CDEMapper: Enhancing NIH Common Data Element Normalization using Large Language Models

Common Data Elements (CDEs) standardize data collection and sharing across studies, enhancing data interoperability and improving research reproducibility. However, implementing CDEs presents challenges due to the broad range and variety of data elements. This study aims to develop an effective and efficient mapping tool to bridge the gap between local data elements and National Institutes of Health (NIH) CDEs. We propose CDEMapper, a large language model (LLM) powered mapping tool designed to assist in mapping local data elements to NIH CDEs. CDEMapper has three core modules: (1) CDE indexing and embeddings. NIH CDEs were indexed and embedded to support semantic search; (2) CDE recommendations. The tool combines Elasticsearch (BM25 similarity methods) with state of the art GPT services to recommend candidate CDEs and their permissible values; and (3) Human review. Users review and select the NIH CDEs and values that best match their data elements and value sets. We evaluate the tool recommendation accuracy against manually annotated mapping results. CDEMapper offers a publicly available, LLM-powered, and intuitive user interface that consolidates essential and advanced mapping services into a streamlined pipeline. It provides a step by step, quality assured mapping workflow designed with a user-centered approach. The evaluation results demonstrated that augmenting BM25 with GPT embeddings and a ranker consistently enhances CDEMapper mapping accuracy in three different mapping settings across four evaluation datasets. This work opens up the potential of using LLMs to assist with CDE recommendation and human curation when aligning local data elements with NIH CDEs. Additionally, this effort enhances clinical research data interoperability and helps researchers better understand the gaps between local data elements and NIH CDEs.

Information Extraction from Clinical Notes: Are We Ready to Switch to Large Language Models?

Backgrounds: Information extraction (IE) is critical in clinical natural language processing (NLP). While large language models (LLMs) excel on generative tasks, their performance on extractive tasks remains debated. Methods: We investigated Named Entity Recognition (NER) and Relation Extraction (RE) using 1,588 clinical notes from four sources (UT Physicians, MTSamples, MIMIC-III, and i2b2). We developed an annotated corpus covering 4 clinical entities and 16 modifiers, and compared instruction-tuned LLaMA-2 and LLaMA-3 against BiomedBERT in terms of performance, generalizability, computational resources, and throughput to BiomedBERT. Results: LLaMA models outperformed BiomedBERT across datasets. With sufficient training data, LLaMA showed modest improvements (1% on NER, 1.5-3.7% on RE); improvements were larger with limited training data. On unseen i2b2 data, LLaMA-3-70B outperformed BiomedBERT by 7% (F1) on NER and 4% on RE. However, LLaMA models required more computing resources and ran up to 28 times slower. We implemented "Kiwi," a clinical IE package featuring both models, available at https://kiwi.clinicalnlp.org/. Conclusion: This study is among the first to develop and evaluate a comprehensive clinical IE system using open-source LLMs. Results indicate that LLaMA models outperform BiomedBERT for clinical NER and RE but with higher computational costs and lower throughputs. These findings highlight that choosing between LLMs and traditional deep learning methods for clinical IE applications should remain task-specific, taking into account both performance metrics and practical considerations such as available computing resources and the intended use case scenarios.

A Comparative Study of Recent Large Language Models on Generating Hospital Discharge Summaries for Lung Cancer Patients

Generating discharge summaries is a crucial yet time-consuming task in clinical practice, essential for conveying pertinent patient information and facilitating continuity of care. Recent advancements in large language models (LLMs) have significantly enhanced their capability in understanding and summarizing complex medical texts. This research aims to explore how LLMs can alleviate the burden of manual summarization, streamline workflow efficiencies, and support informed decision-making in healthcare settings. Clinical notes from a cohort of 1,099 lung cancer patients were utilized, with a subset of 50 patients for testing purposes, and 102 patients used for model fine-tuning. This study evaluates the performance of multiple LLMs, including GPT-3.5, GPT-4, GPT-4o, and LLaMA 3 8b, in generating discharge summaries. Evaluation metrics included token-level analysis (BLEU, ROUGE-1, ROUGE-2, ROUGE-L) and semantic similarity scores between model-generated summaries and physician-written gold standards. LLaMA 3 8b was further tested on clinical notes of varying lengths to examine the stability of its performance. The study found notable variations in summarization capabilities among LLMs. GPT-4o and fine-tuned LLaMA 3 demonstrated superior token-level evaluation metrics, while LLaMA 3 consistently produced concise summaries across different input lengths. Semantic similarity scores indicated GPT-4o and LLaMA 3 as leading models in capturing clinical relevance. This study contributes insights into the efficacy of LLMs for generating discharge summaries, highlighting LLaMA 3's robust performance in maintaining clarity and relevance across varying clinical contexts. These findings underscore the potential of automated summarization tools to enhance documentation precision and efficiency, ultimately improving patient care and operational capability in healthcare settings.

