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Mar 18

Panacea: A foundation model for clinical trial search, summarization, design, and recruitment

Clinical trials are fundamental in developing new drugs, medical devices, and treatments. However, they are often time-consuming and have low success rates. Although there have been initial attempts to create large language models (LLMs) for clinical trial design and patient-trial matching, these models remain task-specific and not adaptable to diverse clinical trial tasks. To address this challenge, we propose a clinical trial foundation model named Panacea, designed to handle multiple tasks, including trial search, trial summarization, trial design, and patient-trial matching. We also assemble a large-scale dataset, named TrialAlign, of 793,279 trial documents and 1,113,207 trial-related scientific papers, to infuse clinical knowledge into the model by pre-training. We further curate TrialInstruct, which has 200,866 of instruction data for fine-tuning. These resources enable Panacea to be widely applicable for a range of clinical trial tasks based on user requirements. We evaluated Panacea on a new benchmark, named TrialPanorama, which covers eight clinical trial tasks. Our method performed the best on seven of the eight tasks compared to six cutting-edge generic or medicine-specific LLMs. Specifically, Panacea showed great potential to collaborate with human experts in crafting the design of eligibility criteria, study arms, and outcome measures, in multi-round conversations. In addition, Panacea achieved 14.42% improvement in patient-trial matching, 41.78% to 52.02% improvement in trial search, and consistently ranked at the top for five aspects of trial summarization. Our approach demonstrates the effectiveness of Panacea in clinical trials and establishes a comprehensive resource, including training data, model, and benchmark, for developing clinical trial foundation models, paving the path for AI-based clinical trial development.

MedAgents: Large Language Models as Collaborators for Zero-shot Medical Reasoning

Large Language Models (LLMs), despite their remarkable progress across various general domains, encounter significant barriers in medicine and healthcare. This field faces unique challenges such as domain-specific terminologies and the reasoning over specialized knowledge. To address these obstinate issues, we propose a novel Multi-disciplinary Collaboration (MC) framework for the medical domain that leverages role-playing LLM-based agents who participate in a collaborative multi-round discussion, thereby enhancing LLM proficiency and reasoning capabilities. This training-free and interpretable framework encompasses five critical steps: gathering domain experts, proposing individual analyses, summarising these analyses into a report, iterating over discussions until a consensus is reached, and ultimately making a decision. Our work particularly focuses on the zero-shot scenario, our results on nine data sets (MedQA, MedMCQA, PubMedQA, and six subtasks from MMLU) establish that our proposed MC framework excels at mining and harnessing the medical expertise in LLMs, as well as extending its reasoning abilities. Based on these outcomes, we further conduct a human evaluation to pinpoint and categorize common errors within our method, as well as ablation studies aimed at understanding the impact of various factors on overall performance. Our code can be found at https://github.com/gersteinlab/MedAgents.

The Minimum Information about CLinical Artificial Intelligence Checklist for Generative Modeling Research (MI-CLAIM-GEN)

Recent advances in generative models, including large language models (LLMs), vision language models (VLMs), and diffusion models, have accelerated the field of natural language and image processing in medicine and marked a significant paradigm shift in how biomedical models can be developed and deployed. While these models are highly adaptable to new tasks, scaling and evaluating their usage presents new challenges not addressed in previous frameworks. In particular, the ability of these models to produce useful outputs with little to no specialized training data ("zero-" or "few-shot" approaches), as well as the open-ended nature of their outputs, necessitate the development of new guidelines for robust reporting of clinical generative model research. In response to gaps in standards and best practices for the development of clinical AI tools identified by US Executive Order 141103 and several emerging national networks for clinical AI evaluation, we begin to formalize some of these guidelines by building on the original MI-CLAIM checklist. The new checklist, MI-CLAIM-GEN (Table 1), aims to address differences in training, evaluation, interpretability, and reproducibility of new generative models compared to non-generative ("predictive") AI models. This MI-CLAIM-GEN checklist also seeks to clarify cohort selection reporting with unstructured clinical data and adds additional items on alignment with ethical standards for clinical AI research.

Towards Generalist Biomedical AI

Medicine is inherently multimodal, with rich data modalities spanning text, imaging, genomics, and more. Generalist biomedical artificial intelligence (AI) systems that flexibly encode, integrate, and interpret this data at scale can potentially enable impactful applications ranging from scientific discovery to care delivery. To enable the development of these models, we first curate MultiMedBench, a new multimodal biomedical benchmark. MultiMedBench encompasses 14 diverse tasks such as medical question answering, mammography and dermatology image interpretation, radiology report generation and summarization, and genomic variant calling. We then introduce Med-PaLM Multimodal (Med-PaLM M), our proof of concept for a generalist biomedical AI system. Med-PaLM M is a large multimodal generative model that flexibly encodes and interprets biomedical data including clinical language, imaging, and genomics with the same set of model weights. Med-PaLM M reaches performance competitive with or exceeding the state of the art on all MultiMedBench tasks, often surpassing specialist models by a wide margin. We also report examples of zero-shot generalization to novel medical concepts and tasks, positive transfer learning across tasks, and emergent zero-shot medical reasoning. To further probe the capabilities and limitations of Med-PaLM M, we conduct a radiologist evaluation of model-generated (and human) chest X-ray reports and observe encouraging performance across model scales. In a side-by-side ranking on 246 retrospective chest X-rays, clinicians express a pairwise preference for Med-PaLM M reports over those produced by radiologists in up to 40.50% of cases, suggesting potential clinical utility. While considerable work is needed to validate these models in real-world use cases, our results represent a milestone towards the development of generalist biomedical AI systems.

README: Bridging Medical Jargon and Lay Understanding for Patient Education through Data-Centric NLP

The advancement in healthcare has shifted focus toward patient-centric approaches, particularly in self-care and patient education, facilitated by access to Electronic Health Records (EHR). However, medical jargon in EHRs poses significant challenges in patient comprehension. To address this, we introduce a new task of automatically generating lay definitions, aiming to simplify complex medical terms into patient-friendly lay language. We first created the README dataset, an extensive collection of over 50,000 unique (medical term, lay definition) pairs and 300,000 mentions, each offering context-aware lay definitions manually annotated by domain experts. We have also engineered a data-centric Human-AI pipeline that synergizes data filtering, augmentation, and selection to improve data quality. We then used README as the training data for models and leveraged a Retrieval-Augmented Generation method to reduce hallucinations and improve the quality of model outputs. Our extensive automatic and human evaluations demonstrate that open-source mobile-friendly models, when fine-tuned with high-quality data, are capable of matching or even surpassing the performance of state-of-the-art closed-source large language models like ChatGPT. This research represents a significant stride in closing the knowledge gap in patient education and advancing patient-centric healthcare solutions.

CliBench: Multifaceted Evaluation of Large Language Models in Clinical Decisions on Diagnoses, Procedures, Lab Tests Orders and Prescriptions

The integration of Artificial Intelligence (AI), especially Large Language Models (LLMs), into the clinical diagnosis process offers significant potential to improve the efficiency and accessibility of medical care. While LLMs have shown some promise in the medical domain, their application in clinical diagnosis remains underexplored, especially in real-world clinical practice, where highly sophisticated, patient-specific decisions need to be made. Current evaluations of LLMs in this field are often narrow in scope, focusing on specific diseases or specialties and employing simplified diagnostic tasks. To bridge this gap, we introduce CliBench, a novel benchmark developed from the MIMIC IV dataset, offering a comprehensive and realistic assessment of LLMs' capabilities in clinical diagnosis. This benchmark not only covers diagnoses from a diverse range of medical cases across various specialties but also incorporates tasks of clinical significance: treatment procedure identification, lab test ordering and medication prescriptions. Supported by structured output ontologies, CliBench enables a precise and multi-granular evaluation, offering an in-depth understanding of LLM's capability on diverse clinical tasks of desired granularity. We conduct a zero-shot evaluation of leading LLMs to assess their proficiency in clinical decision-making. Our preliminary results shed light on the potential and limitations of current LLMs in clinical settings, providing valuable insights for future advancements in LLM-powered healthcare.

Improving Retrieval-Augmented Generation in Medicine with Iterative Follow-up Questions

The emergent abilities of large language models (LLMs) have demonstrated great potential in solving medical questions. They can possess considerable medical knowledge, but may still hallucinate and are inflexible in the knowledge updates. While Retrieval-Augmented Generation (RAG) has been proposed to enhance the medical question-answering capabilities of LLMs with external knowledge bases, it may still fail in complex cases where multiple rounds of information-seeking are required. To address such an issue, we propose iterative RAG for medicine (i-MedRAG), where LLMs can iteratively ask follow-up queries based on previous information-seeking attempts. In each iteration of i-MedRAG, the follow-up queries will be answered by a vanilla RAG system and they will be further used to guide the query generation in the next iteration. Our experiments show the improved performance of various LLMs brought by i-MedRAG compared with vanilla RAG on complex questions from clinical vignettes in the United States Medical Licensing Examination (USMLE), as well as various knowledge tests in the Massive Multitask Language Understanding (MMLU) dataset. Notably, our zero-shot i-MedRAG outperforms all existing prompt engineering and fine-tuning methods on GPT-3.5, achieving an accuracy of 69.68\% on the MedQA dataset. In addition, we characterize the scaling properties of i-MedRAG with different iterations of follow-up queries and different numbers of queries per iteration. Our case studies show that i-MedRAG can flexibly ask follow-up queries to form reasoning chains, providing an in-depth analysis of medical questions. To the best of our knowledge, this is the first-of-its-kind study on incorporating follow-up queries into medical RAG.

A Survey for Large Language Models in Biomedicine

Recent breakthroughs in large language models (LLMs) offer unprecedented natural language understanding and generation capabilities. However, existing surveys on LLMs in biomedicine often focus on specific applications or model architectures, lacking a comprehensive analysis that integrates the latest advancements across various biomedical domains. This review, based on an analysis of 484 publications sourced from databases including PubMed, Web of Science, and arXiv, provides an in-depth examination of the current landscape, applications, challenges, and prospects of LLMs in biomedicine, distinguishing itself by focusing on the practical implications of these models in real-world biomedical contexts. Firstly, we explore the capabilities of LLMs in zero-shot learning across a broad spectrum of biomedical tasks, including diagnostic assistance, drug discovery, and personalized medicine, among others, with insights drawn from 137 key studies. Then, we discuss adaptation strategies of LLMs, including fine-tuning methods for both uni-modal and multi-modal LLMs to enhance their performance in specialized biomedical contexts where zero-shot fails to achieve, such as medical question answering and efficient processing of biomedical literature. Finally, we discuss the challenges that LLMs face in the biomedicine domain including data privacy concerns, limited model interpretability, issues with dataset quality, and ethics due to the sensitive nature of biomedical data, the need for highly reliable model outputs, and the ethical implications of deploying AI in healthcare. To address these challenges, we also identify future research directions of LLM in biomedicine including federated learning methods to preserve data privacy and integrating explainable AI methodologies to enhance the transparency of LLMs.

The Limited Impact of Medical Adaptation of Large Language and Vision-Language Models

Several recent works seek to develop foundation models specifically for medical applications, adapting general-purpose large language models (LLMs) and vision-language models (VLMs) via continued pretraining on publicly available biomedical corpora. These works typically claim that such domain-adaptive pretraining (DAPT) improves performance on downstream medical tasks, such as answering medical licensing exam questions. In this paper, we compare ten public "medical" LLMs and two VLMs against their corresponding base models, arriving at a different conclusion: all medical VLMs and nearly all medical LLMs fail to consistently improve over their base models in the zero-/few-shot prompting and supervised fine-tuning regimes for medical question-answering (QA). For instance, across all tasks and model pairs we consider in the 3-shot setting, medical LLMs only outperform their base models in 22.7% of cases, reach a (statistical) tie in 36.8% of cases, and are significantly worse than their base models in the remaining 40.5% of cases. Our conclusions are based on (i) comparing each medical model head-to-head, directly against the corresponding base model; (ii) optimizing the prompts for each model separately in zero-/few-shot prompting; and (iii) accounting for statistical uncertainty in comparisons. While these basic practices are not consistently adopted in the literature, our ablations show that they substantially impact conclusions. Meanwhile, we find that after fine-tuning on specific QA tasks, medical LLMs can show performance improvements, but the benefits do not carry over to tasks based on clinical notes. Our findings suggest that state-of-the-art general-domain models may already exhibit strong medical knowledge and reasoning capabilities, and offer recommendations to strengthen the conclusions of future studies.

Familiarity: Better Evaluation of Zero-Shot Named Entity Recognition by Quantifying Label Shifts in Synthetic Training Data

Zero-shot named entity recognition (NER) is the task of detecting named entities of specific types (such as 'Person' or 'Medicine') without any training examples. Current research increasingly relies on large synthetic datasets, automatically generated to cover tens of thousands of distinct entity types, to train zero-shot NER models. However, in this paper, we find that these synthetic datasets often contain entity types that are semantically highly similar to (or even the same as) those in standard evaluation benchmarks. Because of this overlap, we argue that reported F1 scores for zero-shot NER overestimate the true capabilities of these approaches. Further, we argue that current evaluation setups provide an incomplete picture of zero-shot abilities since they do not quantify the label shift (i.e., the similarity of labels) between training and evaluation datasets. To address these issues, we propose Familiarity, a novel metric that captures both the semantic similarity between entity types in training and evaluation, as well as their frequency in the training data, to provide an estimate of label shift. It allows researchers to contextualize reported zero-shot NER scores when using custom synthetic training datasets. Further, it enables researchers to generate evaluation setups of various transfer difficulties for fine-grained analysis of zero-shot NER.

Adapting Language Models for Zero-shot Learning by Meta-tuning on Dataset and Prompt Collections

Large pre-trained language models (LMs) such as GPT-3 have acquired a surprising ability to perform zero-shot learning. For example, to classify sentiment without any training examples, we can "prompt" the LM with the review and the label description "Does the user like this movie?", and ask whether the next word is "yes" or "no". However, the next word prediction training objective is still misaligned with the target zero-shot learning objective. To address this weakness, we propose meta-tuning, which directly optimizes the zero-shot learning objective by fine-tuning pre-trained language models on a collection of datasets. We focus on classification tasks, and construct the meta-dataset by aggregating 43 existing datasets and annotating 441 label descriptions in a question-answering (QA) format. When evaluated on unseen tasks, meta-tuned models outperform a same-sized QA model and the previous SOTA zero-shot learning system based on natural language inference. Additionally, increasing parameter count from 220M to 770M improves AUC-ROC scores by 6.3%, and we forecast that even larger models would perform better. Therefore, measuring zero-shot learning performance on language models out-of-the-box might underestimate their true potential, and community-wide efforts on aggregating datasets and unifying their formats can help build models that answer prompts better.

Few-Shot Learning for Clinical Natural Language Processing Using Siamese Neural Networks

Clinical Natural Language Processing (NLP) has become an emerging technology in healthcare that leverages a large amount of free-text data in electronic health records (EHRs) to improve patient care, support clinical decisions, and facilitate clinical and translational science research. Recently, deep learning has achieved state-of-the-art performance in many clinical NLP tasks. However, training deep learning models usually requires large annotated datasets, which are normally not publicly available and can be time-consuming to build in clinical domains. Working with smaller annotated datasets is typical in clinical NLP and therefore, ensuring that deep learning models perform well is crucial for the models to be used in real-world applications. A widely adopted approach is fine-tuning existing Pre-trained Language Models (PLMs), but these attempts fall short when the training dataset contains only a few annotated samples. Few-Shot Learning (FSL) has recently been investigated to tackle this problem. Siamese Neural Network (SNN) has been widely utilized as an FSL approach in computer vision, but has not been studied well in NLP. Furthermore, the literature on its applications in clinical domains is scarce. In this paper, we propose two SNN-based FSL approaches for clinical NLP, including Pre-Trained SNN (PT-SNN) and SNN with Second-Order Embeddings (SOE-SNN). We evaluated the proposed approaches on two clinical tasks, namely clinical text classification and clinical named entity recognition. We tested three few-shot settings including 4-shot, 8-shot, and 16-shot learning. Both clinical NLP tasks were benchmarked using three PLMs, including BERT,BioBERT, and BioClinicalBERT. The experimental results verified the effectiveness of the proposed SNN-based FSL approaches in both NLP tasks.

