Reinforcement Learning in Dynamic Treatment Regimes Needs Critical Reexamination

In the rapidly changing healthcare landscape, the implementation of offline reinforcement learning (RL) in dynamic treatment regimes (DTRs) presents a mix of unprecedented opportunities and challenges. This position paper offers a critical examination of the current status of offline RL in the context of DTRs. We argue for a reassessment of applying RL in DTRs, citing concerns such as inconsistent and potentially inconclusive evaluation metrics, the absence of naive and supervised learning baselines, and the diverse choice of RL formulation in existing research. Through a case study with more than 17,000 evaluation experiments using a publicly available Sepsis dataset, we demonstrate that the performance of RL algorithms can significantly vary with changes in evaluation metrics and Markov Decision Process (MDP) formulations. Surprisingly, it is observed that in some instances, RL algorithms can be surpassed by random baselines subjected to policy evaluation methods and reward design. This calls for more careful policy evaluation and algorithm development in future DTR works. Additionally, we discussed potential enhancements toward more reliable development of RL-based dynamic treatment regimes and invited further discussion within the community. Code is available at https://github.com/GilesLuo/ReassessDTR.

DTR-Bench: An in silico Environment and Benchmark Platform for Reinforcement Learning Based Dynamic Treatment Regime

Reinforcement learning (RL) has garnered increasing recognition for its potential to optimise dynamic treatment regimes (DTRs) in personalised medicine, particularly for drug dosage prescriptions and medication recommendations. However, a significant challenge persists: the absence of a unified framework for simulating diverse healthcare scenarios and a comprehensive analysis to benchmark the effectiveness of RL algorithms within these contexts. To address this gap, we introduce \textit{DTR-Bench}, a benchmarking platform comprising four distinct simulation environments tailored to common DTR applications, including cancer chemotherapy, radiotherapy, glucose management in diabetes, and sepsis treatment. We evaluate various state-of-the-art RL algorithms across these settings, particularly highlighting their performance amidst real-world challenges such as pharmacokinetic/pharmacodynamic (PK/PD) variability, noise, and missing data. Our experiments reveal varying degrees of performance degradation among RL algorithms in the presence of noise and patient variability, with some algorithms failing to converge. Additionally, we observe that using temporal observation representations does not consistently lead to improved performance in DTR settings. Our findings underscore the necessity of developing robust, adaptive RL algorithms capable of effectively managing these complexities to enhance patient-specific healthcare. We have open-sourced our benchmark and code at https://github.com/GilesLuo/DTR-Bench.

A Survey of Few-Shot Learning for Biomedical Time Series

Advancements in wearable sensor technologies and the digitization of medical records have contributed to the unprecedented ubiquity of biomedical time series data. Data-driven models have tremendous potential to assist clinical diagnosis and improve patient care by improving long-term monitoring capabilities, facilitating early disease detection and intervention, as well as promoting personalized healthcare delivery. However, accessing extensively labeled datasets to train data-hungry deep learning models encounters many barriers, such as long-tail distribution of rare diseases, cost of annotation, privacy and security concerns, data-sharing regulations, and ethical considerations. An emerging approach to overcome the scarcity of labeled data is to augment AI methods with human-like capabilities to leverage past experiences to learn new tasks with limited examples, called few-shot learning. This survey provides a comprehensive review and comparison of few-shot learning methods for biomedical time series applications. The clinical benefits and limitations of such methods are discussed in relation to traditional data-driven approaches. This paper aims to provide insights into the current landscape of few-shot learning for biomedical time series and its implications for future research and applications.

Understanding Missingness in Time-series Electronic Health Records for Individualized Representation

With the widespread of machine learning models for healthcare applications, there is increased interest in building applications for personalized medicine. Despite the plethora of proposed research for personalized medicine, very few focus on representing missingness and learning from the missingness patterns in time-series Electronic Health Records (EHR) data. The lack of focus on missingness representation in an individualized way limits the full utilization of machine learning applications towards true personalization. In this brief communication, we highlight new insights into patterns of missingness with real-world examples and implications of missingness in EHRs. The insights in this work aim to bridge the gap between theoretical assumptions and practical observations in real-world EHRs. We hope this work will open new doors for exploring directions for better representation in predictive modelling for true personalization.

A Perspective on Individualized Treatment Effects Estimation from Time-series Health Data

The burden of diseases is rising worldwide, with unequal treatment efficacy for patient populations that are underrepresented in clinical trials. Healthcare, however, is driven by the average population effect of medical treatments and, therefore, operates in a "one-size-fits-all" approach, not necessarily what best fits each patient. These facts suggest a pressing need for methodologies to study individualized treatment effects (ITE) to drive personalized treatment. Despite the increased interest in machine-learning-driven ITE estimation models, the vast majority focus on tabular data with limited review and understanding of methodologies proposed for time-series electronic health records (EHRs). To this end, this work provides an overview of ITE works for time-series data and insights into future research. The work summarizes the latest work in the literature and reviews it in light of theoretical assumptions, types of treatment settings, and computational frameworks. Furthermore, this work discusses challenges and future research directions for ITEs in a time-series setting. We hope this work opens new directions and serves as a resource for understanding one of the exciting yet under-studied research areas.

