The escalating integration of machine learning in high-stakes fields such as healthcare raises substantial concerns about model fairness. We propose an interpretable framework - Fairness-Aware Interpretable Modeling (FAIM), to improve model fairness without compromising performance, featuring an interactive interface to identify a "fairer" model from a set of high-performing models and promoting the integration of data-driven evidence and clinical expertise to enhance contextualized fairness. We demonstrated FAIM's value in reducing sex and race biases by predicting hospital admission with two real-world databases, MIMIC-IV-ED and SGH-ED. We show that for both datasets, FAIM models not only exhibited satisfactory discriminatory performance but also significantly mitigated biases as measured by well-established fairness metrics, outperforming commonly used bias-mitigation methods. Our approach demonstrates the feasibility of improving fairness without sacrificing performance and provides an a modeling mode that invites domain experts to engage, fostering a multidisciplinary effort toward tailored AI fairness.

Survival analysis serves as a fundamental component in numerous healthcare applications, where the determination of the time to specific events (such as the onset of a certain disease or death) for patients is crucial for clinical decision-making. Scoring systems are widely used for swift and efficient risk prediction. However, existing methods for constructing survival scores presume that data originates from a single source, posing privacy challenges in collaborations with multiple data owners. We propose a novel framework for building federated scoring systems for multi-site survival outcomes, ensuring both privacy and communication efficiency. We applied our approach to sites with heterogeneous survival data originating from emergency departments in Singapore and the United States. Additionally, we independently developed local scores at each site. In testing datasets from each participant site, our proposed federated scoring system consistently outperformed all local models, evidenced by higher integrated area under the receiver operating characteristic curve (iAUC) values, with a maximum improvement of 11.6%. Additionally, the federated score's time-dependent AUC(t) values showed advantages over local scores, exhibiting narrower confidence intervals (CIs) across most time points. The model developed through our proposed method exhibits effective performance on each local site, signifying noteworthy implications for healthcare research. Sites participating in our proposed federated scoring model training gained benefits by acquiring survival models with enhanced prediction accuracy and efficiency. This study demonstrates the effectiveness of our privacy-preserving federated survival score generation framework and its applicability to real-world heterogeneous survival data.

Real-world datasets often exhibit imbalanced data distribution, where certain class levels are severely underrepresented. In such cases, traditional pattern classifiers have shown a bias towards the majority class, impeding accurate predictions for the minority class. This paper introduces an imbalanced data-oriented approach using probabilistic neural networks (PNNs) with a skew normal probability kernel to address this major challenge. PNNs are known for providing probabilistic outputs, enabling quantification of prediction confidence and uncertainty handling. By leveraging the skew normal distribution, which offers increased flexibility, particularly for imbalanced and non-symmetric data, our proposed Skew Probabilistic Neural Networks (SkewPNNs) can better represent underlying class densities. To optimize the performance of the proposed approach on imbalanced datasets, hyperparameter fine-tuning is imperative. To this end, we employ a population-based heuristic algorithm, Bat optimization algorithms, for effectively exploring the hyperparameter space. We also prove the statistical consistency of the density estimates which suggests that the true distribution will be approached smoothly as the sample size increases. Experimental simulations have been conducted on different synthetic datasets, comparing various benchmark-imbalanced learners. Our real-data analysis shows that SkewPNNs substantially outperform state-of-the-art machine learning methods for both balanced and imbalanced datasets in most experimental settings.

Mobile health (mHealth) technologies aim to improve distal outcomes, such as clinical conditions, by optimizing proximal outcomes through just-in-time adaptive interventions. Contextual bandits provide a suitable framework for customizing such interventions according to individual time-varying contexts, intending to maximize cumulative proximal outcomes. However, unique challenges such as modeling count outcomes within bandit frameworks have hindered the widespread application of contextual bandits to mHealth studies. The current work addresses this challenge by leveraging count data models into online decision-making approaches. Specifically, we combine four common offline count data models (Poisson, negative binomial, zero-inflated Poisson, and zero-inflated negative binomial regressions) with Thompson sampling, a popular contextual bandit algorithm. The proposed algorithms are motivated by and evaluated on a real dataset from the Drink Less trial, where they are shown to improve user engagement with the mHealth system. The proposed methods are further evaluated on simulated data, achieving improvement in maximizing cumulative proximal outcomes over existing algorithms. Theoretical results on regret bounds are also derived. A user-friendly R package countts that implements the proposed methods for assessing contextual bandit algorithms is made publicly available at https://cran.r-project.org/web/packages/countts.

In recent years, reinforcement learning (RL) has acquired a prominent position in the space of health-related sequential decision-making, becoming an increasingly popular tool for delivering adaptive interventions (AIs). However, despite potential benefits, its real-life application is still limited, partly due to a poor synergy between the methodological and the applied communities. In this work, we provide the first unified survey on RL methods for learning AIs, using the common methodological umbrella of RL to bridge the two AI areas of dynamic treatment regimes and just-in-time adaptive interventions in mobile health. We outline similarities and differences between these two AI domains and discuss their implications for using RL. Finally, we leverage our experience in designing case studies in both areas to illustrate the tremendous collaboration opportunities between statistical, RL, and healthcare researchers in the space of AIs.