LLM-MedQA: Enhancing Medical Question Answering through Case Studies in Large Language Models

Accurate and efficient question-answering systems are essential for delivering high-quality patient care in the medical field. While Large Language Models (LLMs) have made remarkable strides across various domains, they continue to face significant challenges in medical question answering, particularly in understanding domain-specific terminologies and performing complex reasoning. These limitations undermine their effectiveness in critical medical applications. To address these issues, we propose a novel approach incorporating similar case generation within a multi-agent medical question-answering (MedQA) system. Specifically, we leverage the Llama3.1:70B model, a state-of-the-art LLM, in a multi-agent architecture to enhance performance on the MedQA dataset using zero-shot learning. Our method capitalizes on the model's inherent medical knowledge and reasoning capabilities, eliminating the need for additional training data. Experimental results show substantial performance gains over existing benchmark models, with improvements of 7% in both accuracy and F1-score across various medical QA tasks. Furthermore, we examine the model's interpretability and reliability in addressing complex medical queries. This research not only offers a robust solution for medical question answering but also establishes a foundation for broader applications of LLMs in the medical domain.

Hippocrates: An Open-Source Framework for Advancing Large Language Models in Healthcare

The integration of Large Language Models (LLMs) into healthcare promises to transform medical diagnostics, research, and patient care. Yet, the progression of medical LLMs faces obstacles such as complex training requirements, rigorous evaluation demands, and the dominance of proprietary models that restrict academic exploration. Transparent, comprehensive access to LLM resources is essential for advancing the field, fostering reproducibility, and encouraging innovation in healthcare AI. We present Hippocrates, an open-source LLM framework specifically developed for the medical domain. In stark contrast to previous efforts, it offers unrestricted access to its training datasets, codebase, checkpoints, and evaluation protocols. This open approach is designed to stimulate collaborative research, allowing the community to build upon, refine, and rigorously evaluate medical LLMs within a transparent ecosystem. Also, we introduce Hippo, a family of 7B models tailored for the medical domain, fine-tuned from Mistral and LLaMA2 through continual pre-training, instruction tuning, and reinforcement learning from human and AI feedback. Our models outperform existing open medical LLMs models by a large-margin, even surpassing models with 70B parameters. Through Hippocrates, we aspire to unlock the full potential of LLMs not just to advance medical knowledge and patient care but also to democratize the benefits of AI research in healthcare, making them available across the globe.

Clinical Camel: An Open-Source Expert-Level Medical Language Model with Dialogue-Based Knowledge Encoding

Large Language Models (LLMs) present immense potential in the medical field, yet concerns over data privacy, regulatory compliance, and model stability restrict their widespread adoption. Although the distillation of high-performing closed-source LLMs has proven effective for general tasks, their application in healthcare is limited due to reduced domain knowledge and remnants of alignment behavior hindering clinical tasks. To address these challenges, we propose Dialogue-Based Knowledge Encoding (DBKE). DBKE enhances models' implicit knowledge base and primes them for conversational recall, augmenting their conversational capabilities and enabling a soft alignment for subsequent use cases. By transforming dense academic source text into synthetic dialogue, DBKE broadens the model's knowledge base and enables a soft alignment that guides downstream behaviours. We present Clinical Camel, an open-source, healthcare-focused conversational model, to showcase the effectiveness of DBKE. Clinical Camel outperforms GPT-3.5 on the United States Medical Licensing Examination (USMLE) Step 1 and Step 3 with scores of 53.2 % and 58.2 %, respectively, compared to GPT-3.5's scores of 36.1 % and 55.7 %. Clinical Camel adeptly handles multi-stage clinical case problems, provides adaptive counseling, and generates clinical notes. However, it is prone to hallucinations, which pose a significant obstacle in safety-critical settings. The performance of Clinical Camel underscores the importance of continued research and development of open-source models for the safe and effective integration of LLMs in healthcare settings.

Large Language Models to Identify Social Determinants of Health in Electronic Health Records

Social determinants of health (SDoH) have an important impact on patient outcomes but are incompletely collected from the electronic health records (EHR). This study researched the ability of large language models to extract SDoH from free text in EHRs, where they are most commonly documented, and explored the role of synthetic clinical text for improving the extraction of these scarcely documented, yet extremely valuable, clinical data. 800 patient notes were annotated for SDoH categories, and several transformer-based models were evaluated. The study also experimented with synthetic data generation and assessed for algorithmic bias. Our best-performing models were fine-tuned Flan-T5 XL (macro-F1 0.71) for any SDoH, and Flan-T5 XXL (macro-F1 0.70). The benefit of augmenting fine-tuning with synthetic data varied across model architecture and size, with smaller Flan-T5 models (base and large) showing the greatest improvements in performance (delta F1 +0.12 to +0.23). Model performance was similar on the in-hospital system dataset but worse on the MIMIC-III dataset. Our best-performing fine-tuned models outperformed zero- and few-shot performance of ChatGPT-family models for both tasks. These fine-tuned models were less likely than ChatGPT to change their prediction when race/ethnicity and gender descriptors were added to the text, suggesting less algorithmic bias (p<0.05). At the patient-level, our models identified 93.8% of patients with adverse SDoH, while ICD-10 codes captured 2.0%. Our method can effectively extracted SDoH information from clinic notes, performing better compare to GPT zero- and few-shot settings. These models could enhance real-world evidence on SDoH and aid in identifying patients needing social support.

Spoken Dialogue System for Medical Prescription Acquisition on Smartphone: Development, Corpus and Evaluation

Hospital information systems (HIS) have become an essential part of healthcare institutions and now incorporate prescribing support software. Prescription support software allows for structured information capture, which improves the safety, appropriateness and efficiency of prescriptions and reduces the number of adverse drug events (ADEs). However, such a system increases the amount of time physicians spend at a computer entering information instead of providing medical care. In addition, any new visiting clinician must learn to manage complex interfaces since each HIS has its own interfaces. In this paper, we present a natural language interface for e-prescribing software in the form of a spoken dialogue system accessible on a smartphone. This system allows prescribers to record their prescriptions verbally, a form of interaction closer to their usual practice. The system extracts the formal representation of the prescription ready to be checked by the prescribing software and uses the dialogue to request mandatory information, correct errors or warn of particular situations. Since, to the best of our knowledge, there is no existing voice-based prescription dialogue system, we present the system developed in a low-resource environment, focusing on dialogue modeling, semantic extraction and data augmentation. The system was evaluated in the wild with 55 participants. This evaluation showed that our system has an average prescription time of 66.15 seconds for physicians and 35.64 seconds for other experts, and a task success rate of 76\% for physicians and 72\% for other experts. All evaluation data were recorded and annotated to form PxCorpus, the first spoken drug prescription corpus that has been made fully available to the community (https://doi.org/10.5281/zenodo.6524162).

Closing the gap between open-source and commercial large language models for medical evidence summarization

Large language models (LLMs) hold great promise in summarizing medical evidence. Most recent studies focus on the application of proprietary LLMs. Using proprietary LLMs introduces multiple risk factors, including a lack of transparency and vendor dependency. While open-source LLMs allow better transparency and customization, their performance falls short compared to proprietary ones. In this study, we investigated to what extent fine-tuning open-source LLMs can further improve their performance in summarizing medical evidence. Utilizing a benchmark dataset, MedReview, consisting of 8,161 pairs of systematic reviews and summaries, we fine-tuned three broadly-used, open-sourced LLMs, namely PRIMERA, LongT5, and Llama-2. Overall, the fine-tuned LLMs obtained an increase of 9.89 in ROUGE-L (95% confidence interval: 8.94-10.81), 13.21 in METEOR score (95% confidence interval: 12.05-14.37), and 15.82 in CHRF score (95% confidence interval: 13.89-16.44). The performance of fine-tuned LongT5 is close to GPT-3.5 with zero-shot settings. Furthermore, smaller fine-tuned models sometimes even demonstrated superior performance compared to larger zero-shot models. The above trends of improvement were also manifested in both human and GPT4-simulated evaluations. Our results can be applied to guide model selection for tasks demanding particular domain knowledge, such as medical evidence summarization.

Enhancing CLIP with CLIP: Exploring Pseudolabeling for Limited-Label Prompt Tuning

Fine-tuning vision-language models (VLMs) like CLIP to downstream tasks is often necessary to optimize their performance. However, a major obstacle is the limited availability of labeled data. We study the use of pseudolabels, i.e., heuristic labels for unlabeled data, to enhance CLIP via prompt tuning. Conventional pseudolabeling trains a model on labeled data and then generates labels for unlabeled data. VLMs' zero-shot capabilities enable a ``second generation'' of pseudolabeling approaches that do not require task-specific training on labeled data. By using zero-shot pseudolabels as a source of supervision, we observe that learning paradigms such as semi-supervised, transductive zero-shot, and unsupervised learning can all be seen as optimizing the same loss function. This unified view enables the development of versatile training strategies that are applicable across learning paradigms. We investigate them on image classification tasks where CLIP exhibits limitations, by varying prompt modalities, e.g., textual or visual prompts, and learning paradigms. We find that (1) unexplored prompt tuning strategies that iteratively refine pseudolabels consistently improve CLIP accuracy, by 19.5 points in semi-supervised learning, by 28.4 points in transductive zero-shot learning, and by 15.2 points in unsupervised learning, and (2) unlike conventional semi-supervised pseudolabeling, which exacerbates model biases toward classes with higher-quality pseudolabels, prompt tuning leads to a more equitable distribution of per-class accuracy. The code to reproduce the experiments is at github.com/BatsResearch/menghini-enhanceCLIPwithCLIP-code.

Merlin: A Vision Language Foundation Model for 3D Computed Tomography

Over 85 million computed tomography (CT) scans are performed annually in the US, of which approximately one quarter focus on the abdomen. Given the current radiologist shortage, there is a large impetus to use artificial intelligence to alleviate the burden of interpreting these complex imaging studies. Prior state-of-the-art approaches for automated medical image interpretation leverage vision language models (VLMs). However, current medical VLMs are generally limited to 2D images and short reports, and do not leverage electronic health record (EHR) data for supervision. We introduce Merlin - a 3D VLM that we train using paired CT scans (6+ million images from 15,331 CTs), EHR diagnosis codes (1.8+ million codes), and radiology reports (6+ million tokens). We evaluate Merlin on 6 task types and 752 individual tasks. The non-adapted (off-the-shelf) tasks include zero-shot findings classification (31 findings), phenotype classification (692 phenotypes), and zero-shot cross-modal retrieval (image to findings and image to impressions), while model adapted tasks include 5-year disease prediction (6 diseases), radiology report generation, and 3D semantic segmentation (20 organs). We perform internal validation on a test set of 5,137 CTs, and external validation on 7,000 clinical CTs and on two public CT datasets (VerSe, TotalSegmentator). Beyond these clinically-relevant evaluations, we assess the efficacy of various network architectures and training strategies to depict that Merlin has favorable performance to existing task-specific baselines. We derive data scaling laws to empirically assess training data needs for requisite downstream task performance. Furthermore, unlike conventional VLMs that require hundreds of GPUs for training, we perform all training on a single GPU.

Eir: Thai Medical Large Language Models

We present Eir Thai Medical LLM, a large language model with 8 billion parameters, specifically designed to enhance the accuracy of handling medical tasks in the Thai language. This model focuses on providing clear and easy-to-understand answers for both healthcare professionals and patients, thereby improving the efficiency of diagnosis and treatment processes. Human evaluation was conducted to ensure that the model adheres to care standards and provides unbiased answers. To prioritize data security, the model is deployed within the hospital's internal network, ensuring both high security and faster processing speeds. The internal API connection is secured with encryption and strict authentication measures to prevent data leaks and unauthorized access. We evaluated several open-source large language models with 8 billion parameters on four medical benchmarks: MedQA, MedMCQA, PubMedQA, and the medical subset of MMLU. The best-performing baselines were used to develop Eir Thai Medical LLM. Our evaluation employed multiple questioning strategies, including zero-shot, few-shot, chain-of-thought reasoning, and ensemble/self-consistency voting methods. Our model outperformed commercially available Thai-language large language models by more than 10%. In addition, we developed enhanced model testing tailored for clinical use in Thai across 18 clinical tasks, where our model exceeded GPT-4o performance by more than 11%

IryoNLP at MEDIQA-CORR 2024: Tackling the Medical Error Detection & Correction Task On the Shoulders of Medical Agents

In natural language processing applied to the clinical domain, utilizing large language models has emerged as a promising avenue for error detection and correction on clinical notes, a knowledge-intensive task for which annotated data is scarce. This paper presents MedReAct'N'MedReFlex, which leverages a suite of four LLM-based medical agents. The MedReAct agent initiates the process by observing, analyzing, and taking action, generating trajectories to guide the search to target a potential error in the clinical notes. Subsequently, the MedEval agent employs five evaluators to assess the targeted error and the proposed correction. In cases where MedReAct's actions prove insufficient, the MedReFlex agent intervenes, engaging in reflective analysis and proposing alternative strategies. Finally, the MedFinalParser agent formats the final output, preserving the original style while ensuring the integrity of the error correction process. One core component of our method is our RAG pipeline based on our ClinicalCorp corpora. Among other well-known sources containing clinical guidelines and information, we preprocess and release the open-source MedWiki dataset for clinical RAG application. Our results demonstrate the central role of our RAG approach with ClinicalCorp leveraged through the MedReAct'N'MedReFlex framework. It achieved the ninth rank on the MEDIQA-CORR 2024 final leaderboard.

MedS^3: Towards Medical Small Language Models with Self-Evolved Slow Thinking

Medical language models (MLMs) have become pivotal in advancing medical natural language processing. However, prior models that rely on pre-training or supervised fine-tuning often exhibit low data efficiency and limited practicality in real-world clinical applications. While OpenAIs O1 highlights test-time scaling in mathematics, attempts to replicate this approach in medicine typically distill responses from GPT-series models to open-source models, focusing primarily on multiple-choice tasks. This strategy, though straightforward, neglects critical concerns like data privacy and realistic deployment in clinical settings. In this work, we present a deployable, small-scale medical language model, \mone, designed for long-chain reasoning in clinical tasks using a self-evolution paradigm. Starting with a seed dataset of around 8,000 instances spanning five domains and 16 datasets, we prompt a base policy model to perform Monte Carlo Tree Search (MCTS) to construct verifiable reasoning chains. Each reasoning step is assigned an evolution rollout value, allowing verified trajectories to train the policy model and the reward model. During inference, the policy model generates multiple responses, and the reward model selects the one with the highest reward score. Experiments on eleven evaluation datasets demonstrate that \mone outperforms prior open-source models by 2 points, with the addition of the reward model further boosting performance (sim13 points), surpassing GPT-4o-mini. Code and data are available at https://github.com/pixas/MedSSS.

Do We Still Need Clinical Language Models?

Although recent advances in scaling large language models (LLMs) have resulted in improvements on many NLP tasks, it remains unclear whether these models trained primarily with general web text are the right tool in highly specialized, safety critical domains such as clinical text. Recent results have suggested that LLMs encode a surprising amount of medical knowledge. This raises an important question regarding the utility of smaller domain-specific language models. With the success of general-domain LLMs, is there still a need for specialized clinical models? To investigate this question, we conduct an extensive empirical analysis of 12 language models, ranging from 220M to 175B parameters, measuring their performance on 3 different clinical tasks that test their ability to parse and reason over electronic health records. As part of our experiments, we train T5-Base and T5-Large models from scratch on clinical notes from MIMIC III and IV to directly investigate the efficiency of clinical tokens. We show that relatively small specialized clinical models substantially outperform all in-context learning approaches, even when finetuned on limited annotated data. Further, we find that pretraining on clinical tokens allows for smaller, more parameter-efficient models that either match or outperform much larger language models trained on general text. We release the code and the models used under the PhysioNet Credentialed Health Data license and data use agreement.

