We propose a framework for building patient-specific treatment recommendation models, building on the large recent literature on learning patient-level causal models and inspired by the target trial paradigm of Hernan and Robins. We focus on safety and validity, including the crucial issue of causal identification when using observational data. We do not provide a specific model, but rather a way to integrate existing methods and know-how into a practical pipeline. We further provide a real world use-case of treatment optimization for patients with heart failure who develop acute kidney injury during hospitalization. The results suggest our pipeline can improve patient outcomes over the current treatment regime.

Clinical robustness is critical to the safe deployment of medical Large Language Models (LLMs), but key questions remain about how LLMs and humans may differ in response to the real-world variability typified by clinical settings. To address this, we introduce MedPerturb, a dataset designed to systematically evaluate medical LLMs under controlled perturbations of clinical input. MedPerturb consists of clinical vignettes spanning a range of pathologies, each transformed along three axes: (1) gender modifications (e.g., gender-swapping or gender-removal); (2) style variation (e.g., uncertain phrasing or colloquial tone); and (3) format changes (e.g., LLM-generated multi-turn conversations or summaries). With MedPerturb, we release a dataset of 800 clinical contexts grounded in realistic input variability, outputs from four LLMs, and three human expert reads per clinical context. We use MedPerturb in two case studies to reveal how shifts in gender identity cues, language style, or format reflect diverging treatment selections between humans and LLMs. We find that LLMs are more sensitive to gender and style perturbations while human annotators are more sensitive to LLM-generated format perturbations such as clinical summaries. Our results highlight the need for evaluation frameworks that go beyond static benchmarks to assess the similarity between human clinician and LLM decisions under the variability characteristic of clinical settings.

Fairness studies of algorithmic decision-making systems often simplify complex decision processes, such as bail or loan approvals, into binary classification tasks. However, these approaches overlook that such decisions are not inherently binary (e.g., approve or not approve bail or loan); they also involve non-binary treatment decisions (e.g., bail conditions or loan terms) that can influence the downstream outcomes (e.g., loan repayment or reoffending). In this paper, we argue that non-binary treatment decisions are integral to the decision process and controlled by decision-makers and, therefore, should be central to fairness analyses in algorithmic decision-making. We propose a causal framework that extends fairness analyses and explicitly distinguishes between decision-subjects' covariates and the treatment decisions. This specification allows decision-makers to use our framework to (i) measure treatment disparity and its downstream effects in historical data and, using counterfactual reasoning, (ii) mitigate the impact of past unfair treatment decisions when automating decision-making. We use our framework to empirically analyze four widely used loan approval datasets to reveal potential disparity in non-binary treatment decisions and their discriminatory impact on outcomes, highlighting the need to incorporate treatment decisions in fairness assessments. Moreover, by intervening in treatment decisions, we show that our framework effectively mitigates treatment discrimination from historical data to ensure fair risk score estimation and (non-binary) decision-making processes that benefit all stakeholders.

Over the past few years, the field of artificial intelligence (AI) has shown great promise in various domains, including medicine. A potential use case for AI in medicine is its application in managing advanced-stage cancer treatment, where limited evidence often makes treatment choices reliant on the personal expertise of the physicians. The complex nature of oncological disease processes and the multitude of factors that need to be considered when making treatment decisions make it difficult to rely solely on evidence-based trial data, which is often limited and may exclude certain patient populations. This results in physicians making decisions on a case-by-case basis, drawing on their experience of previous cases, which is not always objective and may be limited by the small number of cases they have observed. In this context, the use of clinical decision support systems (CDSS) using similaritybased AI approaches can potentially contribute to better oncology treatment by supporting physicians in the selection of treatment methods [1, 2]. One approach is Case-Based Reasoning (CBR), a subfield of AI that deals with experience-based problem solving.

Offline reinforcement learning has shown promise for solving tasks in safety-critical settings, such as clinical decision support. Its application, however, has been limited by the lack of interpretability and interactivity for clinicians. To address these challenges, we propose the medical decision transformer (MeDT), a novel and versatile framework based on the goal-conditioned reinforcement learning paradigm for sepsis treatment recommendation. MeDT uses the decision transformer architecture to learn a policy for drug dosage recommendation. During offline training, MeDT utilizes collected treatment trajectories to predict administered treatments for each time step, incorporating known treatment outcomes, target acuity scores, past treatment decisions, and current and past medical states. This analysis enables MeDT to capture complex dependencies among a patient's medical history, treatment decisions, outcomes, and short-term effects on stability. Our proposed conditioning uses acuity scores to address sparse reward issues and to facilitate clinician-model interactions, enhancing decision-making. Following training, MeDT can generate tailored treatment recommendations by conditioning on the desired positive outcome (survival) and user-specified short-term stability improvements. We carry out rigorous experiments on data from the MIMIC-III dataset and use off-policy evaluation to demonstrate that MeDT recommends interventions that outperform or are competitive with existing offline reinforcement learning methods while enabling a more interpretable, personalized and clinician-directed approach.

