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Mar 12

Generative Large Language Models Are All-purpose Text Analytics Engines: Text-to-text Learning Is All Your Need

Objective To solve major clinical natural language processing (NLP) tasks using a unified text-to-text learning architecture based on a generative large language model (LLM) via prompt tuning. Methods We formulated 7 key clinical NLP tasks as text-to-text learning and solved them using one unified generative clinical LLM, GatorTronGPT, developed using GPT-3 architecture and trained with up to 20 billion parameters. We adopted soft prompts (i.e., trainable vectors) with frozen LLM, where the LLM parameters were not updated (i.e., frozen) and only the vectors of soft prompts were updated, known as prompt tuning. We added additional soft prompts as a prefix to the input layer, which were optimized during the prompt tuning. We evaluated the proposed method using 7 clinical NLP tasks and compared them with previous task-specific solutions based on Transformer models. Results and Conclusion The proposed approach achieved state-of-the-art performance for 5 out of 7 major clinical NLP tasks using one unified generative LLM. Our approach outperformed previous task-specific transformer models by ~3% for concept extraction and 7% for relation extraction applied to social determinants of health, 3.4% for clinical concept normalization, 3.4~10% for clinical abbreviation disambiguation, and 5.5~9% for natural language inference. Our approach also outperformed a previously developed prompt-based machine reading comprehension (MRC) model, GatorTron-MRC, for clinical concept and relation extraction. The proposed approach can deliver the ``one model for all`` promise from training to deployment using a unified generative LLM.

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.

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.

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.

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.

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.

Dr-LLaVA: Visual Instruction Tuning with Symbolic Clinical Grounding

Vision-Language Models (VLM) can support clinicians by analyzing medical images and engaging in natural language interactions to assist in diagnostic and treatment tasks. However, VLMs often exhibit "hallucinogenic" behavior, generating textual outputs not grounded in contextual multimodal information. This challenge is particularly pronounced in the medical domain, where we do not only require VLM outputs to be accurate in single interactions but also to be consistent with clinical reasoning and diagnostic pathways throughout multi-turn conversations. For this purpose, we propose a new alignment algorithm that uses symbolic representations of clinical reasoning to ground VLMs in medical knowledge. These representations are utilized to (i) generate GPT-4-guided visual instruction tuning data at scale, simulating clinician-VLM conversations with demonstrations of clinical reasoning, and (ii) create an automatic reward function that evaluates the clinical validity of VLM generations throughout clinician-VLM interactions. Our algorithm eliminates the need for human involvement in training data generation or reward model construction, reducing costs compared to standard reinforcement learning with human feedback (RLHF). We apply our alignment algorithm to develop Dr-LLaVA, a conversational VLM finetuned for analyzing bone marrow pathology slides, demonstrating strong performance in multi-turn medical conversations.

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.

SEED-Bench: Benchmarking Multimodal LLMs with Generative Comprehension

Based on powerful Large Language Models (LLMs), recent generative Multimodal Large Language Models (MLLMs) have gained prominence as a pivotal research area, exhibiting remarkable capability for both comprehension and generation. In this work, we address the evaluation of generative comprehension in MLLMs as a preliminary step towards a comprehensive assessment of generative models, by introducing a benchmark named SEED-Bench. SEED-Bench consists of 19K multiple choice questions with accurate human annotations (x 6 larger than existing benchmarks), which spans 12 evaluation dimensions including the comprehension of both the image and video modality. We develop an advanced pipeline for generating multiple-choice questions that target specific evaluation dimensions, integrating both automatic filtering and manual verification processes. Multiple-choice questions with groundtruth options derived from human annotation enables an objective and efficient assessment of model performance, eliminating the need for human or GPT intervention during evaluation. We further evaluate the performance of 18 models across all 12 dimensions, covering both the spatial and temporal understanding. By revealing the limitations of existing MLLMs through evaluation results, we aim for SEED-Bench to provide insights for motivating future research. We will launch and consistently maintain a leaderboard to provide a platform for the community to assess and investigate model capability.

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.