Instance Needs More Care: Rewriting Prompts for Instances Yields Better Zero-Shot Performance

Enabling large language models (LLMs) to perform tasks in zero-shot has been an appealing goal owing to its labor-saving (i.e., requiring no task-specific annotations); as such, zero-shot prompting approaches also enjoy better task generalizability. To improve LLMs' zero-shot performance, prior work has focused on devising more effective task instructions (e.g., ``let's think step by step'' ). However, we argue that, in order for an LLM to solve them correctly in zero-shot, individual test instances need more carefully designed and customized instructions. To this end, we propose PRoMPTd, an approach that rewrites the task prompt for each individual test input to be more specific, unambiguous, and complete, so as to provide better guidance to the task LLM. We evaluated PRoMPTd on eight datasets covering tasks including arithmetics, logical reasoning, and code generation, using GPT-4 as the task LLM. Notably, PRoMPTd achieves an absolute improvement of around 10% on the complex MATH dataset and 5% on the code generation task on HumanEval, outperforming conventional zero-shot methods. In addition, we also showed that the rewritten prompt can provide better interpretability of how the LLM resolves each test instance, which can potentially be leveraged as a defense mechanism against adversarial prompting. The source code and dataset can be obtained from https://github.com/salokr/PRoMPTd

A Comparative Study of Open-Source Large Language Models, GPT-4 and Claude 2: Multiple-Choice Test Taking in Nephrology

In recent years, there have been significant breakthroughs in the field of natural language processing, particularly with the development of large language models (LLMs). These LLMs have showcased remarkable capabilities on various benchmarks. In the healthcare field, the exact role LLMs and other future AI models will play remains unclear. There is a potential for these models in the future to be used as part of adaptive physician training, medical co-pilot applications, and digital patient interaction scenarios. The ability of AI models to participate in medical training and patient care will depend in part on their mastery of the knowledge content of specific medical fields. This study investigated the medical knowledge capability of LLMs, specifically in the context of internal medicine subspecialty multiple-choice test-taking ability. We compared the performance of several open-source LLMs (Koala 7B, Falcon 7B, Stable-Vicuna 13B, and Orca Mini 13B), to GPT-4 and Claude 2 on multiple-choice questions in the field of Nephrology. Nephrology was chosen as an example of a particularly conceptually complex subspecialty field within internal medicine. The study was conducted to evaluate the ability of LLM models to provide correct answers to nephSAP (Nephrology Self-Assessment Program) multiple-choice questions. The overall success of open-sourced LLMs in answering the 858 nephSAP multiple-choice questions correctly was 17.1% - 25.5%. In contrast, Claude 2 answered 54.4% of the questions correctly, whereas GPT-4 achieved a score of 73.3%. We show that current widely used open-sourced LLMs do poorly in their ability for zero-shot reasoning when compared to GPT-4 and Claude 2. The findings of this study potentially have significant implications for the future of subspecialty medical training and patient care.

OpenMedLM: Prompt engineering can out-perform fine-tuning in medical question-answering with open-source large language models

LLMs have become increasingly capable at accomplishing a range of specialized-tasks and can be utilized to expand equitable access to medical knowledge. Most medical LLMs have involved extensive fine-tuning, leveraging specialized medical data and significant, thus costly, amounts of computational power. Many of the top performing LLMs are proprietary and their access is limited to very few research groups. However, open-source (OS) models represent a key area of growth for medical LLMs due to significant improvements in performance and an inherent ability to provide the transparency and compliance required in healthcare. We present OpenMedLM, a prompting platform which delivers state-of-the-art (SOTA) performance for OS LLMs on medical benchmarks. We evaluated a range of OS foundation LLMs (7B-70B) on four medical benchmarks (MedQA, MedMCQA, PubMedQA, MMLU medical-subset). We employed a series of prompting strategies, including zero-shot, few-shot, chain-of-thought (random selection and kNN selection), and ensemble/self-consistency voting. We found that OpenMedLM delivers OS SOTA results on three common medical LLM benchmarks, surpassing the previous best performing OS models that leveraged computationally costly extensive fine-tuning. The model delivers a 72.6% accuracy on the MedQA benchmark, outperforming the previous SOTA by 2.4%, and achieves 81.7% accuracy on the MMLU medical-subset, establishing itself as the first OS LLM to surpass 80% accuracy on this benchmark. Our results highlight medical-specific emergent properties in OS LLMs which have not yet been documented to date elsewhere, and showcase the benefits of further leveraging prompt engineering to improve the performance of accessible LLMs for medical applications.

PRISM: Patient Records Interpretation for Semantic Clinical Trial Matching using Large Language Models

Clinical trial matching is the task of identifying trials for which patients may be potentially eligible. Typically, this task is labor-intensive and requires detailed verification of patient electronic health records (EHRs) against the stringent inclusion and exclusion criteria of clinical trials. This process is manual, time-intensive, and challenging to scale up, resulting in many patients missing out on potential therapeutic options. Recent advancements in Large Language Models (LLMs) have made automating patient-trial matching possible, as shown in multiple concurrent research studies. However, the current approaches are confined to constrained, often synthetic datasets that do not adequately mirror the complexities encountered in real-world medical data. In this study, we present the first, end-to-end large-scale empirical evaluation of clinical trial matching using real-world EHRs. Our study showcases the capability of LLMs to accurately match patients with appropriate clinical trials. We perform experiments with proprietary LLMs, including GPT-4 and GPT-3.5, as well as our custom fine-tuned model called OncoLLM and show that OncoLLM, despite its significantly smaller size, not only outperforms GPT-3.5 but also matches the performance of qualified medical doctors. All experiments were carried out on real-world EHRs that include clinical notes and available clinical trials from a single cancer center in the United States.

EHRSHOT: An EHR Benchmark for Few-Shot Evaluation of Foundation Models

While the general machine learning (ML) community has benefited from public datasets, tasks, and models, the progress of ML in healthcare has been hampered by a lack of such shared assets. The success of foundation models creates new challenges for healthcare ML by requiring access to shared pretrained models to validate performance benefits. We help address these challenges through three contributions. First, we publish a new dataset, EHRSHOT, which contains deidentified structured data from the electronic health records (EHRs) of 6,739 patients from Stanford Medicine. Unlike MIMIC-III/IV and other popular EHR datasets, EHRSHOT is longitudinal and not restricted to ICU/ED patients. Second, we publish the weights of CLMBR-T-base, a 141M parameter clinical foundation model pretrained on the structured EHR data of 2.57M patients. We are one of the first to fully release such a model for coded EHR data; in contrast, most prior models released for clinical data (e.g. GatorTron, ClinicalBERT) only work with unstructured text and cannot process the rich, structured data within an EHR. We provide an end-to-end pipeline for the community to validate and build upon its performance. Third, we define 15 few-shot clinical prediction tasks, enabling evaluation of foundation models on benefits such as sample efficiency and task adaptation. Our model and dataset are available via a research data use agreement from the Stanford AIMI Center. Code to reproduce our results are available at our Github repo: https://github.com/som-shahlab/ehrshot-benchmark

Named Clinical Entity Recognition Benchmark

This technical report introduces a Named Clinical Entity Recognition Benchmark for evaluating language models in healthcare, addressing the crucial natural language processing (NLP) task of extracting structured information from clinical narratives to support applications like automated coding, clinical trial cohort identification, and clinical decision support. The leaderboard provides a standardized platform for assessing diverse language models, including encoder and decoder architectures, on their ability to identify and classify clinical entities across multiple medical domains. A curated collection of openly available clinical datasets is utilized, encompassing entities such as diseases, symptoms, medications, procedures, and laboratory measurements. Importantly, these entities are standardized according to the Observational Medical Outcomes Partnership (OMOP) Common Data Model, ensuring consistency and interoperability across different healthcare systems and datasets, and a comprehensive evaluation of model performance. Performance of models is primarily assessed using the F1-score, and it is complemented by various assessment modes to provide comprehensive insights into model performance. The report also includes a brief analysis of models evaluated to date, highlighting observed trends and limitations. By establishing this benchmarking framework, the leaderboard aims to promote transparency, facilitate comparative analyses, and drive innovation in clinical entity recognition tasks, addressing the need for robust evaluation methods in healthcare NLP.

What Does This Acronym Mean? Introducing a New Dataset for Acronym Identification and Disambiguation

Acronyms are the short forms of phrases that facilitate conveying lengthy sentences in documents and serve as one of the mainstays of writing. Due to their importance, identifying acronyms and corresponding phrases (i.e., acronym identification (AI)) and finding the correct meaning of each acronym (i.e., acronym disambiguation (AD)) are crucial for text understanding. Despite the recent progress on this task, there are some limitations in the existing datasets which hinder further improvement. More specifically, limited size of manually annotated AI datasets or noises in the automatically created acronym identification datasets obstruct designing advanced high-performing acronym identification models. Moreover, the existing datasets are mostly limited to the medical domain and ignore other domains. In order to address these two limitations, we first create a manually annotated large AI dataset for scientific domain. This dataset contains 17,506 sentences which is substantially larger than previous scientific AI datasets. Next, we prepare an AD dataset for scientific domain with 62,441 samples which is significantly larger than the previous scientific AD dataset. Our experiments show that the existing state-of-the-art models fall far behind human-level performance on both datasets proposed by this work. In addition, we propose a new deep learning model that utilizes the syntactical structure of the sentence to expand an ambiguous acronym in a sentence. The proposed model outperforms the state-of-the-art models on the new AD dataset, providing a strong baseline for future research on this dataset.

Fine-tuning Large Language Models for Adaptive Machine Translation

This paper presents the outcomes of fine-tuning Mistral 7B, a general-purpose large language model (LLM), for adaptive machine translation (MT). The fine-tuning process involves utilising a combination of zero-shot and one-shot translation prompts within the medical domain. The primary objective is to enhance real-time adaptive MT capabilities of Mistral 7B, enabling it to adapt translations to the required domain at inference time. The results, particularly for Spanish-to-English MT, showcase the efficacy of the fine-tuned model, demonstrating quality improvements in both zero-shot and one-shot translation scenarios, surpassing Mistral 7B's baseline performance. Notably, the fine-tuned Mistral outperforms ChatGPT "gpt-3.5-turbo" in zero-shot translation while achieving comparable one-shot translation quality. Moreover, the zero-shot translation of the fine-tuned Mistral matches NLLB 3.3B's performance, and its one-shot translation quality surpasses that of NLLB 3.3B. These findings emphasise the significance of fine-tuning efficient LLMs like Mistral 7B to yield high-quality zero-shot translations comparable to task-oriented models like NLLB 3.3B. Additionally, the adaptive gains achieved in one-shot translation are comparable to those of commercial LLMs such as ChatGPT. Our experiments demonstrate that, with a relatively small dataset of 20,000 segments that incorporate a mix of zero-shot and one-shot prompts, fine-tuning significantly enhances Mistral's in-context learning ability, especially for real-time adaptive MT.

Can open source large language models be used for tumor documentation in Germany? -- An evaluation on urological doctors' notes

Tumor documentation in Germany is largely done manually, requiring reading patient records and entering data into structured databases. Large language models (LLMs) could potentially enhance this process by improving efficiency and reliability. This evaluation tests eleven different open source LLMs with sizes ranging from 1-70 billion model parameters on three basic tasks of the tumor documentation process: identifying tumor diagnoses, assigning ICD-10 codes, and extracting the date of first diagnosis. For evaluating the LLMs on these tasks, a dataset of annotated text snippets based on anonymized doctors' notes from urology was prepared. Different prompting strategies were used to investigate the effect of the number of examples in few-shot prompting and to explore the capabilities of the LLMs in general. The models Llama 3.1 8B, Mistral 7B, and Mistral NeMo 12 B performed comparably well in the tasks. Models with less extensive training data or having fewer than 7 billion parameters showed notably lower performance, while larger models did not display performance gains. Examples from a different medical domain than urology could also improve the outcome in few-shot prompting, which demonstrates the ability of LLMs to handle tasks needed for tumor documentation. Open source LLMs show a strong potential for automating tumor documentation. Models from 7-12 billion parameters could offer an optimal balance between performance and resource efficiency. With tailored fine-tuning and well-designed prompting, these models might become important tools for clinical documentation in the future. The code for the evaluation is available from https://github.com/stefan-m-lenz/UroLlmEval. We also release the dataset as a new valuable resource that addresses the shortage of authentic and easily accessible benchmarks in German-language medical NLP.

Large Language Models as Biomedical Hypothesis Generators: A Comprehensive Evaluation

The rapid growth of biomedical knowledge has outpaced our ability to efficiently extract insights and generate novel hypotheses. Large language models (LLMs) have emerged as a promising tool to revolutionize knowledge interaction and potentially accelerate biomedical discovery. In this paper, we present a comprehensive evaluation of LLMs as biomedical hypothesis generators. We construct a dataset of background-hypothesis pairs from biomedical literature, carefully partitioned into training, seen, and unseen test sets based on publication date to mitigate data contamination. Using this dataset, we assess the hypothesis generation capabilities of top-tier instructed models in zero-shot, few-shot, and fine-tuning settings. To enhance the exploration of uncertainty, a crucial aspect of scientific discovery, we incorporate tool use and multi-agent interactions in our evaluation framework. Furthermore, we propose four novel metrics grounded in extensive literature review to evaluate the quality of generated hypotheses, considering both LLM-based and human assessments. Our experiments yield two key findings: 1) LLMs can generate novel and validated hypotheses, even when tested on literature unseen during training, and 2) Increasing uncertainty through multi-agent interactions and tool use can facilitate diverse candidate generation and improve zero-shot hypothesis generation performance. However, we also observe that the integration of additional knowledge through few-shot learning and tool use may not always lead to performance gains, highlighting the need for careful consideration of the type and scope of external knowledge incorporated. These findings underscore the potential of LLMs as powerful aids in biomedical hypothesis generation and provide valuable insights to guide further research in this area.

Large Language Models Illuminate a Progressive Pathway to Artificial Healthcare Assistant: A Review

With the rapid development of artificial intelligence, large language models (LLMs) have shown promising capabilities in mimicking human-level language comprehension and reasoning. This has sparked significant interest in applying LLMs to enhance various aspects of healthcare, ranging from medical education to clinical decision support. However, medicine involves multifaceted data modalities and nuanced reasoning skills, presenting challenges for integrating LLMs. This paper provides a comprehensive review on the applications and implications of LLMs in medicine. It begins by examining the fundamental applications of general-purpose and specialized LLMs, demonstrating their utilities in knowledge retrieval, research support, clinical workflow automation, and diagnostic assistance. Recognizing the inherent multimodality of medicine, the review then focuses on multimodal LLMs, investigating their ability to process diverse data types like medical imaging and EHRs to augment diagnostic accuracy. To address LLMs' limitations regarding personalization and complex clinical reasoning, the paper explores the emerging development of LLM-powered autonomous agents for healthcare. Furthermore, it summarizes the evaluation methodologies for assessing LLMs' reliability and safety in medical contexts. Overall, this review offers an extensive analysis on the transformative potential of LLMs in modern medicine. It also highlights the pivotal need for continuous optimizations and ethical oversight before these models can be effectively integrated into clinical practice. Visit https://github.com/mingze-yuan/Awesome-LLM-Healthcare for an accompanying GitHub repository containing latest papers.

Demystifying Large Language Models for Medicine: A Primer

Large language models (LLMs) represent a transformative class of AI tools capable of revolutionizing various aspects of healthcare by generating human-like responses across diverse contexts and adapting to novel tasks following human instructions. Their potential application spans a broad range of medical tasks, such as clinical documentation, matching patients to clinical trials, and answering medical questions. In this primer paper, we propose an actionable guideline to help healthcare professionals more efficiently utilize LLMs in their work, along with a set of best practices. This approach consists of several main phases, including formulating the task, choosing LLMs, prompt engineering, fine-tuning, and deployment. We start with the discussion of critical considerations in identifying healthcare tasks that align with the core capabilities of LLMs and selecting models based on the selected task and data, performance requirements, and model interface. We then review the strategies, such as prompt engineering and fine-tuning, to adapt standard LLMs to specialized medical tasks. Deployment considerations, including regulatory compliance, ethical guidelines, and continuous monitoring for fairness and bias, are also discussed. By providing a structured step-by-step methodology, this tutorial aims to equip healthcare professionals with the tools necessary to effectively integrate LLMs into clinical practice, ensuring that these powerful technologies are applied in a safe, reliable, and impactful manner.

