# COPE: Chain-Of-Thought Prediction Engine for Open-Source Large Language Model Based Stroke Outcome Prediction from Clinical Notes

arXiv: https://arxiv.org/abs/2512.02499 · HTML: https://mlsanity.com/paper/2512.02499/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Clinical and biomedical applications, one of 17 directions in LLM reasoning.
- Builds on 13 of its 30 references that are in the map.
- First posted on arXiv 2 Dec 2025.

## Placed in

- LLM reasoning / [Clinical and biomedical applications](https://mlsanity.com/lr/clinical-and-biomedical-applications/)

## Builds on (most cited first, 13 of 13)

- [The Llama 3 Herd of Models](https://mlsanity.com/paper/2407.21783/) (2024)
- [Chain-of-Thought Prompting Elicits Reasoning in Large Language Models](https://mlsanity.com/paper/2201.11903/) (2022)
- [Large Language Models are Zero-Shot Reasoners](https://mlsanity.com/paper/2205.11916/) (2022)
- [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)
- [Publicly Available Clinical BERT Embeddings](https://mlsanity.com/paper/1904.03323/) (2019)
- [ClinicalBERT: Modeling Clinical Notes and Predicting Hospital Readmission](https://mlsanity.com/paper/1904.05342/) (2019)
- [Scalable and accurate deep learning for electronic health records](https://mlsanity.com/paper/1801.07860/) (2018)
- [Large Language Models are Few-Shot Clinical Information Extractors](https://mlsanity.com/paper/2205.12689/) (2022)
- [Distilling Large Language Models for Matching Patients to Clinical Trials](https://mlsanity.com/paper/2312.09958/) (2023)
- [A Systematic Literature Review of Automated ICD Coding and Classification Systems using Discharge Summaries](https://mlsanity.com/paper/2107.10652/) (2021)
- [Towards unstructured mortality prediction with free-text clinical notes](https://mlsanity.com/paper/1911.08437/) (2019)
- [Position: Open and Closed Large Language Models in Healthcare](https://mlsanity.com/paper/2501.09906/) (2025)

## Abstract (arXiv)

Predicting outcomes in acute ischemic stroke (AIS) guides clinical decision-making, patient counseling, and resource allocation. Clinical notes contain rich contextual information, but their unstructured nature limits their use in traditional predictive models. We developed and evaluated the Chain-of-Thought (CoT) Outcome Prediction Engine (COPE), a reasoning-enhanced large language model framework, for predicting 90-day functional outcomes after AIS from unstructured clinical notes. This study included 464 AIS patients with discharge summaries and 90-day modified Rankin Scale (mRS) scores. COPE uses a two-step CoT framework based on sequential open-source LLaMA-3-8B models: the first generates clinical reasoning, and the second outputs an mRS prediction. We compared COPE with GPT-4.1, ClinicalBERT, a structured variable-based machine learning model (Clinical ML), and a single-step LLM without CoT. Performance was evaluated using mean absolute error (MAE), accuracy within +/-1 mRS point, and exact accuracy. COPE achieved an MAE of 1.01 (95% CI 0.92-1.11), +/-1 accuracy of 74.4% (69.9, 78.8%), and exact accuracy of 32.8% (28.0, 37.6%), comparable to GPT-4.1 and superior to ClinicalBERT [MAE 1.24 (1.13-1.36)], Clinical ML [1.28 (1.18-1.39)], and the single-step LLM [1.20 (1.09-1.33)]. Subgroup analyses showed consistent performance across sex and age, with slightly higher error among older patients, those undergoing thrombectomy, and those with longer summaries. These findings demonstrate that COPE, a lightweight, interpretable, and privacy-preserving open-source framework, provides an accurate and practical solution for outcome prediction from unstructured clinical text.