# ClinicalReTrial: Clinical Trial Redesign with Self-Evolving Agents

arXiv: https://arxiv.org/abs/2601.00290 · HTML: https://mlsanity.com/paper/2601.00290/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 18 of its 34 references that are in the map.
- First posted on arXiv 1 Jan 2026.

## Builds on (most cited first, 18 of 18)

- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [Retrieval-Augmented Generation for Knowledge-Intensive NLP Tasks](https://mlsanity.com/paper/2005.11401/) (2020)
- [ReAct: Synergizing Reasoning and Acting in Language Models](https://mlsanity.com/paper/2210.03629/) (2022)
- [Judging LLM-as-a-Judge with MT-Bench and Chatbot Arena](https://mlsanity.com/paper/2306.05685/) (2023)
- [A Unified Approach to Interpreting Model Predictions](https://mlsanity.com/paper/1705.07874/) (2017)
- [Scaling LLM Test-Time Compute Optimally can be More Effective than Scaling Model Parameters](https://mlsanity.com/paper/2408.03314/) (2024)
- [BioBERT: a pre-trained biomedical language representation model for biomedical text mining](https://mlsanity.com/paper/1901.08746/) (2019)
- [Large Language Models Encode Clinical Knowledge](https://mlsanity.com/paper/2212.13138/) (2022)
- [Least-to-Most Prompting Enables Complex Reasoning in Large Language Models](https://mlsanity.com/paper/2205.10625/) (2022)
- [Continual Lifelong Learning with Neural Networks: A Review](https://mlsanity.com/paper/1802.07569/) (2018)
- [Domain-Specific Language Model Pretraining for Biomedical Natural Language Processing](https://mlsanity.com/paper/2007.15779/) (2020)
- [Beam Search Strategies for Neural Machine Translation](https://mlsanity.com/paper/1702.01806/) (2017)
- [A Systematic Survey of Automatic Prompt Optimization Techniques](https://mlsanity.com/paper/2502.16923/) (2025)
- [A Survey on LLM-based Multi-Agent System: Recent Advances and New Frontiers in Application](https://mlsanity.com/paper/2412.17481/) (2024)
- [HINT: Hierarchical Interaction Network for Trial Outcome Prediction Leveraging Web Data](https://mlsanity.com/paper/2102.04252/) (2021)
- [CoD, Towards an Interpretable Medical Agent using Chain of Diagnosis](https://mlsanity.com/paper/2407.13301/) (2024)
- [Uncertainty Quantification on Clinical Trial Outcome Prediction](https://mlsanity.com/paper/2401.03482/) (2024)
- [AUTOCT: Automating Interpretable Clinical Trial Prediction with LLM Agents](https://mlsanity.com/paper/2506.04293/) (2025)

## Built on by (most cited first, 1 of 1)

- [Agentic Environment Engineering for Large Language Models: A Survey of Environment Modeling, Synthesis, Evaluation, and Application](https://mlsanity.com/paper/2606.12191/) (2026)

## Abstract (arXiv)

Clinical trials constitute a critical yet exceptionally challenging and costly stage of drug development (2.6B per drug), where protocols are encoded as complex natural language documents, motivating the use of AI systems beyond manual analysis. Existing AI methods accurately predict trial failure, but do not provide actionable remedies. To fill this gap, this paper proposes ClinicalReTrial, a multi-agent system that formulates clinical trial optimization as an iterative redesign problem on textual protocols. Our method integrates failure diagnosis, safety-aware modifications, and candidate evaluation in a closed-loop, reward-driven optimization framework. Serving the outcome prediction model as a simulation environment, ClinicalReTrial enables low-cost evaluation and dense reward signals for continuous self-improvement. We further propose a hierarchical memory that captures iteration-level feedback within trials and distills transferable redesign patterns across trials. Empirically, ClinicalReTrial turns 56.7% of failed protocols into predicted successes under the simulation environment, with a mean success probability gain of 7.4% at negligible cost (0.156 per trial). Extensive retrospective case studies further show that ClinicalReTrial recovers clinically meaningful modification patterns that align with real-world expert-driven protocol changes.