Towards Accurate Differential Diagnosis with Large Language Models

An accurate differential diagnosis (DDx) is a cornerstone of medical care, often reached through an iterative process of interpretation that combines clinical history, physical examination, investigations and procedures. Interactive interfaces powered by Large Language Models (LLMs) present new opportunities to both assist and automate aspects of this process. In this study, we introduce an LLM optimized for diagnostic reasoning, and evaluate its ability to generate a DDx alone or as an aid to clinicians. 20 clinicians evaluated 302 challenging, real-world medical cases sourced from the New England Journal of Medicine (NEJM) case reports. Each case report was read by two clinicians, who were randomized to one of two assistive conditions: either assistance from search engines and standard medical resources, or LLM assistance in addition to these tools. All clinicians provided a baseline, unassisted DDx prior to using the respective assistive tools. Our LLM for DDx exhibited standalone performance that exceeded that of unassisted clinicians (top-10 accuracy 59.1% vs 33.6%, [p = 0.04]). Comparing the two assisted study arms, the DDx quality score was higher for clinicians assisted by our LLM (top-10 accuracy 51.7%) compared to clinicians without its assistance (36.1%) (McNemar's Test: 45.7, p < 0.01) and clinicians with search (44.4%) (4.75, p = 0.03). Further, clinicians assisted by our LLM arrived at more comprehensive differential lists than those without its assistance. Our study suggests that our LLM for DDx has potential to improve clinicians' diagnostic reasoning and accuracy in challenging cases, meriting further real-world evaluation for its ability to empower physicians and widen patients' access to specialist-level expertise.

Text-driven Adaptation of Foundation Models for Few-shot Surgical Workflow Analysis

Purpose: Surgical workflow analysis is crucial for improving surgical efficiency and safety. However, previous studies rely heavily on large-scale annotated datasets, posing challenges in cost, scalability, and reliance on expert annotations. To address this, we propose Surg-FTDA (Few-shot Text-driven Adaptation), designed to handle various surgical workflow analysis tasks with minimal paired image-label data. Methods: Our approach has two key components. First, Few-shot selection-based modality alignment selects a small subset of images and aligns their embeddings with text embeddings from the downstream task, bridging the modality gap. Second, Text-driven adaptation leverages only text data to train a decoder, eliminating the need for paired image-text data. This decoder is then applied to aligned image embeddings, enabling image-related tasks without explicit image-text pairs. Results: We evaluate our approach to generative tasks (image captioning) and discriminative tasks (triplet recognition and phase recognition). Results show that Surg-FTDA outperforms baselines and generalizes well across downstream tasks. Conclusion: We propose a text-driven adaptation approach that mitigates the modality gap and handles multiple downstream tasks in surgical workflow analysis, with minimal reliance on large annotated datasets. The code and dataset will be released in https://github.com/CAMMA-public/Surg-FTDA

Medical Adaptation of Large Language and Vision-Language Models: Are We Making Progress?

Several recent works seek to develop foundation models specifically for medical applications, adapting general-purpose large language models (LLMs) and vision-language models (VLMs) via continued pretraining on publicly available biomedical corpora. These works typically claim that such domain-adaptive pretraining (DAPT) improves performance on downstream medical tasks, such as answering medical licensing exam questions. In this paper, we compare seven public "medical" LLMs and two VLMs against their corresponding base models, arriving at a different conclusion: all medical VLMs and nearly all medical LLMs fail to consistently improve over their base models in the zero-/few-shot prompting regime for medical question-answering (QA) tasks. For instance, across the tasks and model pairs we consider in the 3-shot setting, medical LLMs only outperform their base models in 12.1% of cases, reach a (statistical) tie in 49.8% of cases, and are significantly worse than their base models in the remaining 38.2% of cases. Our conclusions are based on (i) comparing each medical model head-to-head, directly against the corresponding base model; (ii) optimizing the prompts for each model separately; and (iii) accounting for statistical uncertainty in comparisons. While these basic practices are not consistently adopted in the literature, our ablations show that they substantially impact conclusions. Our findings suggest that state-of-the-art general-domain models may already exhibit strong medical knowledge and reasoning capabilities, and offer recommendations to strengthen the conclusions of future studies.

Xplainer: From X-Ray Observations to Explainable Zero-Shot Diagnosis

Automated diagnosis prediction from medical images is a valuable resource to support clinical decision-making. However, such systems usually need to be trained on large amounts of annotated data, which often is scarce in the medical domain. Zero-shot methods address this challenge by allowing a flexible adaption to new settings with different clinical findings without relying on labeled data. Further, to integrate automated diagnosis in the clinical workflow, methods should be transparent and explainable, increasing medical professionals' trust and facilitating correctness verification. In this work, we introduce Xplainer, a novel framework for explainable zero-shot diagnosis in the clinical setting. Xplainer adapts the classification-by-description approach of contrastive vision-language models to the multi-label medical diagnosis task. Specifically, instead of directly predicting a diagnosis, we prompt the model to classify the existence of descriptive observations, which a radiologist would look for on an X-Ray scan, and use the descriptor probabilities to estimate the likelihood of a diagnosis. Our model is explainable by design, as the final diagnosis prediction is directly based on the prediction of the underlying descriptors. We evaluate Xplainer on two chest X-ray datasets, CheXpert and ChestX-ray14, and demonstrate its effectiveness in improving the performance and explainability of zero-shot diagnosis. Our results suggest that Xplainer provides a more detailed understanding of the decision-making process and can be a valuable tool for clinical diagnosis.

Knowledge-Rich Self-Supervision for Biomedical Entity Linking

Entity linking faces significant challenges such as prolific variations and prevalent ambiguities, especially in high-value domains with myriad entities. Standard classification approaches suffer from the annotation bottleneck and cannot effectively handle unseen entities. Zero-shot entity linking has emerged as a promising direction for generalizing to new entities, but it still requires example gold entity mentions during training and canonical descriptions for all entities, both of which are rarely available outside of Wikipedia. In this paper, we explore Knowledge-RIch Self-Supervision (tt KRISS) for biomedical entity linking, by leveraging readily available domain knowledge. In training, it generates self-supervised mention examples on unlabeled text using a domain ontology and trains a contextual encoder using contrastive learning. For inference, it samples self-supervised mentions as prototypes for each entity and conducts linking by mapping the test mention to the most similar prototype. Our approach can easily incorporate entity descriptions and gold mention labels if available. We conducted extensive experiments on seven standard datasets spanning biomedical literature and clinical notes. Without using any labeled information, our method produces tt KRISSBERT, a universal entity linker for four million UMLS entities that attains new state of the art, outperforming prior self-supervised methods by as much as 20 absolute points in accuracy.

ClinLinker: Medical Entity Linking of Clinical Concept Mentions in Spanish

Advances in natural language processing techniques, such as named entity recognition and normalization to widely used standardized terminologies like UMLS or SNOMED-CT, along with the digitalization of electronic health records, have significantly advanced clinical text analysis. This study presents ClinLinker, a novel approach employing a two-phase pipeline for medical entity linking that leverages the potential of in-domain adapted language models for biomedical text mining: initial candidate retrieval using a SapBERT-based bi-encoder and subsequent re-ranking with a cross-encoder, trained by following a contrastive-learning strategy to be tailored to medical concepts in Spanish. This methodology, focused initially on content in Spanish, substantially outperforming multilingual language models designed for the same purpose. This is true even for complex scenarios involving heterogeneous medical terminologies and being trained on a subset of the original data. Our results, evaluated using top-k accuracy at 25 and other top-k metrics, demonstrate our approach's performance on two distinct clinical entity linking Gold Standard corpora, DisTEMIST (diseases) and MedProcNER (clinical procedures), outperforming previous benchmarks by 40 points in DisTEMIST and 43 points in MedProcNER, both normalized to SNOMED-CT codes. These findings highlight our approach's ability to address language-specific nuances and set a new benchmark in entity linking, offering a potent tool for enhancing the utility of digital medical records. The resulting system is of practical value, both for large scale automatic generation of structured data derived from clinical records, as well as for exhaustive extraction and harmonization of predefined clinical variables of interest.

Mental-LLM: Leveraging Large Language Models for Mental Health Prediction via Online Text Data

Advances in large language models (LLMs) have empowered a variety of applications. However, there is still a significant gap in research when it comes to understanding and enhancing the capabilities of LLMs in the field of mental health. In this work, we present the first comprehensive evaluation of multiple LLMs, including Alpaca, Alpaca-LoRA, FLAN-T5, GPT-3.5, and GPT-4, on various mental health prediction tasks via online text data. We conduct a broad range of experiments, covering zero-shot prompting, few-shot prompting, and instruction fine-tuning. The results indicate a promising yet limited performance of LLMs with zero-shot and few-shot prompt designs for the mental health tasks. More importantly, our experiments show that instruction finetuning can significantly boost the performance of LLMs for all tasks simultaneously. Our best-finetuned models, Mental-Alpaca and Mental-FLAN-T5, outperform the best prompt design of GPT-3.5 (25 and 15 times bigger) by 10.9% on balanced accuracy and the best of GPT-4 (250 and 150 times bigger) by 4.8%. They further perform on par with the state-of-the-art task-specific language model. We also conduct an exploratory case study on LLMs' capability on the mental health reasoning tasks, illustrating the promising capability of certain models such as GPT-4. We summarize our findings into a set of action guidelines for potential methods to enhance LLMs' capability for mental health tasks. Meanwhile, we also emphasize the important limitations before achieving deployability in real-world mental health settings, such as known racial and gender bias. We highlight the important ethical risks accompanying this line of research.

Lightweight Transformers for Clinical Natural Language Processing

Specialised pre-trained language models are becoming more frequent in NLP since they can potentially outperform models trained on generic texts. BioBERT and BioClinicalBERT are two examples of such models that have shown promise in medical NLP tasks. Many of these models are overparametrised and resource-intensive, but thanks to techniques like Knowledge Distillation (KD), it is possible to create smaller versions that perform almost as well as their larger counterparts. In this work, we specifically focus on development of compact language models for processing clinical texts (i.e. progress notes, discharge summaries etc). We developed a number of efficient lightweight clinical transformers using knowledge distillation and continual learning, with the number of parameters ranging from 15 million to 65 million. These models performed comparably to larger models such as BioBERT and ClinicalBioBERT and significantly outperformed other compact models trained on general or biomedical data. Our extensive evaluation was done across several standard datasets and covered a wide range of clinical text-mining tasks, including Natural Language Inference, Relation Extraction, Named Entity Recognition, and Sequence Classification. To our knowledge, this is the first comprehensive study specifically focused on creating efficient and compact transformers for clinical NLP tasks. The models and code used in this study can be found on our Huggingface profile at https://huggingface.co/nlpie and Github page at https://github.com/nlpie-research/Lightweight-Clinical-Transformers, respectively, promoting reproducibility of our results.

AutoMIR: Effective Zero-Shot Medical Information Retrieval without Relevance Labels

Medical information retrieval (MIR) is essential for retrieving relevant medical knowledge from diverse sources, including electronic health records, scientific literature, and medical databases. However, achieving effective zero-shot dense retrieval in the medical domain poses substantial challenges due to the lack of relevance-labeled data. In this paper, we introduce a novel approach called Self-Learning Hypothetical Document Embeddings (SL-HyDE) to tackle this issue. SL-HyDE leverages large language models (LLMs) as generators to generate hypothetical documents based on a given query. These generated documents encapsulate key medical context, guiding a dense retriever in identifying the most relevant documents. The self-learning framework progressively refines both pseudo-document generation and retrieval, utilizing unlabeled medical corpora without requiring any relevance-labeled data. Additionally, we present the Chinese Medical Information Retrieval Benchmark (CMIRB), a comprehensive evaluation framework grounded in real-world medical scenarios, encompassing five tasks and ten datasets. By benchmarking ten models on CMIRB, we establish a rigorous standard for evaluating medical information retrieval systems. Experimental results demonstrate that SL-HyDE significantly surpasses existing methods in retrieval accuracy while showcasing strong generalization and scalability across various LLM and retriever configurations. CMIRB data and evaluation code are publicly available at: https://github.com/CMIRB-benchmark/CMIRB.

Zero-Shot ECG Classification with Multimodal Learning and Test-time Clinical Knowledge Enhancement

Electrocardiograms (ECGs) are non-invasive diagnostic tools crucial for detecting cardiac arrhythmic diseases in clinical practice. While ECG Self-supervised Learning (eSSL) methods show promise in representation learning from unannotated ECG data, they often overlook the clinical knowledge that can be found in reports. This oversight and the requirement for annotated samples for downstream tasks limit eSSL's versatility. In this work, we address these issues with the Multimodal ECG Representation Learning (MERL}) framework. Through multimodal learning on ECG records and associated reports, MERL is capable of performing zero-shot ECG classification with text prompts, eliminating the need for training data in downstream tasks. At test time, we propose the Clinical Knowledge Enhanced Prompt Engineering (CKEPE) approach, which uses Large Language Models (LLMs) to exploit external expert-verified clinical knowledge databases, generating more descriptive prompts and reducing hallucinations in LLM-generated content to boost zero-shot classification. Based on MERL, we perform the first benchmark across six public ECG datasets, showing the superior performance of MERL compared against eSSL methods. Notably, MERL achieves an average AUC score of 75.2% in zero-shot classification (without training data), 3.2% higher than linear probed eSSL methods with 10\% annotated training data, averaged across all six datasets. Code and models are available at https://github.com/cheliu-computation/MERL

Cross-lingual Argument Mining in the Medical Domain

Nowadays the medical domain is receiving more and more attention in applications involving Artificial Intelligence. Clinicians have to deal with an enormous amount of unstructured textual data to make a conclusion about patients' health in their everyday life. Argument mining helps to provide a structure to such data by detecting argumentative components in the text and classifying the relations between them. However, as it is the case for many tasks in Natural Language Processing in general and in medical text processing in particular, the large majority of the work on computational argumentation has been done only for English. This is also the case with the only dataset available for argumentation in the medical domain, namely, the annotated medical data of abstracts of Randomized Controlled Trials (RCT) from the MEDLINE database. In order to mitigate the lack of annotated data for other languages, we empirically investigate several strategies to perform argument mining and classification in medical texts for a language for which no annotated data is available. This project shows that automatically translating and project annotations from English to a target language (Spanish) is an effective way to generate annotated data without manual intervention. Furthermore, our experiments demonstrate that the translation and projection approach outperforms zero-shot cross-lingual approaches using a large masked multilingual language model. Finally, we show how the automatically generated data in Spanish can also be used to improve results in the original English evaluation setting.

COVID-19 SignSym: a fast adaptation of a general clinical NLP tool to identify and normalize COVID-19 signs and symptoms to OMOP common data model

The COVID-19 pandemic swept across the world rapidly, infecting millions of people. An efficient tool that can accurately recognize important clinical concepts of COVID-19 from free text in electronic health records (EHRs) will be valuable to accelerate COVID-19 clinical research. To this end, this study aims at adapting the existing CLAMP natural language processing tool to quickly build COVID-19 SignSym, which can extract COVID-19 signs/symptoms and their 8 attributes (body location, severity, temporal expression, subject, condition, uncertainty, negation, and course) from clinical text. The extracted information is also mapped to standard concepts in the Observational Medical Outcomes Partnership common data model. A hybrid approach of combining deep learning-based models, curated lexicons, and pattern-based rules was applied to quickly build the COVID-19 SignSym from CLAMP, with optimized performance. Our extensive evaluation using 3 external sites with clinical notes of COVID-19 patients, as well as the online medical dialogues of COVID-19, shows COVID-19 Sign-Sym can achieve high performance across data sources. The workflow used for this study can be generalized to other use cases, where existing clinical natural language processing tools need to be customized for specific information needs within a short time. COVID-19 SignSym is freely accessible to the research community as a downloadable package (https://clamp.uth.edu/covid/nlp.php) and has been used by 16 healthcare organizations to support clinical research of COVID-19.