Generative AI in Health Economics and Outcomes Research: A Taxonomy of Key Definitions and Emerging Applications, an ISPOR Working Group Report

Objective: This article offers a taxonomy of generative artificial intelligence (AI) for health economics and outcomes research (HEOR), explores its emerging applications, and outlines methods to enhance the accuracy and reliability of AI-generated outputs. Methods: The review defines foundational generative AI concepts and highlights current HEOR applications, including systematic literature reviews, health economic modeling, real-world evidence generation, and dossier development. Approaches such as prompt engineering (zero-shot, few-shot, chain-of-thought, persona pattern prompting), retrieval-augmented generation, model fine-tuning, and the use of domain-specific models are introduced to improve AI accuracy and reliability. Results: Generative AI shows significant potential in HEOR, enhancing efficiency, productivity, and offering novel solutions to complex challenges. Foundation models are promising in automating complex tasks, though challenges remain in scientific reliability, bias, interpretability, and workflow integration. The article discusses strategies to improve the accuracy of these AI tools. Conclusion: Generative AI could transform HEOR by increasing efficiency and accuracy across various applications. However, its full potential can only be realized by building HEOR expertise and addressing the limitations of current AI technologies. As AI evolves, ongoing research and innovation will shape its future role in the field.

Suicide Phenotyping from Clinical Notes in Safety-Net Psychiatric Hospital Using Multi-Label Classification with Pre-Trained Language Models

Accurate identification and categorization of suicidal events can yield better suicide precautions, reducing operational burden, and improving care quality in high-acuity psychiatric settings. Pre-trained language models offer promise for identifying suicidality from unstructured clinical narratives. We evaluated the performance of four BERT-based models using two fine-tuning strategies (multiple single-label and single multi-label) for detecting coexisting suicidal events from 500 annotated psychiatric evaluation notes. The notes were labeled for suicidal ideation (SI), suicide attempts (SA), exposure to suicide (ES), and non-suicidal self-injury (NSSI). RoBERTa outperformed other models using binary relevance (acc=0.86, F1=0.78). MentalBERT (F1=0.74) also exceeded BioClinicalBERT (F1=0.72). RoBERTa fine-tuned with a single multi-label classifier further improved performance (acc=0.88, F1=0.81), highlighting that models pre-trained on domain-relevant data and the single multi-label classification strategy enhance efficiency and performance. Keywords: EHR-based Phynotyping; Natural Language Processing; Secondary Use of EHR Data; Suicide Classification; BERT-based Model; Psychiatry; Mental Health

Enhancing Large Language Models with Domain-specific Retrieval Augment Generation: A Case Study on Long-form Consumer Health Question Answering in Ophthalmology

Despite the potential of Large Language Models (LLMs) in medicine, they may generate responses lacking supporting evidence or based on hallucinated evidence. While Retrieval Augment Generation (RAG) is popular to address this issue, few studies implemented and evaluated RAG in downstream domain-specific applications. We developed a RAG pipeline with 70,000 ophthalmology-specific documents that retrieve relevant documents to augment LLMs during inference time. In a case study on long-form consumer health questions, we systematically evaluated the responses including over 500 references of LLMs with and without RAG on 100 questions with 10 healthcare professionals. The evaluation focuses on factuality of evidence, selection and ranking of evidence, attribution of evidence, and answer accuracy and completeness. LLMs without RAG provided 252 references in total. Of which, 45.3% hallucinated, 34.1% consisted of minor errors, and 20.6% were correct. In contrast, LLMs with RAG significantly improved accuracy (54.5% being correct) and reduced error rates (18.8% with minor hallucinations and 26.7% with errors). 62.5% of the top 10 documents retrieved by RAG were selected as the top references in the LLM response, with an average ranking of 4.9. The use of RAG also improved evidence attribution (increasing from 1.85 to 2.49 on a 5-point scale, P<0.001), albeit with slight decreases in accuracy (from 3.52 to 3.23, P=0.03) and completeness (from 3.47 to 3.27, P=0.17). The results demonstrate that LLMs frequently exhibited hallucinated and erroneous evidence in the responses, raising concerns for downstream applications in the medical domain. RAG substantially reduced the proportion of such evidence but encountered challenges.

