An Empirical Evaluation of Prompting Strategies for Large Language Models in Zero-Shot Clinical Natural Language Processing
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Abstract (arXiv)
Large language models (LLMs) have shown remarkable capabilities in Natural Language Processing (NLP), especially in domains where labeled data is scarce or expensive, such as clinical domain. However, to unlock the clinical knowledge hidden in these LLMs, we need to design effective prompts that can guide them to perform specific clinical NLP tasks without any task-specific training data. This is known as in-context learning, which is an art and science that requires understanding the strengths and weaknesses of different LLMs and prompt engineering approaches. In this paper, we present a comprehensive and systematic experimental study on prompt engineering for five clinical NLP tasks: Clinical Sense Disambiguation, Biomedical Evidence Extraction, Coreference Resolution, Medication Status Extraction, and Medication Attribute Extraction. We assessed the prompts proposed in recent literature, including simple prefix, simple cloze, chain of thought, and anticipatory prompts, and introduced two new types of prompts, namely heuristic prompting and ensemble prompting. We evaluated the performance of these prompts on three state-of-the-art LLMs: GPT-3.5, BARD, and LLAMA2. We also contrasted zero-shot prompting with few-shot prompting, and provide novel insights and guidelines for prompt engineering for LLMs in clinical NLP. To the best of our knowledge, this is one of the first works on the empirical evaluation of different prompt engineering approaches for clinical NLP in this era of generative AI, and we hope that it will inspire and inform future research in this area.
Key facts. Cited by 19 papers in the map (data through 7 Oct 2026). Builds on 14 of its 27 references that are in the map. First posted on arXiv 14 Sep 2023.
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14 of 27 references.
References · 14
- 2022Training language models to follow instructions with human feedbackcited by 15,712
- 2023Llama 2: Open Foundation and Fine-Tuned Chat Modelscited by 12,865
- 2022Chain-of-Thought Prompting Elicits Reasoning in Large Language Modelscited by 12,302
- 2021Prefix-Tuning: Optimizing Continuous Prompts for Generationcited by 3,878
- 2021Pre-train, Prompt, and Predict: A Systematic Survey of Prompting Methods in Natural Language Processingcited by 2,222
- 2022Rethinking the Role of Demonstrations: What Makes In-Context Learning Work?cited by 1,413
- 2023A Prompt Pattern Catalog to Enhance Prompt Engineering with ChatGPTcited by 612
- 2022Large Language Models are Few-Shot Clinical Information Extractorscited by 206
- 2019Learning from Dialogue after Deployment: Feed Yourself, Chatbot!cited by 102
- 2018A Corpus with Multi-Level Annotations of Patients, Interventions and Outcomes to Support Language Processing for Medical Literaturecited by 79
- 2023Benchmarking large language models for biomedical natural language processing applications and recommendationscited by 78
- 2023Zero-shot Temporal Relation Extraction with ChatGPTcited by 52
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Citing papers per year: 2023: 1; 2024: 10; 2025: 2; 2026: 6.