Geometry-Aware Adaptation for Pretrained Models

Machine learning models -- including prominent zero-shot models -- are often trained on datasets whose labels are only a small proportion of a larger label space. Such spaces are commonly equipped with a metric that relates the labels via distances between them. We propose a simple approach to exploit this information to adapt the trained model to reliably predict new classes -- or, in the case of zero-shot prediction, to improve its performance -- without any additional training. Our technique is a drop-in replacement of the standard prediction rule, swapping argmax with the Fr\'echet mean. We provide a comprehensive theoretical analysis for this approach, studying (i) learning-theoretic results trading off label space diameter, sample complexity, and model dimension, (ii) characterizations of the full range of scenarios in which it is possible to predict any unobserved class, and (iii) an optimal active learning-like next class selection procedure to obtain optimal training classes for when it is not possible to predict the entire range of unobserved classes. Empirically, using easily-available external metrics, our proposed approach, Loki, gains up to 29.7% relative improvement over SimCLR on ImageNet and scales to hundreds of thousands of classes. When no such metric is available, Loki can use self-derived metrics from class embeddings and obtains a 10.5% improvement on pretrained zero-shot models such as CLIP.

Biomedical Large Languages Models Seem not to be Superior to Generalist Models on Unseen Medical Data

Large language models (LLMs) have shown potential in biomedical applications, leading to efforts to fine-tune them on domain-specific data. However, the effectiveness of this approach remains unclear. This study evaluates the performance of biomedically fine-tuned LLMs against their general-purpose counterparts on a variety of clinical tasks. We evaluated their performance on clinical case challenges from the New England Journal of Medicine (NEJM) and the Journal of the American Medical Association (JAMA) and on several clinical tasks (e.g., information extraction, document summarization, and clinical coding). Using benchmarks specifically chosen to be likely outside the fine-tuning datasets of biomedical models, we found that biomedical LLMs mostly perform inferior to their general-purpose counterparts, especially on tasks not focused on medical knowledge. While larger models showed similar performance on case tasks (e.g., OpenBioLLM-70B: 66.4% vs. Llama-3-70B-Instruct: 65% on JAMA cases), smaller biomedical models showed more pronounced underperformance (e.g., OpenBioLLM-8B: 30% vs. Llama-3-8B-Instruct: 64.3% on NEJM cases). Similar trends were observed across the CLUE (Clinical Language Understanding Evaluation) benchmark tasks, with general-purpose models often performing better on text generation, question answering, and coding tasks. Our results suggest that fine-tuning LLMs to biomedical data may not provide the expected benefits and may potentially lead to reduced performance, challenging prevailing assumptions about domain-specific adaptation of LLMs and highlighting the need for more rigorous evaluation frameworks in healthcare AI. Alternative approaches, such as retrieval-augmented generation, may be more effective in enhancing the biomedical capabilities of LLMs without compromising their general knowledge.

TxAgent: An AI Agent for Therapeutic Reasoning Across a Universe of Tools

Precision therapeutics require multimodal adaptive models that generate personalized treatment recommendations. We introduce TxAgent, an AI agent that leverages multi-step reasoning and real-time biomedical knowledge retrieval across a toolbox of 211 tools to analyze drug interactions, contraindications, and patient-specific treatment strategies. TxAgent evaluates how drugs interact at molecular, pharmacokinetic, and clinical levels, identifies contraindications based on patient comorbidities and concurrent medications, and tailors treatment strategies to individual patient characteristics. It retrieves and synthesizes evidence from multiple biomedical sources, assesses interactions between drugs and patient conditions, and refines treatment recommendations through iterative reasoning. It selects tools based on task objectives and executes structured function calls to solve therapeutic tasks that require clinical reasoning and cross-source validation. The ToolUniverse consolidates 211 tools from trusted sources, including all US FDA-approved drugs since 1939 and validated clinical insights from Open Targets. TxAgent outperforms leading LLMs, tool-use models, and reasoning agents across five new benchmarks: DrugPC, BrandPC, GenericPC, TreatmentPC, and DescriptionPC, covering 3,168 drug reasoning tasks and 456 personalized treatment scenarios. It achieves 92.1% accuracy in open-ended drug reasoning tasks, surpassing GPT-4o and outperforming DeepSeek-R1 (671B) in structured multi-step reasoning. TxAgent generalizes across drug name variants and descriptions. By integrating multi-step inference, real-time knowledge grounding, and tool-assisted decision-making, TxAgent ensures that treatment recommendations align with established clinical guidelines and real-world evidence, reducing the risk of adverse events and improving therapeutic decision-making.

Towards Evaluating and Building Versatile Large Language Models for Medicine

In this study, we present MedS-Bench, a comprehensive benchmark designed to evaluate the performance of large language models (LLMs) in clinical contexts. Unlike existing benchmarks that focus on multiple-choice question answering, MedS-Bench spans 11 high-level clinical tasks, including clinical report summarization, treatment recommendations, diagnosis, named entity recognition, and medical concept explanation, among others. We evaluated six leading LLMs, e.g., MEDITRON, Mistral, InternLM 2, Llama 3, GPT-4, and Claude-3.5 using few-shot prompting, and found that even the most sophisticated models struggle with these complex tasks. To address these limitations, we developed MedS-Ins, a large-scale instruction tuning dataset for medicine. MedS-Ins comprises 58 medically oriented language corpora, totaling 13.5 million samples across 122 tasks. To demonstrate the dataset's utility, we conducted a proof-of-concept experiment by performing instruction tuning on a lightweight, open-source medical language model. The resulting model, MMedIns-Llama 3, significantly outperformed existing models across nearly all clinical tasks. To promote further advancements in the application of LLMs to clinical challenges, we have made the MedS-Ins dataset fully accessible and invite the research community to contribute to its expansion.Additionally, we have launched a dynamic leaderboard for MedS-Bench, which we plan to regularly update the test set to track progress and enhance the adaptation of general LLMs to the medical domain. Leaderboard: https://henrychur.github.io/MedS-Bench/. Github: https://github.com/MAGIC-AI4Med/MedS-Ins.

xMEN: A Modular Toolkit for Cross-Lingual Medical Entity Normalization

Objective: To improve performance of medical entity normalization across many languages, especially when fewer language resources are available compared to English. Materials and Methods: We introduce xMEN, a modular system for cross-lingual medical entity normalization, which performs well in both low- and high-resource scenarios. When synonyms in the target language are scarce for a given terminology, we leverage English aliases via cross-lingual candidate generation. For candidate ranking, we incorporate a trainable cross-encoder model if annotations for the target task are available. We also evaluate cross-encoders trained in a weakly supervised manner based on machine-translated datasets from a high resource domain. Our system is publicly available as an extensible Python toolkit. Results: xMEN improves the state-of-the-art performance across a wide range of multilingual benchmark datasets. Weakly supervised cross-encoders are effective when no training data is available for the target task. Through the compatibility of xMEN with the BigBIO framework, it can be easily used with existing and prospective datasets. Discussion: Our experiments show the importance of balancing the output of general-purpose candidate generators with subsequent trainable re-rankers, which we achieve through a rank regularization term in the loss function of the cross-encoder. However, error analysis reveals that multi-word expressions and other complex entities are still challenging. Conclusion: xMEN exhibits strong performance for medical entity normalization in multiple languages, even when no labeled data and few terminology aliases for the target language are available. Its configuration system and evaluation modules enable reproducible benchmarks. Models and code are available online at the following URL: https://github.com/hpi-dhc/xmen

Italian Crossword Generator: Enhancing Education through Interactive Word Puzzles

Educational crosswords offer numerous benefits for students, including increased engagement, improved understanding, critical thinking, and memory retention. Creating high-quality educational crosswords can be challenging, but recent advances in natural language processing and machine learning have made it possible to use language models to generate nice wordplays. The exploitation of cutting-edge language models like GPT3-DaVinci, GPT3-Curie, GPT3-Babbage, GPT3-Ada, and BERT-uncased has led to the development of a comprehensive system for generating and verifying crossword clues. A large dataset of clue-answer pairs was compiled to fine-tune the models in a supervised manner to generate original and challenging clues from a given keyword. On the other hand, for generating crossword clues from a given text, Zero/Few-shot learning techniques were used to extract clues from the input text, adding variety and creativity to the puzzles. We employed the fine-tuned model to generate data and labeled the acceptability of clue-answer parts with human supervision. To ensure quality, we developed a classifier by fine-tuning existing language models on the labeled dataset. Conversely, to assess the quality of clues generated from the given text using zero/few-shot learning, we employed a zero-shot learning approach to check the quality of generated clues. The results of the evaluation have been very promising, demonstrating the effectiveness of the approach in creating high-standard educational crosswords that offer students engaging and rewarding learning experiences.

LLMs-in-the-loop Part-1: Expert Small AI Models for Bio-Medical Text Translation

Machine translation is indispensable in healthcare for enabling the global dissemination of medical knowledge across languages. However, complex medical terminology poses unique challenges to achieving adequate translation quality and accuracy. This study introduces a novel "LLMs-in-the-loop" approach to develop supervised neural machine translation models optimized specifically for medical texts. While large language models (LLMs) have demonstrated powerful capabilities, this research shows that small, specialized models trained on high-quality in-domain (mostly synthetic) data can outperform even vastly larger LLMs. Custom parallel corpora in six languages were compiled from scientific articles, synthetically generated clinical documents, and medical texts. Our LLMs-in-the-loop methodology employs synthetic data generation, rigorous evaluation, and agent orchestration to enhance performance. We developed small medical translation models using the MarianMT base model. We introduce a new medical translation test dataset to standardize evaluation in this domain. Assessed using BLEU, METEOR, ROUGE, and BERT scores on this test set, our MarianMT-based models outperform Google Translate, DeepL, and GPT-4-Turbo. Results demonstrate that our LLMs-in-the-loop approach, combined with fine-tuning high-quality, domain-specific data, enables specialized models to outperform general-purpose and some larger systems. This research, part of a broader series on expert small models, paves the way for future healthcare-related AI developments, including deidentification and bio-medical entity extraction models. Our study underscores the potential of tailored neural translation models and the LLMs-in-the-loop methodology to advance the field through improved data generation, evaluation, agent, and modeling techniques.

Text2Node: a Cross-Domain System for Mapping Arbitrary Phrases to a Taxonomy

Electronic health record (EHR) systems are used extensively throughout the healthcare domain. However, data interchangeability between EHR systems is limited due to the use of different coding standards across systems. Existing methods of mapping coding standards based on manual human experts mapping, dictionary mapping, symbolic NLP and classification are unscalable and cannot accommodate large scale EHR datasets. In this work, we present Text2Node, a cross-domain mapping system capable of mapping medical phrases to concepts in a large taxonomy (such as SNOMED CT). The system is designed to generalize from a limited set of training samples and map phrases to elements of the taxonomy that are not covered by training data. As a result, our system is scalable, robust to wording variants between coding systems and can output highly relevant concepts when no exact concept exists in the target taxonomy. Text2Node operates in three main stages: first, the lexicon is mapped to word embeddings; second, the taxonomy is vectorized using node embeddings; and finally, the mapping function is trained to connect the two embedding spaces. We compared multiple algorithms and architectures for each stage of the training, including GloVe and FastText word embeddings, CNN and Bi-LSTM mapping functions, and node2vec for node embeddings. We confirmed the robustness and generalisation properties of Text2Node by mapping ICD-9-CM Diagnosis phrases to SNOMED CT and by zero-shot training at comparable accuracy. This system is a novel methodological contribution to the task of normalizing and linking phrases to a taxonomy, advancing data interchangeability in healthcare. When applied, the system can use electronic health records to generate an embedding that incorporates taxonomical medical knowledge to improve clinical predictive models.

Health Text Simplification: An Annotated Corpus for Digestive Cancer Education and Novel Strategies for Reinforcement Learning

Objective: The reading level of health educational materials significantly influences the understandability and accessibility of the information, particularly for minoritized populations. Many patient educational resources surpass the reading level and complexity of widely accepted standards. There is a critical need for high-performing text simplification models in health information to enhance dissemination and literacy. This need is particularly acute in cancer education, where effective prevention and screening education can substantially reduce morbidity and mortality. Methods: We introduce Simplified Digestive Cancer (SimpleDC), a parallel corpus of cancer education materials tailored for health text simplification research, comprising educational content from the American Cancer Society, Centers for Disease Control and Prevention, and National Cancer Institute. Utilizing SimpleDC alongside the existing Med-EASi corpus, we explore Large Language Model (LLM)-based simplification methods, including fine-tuning, reinforcement learning (RL), reinforcement learning with human feedback (RLHF), domain adaptation, and prompt-based approaches. Our experimentation encompasses Llama 2 and GPT-4. A novel RLHF reward function is introduced, featuring a lightweight model adept at distinguishing between original and simplified texts, thereby enhancing the model's effectiveness with unlabeled data. Results: Fine-tuned Llama 2 models demonstrated high performance across various metrics. Our innovative RLHF reward function surpassed existing RL text simplification reward functions in effectiveness. The results underscore that RL/RLHF can augment fine-tuning, facilitating model training on unlabeled text and improving performance.

Accelerating Clinical Evidence Synthesis with Large Language Models

Synthesizing clinical evidence largely relies on systematic reviews of clinical trials and retrospective analyses from medical literature. However, the rapid expansion of publications presents challenges in efficiently identifying, summarizing, and updating clinical evidence. Here, we introduce TrialMind, a generative artificial intelligence (AI) pipeline for facilitating human-AI collaboration in three crucial tasks for evidence synthesis: study search, screening, and data extraction. To assess its performance, we chose published systematic reviews to build the benchmark dataset, named TrialReviewBench, which contains 100 systematic reviews and the associated 2,220 clinical studies. Our results show that TrialMind excels across all three tasks. In study search, it generates diverse and comprehensive search queries to achieve high recall rates (Ours 0.711-0.834 v.s. Human baseline 0.138-0.232). For study screening, TrialMind surpasses traditional embedding-based methods by 30% to 160%. In data extraction, it outperforms a GPT-4 baseline by 29.6% to 61.5%. We further conducted user studies to confirm its practical utility. Compared to manual efforts, human-AI collaboration using TrialMind yielded a 71.4% recall lift and 44.2% time savings in study screening and a 23.5% accuracy lift and 63.4% time savings in data extraction. Additionally, when comparing synthesized clinical evidence presented in forest plots, medical experts favored TrialMind's outputs over GPT-4's outputs in 62.5% to 100% of cases. These findings show the promise of LLM-based approaches like TrialMind to accelerate clinical evidence synthesis via streamlining study search, screening, and data extraction from medical literature, with exceptional performance improvement when working with human experts.

The ELEVATE-AI LLMs Framework: An Evaluation Framework for Use of Large Language Models in HEOR: an ISPOR Working Group Report

Introduction. Generative Artificial Intelligence, particularly large language models (LLMs), offers transformative potential for Health Economics and Outcomes Research (HEOR). However, evaluating the quality, transparency, and rigor of LLM-assisted research lacks standardized guidance. This article introduces the ELEVATE AI LLMs framework and checklist, designed to support researchers and reviewers in assessing LLM use in HEOR. Methods. The ELEVATE AI LLMs framework was developed through a targeted review of existing guidelines and evaluation frameworks. The framework comprises ten evaluation domains, including model characteristics, accuracy, comprehensiveness, and fairness. The accompanying checklist operationalizes the framework. To validate the framework, we applied it to two published studies, demonstrating its usability across different HEOR tasks. Results. The ELEVATE AI LLMs framework provides a comprehensive structure for evaluating LLM-assisted research, while the checklist facilitates practical application. Validation of the framework and checklist on studies of systematic literature reviews and health economic modeling highlighted their ability to identify strengths and gaps in reporting. Limitations. While the ELEVATE AI LLMs framework provides robust guidance, its broader generalizability and applicability to diverse HEOR tasks require further empirical testing. Additionally, several metrics adapted from computer science need further validation in HEOR contexts. Conclusion. The ELEVATE AI LLMs framework and checklist fill a critical gap in HEOR by offering structured guidance for evaluating LLM-assisted research. By promoting transparency, accuracy, and reproducibility, they aim to standardize and improve the integration of LLMs into HEOR, ensuring their outputs meet the field's rigorous standards.