Quantum Long Short-Term Memory for Drug Discovery

Quantum computing combined with machine learning (ML) is an extremely promising research area, with numerous studies demonstrating that quantum machine learning (QML) is expected to solve scientific problems more effectively than classical ML. In this work, we successfully apply QML to drug discovery, showing that QML can significantly improve model performance and achieve faster convergence compared to classical ML. Moreover, we demonstrate that the model accuracy of the QML improves as the number of qubits increases. We also introduce noise to the QML model and find that it has little effect on our experimental conclusions, illustrating the high robustness of the QML model. This work highlights the potential application of quantum computing to yield significant benefits for scientific advancement as the qubit quantity increase and quality improvement in the future.

Improving Entity Recognition Using Ensembles of Deep Learning and Fine-tuned Large Language Models: A Case Study on Adverse Event Extraction from Multiple Sources

Adverse event (AE) extraction following COVID-19 vaccines from text data is crucial for monitoring and analyzing the safety profiles of immunizations. Traditional deep learning models are adept at learning intricate feature representations and dependencies in sequential data, but often require extensive labeled data. In contrast, large language models (LLMs) excel in understanding contextual information, but exhibit unstable performance on named entity recognition tasks, possibly due to their broad but unspecific training. This study aims to evaluate the effectiveness of LLMs and traditional deep learning models in AE extraction, and to assess the impact of ensembling these models on performance. In this study, we utilized reports and posts from the VAERS (n=621), Twitter (n=9,133), and Reddit (n=131) as our corpora. Our goal was to extract three types of entities: "vaccine", "shot", and "ae". We explored and fine-tuned (except GPT-4) multiple LLMs, including GPT-2, GPT-3.5, GPT-4, and Llama-2, as well as traditional deep learning models like RNN and BioBERT. To enhance performance, we created ensembles of the three models with the best performance. For evaluation, we used strict and relaxed F1 scores to evaluate the performance for each entity type, and micro-average F1 was used to assess the overall performance. The ensemble model achieved the highest performance in "vaccine", "shot", and "ae" with strict F1-scores of 0.878, 0.930, and 0.925, respectively, along with a micro-average score of 0.903. In conclusion, this study demonstrates the effectiveness and robustness of ensembling fine-tuned traditional deep learning models and LLMs, for extracting AE-related information. This study contributes to the advancement of biomedical natural language processing, providing valuable insights into improving AE extraction from text data for pharmacovigilance and public health surveillance.

Geneverse: A collection of Open-source Multimodal Large Language Models for Genomic and Proteomic Research

The applications of large language models (LLMs) are promising for biomedical and healthcare research. Despite the availability of open-source LLMs trained using a wide range of biomedical data, current research on the applications of LLMs to genomics and proteomics is still limited. To fill this gap, we propose a collection of finetuned LLMs and multimodal LLMs (MLLMs), known as Geneverse, for three novel tasks in genomic and proteomic research. The models in Geneverse are trained and evaluated based on domain-specific datasets, and we use advanced parameter-efficient finetuning techniques to achieve the model adaptation for tasks including the generation of descriptions for gene functions, protein function inference from its structure, and marker gene selection from spatial transcriptomic data. We demonstrate that adapted LLMs and MLLMs perform well for these tasks and may outperform closed-source large-scale models based on our evaluations focusing on both truthfulness and structural correctness. All of the training strategies and base models we used are freely accessible.

Augmenting Biomedical Named Entity Recognition with General-domain Resources

Training a neural network-based biomedical named entity recognition (BioNER) model usually requires extensive and costly human annotations. While several studies have employed multi-task learning with multiple BioNER datasets to reduce human effort, this approach does not consistently yield performance improvements and may introduce label ambiguity in different biomedical corpora. We aim to tackle those challenges through transfer learning from easily accessible resources with fewer concept overlaps with biomedical datasets. In this paper, we proposed GERBERA, a simple-yet-effective method that utilized a general-domain NER dataset for training. Specifically, we performed multi-task learning to train a pre-trained biomedical language model with both the target BioNER dataset and the general-domain dataset. Subsequently, we fine-tuned the models specifically for the BioNER dataset. We systematically evaluated GERBERA on five datasets of eight entity types, collectively consisting of 81,410 instances. Despite using fewer biomedical resources, our models demonstrated superior performance compared to baseline models trained with multiple additional BioNER datasets. Specifically, our models consistently outperformed the baselines in six out of eight entity types, achieving an average improvement of 0.9% over the best baseline performance across eight biomedical entity types sourced from five different corpora. Our method was especially effective in amplifying performance on BioNER datasets characterized by limited data, with a 4.7% improvement in F1 scores on the JNLPBA-RNA dataset.