# Asclepius: An Adaptive Harness for Long-Horizon Clinical Agents

arXiv: https://arxiv.org/abs/2609.13543 · HTML: https://mlsanity.com/paper/2609.13543/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Medical and scientific domain agents, one of 16 directions in LLM agents and tool use.
- Builds on 12 of its 21 references that are in the map.
- First posted on arXiv 11 Sep 2026.

## Placed in

- LLM agents and tool use / [Medical and scientific domain agents](https://mlsanity.com/agents/medical-and-scientific-domain-agents/)

## Builds on (most cited first, 12 of 12)

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- [Meta-Harness: End-to-End Optimization of Model Harnesses](https://mlsanity.com/paper/2603.28052/) (2026)
- [AgentClinic: a multimodal agent benchmark to evaluate AI in simulated clinical environments](https://mlsanity.com/paper/2405.07960/) (2024)
- [Agent Hospital: A Simulacrum of Hospital with Evolvable Medical Agents](https://mlsanity.com/paper/2405.02957/) (2024)
- [AI Hospital: Benchmarking Large Language Models in a Multi-agent Medical Interaction Simulator](https://mlsanity.com/paper/2402.09742/) (2024)
- [Externalization in LLM Agents: A Unified Review of Memory, Skills, Protocols and Harness Engineering](https://mlsanity.com/paper/2604.08224/) (2026)
- [TxAgent: An AI Agent for Therapeutic Reasoning Across a Universe of Tools](https://mlsanity.com/paper/2503.10970/) (2025)
- [An Agentic System for Rare Disease Diagnosis with Traceable Reasoning](https://mlsanity.com/paper/2506.20430/) (2025)
- [EvoClinician: A Self-Evolving Agent for Multi-Turn Medical Diagnosis via Test-Time Evolutionary Learning](https://mlsanity.com/paper/2601.22964/) (2026)

## Abstract (arXiv)

LLM agents are predominantly benchmarked on short, single-task trajectories, yet real deployments run for hours under contention, surfacing a different class of failures. We use the Clinical Environment Simulator (CES), in which an agent manages an entire emergency-department shift under continuous time and resource pressure, as a testbed: long-horizon execution failures manifest measurably in a single rollout under structured, multi-dimensional grading. On CES, current agents reach the correct diagnosis in most cases yet fail to deliver complete and timely critical actions, revealing an execution gap. We attribute this gap to three long-horizon failure modes, each operationalized as a per-trace counter: instruction-adherence drift, treatment incompleteness, and a severity-equity gap in timeliness. We then introduce Asclepius, an adaptive agent scaffolding with a self-evolving harness that rewrites the operating manual between shifts from trace-level feedback, an externalized clinical skills library for high-stakes regimen knowledge, and three isolated subagents that partition per-turn decisions across the patient queue. On held-out batches never observed during harness evolution, Asclepius improves critical-action correctness by 22% (p = 0.024) over a strong baseline agent framework while preserving diagnostic accuracy, with consistent gains across five LLM judges from three model families; on the full ten-batch set, improvements reach 25% on critical actions and 13% on timeliness. The three failure modes form a coupled bottleneck: decisive reductions appear only when all three components act together.