Biomedical Language Models are Robust to Sub-optimal Tokenization

As opposed to general English, many concepts in biomedical terminology have been designed in recent history by biomedical professionals with the goal of being precise and concise. This is often achieved by concatenating meaningful biomedical morphemes to create new semantic units. Nevertheless, most modern biomedical language models (LMs) are pre-trained using standard domain-specific tokenizers derived from large scale biomedical corpus statistics without explicitly leveraging the agglutinating nature of biomedical language. In this work, we first find that standard open-domain and biomedical tokenizers are largely unable to segment biomedical terms into meaningful components. Therefore, we hypothesize that using a tokenizer which segments biomedical terminology more accurately would enable biomedical LMs to improve their performance on downstream biomedical NLP tasks, especially ones which involve biomedical terms directly such as named entity recognition (NER) and entity linking. Surprisingly, we find that pre-training a biomedical LM using a more accurate biomedical tokenizer does not improve the entity representation quality of a language model as measured by several intrinsic and extrinsic measures such as masked language modeling prediction (MLM) accuracy as well as NER and entity linking performance. These quantitative findings, along with a case study which explores entity representation quality more directly, suggest that the biomedical pre-training process is quite robust to instances of sub-optimal tokenization.

GENIE: Generative Note Information Extraction model for structuring EHR data

Electronic Health Records (EHRs) hold immense potential for advancing healthcare, offering rich, longitudinal data that combines structured information with valuable insights from unstructured clinical notes. However, the unstructured nature of clinical text poses significant challenges for secondary applications. Traditional methods for structuring EHR free-text data, such as rule-based systems and multi-stage pipelines, are often limited by their time-consuming configurations and inability to adapt across clinical notes from diverse healthcare settings. Few systems provide a comprehensive attribute extraction for terminologies. While giant large language models (LLMs) like GPT-4 and LLaMA 405B excel at structuring tasks, they are slow, costly, and impractical for large-scale use. To overcome these limitations, we introduce GENIE, a Generative Note Information Extraction system that leverages LLMs to streamline the structuring of unstructured clinical text into usable data with standardized format. GENIE processes entire paragraphs in a single pass, extracting entities, assertion statuses, locations, modifiers, values, and purposes with high accuracy. Its unified, end-to-end approach simplifies workflows, reduces errors, and eliminates the need for extensive manual intervention. Using a robust data preparation pipeline and fine-tuned small scale LLMs, GENIE achieves competitive performance across multiple information extraction tasks, outperforming traditional tools like cTAKES and MetaMap and can handle extra attributes to be extracted. GENIE strongly enhances real-world applicability and scalability in healthcare systems. By open-sourcing the model and test data, we aim to encourage collaboration and drive further advancements in EHR structurization.

Polaris: A Safety-focused LLM Constellation Architecture for Healthcare

We develop Polaris, the first safety-focused LLM constellation for real-time patient-AI healthcare conversations. Unlike prior LLM works in healthcare focusing on tasks like question answering, our work specifically focuses on long multi-turn voice conversations. Our one-trillion parameter constellation system is composed of several multibillion parameter LLMs as co-operative agents: a stateful primary agent that focuses on driving an engaging conversation and several specialist support agents focused on healthcare tasks performed by nurses to increase safety and reduce hallucinations. We develop a sophisticated training protocol for iterative co-training of the agents that optimize for diverse objectives. We train our models on proprietary data, clinical care plans, healthcare regulatory documents, medical manuals, and other medical reasoning documents. We align our models to speak like medical professionals, using organic healthcare conversations and simulated ones between patient actors and experienced nurses. This allows our system to express unique capabilities such as rapport building, trust building, empathy and bedside manner. Finally, we present the first comprehensive clinician evaluation of an LLM system for healthcare. We recruited over 1100 U.S. licensed nurses and over 130 U.S. licensed physicians to perform end-to-end conversational evaluations of our system by posing as patients and rating the system on several measures. We demonstrate Polaris performs on par with human nurses on aggregate across dimensions such as medical safety, clinical readiness, conversational quality, and bedside manner. Additionally, we conduct a challenging task-based evaluation of the individual specialist support agents, where we demonstrate our LLM agents significantly outperform a much larger general-purpose LLM (GPT-4) as well as from its own medium-size class (LLaMA-2 70B).

Vision Language Models in Medicine

With the advent of Vision-Language Models (VLMs), medical artificial intelligence (AI) has experienced significant technological progress and paradigm shifts. This survey provides an extensive review of recent advancements in Medical Vision-Language Models (Med-VLMs), which integrate visual and textual data to enhance healthcare outcomes. We discuss the foundational technology behind Med-VLMs, illustrating how general models are adapted for complex medical tasks, and examine their applications in healthcare. The transformative impact of Med-VLMs on clinical practice, education, and patient care is highlighted, alongside challenges such as data scarcity, narrow task generalization, interpretability issues, and ethical concerns like fairness, accountability, and privacy. These limitations are exacerbated by uneven dataset distribution, computational demands, and regulatory hurdles. Rigorous evaluation methods and robust regulatory frameworks are essential for safe integration into healthcare workflows. Future directions include leveraging large-scale, diverse datasets, improving cross-modal generalization, and enhancing interpretability. Innovations like federated learning, lightweight architectures, and Electronic Health Record (EHR) integration are explored as pathways to democratize access and improve clinical relevance. This review aims to provide a comprehensive understanding of Med-VLMs' strengths and limitations, fostering their ethical and balanced adoption in healthcare.

Matchmaker: Self-Improving Large Language Model Programs for Schema Matching

Schema matching -- the task of finding matches between attributes across disparate data sources with different tables and hierarchies -- is critical for creating interoperable machine learning (ML)-ready data. Addressing this fundamental data-centric problem has wide implications, especially in domains like healthcare, finance and e-commerce -- but also has the potential to benefit ML models more generally, by increasing the data available for ML model training. However, schema matching is a challenging ML task due to structural/hierarchical and semantic heterogeneity between different schemas. Previous ML approaches to automate schema matching have either required significant labeled data for model training, which is often unrealistic or suffer from poor zero-shot performance. To this end, we propose Matchmaker - a compositional language model program for schema matching, comprised of candidate generation, refinement and confidence scoring. Matchmaker also self-improves in a zero-shot manner without the need for labeled demonstrations via a novel optimization approach, which constructs synthetic in-context demonstrations to guide the language model's reasoning process. Empirically, we demonstrate on real-world medical schema matching benchmarks that Matchmaker outperforms previous ML-based approaches, highlighting its potential to accelerate data integration and interoperability of ML-ready data.

DR.BENCH: Diagnostic Reasoning Benchmark for Clinical Natural Language Processing

The meaningful use of electronic health records (EHR) continues to progress in the digital era with clinical decision support systems augmented by artificial intelligence. A priority in improving provider experience is to overcome information overload and reduce the cognitive burden so fewer medical errors and cognitive biases are introduced during patient care. One major type of medical error is diagnostic error due to systematic or predictable errors in judgment that rely on heuristics. The potential for clinical natural language processing (cNLP) to model diagnostic reasoning in humans with forward reasoning from data to diagnosis and potentially reduce the cognitive burden and medical error has not been investigated. Existing tasks to advance the science in cNLP have largely focused on information extraction and named entity recognition through classification tasks. We introduce a novel suite of tasks coined as Diagnostic Reasoning Benchmarks, DR.BENCH, as a new benchmark for developing and evaluating cNLP models with clinical diagnostic reasoning ability. The suite includes six tasks from ten publicly available datasets addressing clinical text understanding, medical knowledge reasoning, and diagnosis generation. DR.BENCH is the first clinical suite of tasks designed to be a natural language generation framework to evaluate pre-trained language models. Experiments with state-of-the-art pre-trained generative language models using large general domain models and models that were continually trained on a medical corpus demonstrate opportunities for improvement when evaluated in DR. BENCH. We share DR. BENCH as a publicly available GitLab repository with a systematic approach to load and evaluate models for the cNLP community.

Evaluation of Language Models in the Medical Context Under Resource-Constrained Settings

Since the emergence of the Transformer architecture, language model development has increased, driven by their promising potential. However, releasing these models into production requires properly understanding their behavior, particularly in sensitive domains such as medicine. Despite this need, the medical literature still lacks technical assessments of pre-trained language models, which are especially valuable in resource-constrained settings in terms of computational power or limited budget. To address this gap, we provide a comprehensive survey of language models in the medical domain. In addition, we selected a subset of these models for thorough evaluation, focusing on classification and text generation tasks. Our subset encompasses 53 models, ranging from 110 million to 13 billion parameters, spanning the three families of Transformer-based models and from diverse knowledge domains. This study employs a series of approaches for text classification together with zero-shot prompting instead of model training or fine-tuning, which closely resembles the limited resource setting in which many users of language models find themselves. Encouragingly, our findings reveal remarkable performance across various tasks and datasets, underscoring the latent potential of certain models to contain medical knowledge, even without domain specialization. Consequently, our study advocates for further exploration of model applications in medical contexts, particularly in resource-constrained settings. The code is available on https://github.com/anpoc/Language-models-in-medicine.

Towards a Multimodal Large Language Model with Pixel-Level Insight for Biomedicine

In recent years, Multimodal Large Language Models (MLLM) have achieved notable advancements, demonstrating the feasibility of developing an intelligent biomedical assistant. However, current biomedical MLLMs predominantly focus on image-level understanding and restrict interactions to textual commands, thus limiting their capability boundaries and the flexibility of usage. In this paper, we introduce a novel end-to-end multimodal large language model for the biomedical domain, named MedPLIB, which possesses pixel-level understanding. Excitingly, it supports visual question answering (VQA), arbitrary pixel-level prompts (points, bounding boxes, and free-form shapes), and pixel-level grounding. We propose a novel Mixture-of-Experts (MoE) multi-stage training strategy, which divides MoE into separate training phases for a visual-language expert model and a pixel-grounding expert model, followed by fine-tuning using MoE. This strategy effectively coordinates multitask learning while maintaining the computational cost at inference equivalent to that of a single expert model. To advance the research of biomedical MLLMs, we introduce the Medical Complex Vision Question Answering Dataset (MeCoVQA), which comprises an array of 8 modalities for complex medical imaging question answering and image region understanding. Experimental results indicate that MedPLIB has achieved state-of-the-art outcomes across multiple medical visual language tasks. More importantly, in zero-shot evaluations for the pixel grounding task, MedPLIB leads the best small and large models by margins of 19.7 and 15.6 respectively on the mDice metric. The codes, data, and model checkpoints will be made publicly available at https://github.com/ShawnHuang497/MedPLIB.

Multiple Choice Questions and Large Languages Models: A Case Study with Fictional Medical Data

Large Language Models (LLMs) like ChatGPT demonstrate significant potential in the medical field, often evaluated using multiple-choice questions (MCQs) similar to those found on the USMLE. Despite their prevalence in medical education, MCQs have limitations that might be exacerbated when assessing LLMs. To evaluate the effectiveness of MCQs in assessing the performance of LLMs, we developed a fictional medical benchmark focused on a non-existent gland, the Glianorex. This approach allowed us to isolate the knowledge of the LLM from its test-taking abilities. We used GPT-4 to generate a comprehensive textbook on the Glianorex in both English and French and developed corresponding multiple-choice questions in both languages. We evaluated various open-source, proprietary, and domain-specific LLMs using these questions in a zero-shot setting. The models achieved average scores around 67%, with minor performance differences between larger and smaller models. Performance was slightly higher in English than in French. Fine-tuned medical models showed some improvement over their base versions in English but not in French. The uniformly high performance across models suggests that traditional MCQ-based benchmarks may not accurately measure LLMs' clinical knowledge and reasoning abilities, instead highlighting their pattern recognition skills. This study underscores the need for more robust evaluation methods to better assess the true capabilities of LLMs in medical contexts.

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.

A Preliminary Study of o1 in Medicine: Are We Closer to an AI Doctor?

Large language models (LLMs) have exhibited remarkable capabilities across various domains and tasks, pushing the boundaries of our knowledge in learning and cognition. The latest model, OpenAI's o1, stands out as the first LLM with an internalized chain-of-thought technique using reinforcement learning strategies. While it has demonstrated surprisingly strong capabilities on various general language tasks, its performance in specialized fields such as medicine remains unknown. To this end, this report provides a comprehensive exploration of o1 on different medical scenarios, examining 3 key aspects: understanding, reasoning, and multilinguality. Specifically, our evaluation encompasses 6 tasks using data from 37 medical datasets, including two newly constructed and more challenging question-answering (QA) tasks based on professional medical quizzes from the New England Journal of Medicine (NEJM) and The Lancet. These datasets offer greater clinical relevance compared to standard medical QA benchmarks such as MedQA, translating more effectively into real-world clinical utility. Our analysis of o1 suggests that the enhanced reasoning ability of LLMs may (significantly) benefit their capability to understand various medical instructions and reason through complex clinical scenarios. Notably, o1 surpasses the previous GPT-4 in accuracy by an average of 6.2% and 6.6% across 19 datasets and two newly created complex QA scenarios. But meanwhile, we identify several weaknesses in both the model capability and the existing evaluation protocols, including hallucination, inconsistent multilingual ability, and discrepant metrics for evaluation. We release our raw data and model outputs at https://ucsc-vlaa.github.io/o1_medicine/ for future research.

What does a platypus look like? Generating customized prompts for zero-shot image classification

Open-vocabulary models are a promising new paradigm for image classification. Unlike traditional classification models, open-vocabulary models classify among any arbitrary set of categories specified with natural language during inference. This natural language, called "prompts", typically consists of a set of hand-written templates (e.g., "a photo of a {}") which are completed with each of the category names. This work introduces a simple method to generate higher accuracy prompts, without relying on any explicit knowledge of the task domain and with far fewer hand-constructed sentences. To achieve this, we combine open-vocabulary models with large language models (LLMs) to create Customized Prompts via Language models (CuPL, pronounced "couple"). In particular, we leverage the knowledge contained in LLMs in order to generate many descriptive sentences that contain important discriminating characteristics of the image categories. This allows the model to place a greater importance on these regions in the image when making predictions. We find that this straightforward and general approach improves accuracy on a range of zero-shot image classification benchmarks, including over one percentage point gain on ImageNet. Finally, this simple baseline requires no additional training and remains completely zero-shot. Code available at https://github.com/sarahpratt/CuPL.

Evidence Inference 2.0: More Data, Better Models

How do we most effectively treat a disease or condition? Ideally, we could consult a database of evidence gleaned from clinical trials to answer such questions. Unfortunately, no such database exists; clinical trial results are instead disseminated primarily via lengthy natural language articles. Perusing all such articles would be prohibitively time-consuming for healthcare practitioners; they instead tend to depend on manually compiled systematic reviews of medical literature to inform care. NLP may speed this process up, and eventually facilitate immediate consult of published evidence. The Evidence Inference dataset was recently released to facilitate research toward this end. This task entails inferring the comparative performance of two treatments, with respect to a given outcome, from a particular article (describing a clinical trial) and identifying supporting evidence. For instance: Does this article report that chemotherapy performed better than surgery for five-year survival rates of operable cancers? In this paper, we collect additional annotations to expand the Evidence Inference dataset by 25\%, provide stronger baseline models, systematically inspect the errors that these make, and probe dataset quality. We also release an abstract only (as opposed to full-texts) version of the task for rapid model prototyping. The updated corpus, documentation, and code for new baselines and evaluations are available at http://evidence-inference.ebm-nlp.com/.