IGNITE: Individualized GeNeration of Imputations in Time-series Electronic health records

Electronic Health Records present a valuable modality for driving personalized medicine, where treatment is tailored to fit individual-level differences. For this purpose, many data-driven machine learning and statistical models rely on the wealth of longitudinal EHRs to study patients' physiological and treatment effects. However, longitudinal EHRs tend to be sparse and highly missing, where missingness could also be informative and reflect the underlying patient's health status. Therefore, the success of data-driven models for personalized medicine highly depends on how the EHR data is represented from physiological data, treatments, and the missing values in the data. To this end, we propose a novel deep-learning model that learns the underlying patient dynamics over time across multivariate data to generate personalized realistic values conditioning on an individual's demographic characteristics and treatments. Our proposed model, IGNITE (Individualized GeNeration of Imputations in Time-series Electronic health records), utilises a conditional dual-variational autoencoder augmented with dual-stage attention to generate missing values for an individual. In IGNITE, we further propose a novel individualized missingness mask (IMM), which helps our model generate values based on the individual's observed data and missingness patterns. We further extend the use of IGNITE from imputing missingness to a personalized data synthesizer, where it generates missing EHRs that were never observed prior or even generates new patients for various applications. We validate our model on three large publicly available datasets and show that IGNITE outperforms state-of-the-art approaches in missing data reconstruction and task prediction.

DySurv: Dynamic Deep Learning Model for Survival Prediction in the ICU

Survival analysis helps approximate underlying distributions of time-to-events which in the case of critical care like in the ICU can be a powerful tool for dynamic mortality risk prediction. Extending beyond the classical Cox model, deep learning techniques have been leveraged over the last years relaxing the many constraints of their counterparts from statistical methods. In this work, we propose a novel conditional variational autoencoder-based method called DySurv which uses a combination of static and time-series measurements from patient electronic health records in estimating risk of death dynamically in the ICU. DySurv has been tested on standard benchmarks where it outperforms most existing methods including other deep learning methods and we evaluate it on a real-world patient database from MIMIC-IV. The predictive capacity of DySurv is consistent and the survival estimates remain disentangled across different datasets supporting the idea that dynamic deep learning models based on conditional variational inference in multi-task cases can be robust models for survival analysis.

How to Evaluate Semantic Communications for Images with ViTScore Metric?

Semantic communications (SC) have been expected to be a new paradigm shifting to catalyze the next generation communication, whose main concerns shift from accurate bit transmission to effective semantic information exchange in communications. However, the previous and widely-used metrics for images are not applicable to evaluate the image semantic similarity in SC. Classical metrics to measure the similarity between two images usually rely on the pixel level or the structural level, such as the PSNR and the MS-SSIM. Straightforwardly using some tailored metrics based on deep-learning methods in CV community, such as the LPIPS, is infeasible for SC. To tackle this, inspired by BERTScore in NLP community, we propose a novel metric for evaluating image semantic similarity, named Vision Transformer Score (ViTScore). We prove theoretically that ViTScore has 3 important properties, including symmetry, boundedness, and normalization, which make ViTScore convenient and intuitive for image measurement. To evaluate the performance of ViTScore, we compare ViTScore with 3 typical metrics (PSNR, MS-SSIM, and LPIPS) through 5 classes of experiments. Experimental results demonstrate that ViTScore can better evaluate the image semantic similarity than the other 3 typical metrics, which indicates that ViTScore is an effective performance metric when deployed in SC scenarios.

Explainable AI for clinical risk prediction: a survey of concepts, methods, and modalities

Recent advancements in AI applications to healthcare have shown incredible promise in surpassing human performance in diagnosis and disease prognosis. With the increasing complexity of AI models, however, concerns regarding their opacity, potential biases, and the need for interpretability. To ensure trust and reliability in AI systems, especially in clinical risk prediction models, explainability becomes crucial. Explainability is usually referred to as an AI system's ability to provide a robust interpretation of its decision-making logic or the decisions themselves to human stakeholders. In clinical risk prediction, other aspects of explainability like fairness, bias, trust, and transparency also represent important concepts beyond just interpretability. In this review, we address the relationship between these concepts as they are often used together or interchangeably. This review also discusses recent progress in developing explainable models for clinical risk prediction, highlighting the importance of quantitative and clinical evaluation and validation across multiple common modalities in clinical practice. It emphasizes the need for external validation and the combination of diverse interpretability methods to enhance trust and fairness. Adopting rigorous testing, such as using synthetic datasets with known generative factors, can further improve the reliability of explainability methods. Open access and code-sharing resources are essential for transparency and reproducibility, enabling the growth and trustworthiness of explainable research. While challenges exist, an end-to-end approach to explainability in clinical risk prediction, incorporating stakeholders from clinicians to developers, is essential for success.

All models are local: time to replace external validation with recurrent local validation

External validation is often recommended to ensure the generalizability of ML models. However, it neither guarantees generalizability nor equates to a model's clinical usefulness (the ultimate goal of any clinical decision-support tool). External validation is misaligned with current healthcare ML needs. First, patient data changes across time, geography, and facilities. These changes create significant volatility in the performance of a single fixed model (especially for deep learning models, which dominate clinical ML). Second, newer ML techniques, current market forces, and updated regulatory frameworks are enabling frequent updating and monitoring of individual deployed model instances. We submit that external validation is insufficient to establish ML models' safety or utility. Proposals to fix the external validation paradigm do not go far enough. Continued reliance on it as the ultimate test is likely to lead us astray. We propose the MLOps-inspired paradigm of recurring local validation as an alternative that ensures the validity of models while protecting against performance-disruptive data variability. This paradigm relies on site-specific reliability tests before every deployment, followed by regular and recurrent checks throughout the life cycle of the deployed algorithm. Initial and recurrent reliability tests protect against performance-disruptive distribution shifts, and concept drifts that jeopardize patient safety.