when addressing unbalanced data of rare events. Methods: Using machine intelligence approaches, we developed AutoScore-Imbalance, which comprises three components: training dataset optimization, sample weight optimization, and adjusted AutoScore. All scoring models were evaluated on the basis of their area under the curve (AUC) in the receiver operating characteristic analysis and balanced accuracy (i.e., mean value of sensitivity and specificity). By utilizing a publicly accessible dataset from Beth Israel Deaconess Medical Center, we assessed the proposed model and baseline approaches in the prediction of inpatient mortality. Results: AutoScore-Imbalance outperformed baselines in terms of AUC and balanced accuracy. The nine-variable AutoScore-Imbalance sub-model achieved the highest AUC of 0.786 (0.732-0.839) while the eleven-variable original AutoScore obtained an AUC of 0.723 (0.663-0.783), and the logistic regression with 21 variables obtained an AUC of 0.743 (0.685-0.800). The AutoScore-Imbalance sub-model (using down-sampling algorithm) yielded an AUC of 0. 0.771 (0.718-0.823) with only five variables, demonstrating a good balance between performance and variable sparsity. Conclusions: The AutoScore-Imbalance tool has the potential to be applied to highly unbalanced datasets to gain further insight into rare medical events and to facilitate real-world clinical decision-making.

Feng Xie, Yilin Ning, Han Yuan et al.

Scoring systems are highly interpretable and widely used to evaluate time-to-event outcomes in healthcare research. However, existing time-to-event scores are predominantly created ad-hoc using a few manually selected variables based on clinician's knowledge, suggesting an unmet need for a robust and efficient generic score-generating method. AutoScore was previously developed as an interpretable machine learning score generator, integrated both machine learning and point-based scores in the strong discriminability and accessibility. We have further extended it to time-to-event data and developed AutoScore-Survival, for automatically generating time-to-event scores with right-censored survival data. Random survival forest provides an efficient solution for selecting variables, and Cox regression was used for score weighting. We illustrated our method in a real-life study of 90-day mortality of patients in intensive care units and compared its performance with survival models (i.e., Cox) and the random survival forest. The AutoScore-Survival-derived scoring model was more parsimonious than survival models built using traditional variable selection methods (e.g., penalized likelihood approach and stepwise variable selection), and its performance was comparable to survival models using the same set of variables. Although AutoScore-Survival achieved a comparable integrated area under the curve of 0.782 (95% CI: 0.767-0.794), the integer-valued time-to-event scores generated are favorable in clinical applications because they are easier to compute and interpret. Our proposed AutoScore-Survival provides an automated, robust and easy-to-use machine learning-based clinical score generator to studies of time-to-event outcomes. It provides a systematic guideline to facilitate the future development of time-to-event scores for clinical applications.

Zidi Xiu, Junya Chen, Ricardo Henao et al.

Dealing with severe class imbalance poses a major challenge for real-world applications, especially when the accurate classification and generalization of minority classes is of primary interest. In computer vision, learning from long tailed datasets is a recurring theme, especially for natural image datasets. While existing solutions mostly appeal to sampling or weighting adjustments to alleviate the pathological imbalance, or imposing inductive bias to prioritize non-spurious associations, we take novel perspectives to promote sample efficiency and model generalization based on the invariance principles of causality. Our proposal posits a meta-distributional scenario, where the data generating mechanism is invariant across the label-conditional feature distributions. Such causal assumption enables efficient knowledge transfer from the dominant classes to their under-represented counterparts, even if the respective feature distributions show apparent disparities. This allows us to leverage a causal data inflation procedure to enlarge the representation of minority classes. Our development is orthogonal to the existing extreme classification techniques thus can be seamlessly integrated. The utility of our proposal is validated with an extensive set of synthetic and real-world computer vision tasks against SOTA solutions.

Zidi Xiu, Chenyang Tao, Michael Gao et al.

Combining the increasing availability and abundance of healthcare data and the current advances in machine learning methods have created renewed opportunities to improve clinical decision support systems. However, in healthcare risk prediction applications, the proportion of cases with the condition (label) of interest is often very low relative to the available sample size. Though very prevalent in healthcare, such imbalanced classification settings are also common and challenging in many other scenarios. So motivated, we propose a variational disentanglement approach to semi-parametrically learn from rare events in heavily imbalanced classification problems. Specifically, we leverage the imposed extreme-distribution behavior on a latent space to extract information from low-prevalence events, and develop a robust prediction arm that joins the merits of the generalized additive model and isotonic neural nets. Results on synthetic studies and diverse real-world datasets, including mortality prediction on a COVID-19 cohort, demonstrate that the proposed approach outperforms existing alternatives.

Benjamin A. Goldstein, Matthew Phelan, Neha J. Pagidipati et al.

Participants enrolled into randomized controlled trials (RCTs) often do not reflect real-world populations. Previous research in how best to translate RCT results to target populations has focused on weighting RCT data to look like the target data. Simulation work, however, has suggested that an outcome model approach may be preferable. Here we describe such an approach using source data from the 2x2 factorial NAVIGATOR trial which evaluated the impact of valsartan and nateglinide on cardiovascular outcomes and new-onset diabetes in a pre-diabetic population. Our target data consisted of people with pre-diabetes serviced at our institution. We used Random Survival Forests to develop separate outcome models for each of the 4 treatments, estimating the 5-year risk difference for progression to diabetes and estimated the treatment effect in our local patient populations, as well as sub-populations, and the results compared to the traditional weighting approach. Our models suggested that the treatment effect for valsartan in our patient population was the same as in the trial, whereas for nateglinide treatment effect was stronger than observed in the original trial. Our effect estimates were more efficient than the weighting approach.

Paidamoyo Chapfuwa, Chenyang Tao, Chunyuan Li et al.

Modern health data science applications leverage abundant molecular and electronic health data, providing opportunities for machine learning to build statistical models to support clinical practice. Time-to-event analysis, also called survival analysis, stands as one of the most representative examples of such statistical models. We present a deep-network-based approach that leverages adversarial learning to address a key challenge in modern time-to-event modeling: nonparametric estimation of event-time distributions. We also introduce a principled cost function to exploit information from censored events (events that occur subsequent to the observation window). Unlike most time-to-event models, we focus on the estimation of time-to-event distributions, rather than time ordering. We validate our model on both benchmark and real datasets, demonstrating that the proposed formulation yields significant performance gains relative to a parametric alternative, which we also propose.