Can Open-Source LLMs Compete with Commercial Models? Exploring the Few-Shot Performance of Current GPT Models in Biomedical Tasks

Commercial large language models (LLMs), like OpenAI's GPT-4 powering ChatGPT and Anthropic's Claude 3 Opus, have dominated natural language processing (NLP) benchmarks across different domains. New competing Open-Source alternatives like Mixtral 8x7B or Llama 3 have emerged and seem to be closing the gap while often offering higher throughput and being less costly to use. Open-Source LLMs can also be self-hosted, which makes them interesting for enterprise and clinical use cases where sensitive data should not be processed by third parties. We participated in the 12th BioASQ challenge, which is a retrieval augmented generation (RAG) setting, and explored the performance of current GPT models Claude 3 Opus, GPT-3.5-turbo and Mixtral 8x7b with in-context learning (zero-shot, few-shot) and QLoRa fine-tuning. We also explored how additional relevant knowledge from Wikipedia added to the context-window of the LLM might improve their performance. Mixtral 8x7b was competitive in the 10-shot setting, both with and without fine-tuning, but failed to produce usable results in the zero-shot setting. QLoRa fine-tuning and Wikipedia context did not lead to measurable performance gains. Our results indicate that the performance gap between commercial and open-source models in RAG setups exists mainly in the zero-shot setting and can be closed by simply collecting few-shot examples for domain-specific use cases. The code needed to rerun these experiments is available through GitHub.

OLAPH: Improving Factuality in Biomedical Long-form Question Answering

In the medical domain, numerous scenarios necessitate the long-form generation ability of large language models (LLMs). Specifically, when addressing patients' questions, it is essential that the model's response conveys factual claims, highlighting the need for an automated method to evaluate those claims. Thus, we introduce MedLFQA, a benchmark dataset reconstructed using long-form question-answering datasets related to the biomedical domain. We use MedLFQA to facilitate the automatic evaluations of factuality. We also propose OLAPH, a simple and novel framework that enables the improvement of factuality through automatic evaluations. The OLAPH framework iteratively trains LLMs to mitigate hallucinations using sampling predictions and preference optimization. In other words, we iteratively set the highest-scoring response as a preferred response derived from sampling predictions and train LLMs to align with the preferred response that improves factuality. We highlight that, even on evaluation metrics not used during training, LLMs trained with our OLAPH framework demonstrate significant performance improvement in factuality. Our findings reveal that a 7B LLM trained with our OLAPH framework can provide long answers comparable to the medical experts' answers in terms of factuality. We believe that our work could shed light on gauging the long-text generation ability of LLMs in the medical domain. Our code and datasets are available at https://github.com/dmis-lab/OLAPH}{https://github.com/dmis-lab/OLAPH.

Zero-shot information extraction from radiological reports using ChatGPT

Electronic health records contain an enormous amount of valuable information, but many are recorded in free text. Information extraction is the strategy to transform the sequence of characters into structured data, which can be employed for secondary analysis. However, the traditional information extraction components, such as named entity recognition and relation extraction, require annotated data to optimize the model parameters, which has become one of the major bottlenecks in building information extraction systems. With the large language models achieving good performances on various downstream NLP tasks without parameter tuning, it becomes possible to use large language models for zero-shot information extraction. In this study, we aim to explore whether the most popular large language model, ChatGPT, can extract useful information from the radiological reports. We first design the prompt template for the interested information in the CT reports. Then, we generate the prompts by combining the prompt template with the CT reports as the inputs of ChatGPT to obtain the responses. A post-processing module is developed to transform the responses into structured extraction results. We conducted the experiments with 847 CT reports collected from Peking University Cancer Hospital. The experimental results indicate that ChatGPT can achieve competitive performances for some extraction tasks compared with the baseline information extraction system, but some limitations need to be further improved.

A Benchmark of Domain-Adapted Large Language Models for Generating Brief Hospital Course Summaries

Brief hospital course (BHC) summaries are common clinical documents generated by summarizing clinical notes. While large language models (LLMs) depict remarkable capabilities in automating real-world tasks, their capabilities for healthcare applications such as BHC synthesis have not been shown. To enable the adaptation of LLMs for BHC synthesis, we introduce a novel benchmark consisting of a pre-processed dataset extracted from MIMIC-IV notes, encapsulating clinical note, and brief hospital course (BHC) pairs. We assess the performance of two general-purpose LLMs and three healthcare-adapted LLMs to improve BHC synthesis from clinical notes. Using clinical notes as input for generating BHCs, we apply prompting-based (using in-context learning) and fine-tuning-based adaptation strategies to three open-source LLMs (Clinical-T5-Large, Llama2-13B, FLAN-UL2) and two proprietary LLMs (GPT-3.5, GPT-4). We quantitatively evaluate the performance of these LLMs across varying context-length inputs using conventional natural language similarity metrics. We further perform a qualitative study where five diverse clinicians blindly compare clinician-written BHCs and two LLM-generated BHCs for 30 samples across metrics of comprehensiveness, conciseness, factual correctness, and fluency. Overall, we present a new benchmark and pre-processed dataset for using LLMs in BHC synthesis from clinical notes. We observe high-quality summarization performance for both in-context proprietary and fine-tuned open-source LLMs using both quantitative metrics and a qualitative clinical reader study. We propose our work as a benchmark to motivate future works to adapt and assess the performance of LLMs in BHC synthesis.

RareBench: Can LLMs Serve as Rare Diseases Specialists?

Generalist Large Language Models (LLMs), such as GPT-4, have shown considerable promise in various domains, including medical diagnosis. Rare diseases, affecting approximately 300 million people worldwide, often have unsatisfactory clinical diagnosis rates primarily due to a lack of experienced physicians and the complexity of differentiating among many rare diseases. In this context, recent news such as "ChatGPT correctly diagnosed a 4-year-old's rare disease after 17 doctors failed" underscore LLMs' potential, yet underexplored, role in clinically diagnosing rare diseases. To bridge this research gap, we introduce RareBench, a pioneering benchmark designed to systematically evaluate the capabilities of LLMs on 4 critical dimensions within the realm of rare diseases. Meanwhile, we have compiled the largest open-source dataset on rare disease patients, establishing a benchmark for future studies in this domain. To facilitate differential diagnosis of rare diseases, we develop a dynamic few-shot prompt methodology, leveraging a comprehensive rare disease knowledge graph synthesized from multiple knowledge bases, significantly enhancing LLMs' diagnostic performance. Moreover, we present an exhaustive comparative study of GPT-4's diagnostic capabilities against those of specialist physicians. Our experimental findings underscore the promising potential of integrating LLMs into the clinical diagnostic process for rare diseases. This paves the way for exciting possibilities in future advancements in this field.

MeDSLIP: Medical Dual-Stream Language-Image Pre-training for Fine-grained Alignment

Vision-language pre-training (VLP) models have shown significant advancements in the medical domain. Yet, most VLP models align raw reports to images at a very coarse level, without modeling fine-grained relationships between anatomical and pathological concepts outlined in reports and the corresponding semantic counterparts in images. To address this problem, we propose a Medical Dual-Stream Language-Image Pre-training (MeDSLIP) framework. Specifically, MeDSLIP establishes vision-language fine-grained alignments via disentangling visual and textual representations into anatomy-relevant and pathology-relevant streams. Moreover, a novel vision-language Prototypical Contr-astive Learning (ProtoCL) method is adopted in MeDSLIP to enhance the alignment within the anatomical and pathological streams. MeDSLIP further employs cross-stream Intra-image Contrastive Learning (ICL) to ensure the consistent coexistence of paired anatomical and pathological concepts within the same image. Such a cross-stream regularization encourages the model to exploit the synchrony between two streams for a more comprehensive representation learning. MeDSLIP is evaluated under zero-shot and supervised fine-tuning settings on three public datasets: NIH CXR14, RSNA Pneumonia, and SIIM-ACR Pneumothorax. Under these settings, MeDSLIP outperforms six leading CNN-based models on classification, grounding, and segmentation tasks.

Large language models in healthcare and medical domain: A review

The deployment of large language models (LLMs) within the healthcare sector has sparked both enthusiasm and apprehension. These models exhibit the remarkable capability to provide proficient responses to free-text queries, demonstrating a nuanced understanding of professional medical knowledge. This comprehensive survey delves into the functionalities of existing LLMs designed for healthcare applications, elucidating the trajectory of their development, starting from traditional Pretrained Language Models (PLMs) to the present state of LLMs in healthcare sector. First, we explore the potential of LLMs to amplify the efficiency and effectiveness of diverse healthcare applications, particularly focusing on clinical language understanding tasks. These tasks encompass a wide spectrum, ranging from named entity recognition and relation extraction to natural language inference, multi-modal medical applications, document classification, and question-answering. Additionally, we conduct an extensive comparison of the most recent state-of-the-art LLMs in the healthcare domain, while also assessing the utilization of various open-source LLMs and highlighting their significance in healthcare applications. Furthermore, we present the essential performance metrics employed to evaluate LLMs in the biomedical domain, shedding light on their effectiveness and limitations. Finally, we summarize the prominent challenges and constraints faced by large language models in the healthcare sector, offering a holistic perspective on their potential benefits and shortcomings. This review provides a comprehensive exploration of the current landscape of LLMs in healthcare, addressing their role in transforming medical applications and the areas that warrant further research and development.

MEDIC: Towards a Comprehensive Framework for Evaluating LLMs in Clinical Applications

The rapid development of Large Language Models (LLMs) for healthcare applications has spurred calls for holistic evaluation beyond frequently-cited benchmarks like USMLE, to better reflect real-world performance. While real-world assessments are valuable indicators of utility, they often lag behind the pace of LLM evolution, likely rendering findings obsolete upon deployment. This temporal disconnect necessitates a comprehensive upfront evaluation that can guide model selection for specific clinical applications. We introduce MEDIC, a framework assessing LLMs across five critical dimensions of clinical competence: medical reasoning, ethics and bias, data and language understanding, in-context learning, and clinical safety. MEDIC features a novel cross-examination framework quantifying LLM performance across areas like coverage and hallucination detection, without requiring reference outputs. We apply MEDIC to evaluate LLMs on medical question-answering, safety, summarization, note generation, and other tasks. Our results show performance disparities across model sizes, baseline vs medically finetuned models, and have implications on model selection for applications requiring specific model strengths, such as low hallucination or lower cost of inference. MEDIC's multifaceted evaluation reveals these performance trade-offs, bridging the gap between theoretical capabilities and practical implementation in healthcare settings, ensuring that the most promising models are identified and adapted for diverse healthcare applications.

Rapid Biomedical Research Classification: The Pandemic PACT Advanced Categorisation Engine

This paper introduces the Pandemic PACT Advanced Categorisation Engine (PPACE) along with its associated dataset. PPACE is a fine-tuned model developed to automatically classify research abstracts from funded biomedical projects according to WHO-aligned research priorities. This task is crucial for monitoring research trends and identifying gaps in global health preparedness and response. Our approach builds on human-annotated projects, which are allocated one or more categories from a predefined list. A large language model is then used to generate `rationales' explaining the reasoning behind these annotations. This augmented data, comprising expert annotations and rationales, is subsequently used to fine-tune a smaller, more efficient model. Developed as part of the Pandemic PACT project, which aims to track and analyse research funding and clinical evidence for a wide range of diseases with outbreak potential, PPACE supports informed decision-making by research funders, policymakers, and independent researchers. We introduce and release both the trained model and the instruction-based dataset used for its training. Our evaluation shows that PPACE significantly outperforms its baselines. The release of PPACE and its associated dataset offers valuable resources for researchers in multilabel biomedical document classification and supports advancements in aligning biomedical research with key global health priorities.

Localising In-Domain Adaptation of Transformer-Based Biomedical Language Models

In the era of digital healthcare, the huge volumes of textual information generated every day in hospitals constitute an essential but underused asset that could be exploited with task-specific, fine-tuned biomedical language representation models, improving patient care and management. For such specialized domains, previous research has shown that fine-tuning models stemming from broad-coverage checkpoints can largely benefit additional training rounds over large-scale in-domain resources. However, these resources are often unreachable for less-resourced languages like Italian, preventing local medical institutions to employ in-domain adaptation. In order to reduce this gap, our work investigates two accessible approaches to derive biomedical language models in languages other than English, taking Italian as a concrete use-case: one based on neural machine translation of English resources, favoring quantity over quality; the other based on a high-grade, narrow-scoped corpus natively written in Italian, thus preferring quality over quantity. Our study shows that data quantity is a harder constraint than data quality for biomedical adaptation, but the concatenation of high-quality data can improve model performance even when dealing with relatively size-limited corpora. The models published from our investigations have the potential to unlock important research opportunities for Italian hospitals and academia. Finally, the set of lessons learned from the study constitutes valuable insights towards a solution to build biomedical language models that are generalizable to other less-resourced languages and different domain settings.

GatorTron: A Large Clinical Language Model to Unlock Patient Information from Unstructured Electronic Health Records

There is an increasing interest in developing artificial intelligence (AI) systems to process and interpret electronic health records (EHRs). Natural language processing (NLP) powered by pretrained language models is the key technology for medical AI systems utilizing clinical narratives. However, there are few clinical language models, the largest of which trained in the clinical domain is comparatively small at 110 million parameters (compared with billions of parameters in the general domain). It is not clear how large clinical language models with billions of parameters can help medical AI systems utilize unstructured EHRs. In this study, we develop from scratch a large clinical language model - GatorTron - using >90 billion words of text (including >82 billion words of de-identified clinical text) and systematically evaluate it on 5 clinical NLP tasks including clinical concept extraction, medical relation extraction, semantic textual similarity, natural language inference (NLI), and medical question answering (MQA). We examine how (1) scaling up the number of parameters and (2) scaling up the size of the training data could benefit these NLP tasks. GatorTron models scale up the clinical language model from 110 million to 8.9 billion parameters and improve 5 clinical NLP tasks (e.g., 9.6% and 9.5% improvement in accuracy for NLI and MQA), which can be applied to medical AI systems to improve healthcare delivery. The GatorTron models are publicly available at: https://catalog.ngc.nvidia.com/orgs/nvidia/teams/clara/models/gatortron_og.

OrthoDoc: Multimodal Large Language Model for Assisting Diagnosis in Computed Tomography

Multimodal large language models (MLLMs) have achieved significant success in the general field of image processing. Their emerging task generalization and freeform conversational capabilities can greatly facilitate medical diagnostic assistance, helping patients better understand their conditions and enhancing doctor-patient trust. Computed Tomography (CT) is a non-invasive imaging technique used to capture the internal mechanisms of a patient's condition and is widely utilized. However, in past research, the complex textural features of this imaging data have made accurate interpretation by algorithms challenging, impeding the performance of general LLMs in diagnostic assistance. To address this, we developed OrthoDoc, a MLLM designed for CT diagnostics. OrthoDoc is trained on 120,000 CT images and diagnostic reports and includes a Retrieval-Augmented Generation (RAG) module capable of effectively mitigating model hallucinations. This module is informed by extensive medical literature, textbooks, and explanatory data. Thus, OrthoDoc not only processes complex CT images but also stores, understands, and reasons over medical knowledge and language. In extensive experiments, OrthoDoc outperforms commercial models led by GPT-4, demonstrating superior diagnostic capabilities and accuracy. Specifically, OrthoDoc significantly surpasses existing models in the diagnosis of common orthopedic conditions such as fractures, arthritis, and tumors. Additionally, OrthoDoc exhibits robust generalization and stability when handling rare and complex cases.

