mlsanityData to 14 Oct 2026

Case-Based Reasoning Enhances the Predictive Power of LLMs in Drug-Drug Interaction

arXiv 2505.23034 ↗First posted 29 May 2025cs.AI cs.LGcited by 2

On the map: LLM reasoning → Clinical and biomedical applications

Abstract (arXiv)

Drug-drug interaction (DDI) prediction is critical for treatment safety. While large language models (LLMs) show promise in pharmaceutical tasks, their effectiveness in DDI prediction remains challenging. Inspired by the well-established clinical practice where physicians routinely reference similar historical cases to guide their decisions through case-based reasoning (CBR), we propose CBR-DDI, a novel framework that distills pharmacological principles from historical cases to improve LLM reasoning for DDI tasks. CBR-DDI constructs a knowledge repository by leveraging LLMs to extract pharmacological insights and graph neural networks (GNNs) to model drug associations. A hybrid retrieval mechanism and dual-layer knowledge-enhanced prompting allow LLMs to effectively retrieve and reuse relevant cases. We further introduce a representative sampling strategy for dynamic case refinement. Extensive experiments demonstrate that CBR-DDI achieves state-of-the-art performance, with a significant 28.7% accuracy improvement over both popular LLMs and CBR baseline, while maintaining high interpretability and flexibility.

Key facts. Cited by 2 papers in the map (data through 14 Oct 2026). Placed in Clinical and biomedical applications, one of 17 directions in LLM reasoning. Builds on 28 of its 67 references that are in the map. First posted on arXiv 29 May 2025.

Builds on

28 of 67 references.

Closest ancestors · 2

Same direction, newest first

  1. 2025K-Paths: Reasoning over Graph Paths for Drug Repurposing and Drug Interaction Prediction18 Feb
  2. 2024CaseGPT: a case reasoning framework based on language models and retrieval-augmented generation4 Jul

Other references · 26

  1. 2020Language Models are Few-Shot Learnerscited by 32,419
  2. 2024The Llama 3 Herd of Modelscited by 14,715
  3. 2019RoBERTa: A Robustly Optimized BERT Pretraining Approachcited by 13,372
  4. 2022Chain-of-Thought Prompting Elicits Reasoning in Large Language Modelscited by 12,459
  5. 2025DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learningcited by 6,330
  6. 2023Retrieval-Augmented Generation for Large Language Models: A Surveycited by 2,212
  7. 2023SelfCheckGPT: Zero-Resource Black-Box Hallucination Detection for Generative Large Language Modelscited by 810
  8. 2023Unifying Large Language Models and Knowledge Graphs: A Roadmapcited by 668
  9. 2023Reasoning on Graphs: Faithful and Interpretable Large Language Model Reasoningcited by 328
  10. 2023Think-on-Graph: Deep and Responsible Reasoning of Large Language Model on Knowledge Graphcited by 238
  11. 2018Modeling polypharmacy side effects with graph convolutional networkscited by 237
  12. 2024DS-Agent: Automated Data Science by Empowering Large Language Models with Case-Based Reasoningcited by 125
14 more
  1. 2023Can Knowledge Graphs Reduce Hallucinations in LLMs? : A Surveycited by 92
  2. 2024Buffer of Thoughts: Thought-Augmented Reasoning with Large Language Modelscited by 91
  3. 2017Knowledge Graph Completion via Complex Tensor Factorizationcited by 80
  4. 2024A Survey on Retrieval-Augmented Text Generation for Large Language Modelscited by 77
  5. 2023DrugChat: Towards Enabling ChatGPT-Like Capabilities on Drug Molecule Graphscited by 40
  6. 2020SumGNN: Multi-typed Drug Interaction Prediction via Efficient Knowledge Graph Summarizationcited by 33
  7. 2024Tx-LLM: A Large Language Model for Therapeuticscited by 25
  8. 2023Emerging Drug Interaction Prediction Enabled by Flow-based Graph Neural Network with Biomedical Networkcited by 24
  9. 2025Review of Case-Based Reasoning for LLM Agents: Theoretical Foundations, Architectural Components, and Cognitive Integrationcited by 12
  10. 2023Accurate and interpretable drug-drug interaction prediction enabled by knowledge subgraph learningcited by 9
  11. 2024Learning to Describe for Predicting Zero-shot Drug-Drug Interactionscited by 5
  12. 2025LLMs for Drug-Drug Interaction Prediction: A Comprehensive Comparisoncited by 5
  13. 2024Customized Subgraph Selection and Encoding for Drug-drug Interaction Predictioncited by 4
  14. 2024ExDDI: Explaining Drug-Drug Interaction Predictions with Natural Languagecited by 2

Built on by

Cited by year (2026 to 14 Oct)

Citing papers per year: 2026: 2.

2 papers.

  1. 2026CASCADE: Case-Based Continual Adaptation for Large Language Models During Deploymentcited by 1
  2. 2026MARD: Mirror-Augmented Reasoning Distillation for Mechanism-Level Drug-Drug Interaction Predictioncited by 0

Similar, not cited

Close in wording, no citation either way

  1. 2025How Well Do LLMs Understand Drug Mechanisms? A Knowledge + Reasoning Evaluation Dataset
  2. 2026Enhanced Drug-drug Interaction Prediction Using Adaptive Knowledge Integration
  3. 2026DrugReason: Dynamic Multi-View Reasoning over Knowledge Graph and Language Evidence for Drug Repurposing
  4. 2026RexDrug: Reliable Multi-Drug Combination Extraction through Reasoning-Enhanced LLMs
  5. 2026LLM-Guided Monte Carlo Tree Search over Knowledge Graphs: Composing Mechanistic Explanations for Drug-Disease Pairs
  6. 2026Tracing Pharmacological Knowledge In Large Language Models
  7. 2026UniD3: A Knowledge Graph-Enhanced RAG Framework for Drug-Disease Discovery and Reasoning
  8. 2026RES-MR: Risk-Aware Reasoning for Explainable and Safe Medication Recommendation