Sepsis, a life-threatening condition triggered by the body's exaggerated response to infection, demands urgent intervention to prevent severe complications. Existing machine learning methods for managing sepsis struggle in offline scenarios, exhibiting suboptimal performance with survival rates below 50%. This paper introduces the POSNEGDM -- ``Reinforcement Learning with Positive and Negative Demonstrations for Sequential Decision-Making" framework utilizing an innovative transformer-based model and a feedback reinforcer to replicate expert actions while considering individual patient characteristics. A mortality classifier with 96.7\% accuracy guides treatment decisions towards positive outcomes. The POSNEGDM framework significantly improves patient survival, saving 97.39% of patients, outperforming established machine learning algorithms (Decision Transformer and Behavioral Cloning) with survival rates of 33.4% and 43.5%, respectively. Additionally, ablation studies underscore the critical role of the transformer-based decision maker and the integration of a mortality classifier in enhancing overall survival rates. In summary, our proposed approach presents a promising avenue for enhancing sepsis treatment outcomes, contributing to improved patient care and reduced healthcare costs.

Prediction models are popular in medical research and practice. By predicting an outcome of interest for specific patients, these models may help inform difficult treatment decisions, and are often hailed as the poster children for personalized, data-driven healthcare. We show however, that using prediction models for decision making can lead to harmful decisions, even when the predictions exhibit good discrimination after deployment. These models are harmful self-fulfilling prophecies: their deployment harms a group of patients but the worse outcome of these patients does not invalidate the predictive power of the model. Our main result is a formal characterization of a set of such prediction models. Next we show that models that are well calibrated before and after deployment are useless for decision making as they made no change in the data distribution. These results point to the need to revise standard practices for validation, deployment and evaluation of prediction models that are used in medical decisions.

Personalized treatment decisions have become an integral part of modern medicine. Thereby, the aim is to make treatment decisions based on individual patient characteristics. Numerous methods have been developed for learning such policies from observational data that achieve the best outcome across a certain policy class. Yet these methods are rarely interpretable. However, interpretability is often a prerequisite for policy learning in clinical practice. In this paper, we propose an algorithm for interpretable off-policy learning via hyperbox search. In particular, our policies can be represented in disjunctive normal form (i.e., OR-of-ANDs) and are thus intelligible. We prove a universal approximation theorem that shows that our policy class is flexible enough to approximate any measurable function arbitrarily well. For optimization, we develop a tailored column generation procedure within a branch-and-bound framework. Using a simulation study, we demonstrate that our algorithm outperforms state-of-the-art methods from interpretable off-policy learning in terms of regret. Using real-word clinical data, we perform a user study with actual clinical experts, who rate our policies as highly interpretable.

Dynamic treatment regimes (DTRs) are used in medicine to tailor sequential treatment decisions to patients by considering patient heterogeneity. Common methods for learning optimal DTRs, however, have shortcomings: they are typically based on outcome prediction and not treatment effect estimation, or they use linear models that are restrictive for patient data from modern electronic health records. To address these shortcomings, we develop two novel methods for learning optimal DTRs that effectively handle complex patient data. We call our methods DTR-CT and DTR-CF. Our methods are based on a data-driven estimation of heterogeneous treatment effects using causal tree methods, specifically causal trees and causal forests, that learn non-linear relationships, control for time-varying confounding, are doubly robust, and explainable. To the best of our knowledge, our paper is the first that adapts causal tree methods for learning optimal DTRs. We evaluate our proposed methods using synthetic data and then apply them to real-world data from intensive care units. Our methods outperform state-of-the-art baselines in terms of cumulative regret and percentage of optimal decisions by a considerable margin. Our work improves treatment recommendations from electronic health record and is thus of direct relevance for personalized medicine.

In recent years, large amounts of electronic health records (EHRs) concerning chronic diseases, such as cancer, diabetes, and mental disease, have been collected to facilitate medical diagnosis. Modeling the dynamic properties of EHRs related to chronic diseases can be efficiently done using dynamic treatment regimes (DTRs), which are a set of sequential decision rules. While Reinforcement learning (RL) is a widely used method for creating DTRs, there is ongoing research in developing RL algorithms that can effectively handle large amounts of data. In this paper, we present a novel approach, a distributed Q-learning algorithm, for generating DTRs. The novelties of our research are as follows: 1) From a methodological perspective, we present a novel and scalable approach for generating DTRs by combining distributed learning with Q-learning. The proposed approach is specifically designed to handle large amounts of data and effectively generate DTRs. 2) From a theoretical standpoint, we provide generalization error bounds for the proposed distributed Q-learning algorithm, which are derived within the framework of statistical learning theory. These bounds quantify the relationships between sample size, prediction accuracy, and computational burden, providing insights into the performance of the algorithm. 3) From an applied perspective, we demonstrate the effectiveness of our proposed distributed Q-learning algorithm for DTRs by applying it to clinical cancer treatments. The results show that our algorithm outperforms both traditional linear Q-learning and commonly used deep Q-learning in terms of both prediction accuracy and computation cost.