DeViDe: Faceted medical knowledge for improved medical vision-language pre-training

Vision-language pre-training for chest X-rays has made significant strides, primarily by utilizing paired radiographs and radiology reports. However, existing approaches often face challenges in encoding medical knowledge effectively. While radiology reports provide insights into the current disease manifestation, medical definitions (as used by contemporary methods) tend to be overly abstract, creating a gap in knowledge. To address this, we propose DeViDe, a novel transformer-based method that leverages radiographic descriptions from the open web. These descriptions outline general visual characteristics of diseases in radiographs, and when combined with abstract definitions and radiology reports, provide a holistic snapshot of knowledge. DeViDe incorporates three key features for knowledge-augmented vision language alignment: First, a large-language model-based augmentation is employed to homogenise medical knowledge from diverse sources. Second, this knowledge is aligned with image information at various levels of granularity. Third, a novel projection layer is proposed to handle the complexity of aligning each image with multiple descriptions arising in a multi-label setting. In zero-shot settings, DeViDe performs comparably to fully supervised models on external datasets and achieves state-of-the-art results on three large-scale datasets. Additionally, fine-tuning DeViDe on four downstream tasks and six segmentation tasks showcases its superior performance across data from diverse distributions.

Clinical Document Corpora and Assorted Domain Proxies: A Survey of Diversity in Corpus Design, with Focus on German Text Data

We survey clinical document corpora, with focus on German textual data. Due to rigid data privacy legislation in Germany these resources, with only few exceptions, are stored in safe clinical data spaces and locked against clinic-external researchers. This situation stands in stark contrast with established workflows in the field of natural language processing where easy accessibility and reuse of data collections are common practice. Hence, alternative corpus designs have been examined to escape from this data poverty. Besides machine translation of English clinical datasets and the generation of synthetic corpora with fictitious clinical contents, several other types of domain proxies have come up as substitutes for authentic clinical documents. Common instances of close proxies are medical journal publications, clinical therapy guidelines, drug labels, etc., more distant proxies include online encyclopedic medical articles or medical contents from social media channels. After PRISM-conformant screening of 359 hits from four bibliographic systems, 75 relevant documents were finally selected for this review and 59 distinct corpora were determined. We identified 24 real clinical corpora (from 40 publications) out of which only 5 are publicly distributable. 2 translations of real corpora and 3 synthetic ones complement the set of clinical corpora. 14 corpora were categorized as close domain proxies, 16 as distant ones. There is a clear divide between the large number of non-accessible authentic clinical German-language corpora and their publicly accessible substitutes: translated or synthetic, close or more distant proxies. So on first sight, the data bottleneck seems broken. Intuitively yet, differences in genre-specific writing style, wording and medical domain expertise in this typological space are also obvious. This raises the question how valid alternative corpus designs really are.

Clinical Text Summarization: Adapting Large Language Models Can Outperform Human Experts

Sifting through vast textual data and summarizing key information imposes a substantial burden on how clinicians allocate their time. Although large language models (LLMs) have shown immense promise in natural language processing (NLP) tasks, their efficacy across diverse clinical summarization tasks has not yet been rigorously examined. In this work, we employ domain adaptation methods on eight LLMs, spanning six datasets and four distinct summarization tasks: radiology reports, patient questions, progress notes, and doctor-patient dialogue. Our thorough quantitative assessment reveals trade-offs between models and adaptation methods in addition to instances where recent advances in LLMs may not lead to improved results. Further, in a clinical reader study with six physicians, we depict that summaries from the best adapted LLM are preferable to human summaries in terms of completeness and correctness. Our ensuing qualitative analysis delineates mutual challenges faced by both LLMs and human experts. Lastly, we correlate traditional quantitative NLP metrics with reader study scores to enhance our understanding of how these metrics align with physician preferences. Our research marks the first evidence of LLMs outperforming human experts in clinical text summarization across multiple tasks. This implies that integrating LLMs into clinical workflows could alleviate documentation burden, empowering clinicians to focus more on personalized patient care and other irreplaceable human aspects of medicine.

From Beginner to Expert: Modeling Medical Knowledge into General LLMs

Recently, large language model (LLM) based artificial intelligence (AI) systems have demonstrated remarkable capabilities in natural language understanding and generation. However, these models face a significant challenge when it comes to sensitive applications, such as reasoning over medical knowledge and answering medical questions in a physician-like manner. Prior studies attempted to overcome this challenge by increasing the model size (>100B) to learn more general medical knowledge, while there is still room for improvement in LLMs with smaller-scale model sizes (<100B). In this work, we start from a pre-trained general LLM model (AntGLM-10B) and fine-tune it from a medical beginner towards a medical expert (called AntGLM-Med-10B), which leverages a 3-stage optimization procedure, i.e., general medical knowledge injection, medical domain instruction tuning, and specific medical task adaptation. Our contributions are threefold: (1) We specifically investigate how to adapt a pre-trained general LLM in medical domain, especially for a specific medical task. (2) We collect and construct large-scale medical datasets for each stage of the optimization process. These datasets encompass various data types and tasks, such as question-answering, medical reasoning, multi-choice questions, and medical conversations. (3) Specifically for multi-choice questions in the medical domain, we propose a novel Verification-of-Choice approach for prompting engineering, which significantly enhances the reasoning ability of LLMs. Remarkably, by combining the above approaches, our AntGLM-Med-10B model can outperform the most of LLMs on PubMedQA, including both general and medical LLMs, even when these LLMs have larger model size.

MedFuzz: Exploring the Robustness of Large Language Models in Medical Question Answering

Large language models (LLM) have achieved impressive performance on medical question-answering benchmarks. However, high benchmark accuracy does not imply that the performance generalizes to real-world clinical settings. Medical question-answering benchmarks rely on assumptions consistent with quantifying LLM performance but that may not hold in the open world of the clinic. Yet LLMs learn broad knowledge that can help the LLM generalize to practical conditions regardless of unrealistic assumptions in celebrated benchmarks. We seek to quantify how well LLM medical question-answering benchmark performance generalizes when benchmark assumptions are violated. Specifically, we present an adversarial method that we call MedFuzz (for medical fuzzing). MedFuzz attempts to modify benchmark questions in ways aimed at confounding the LLM. We demonstrate the approach by targeting strong assumptions about patient characteristics presented in the MedQA benchmark. Successful "attacks" modify a benchmark item in ways that would be unlikely to fool a medical expert but nonetheless "trick" the LLM into changing from a correct to an incorrect answer. Further, we present a permutation test technique that can ensure a successful attack is statistically significant. We show how to use performance on a "MedFuzzed" benchmark, as well as individual successful attacks. The methods show promise at providing insights into the ability of an LLM to operate robustly in more realistic settings.

FineTuneBench: How well do commercial fine-tuning APIs infuse knowledge into LLMs?

There is great interest in fine-tuning frontier large language models (LLMs) to inject new information and update existing knowledge. While commercial LLM fine-tuning APIs from providers such as OpenAI and Google promise flexible adaptation for various applications, the efficacy of fine-tuning remains unclear. In this study, we introduce FineTuneBench, an evaluation framework and dataset for understanding how well commercial fine-tuning APIs can successfully learn new and updated knowledge. We analyze five frontier LLMs with commercially available fine-tuning APIs, including GPT-4o and Gemini 1.5 Pro, on their effectiveness in two settings: (1) ingesting novel information, such as recent news events and new people profiles, and (2) updating existing knowledge, such as updated medical guidelines and code frameworks. Our results reveal substantial shortcomings in all the models' abilities to effectively learn new information through fine-tuning, with an average generalization accuracy of 37% across all models. When updating existing knowledge, such as incorporating medical guideline updates, commercial fine-tuning APIs show even more limited capability (average generalization accuracy of 19%). Overall, fine-tuning GPT-4o mini is the most effective for infusing new knowledge and updating knowledge, followed by GPT-3.5 Turbo and GPT-4o. The fine-tuning APIs for Gemini 1.5 Flesh and Gemini 1.5 Pro are unable to learn new knowledge or update existing knowledge. These findings underscore a major shortcoming in using current commercial fine-tuning services to achieve reliable knowledge infusion in common scenarios. We open source the FineTuneBench dataset at https://github.com/kevinwu23/StanfordFineTuneBench.

Clinical-Longformer and Clinical-BigBird: Transformers for long clinical sequences

Transformers-based models, such as BERT, have dramatically improved the performance for various natural language processing tasks. The clinical knowledge enriched model, namely ClinicalBERT, also achieved state-of-the-art results when performed on clinical named entity recognition and natural language inference tasks. One of the core limitations of these transformers is the substantial memory consumption due to their full self-attention mechanism. To overcome this, long sequence transformer models, e.g. Longformer and BigBird, were proposed with the idea of sparse attention mechanism to reduce the memory usage from quadratic to the sequence length to a linear scale. These models extended the maximum input sequence length from 512 to 4096, which enhanced the ability of modeling long-term dependency and consequently achieved optimal results in a variety of tasks. Inspired by the success of these long sequence transformer models, we introduce two domain enriched language models, namely Clinical-Longformer and Clinical-BigBird, which are pre-trained from large-scale clinical corpora. We evaluate both pre-trained models using 10 baseline tasks including named entity recognition, question answering, and document classification tasks. The results demonstrate that Clinical-Longformer and Clinical-BigBird consistently and significantly outperform ClinicalBERT as well as other short-sequence transformers in all downstream tasks. We have made our source code available at [https://github.com/luoyuanlab/Clinical-Longformer] the pre-trained models available for public download at: [https://huggingface.co/yikuan8/Clinical-Longformer].

A Survey of Large Language Models for Healthcare: from Data, Technology, and Applications to Accountability and Ethics

The utilization of large language models (LLMs) in the Healthcare domain has generated both excitement and concern due to their ability to effectively respond to freetext queries with certain professional knowledge. This survey outlines the capabilities of the currently developed LLMs for Healthcare and explicates their development process, with the aim of providing an overview of the development roadmap from traditional Pretrained Language Models (PLMs) to LLMs. Specifically, we first explore the potential of LLMs to enhance the efficiency and effectiveness of various Healthcare applications highlighting both the strengths and limitations. Secondly, we conduct a comparison between the previous PLMs and the latest LLMs, as well as comparing various LLMs with each other. Then we summarize related Healthcare training data, training methods, optimization strategies, and usage. Finally, the unique concerns associated with deploying LLMs in Healthcare settings are investigated, particularly regarding fairness, accountability, transparency and ethics. Our survey provide a comprehensive investigation from perspectives of both computer science and Healthcare specialty. Besides the discussion about Healthcare concerns, we supports the computer science community by compiling a collection of open source resources, such as accessible datasets, the latest methodologies, code implementations, and evaluation benchmarks in the Github. Summarily, we contend that a significant paradigm shift is underway, transitioning from PLMs to LLMs. This shift encompasses a move from discriminative AI approaches to generative AI approaches, as well as a shift from model-centered methodologies to datacentered methodologies.

Capabilities of GPT-4 on Medical Challenge Problems

Large language models (LLMs) have demonstrated remarkable capabilities in natural language understanding and generation across various domains, including medicine. We present a comprehensive evaluation of GPT-4, a state-of-the-art LLM, on medical competency examinations and benchmark datasets. GPT-4 is a general-purpose model that is not specialized for medical problems through training or engineered to solve clinical tasks. Our analysis covers two sets of official practice materials for the USMLE, a three-step examination program used to assess clinical competency and grant licensure in the United States. We also evaluate performance on the MultiMedQA suite of benchmark datasets. Beyond measuring model performance, experiments were conducted to investigate the influence of test questions containing both text and images on model performance, probe for memorization of content during training, and study probability calibration, which is of critical importance in high-stakes applications like medicine. Our results show that GPT-4, without any specialized prompt crafting, exceeds the passing score on USMLE by over 20 points and outperforms earlier general-purpose models (GPT-3.5) as well as models specifically fine-tuned on medical knowledge (Med-PaLM, a prompt-tuned version of Flan-PaLM 540B). In addition, GPT-4 is significantly better calibrated than GPT-3.5, demonstrating a much-improved ability to predict the likelihood that its answers are correct. We also explore the behavior of the model qualitatively through a case study that shows the ability of GPT-4 to explain medical reasoning, personalize explanations to students, and interactively craft new counterfactual scenarios around a medical case. Implications of the findings are discussed for potential uses of GPT-4 in medical education, assessment, and clinical practice, with appropriate attention to challenges of accuracy and safety.

Large Language Model Distilling Medication Recommendation Model

The recommendation of medication is a vital aspect of intelligent healthcare systems, as it involves prescribing the most suitable drugs based on a patient's specific health needs. Unfortunately, many sophisticated models currently in use tend to overlook the nuanced semantics of medical data, while only relying heavily on identities. Furthermore, these models face significant challenges in handling cases involving patients who are visiting the hospital for the first time, as they lack prior prescription histories to draw upon. To tackle these issues, we harness the powerful semantic comprehension and input-agnostic characteristics of Large Language Models (LLMs). Our research aims to transform existing medication recommendation methodologies using LLMs. In this paper, we introduce a novel approach called Large Language Model Distilling Medication Recommendation (LEADER). We begin by creating appropriate prompt templates that enable LLMs to suggest medications effectively. However, the straightforward integration of LLMs into recommender systems leads to an out-of-corpus issue specific to drugs. We handle it by adapting the LLMs with a novel output layer and a refined tuning loss function. Although LLM-based models exhibit remarkable capabilities, they are plagued by high computational costs during inference, which is impractical for the healthcare sector. To mitigate this, we have developed a feature-level knowledge distillation technique, which transfers the LLM's proficiency to a more compact model. Extensive experiments conducted on two real-world datasets, MIMIC-III and MIMIC-IV, demonstrate that our proposed model not only delivers effective results but also is efficient. To ease the reproducibility of our experiments, we release the implementation code online.

SYNFAC-EDIT: Synthetic Imitation Edit Feedback for Factual Alignment in Clinical Summarization

Large Language Models (LLMs) such as GPT & Llama have demonstrated significant achievements in summarization tasks but struggle with factual inaccuracies, a critical issue in clinical NLP applications where errors could lead to serious consequences. To counter the high costs and limited availability of expert-annotated data for factual alignment, this study introduces an innovative pipeline that utilizes >100B parameter GPT variants like GPT-3.5 & GPT-4 to act as synthetic experts to generate high-quality synthetics feedback aimed at enhancing factual consistency in clinical note summarization. Our research primarily focuses on edit feedback generated by these synthetic feedback experts without additional human annotations, mirroring and optimizing the practical scenario in which medical professionals refine AI system outputs. Although such 100B+ parameter GPT variants have proven to demonstrate expertise in various clinical NLP tasks, such as the Medical Licensing Examination, there is scant research on their capacity to act as synthetic feedback experts and deliver expert-level edit feedback for improving the generation quality of weaker (<10B parameter) LLMs like GPT-2 (1.5B) & Llama 2 (7B) in clinical domain. So in this work, we leverage 100B+ GPT variants to act as synthetic feedback experts offering expert-level edit feedback, that is used to reduce hallucinations and align weaker (<10B parameter) LLMs with medical facts using two distinct alignment algorithms (DPO & SALT), endeavoring to narrow the divide between AI-generated content and factual accuracy. This highlights the substantial potential of LLM-based synthetic edits in enhancing the alignment of clinical factuality.

MedAlign: A Clinician-Generated Dataset for Instruction Following with Electronic Medical Records

The ability of large language models (LLMs) to follow natural language instructions with human-level fluency suggests many opportunities in healthcare to reduce administrative burden and improve quality of care. However, evaluating LLMs on realistic text generation tasks for healthcare remains challenging. Existing question answering datasets for electronic health record (EHR) data fail to capture the complexity of information needs and documentation burdens experienced by clinicians. To address these challenges, we introduce MedAlign, a benchmark dataset of 983 natural language instructions for EHR data. MedAlign is curated by 15 clinicians (7 specialities), includes clinician-written reference responses for 303 instructions, and provides 276 longitudinal EHRs for grounding instruction-response pairs. We used MedAlign to evaluate 6 general domain LLMs, having clinicians rank the accuracy and quality of each LLM response. We found high error rates, ranging from 35% (GPT-4) to 68% (MPT-7B-Instruct), and an 8.3% drop in accuracy moving from 32k to 2k context lengths for GPT-4. Finally, we report correlations between clinician rankings and automated natural language generation metrics as a way to rank LLMs without human review. We make MedAlign available under a research data use agreement to enable LLM evaluations on tasks aligned with clinician needs and preferences.