Federated learning (FL) has gained popularity in clinical research in recent years to facilitate privacy-preserving collaboration. Structured data, one of the most prevalent forms of clinical data, has experienced significant growth in volume concurrently, notably with the widespread adoption of electronic health records in clinical practice. This review examines FL applications on structured medical data, identifies contemporary limitations and discusses potential innovations. We searched five databases, SCOPUS, MEDLINE, Web of Science, Embase, and CINAHL, to identify articles that applied FL to structured medical data and reported results following the PRISMA guidelines. Each selected publication was evaluated from three primary perspectives, including data quality, modeling strategies, and FL frameworks. Out of the 1160 papers screened, 34 met the inclusion criteria, with each article consisting of one or more studies that used FL to handle structured clinical/medical data. Of these, 24 utilized data acquired from electronic health records, with clinical predictions and association studies being the most common clinical research tasks that FL was applied to. Only one article exclusively explored the vertical FL setting, while the remaining 33 explored the horizontal FL setting, with only 14 discussing comparisons between single-site (local) and FL (global) analysis. The existing FL applications on structured medical data lack sufficient evaluations of clinically meaningful benefits, particularly when compared to single-site analyses. Therefore, it is crucial for future FL applications to prioritize clinical motivations and develop designs and methodologies that can effectively support and aid clinical practice and research.

We propose FedScore, a privacy-preserving federated learning framework for scoring system generation across multiple sites to facilitate cross-institutional collaborations. The FedScore framework includes five modules: federated variable ranking, federated variable transformation, federated score derivation, federated model selection and federated model evaluation. To illustrate usage and assess FedScore's performance, we built a hypothetical global scoring system for mortality prediction within 30 days after a visit to an emergency department using 10 simulated sites divided from a tertiary hospital in Singapore. We employed a pre-existing score generator to construct 10 local scoring systems independently at each site and we also developed a scoring system using centralized data for comparison. We compared the acquired FedScore model's performance with that of other scoring models using the receiver operating characteristic (ROC) analysis. The FedScore model achieved an average area under the curve (AUC) value of 0.763 across all sites, with a standard deviation (SD) of 0.020. We also calculated the average AUC values and SDs for each local model, and the FedScore model showed promising accuracy and stability with a high average AUC value which was closest to the one of the pooled model and SD which was lower than that of most local models. This study demonstrates that FedScore is a privacy-preserving scoring system generator with potentially good generalizability.

The demand for emergency department (ED) services is increasing across the globe, particularly during the current COVID-19 pandemic. Clinical triage and risk assessment have become increasingly challenging due to the shortage of medical resources and the strain on hospital infrastructure caused by the pandemic. As a result of the widespread use of electronic health records (EHRs), we now have access to a vast amount of clinical data, which allows us to develop predictive models and decision support systems to address these challenges. To date, however, there are no widely accepted benchmark ED triage prediction models based on large-scale public EHR data. An open-source benchmarking platform would streamline research workflows by eliminating cumbersome data preprocessing, and facilitate comparisons among different studies and methodologies. In this paper, based on the Medical Information Mart for Intensive Care IV Emergency Department (MIMIC-IV-ED) database, we developed a publicly available benchmark suite for ED triage predictive models and created a benchmark dataset that contains over 400,000 ED visits from 2011 to 2019. We introduced three ED-based outcomes (hospitalization, critical outcomes, and 72-hour ED reattendance) and implemented a variety of popular methodologies, ranging from machine learning methods to clinical scoring systems. We evaluated and compared the performance of these methods against benchmark tasks. Our codes are open-source, allowing anyone with MIMIC-IV-ED data access to perform the same steps in data processing, benchmark model building, and experiments. This study provides future researchers with insights, suggestions, and protocols for managing raw data and developing risk triaging tools for emergency care.

Risk scores are widely used for clinical decision making and commonly generated from logistic regression models. Machine-learning-based methods may work well for identifying important predictors, but such 'black box' variable selection limits interpretability, and variable importance evaluated from a single model can be biased. We propose a robust and interpretable variable selection approach using the recently developed Shapley variable importance cloud (ShapleyVIC) that accounts for variability across models. Our approach evaluates and visualizes overall variable contributions for in-depth inference and transparent variable selection, and filters out non-significant contributors to simplify model building steps. We derive an ensemble variable ranking from variable contributions, which is easily integrated with an automated and modularized risk score generator, AutoScore, for convenient implementation. In a study of early death or unplanned readmission, ShapleyVIC selected 6 of 41 candidate variables to create a well-performing model, which had similar performance to a 16-variable model from machine-learning-based ranking.

Objective: Temporal electronic health records (EHRs) can be a wealth of information for secondary uses, such as clinical events prediction or chronic disease management. However, challenges exist for temporal data representation. We therefore sought to identify these challenges and evaluate novel methodologies for addressing them through a systematic examination of deep learning solutions. Methods: We searched five databases (PubMed, EMBASE, the Institute of Electrical and Electronics Engineers [IEEE] Xplore Digital Library, the Association for Computing Machinery [ACM] digital library, and Web of Science) complemented with hand-searching in several prestigious computer science conference proceedings. We sought articles that reported deep learning methodologies on temporal data representation in structured EHR data from January 1, 2010, to August 30, 2020. We summarized and analyzed the selected articles from three perspectives: nature of time series, methodology, and model implementation. Results: We included 98 articles related to temporal data representation using deep learning. Four major challenges were identified, including data irregularity, data heterogeneity, data sparsity, and model opacity. We then studied how deep learning techniques were applied to address these challenges. Finally, we discuss some open challenges arising from deep learning. Conclusion: Temporal EHR data present several major challenges for clinical prediction modeling and data utilization. To some extent, current deep learning solutions can address these challenges. Future studies can consider designing comprehensive and integrated solutions. Moreover, researchers should incorporate additional clinical domain knowledge into study designs and enhance the interpretability of the model to facilitate its implementation in clinical practice.