# Offline reinforcement learning with uncertainty for treatment strategies in sepsis

arXiv: https://arxiv.org/abs/2107.04491 · HTML: https://mlsanity.com/paper/2107.04491/

## Key facts

- Cited by 9 papers in the map (data through 14 Oct 2026).
- Placed in Safe offline RL, one of 13 directions in Offline RL and imitation learning from data.
- Builds on 9 of its 46 references that are in the map.
- First posted on arXiv 9 Jul 2021.

## Placed in

- Offline RL and imitation learning from data / [Safe offline RL](https://mlsanity.com/offlinerl/safe-offline-rl/)

## Builds on (most cited first, 9 of 9)

- [Offline Reinforcement Learning: Tutorial, Review, and Perspectives on Open Problems](https://mlsanity.com/paper/2005.01643/) (2020)
- [Conservative Q-Learning for Offline Reinforcement Learning](https://mlsanity.com/paper/2006.04779/) (2020)
- [Stabilizing Off-Policy Q-Learning via Bootstrapping Error Reduction](https://mlsanity.com/paper/1906.00949/) (2019)
- [MOPO: Model-based Offline Policy Optimization](https://mlsanity.com/paper/2005.13239/) (2020)
- [Deep Exploration via Bootstrapped DQN](https://mlsanity.com/paper/1602.04621/) (2016)
- [Uncertainty-Aware Reinforcement Learning for Collision Avoidance](https://mlsanity.com/paper/1702.01182/) (2017)
- [Explainable artificial intelligence model to predict acute critical illness from electronic health records](https://mlsanity.com/paper/1912.01266/) (2019)
- [Improving Sepsis Treatment Strategies by Combining Deep and Kernel-Based Reinforcement Learning](https://mlsanity.com/paper/1901.04670/) (2019)
- [Optimizing Sequential Medical Treatments with Auto-Encoding Heuristic Search in POMDPs](https://mlsanity.com/paper/1905.07465/) (2019)

## Built on by (most cited first, 9 of 9)

- [Elastic Decision Transformer](https://mlsanity.com/paper/2307.02484/) (2023)
- [Offline Reinforcement Learning for Safer Blood Glucose Control in People with Type 1 Diabetes](https://mlsanity.com/paper/2204.03376/) (2022)
- [The Health Gym: Synthetic Health-Related Datasets for the Development of Reinforcement Learning Algorithms](https://mlsanity.com/paper/2203.06369/) (2022)
- [Generating Synthetic Clinical Data that Capture Class Imbalanced Distributions with Generative Adversarial Networks: Example using Antiretroviral Therapy for HIV](https://mlsanity.com/paper/2208.08655/) (2022)
- [Synthetic Health-related Longitudinal Data with Mixed-type Variables Generated using Diffusion Models](https://mlsanity.com/paper/2303.12281/) (2023)
- [Formally Verifying and Explaining Sepsis Treatment Policies with COOL-MC](https://mlsanity.com/paper/2602.14505/) (2026)
- [How Consistent are Clinicians? Evaluating the Predictability of Sepsis Disease Progression with Dynamics Models](https://mlsanity.com/paper/2404.07148/) (2024)
- [The hidden risks of temporal resampling in clinical reinforcement learning](https://mlsanity.com/paper/2602.06603/) (2026)
- [EHR-MPC: Inference-Time Control for Sepsis Treatment with Generative Patient Digital Twins](https://mlsanity.com/paper/2607.08793/) (2026)

## Abstract (arXiv)

Guideline-based treatment for sepsis and septic shock is difficult because sepsis is a disparate range of life-threatening organ dysfunctions whose pathophysiology is not fully understood. Early intervention in sepsis is crucial for patient outcome, yet those interventions have adverse effects and are frequently overadministered. Greater personalization is necessary, as no single action is suitable for all patients. We present a novel application of reinforcement learning in which we identify optimal recommendations for sepsis treatment from data, estimate their confidence level, and identify treatment options infrequently observed in training data. Rather than a single recommendation, our method can present several treatment options. We examine learned policies and discover that reinforcement learning is biased against aggressive intervention due to the confounding relationship between mortality and level of treatment received. We mitigate this bias using subspace learning, and develop methodology that can yield more accurate learning policies across healthcare applications.