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- 2023Chain of Empathy: Enhancing Empathetic Response of Large Language Models Based on Psychotherapy Modelscited by 24
- 2024Strategic Chain-of-Thought: Guiding Accurate Reasoning in LLMs through Strategy Elicitationcited by 19
- 2024LLM-3D Print: Large Language Models To Monitor and Control 3D Printingcited by 18
- 2024Prompt engineering paradigms for medical applications: scoping review and recommendations for better practicescited by 13
- 2025BARE: Leveraging Base Language Models for Few-Shot Synthetic Data Generationcited by 8
- 2024Clinical Insights: A Comprehensive Review of Language Models in Medicinecited by 6
- 2026Can AI Be a Good Peer Reviewer? A Survey of Peer Review Process, Evaluation, and the Futurecited by 6
- 2024Beyond Self-Consistency: Ensemble Reasoning Boosts Consistency and Accuracy of LLMs in Cancer Stagingcited by 4
- 2024Human Pose Descriptions and Subject-Focused Attention for Improved Zero-Shot Transfer in Human-Centric Classification Taskscited by 3
- 2024Improving Factual Accuracy of Neural Table-to-Text Output by Addressing Input Problems in ToTTocited by 3
- 2024Construction of Hyper-Relational Knowledge Graphs Using Pre-Trained Large Language Modelscited by 2
- 2024Evaluation of General Large Language Models in Contextually Assessing Semantic Concepts Extracted from Adult Critical Care Electronic Health Record Notescited by 1
7 more
- 2024Assertion Detection Large Language Model In-context Learning LoRA Fine-tuningcited by 1
- 2026Retrieve, Then Classify: Corpus-Grounded Automation of Clinical Value Set Authoringcited by 1
- 2025Logic Sketch Prompting (LSP): A Deterministic and Interpretable Prompting Methodcited by 0
- 2026Beyond Calibration: Confounding Pathology Limits Foundation Model Specificity in Abdominal Trauma CTcited by 0
- 2026Evaluating Zero-Shot and One-Shot Adaptation of Small Language Models in Leader-Follower Interactioncited by 0
- 2026Schema-Constrained Document-Level Event Argument Extraction with Lightweight LLM Fine-Tuningcited by 0
- 2026Constructing and Evaluating Clinical Reasoning Trajectories for Medical Agentcited by 0
- 2026Constructing and Evaluating Clinical Reasoning Trajectories for Medical Agent4 Sep 2026
- 2026Schema-Constrained Document-Level Event Argument Extraction with Lightweight LLM Fine-Tuning18 Jul 2026
- 2026Can AI Be a Good Peer Reviewer? A Survey of Peer Review Process, Evaluation, and the Future30 Apr 2026
- 2026Retrieve, Then Classify: Corpus-Grounded Automation of Clinical Value Set Authoring16 Apr 2026
- 2026Evaluating Zero-Shot and One-Shot Adaptation of Small Language Models in Leader-Follower Interaction26 Feb 2026
- 2026Beyond Calibration: Confounding Pathology Limits Foundation Model Specificity in Abdominal Trauma CT10 Feb 2026
- 2025Logic Sketch Prompting (LSP): A Deterministic and Interpretable Prompting Method24 Dec 2025
- 2025BARE: Leveraging Base Language Models for Few-Shot Synthetic Data Generation3 Feb 2025
- 2024Strategic Chain-of-Thought: Guiding Accurate Reasoning in LLMs through Strategy Elicitation5 Sep 2024
- 2024LLM-3D Print: Large Language Models To Monitor and Control 3D Printing26 Aug 2024
- 2024Clinical Insights: A Comprehensive Review of Language Models in Medicine21 Aug 2024
- 2024Prompt engineering paradigms for medical applications: scoping review and recommendations for better practices2 May 2024
7 more
- 2024Beyond Self-Consistency: Ensemble Reasoning Boosts Consistency and Accuracy of LLMs in Cancer Staging19 Apr 2024
- 2024Improving Factual Accuracy of Neural Table-to-Text Output by Addressing Input Problems in ToTTo5 Apr 2024
- 2024Construction of Hyper-Relational Knowledge Graphs Using Pre-Trained Large Language Models18 Mar 2024
- 2024Human Pose Descriptions and Subject-Focused Attention for Improved Zero-Shot Transfer in Human-Centric Classification Tasks11 Mar 2024
- 2024Assertion Detection Large Language Model In-context Learning LoRA Fine-tuning31 Jan 2024
- 2024Evaluation of General Large Language Models in Contextually Assessing Semantic Concepts Extracted from Adult Critical Care Electronic Health Record Notes24 Jan 2024
- 2023Chain of Empathy: Enhancing Empathetic Response of Large Language Models Based on Psychotherapy Models2 Nov 2023
- 2024Strategic Chain-of-Thought: Guiding Accurate Reasoning in LLMs through Strategy Elicitationcited by 19
