Unmasking Bias and Inequities: A Systematic Review of Bias Detection and Mitigation in Healthcare Artificial Intelligence Using Electronic Health Records

Objectives: Artificial intelligence (AI) applications utilizing electronic health records (EHRs) have gained popularity, but they also introduce various types of bias. This study aims to systematically review the literature that address bias in AI research utilizing EHR data. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. We retrieved articles published between January 1, 2010, and October 31, 2022, from PubMed, Web of Science, and the Institute of Electrical and Electronics Engineers. We defined six major types of bias and summarized the existing approaches in bias handling. Results: Out of the 252 retrieved articles, 20 met the inclusion criteria for the final review. Five out of six bias were covered in this review: eight studies analyzed selection bias; six on implicit bias; five on confounding bias; four on measurement bias; two on algorithmic bias. For bias handling approaches, ten studies identified bias during model development, while seventeen presented methods to mitigate the bias. Discussion: Bias may infiltrate the AI application development process at various stages. Although this review discusses methods for addressing bias at different development stages, there is room for implementing additional effective approaches. Conclusion: Despite growing attention to bias in healthcare AI, research using EHR data on this topic is still limited. Detecting and mitigating AI bias with EHR data continues to pose challenges. Further research is needed to raise a standardized method that is generalizable and interpretable to detect, mitigate and evaluate bias in medical AI.Comment: 29 pages, 2 figures, 2 tables, 2 supplementary files, 66 reference

Representation learning for uncertainty-aware clinical decision support

Over the last decade, there has been an increasing trend towards digitalization in healthcare, where a growing amount of patient data is collected and stored electronically. These recorded data are known as electronic health records. They are the basis for state-of-the-art research on clinical decision support so that better patient care can be delivered with the help of advanced analytical techniques like machine learning. Among various technical fields in machine learning, representation learning is about learning good representations from raw data to extract useful information for downstream prediction tasks. Deep learning, a crucial class of methods in representation learning, has achieved great success in many fields such as computer vision and natural language processing. These technical breakthroughs would presumably further advance the research and development of data analytics in healthcare. This thesis addresses clinically relevant research questions by developing algorithms based on state-of-the-art representation learning techniques. When a patient visits the hospital, a physician will suggest a treatment in a deterministic manner. Meanwhile, uncertainty comes into play when the past statistics of treatment decisions from various physicians are analyzed, as they would possibly suggest different treatments, depending on their training and experiences. The uncertainty in clinical decision-making processes is the focus of this thesis. The models developed for supporting these processes will therefore have a probabilistic nature. More specifically, the predictions are predictive distributions in regression tasks and probability distributions over, e.g., different treatment decisions, in classification tasks. The first part of the thesis is concerned with prescriptive analytics to provide treatment recommendations. Apart from patient information and treatment decisions, the outcome after the respective treatment is included in learning treatment suggestions. The problem setting is known as learning individualized treatment rules and is formulated as a contextual bandit problem. A general framework for learning individualized treatment rules using data from observational studies is presented based on state-of-the-art representation learning techniques. From various offline evaluation methods, it is shown that the treatment policy in our proposed framework can demonstrate better performance than both physicians and competitive baselines. Subsequently, the uncertainty-aware regression models in diagnostic and predictive analytics are studied. Uncertainty-aware deep kernel learning models are proposed, which allow the estimation of the predictive uncertainty by a pipeline of neural networks and a sparse Gaussian process. By considering the input data structure, respective models are developed for diagnostic medical image data and sequential electronic health records. Various pre-training methods from representation learning are adapted to investigate their impacts on the proposed models. Through extensive experiments, it is shown that the proposed models delivered better performance than common architectures in most cases. More importantly, uncertainty-awareness of the proposed models is illustrated by systematically expressing higher confidence in more accurate predictions and less confidence in less accurate ones. The last part of the thesis is about missing data imputation in descriptive analytics, which provides essential evidence for subsequent decision-making processes. Rather than traditional mean and median imputation, a more advanced solution based on generative adversarial networks is proposed. The presented method takes the categorical nature of patient features into consideration, which enables the stabilization of the adversarial training. It is shown that the proposed method can better improve the predictive accuracy compared to traditional imputation baselines

Machine Learning and Integrative Analysis of Biomedical Big Data.

Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues

Use of deep learning to develop continuous-risk models for adverse event prediction from electronic health records

Early prediction of patient outcomes is important for targeting preventive care. This protocol describes a practical workflow for developing deep-learning risk models that can predict various clinical and operational outcomes from structured electronic health record (EHR) data. The protocol comprises five main stages: formal problem definition, data pre-processing, architecture selection, calibration and uncertainty, and generalizability evaluation. We have applied the workflow to four endpoints (acute kidney injury, mortality, length of stay and 30-day hospital readmission). The workflow can enable continuous (e.g., triggered every 6 h) and static (e.g., triggered at 24 h after admission) predictions. We also provide an open-source codebase that illustrates some key principles in EHR modeling. This protocol can be used by interdisciplinary teams with programming and clinical expertise to build deep-learning prediction models with alternate data sources and prediction tasks

Deep Risk Prediction and Embedding of Patient Data: Application to Acute Gastrointestinal Bleeding

Acute gastrointestinal bleeding is a common and costly condition, accounting for over 2.2 million hospital days and 19.2 billion dollars of medical charges annually. Risk stratification is a critical part of initial assessment of patients with acute gastrointestinal bleeding. Although all national and international guidelines recommend the use of risk-assessment scoring systems, they are not commonly used in practice, have sub-optimal performance, may be applied incorrectly, and are not easily updated. With the advent of widespread electronic health record adoption, longitudinal clinical data captured during the clinical encounter is now available. However, this data is often noisy, sparse, and heterogeneous. Unsupervised machine learning algorithms may be able to identify structure within electronic health record data while accounting for key issues with the data generation process: measurements missing-not-at-random and information captured in unstructured clinical note text. Deep learning tools can create electronic health record-based models that perform better than clinical risk scores for gastrointestinal bleeding and are well-suited for learning from new data. Furthermore, these models can be used to predict risk trajectories over time, leveraging the longitudinal nature of the electronic health record. The foundation of creating relevant tools is the definition of a relevant outcome measure; in acute gastrointestinal bleeding, a composite outcome of red blood cell transfusion, hemostatic intervention, and all-cause 30-day mortality is a relevant, actionable outcome that reflects the need for hospital-based intervention. However, epidemiological trends may affect the relevance and effectiveness of the outcome measure when applied across multiple settings and patient populations. Understanding the trends in practice, potential areas of disparities, and value proposition for using risk stratification in patients presenting to the Emergency Department with acute gastrointestinal bleeding is important in understanding how to best implement a robust, generalizable risk stratification tool. Key findings include a decrease in the rate of red blood cell transfusion since 2014 and disparities in access to upper endoscopy for patients with upper gastrointestinal bleeding by race/ethnicity across urban and rural hospitals. Projected accumulated savings of consistent implementation of risk stratification tools for upper gastrointestinal bleeding total approximately $1 billion 5 years after implementation. Most current risk scores were designed for use based on the location of the bleeding source: upper or lower gastrointestinal tract. However, the location of the bleeding source is not always clear at presentation. I develop and validate electronic health record based deep learning and machine learning tools for patients presenting with symptoms of acute gastrointestinal bleeding (e.g., hematemesis, melena, hematochezia), which is more relevant and useful in clinical practice. I show that they outperform leading clinical risk scores for upper and lower gastrointestinal bleeding, the Glasgow Blatchford Score and the Oakland score. While the best performing gradient boosted decision tree model has equivalent overall performance to the fully connected feedforward neural network model, at the very low risk threshold of 99% sensitivity the deep learning model identifies more very low risk patients. Using another deep learning model that can model longitudinal risk, the long-short-term memory recurrent neural network, need for transfusion of red blood cells can be predicted at every 4-hour interval in the first 24 hours of intensive care unit stay for high risk patients with acute gastrointestinal bleeding. Finally, for implementation it is important to find patients with symptoms of acute gastrointestinal bleeding in real time and characterize patients by risk using available data in the electronic health record. A decision rule-based electronic health record phenotype has equivalent performance as measured by positive predictive value compared to deep learning and natural language processing-based models, and after live implementation appears to have increased the use of the Acute Gastrointestinal Bleeding Clinical Care pathway. Patients with acute gastrointestinal bleeding but with other groups of disease concepts can be differentiated by directly mapping unstructured clinical text to a common ontology and treating the vector of concepts as signals on a knowledge graph; these patients can be differentiated using unbalanced diffusion earth mover’s distances on the graph. For electronic health record data with data missing not at random, MURAL, an unsupervised random forest-based method, handles data with missing values and generates visualizations that characterize patients with gastrointestinal bleeding. This thesis forms a basis for understanding the potential for machine learning and deep learning tools to characterize risk for patients with acute gastrointestinal bleeding. In the future, these tools may be critical in implementing integrated risk assessment to keep low risk patients out of the hospital and guide resuscitation and timely endoscopic procedures for patients at higher risk for clinical decompensation