- 2024Beyond Self-Consistency: Ensemble Reasoning Boosts Consistency and Accuracy of LLMs in Cancer Stagingcited by 4
- 2025Logic Sketch Prompting (LSP): A Deterministic and Interpretable Prompting Methodcited by 0
- 2026Constructing and Evaluating Clinical Reasoning Trajectories for Medical Agentcited by 0
- 2026Constructing and Evaluating Clinical Reasoning Trajectories for Medical Agent4 Sep 2026
- 2025Logic Sketch Prompting (LSP): A Deterministic and Interpretable Prompting Method24 Dec 2025
- 2024Strategic Chain-of-Thought: Guiding Accurate Reasoning in LLMs through Strategy Elicitation5 Sep 2024
- 2024Beyond Self-Consistency: Ensemble Reasoning Boosts Consistency and Accuracy of LLMs in Cancer Staging19 Apr 2024
- 2023Chain of Empathy: Enhancing Empathetic Response of Large Language Models Based on Psychotherapy Modelscited by 24
- 2024LLM-3D Print: Large Language Models To Monitor and Control 3D Printingcited by 18
- 2024Prompt engineering paradigms for medical applications: scoping review and recommendations for better practicescited by 13
- 2024Clinical Insights: A Comprehensive Review of Language Models in Medicinecited by 6
- 2026Can AI Be a Good Peer Reviewer? A Survey of Peer Review Process, Evaluation, and the Futurecited by 6
- 2024Human Pose Descriptions and Subject-Focused Attention for Improved Zero-Shot Transfer in Human-Centric Classification Taskscited by 3
- 2024Improving Factual Accuracy of Neural Table-to-Text Output by Addressing Input Problems in ToTTocited by 3
- 2024Construction of Hyper-Relational Knowledge Graphs Using Pre-Trained Large Language Modelscited by 2
- 2024Evaluation of General Large Language Models in Contextually Assessing Semantic Concepts Extracted from Adult Critical Care Electronic Health Record Notescited by 1
- 2024Assertion Detection Large Language Model In-context Learning LoRA Fine-tuningcited by 1
- 2026Retrieve, Then Classify: Corpus-Grounded Automation of Clinical Value Set Authoringcited by 1
- 2026Beyond Calibration: Confounding Pathology Limits Foundation Model Specificity in Abdominal Trauma CTcited by 0
12 most cited of 14 All 14 (JSON)
- 2026Schema-Constrained Document-Level Event Argument Extraction with Lightweight LLM Fine-Tuning18 Jul 2026
- 2026Can AI Be a Good Peer Reviewer? A Survey of Peer Review Process, Evaluation, and the Future30 Apr 2026
- 2026Retrieve, Then Classify: Corpus-Grounded Automation of Clinical Value Set Authoring16 Apr 2026
- 2026Evaluating Zero-Shot and One-Shot Adaptation of Small Language Models in Leader-Follower Interaction26 Feb 2026
- 2026Beyond Calibration: Confounding Pathology Limits Foundation Model Specificity in Abdominal Trauma CT10 Feb 2026
- 2024LLM-3D Print: Large Language Models To Monitor and Control 3D Printing26 Aug 2024
- 2024Clinical Insights: A Comprehensive Review of Language Models in Medicine21 Aug 2024
- 2024Prompt engineering paradigms for medical applications: scoping review and recommendations for better practices2 May 2024
- 2024Improving Factual Accuracy of Neural Table-to-Text Output by Addressing Input Problems in ToTTo5 Apr 2024
- 2024Construction of Hyper-Relational Knowledge Graphs Using Pre-Trained Large Language Models18 Mar 2024
- 2024Human Pose Descriptions and Subject-Focused Attention for Improved Zero-Shot Transfer in Human-Centric Classification Tasks11 Mar 2024
- 2024Assertion Detection Large Language Model In-context Learning LoRA Fine-tuning31 Jan 2024
12 newest of 14 All 14 (JSON)
Similar, not cited
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- 2025Dissecting Clinical Reasoning in Language Models: A Comparative Study of Prompts and Model Adaptation Strategies
- 2024LLMs in Biomedicine: A study on clinical Named Entity Recognition
- 2025AutoMedPrompt: A New Framework for Optimizing LLM Medical Prompts Using Textual Gradients
- 2026Relation Extraction Capabilities of LLMs on Clinical Text: A Bilingual Evaluation for English and Turkish
- 2023ClinicalGPT: Large Language Models Finetuned with Diverse Medical Data and Comprehensive Evaluation
- 2024Large Language Models Struggle in Token-Level Clinical Named Entity Recognition
- 2024The Limited Impact of Medical Adaptation of Large Language and Vision-Language Models
- 2025Why Chain of Thought Fails in Clinical Text Understanding