Language Models And A Second Opinion Use Case: The Pocket Professional

This research tests the role of Large Language Models (LLMs) as formal second opinion tools in professional decision-making, particularly focusing on complex medical cases where even experienced physicians seek peer consultation. The work analyzed 183 challenging medical cases from Medscape over a 20-month period, testing multiple LLMs' performance against crowd-sourced physician responses. A key finding was the high overall score possible in the latest foundational models (>80% accuracy compared to consensus opinion), which exceeds most human metrics reported on the same clinical cases (450 pages of patient profiles, test results). The study rates the LLMs' performance disparity between straightforward cases (>81% accuracy) and complex scenarios (43% accuracy), particularly in these cases generating substantial debate among human physicians. The research demonstrates that LLMs may be valuable as generators of comprehensive differential diagnoses rather than as primary diagnostic tools, potentially helping to counter cognitive biases in clinical decision-making, reduce cognitive loads, and thus remove some sources of medical error. The inclusion of a second comparative legal dataset (Supreme Court cases, N=21) provides added empirical context to the AI use to foster second opinions, though these legal challenges proved considerably easier for LLMs to analyze. In addition to the original contributions of empirical evidence for LLM accuracy, the research aggregated a novel benchmark for others to score highly contested question and answer reliability between both LLMs and disagreeing human practitioners. These results suggest that the optimal deployment of LLMs in professional settings may differ substantially from current approaches that emphasize automation of routine tasks.

LLM-CXR: Instruction-Finetuned LLM for CXR Image Understanding and Generation

Following the impressive development of LLMs, vision-language alignment in LLMs is actively being researched to enable multimodal reasoning and visual IO. This direction of research is particularly relevant to medical imaging because medical image analysis and generation consist of reasoning based on a combination of visual features and prior knowledge. Many recent works have focused on training adapter networks that serve as an information bridge between image processing networks and LLMs; but presumably, in order to achieve maximum reasoning potential of LLMs on visual information as well, visual and language features should be allowed to interact more freely. This is especially important in the medical domain because understanding and generating medical images such as chest X-rays (CXR) require not only accurate visual and language-based reasoning but also a more intimate mapping between the two modalities. Thus, taking inspiration from previous work on the transformer and VQ-GAN combination for bidirectional image and text generation, we build upon this approach and develop a method for instruction-tuning an LLM pre-trained only on text to gain vision-language capabilities for medical images. Specifically, we leverage a pretrained LLM's existing question-answering and instruction-following abilities to teach it to understand visual inputs by instructing it to answer questions about image inputs and, symmetrically, output both text and image responses appropriate to a given query by tuning the LLM with diverse tasks that encompass image-based text-generation and text-based image-generation. We show that our model, LLM-CXR, trained in this approach shows better image-text alignment in both CXR understanding and generation tasks while being smaller in size compared to previously developed models that perform a narrower range of tasks. The code is at https://github.com/hyn2028/llm-cxr.

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.

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.

The Potential of LLMs in Medical Education: Generating Questions and Answers for Qualification Exams

Recent research on large language models (LLMs) has primarily focused on their adaptation and application in specialized domains. The application of LLMs in the medical field is mainly concentrated on tasks such as the automation of medical report generation, summarization, diagnostic reasoning, and question-and-answer interactions between doctors and patients. The challenge of becoming a good teacher is more formidable than that of becoming a good student, and this study pioneers the application of LLMs in the field of medical education. In this work, we investigate the extent to which LLMs can generate medical qualification exam questions and corresponding answers based on few-shot prompts. Utilizing a real-world Chinese dataset of elderly chronic diseases, we tasked the LLMs with generating open-ended questions and answers based on a subset of sampled admission reports across eight widely used LLMs, including ERNIE 4, ChatGLM 4, Doubao, Hunyuan, Spark 4, Qwen, Llama 3, and Mistral. Furthermore, we engaged medical experts to manually evaluate these open-ended questions and answers across multiple dimensions. The study found that LLMs, after using few-shot prompts, can effectively mimic real-world medical qualification exam questions, whereas there is room for improvement in the correctness, evidence-based statements, and professionalism of the generated answers. Moreover, LLMs also demonstrate a decent level of ability to correct and rectify reference answers. Given the immense potential of artificial intelligence in the medical field, the task of generating questions and answers for medical qualification exams aimed at medical students, interns and residents can be a significant focus of future research.

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.

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.

Large Language Models Encode Clinical Knowledge

Large language models (LLMs) have demonstrated impressive capabilities in natural language understanding and generation, but the quality bar for medical and clinical applications is high. Today, attempts to assess models' clinical knowledge typically rely on automated evaluations on limited benchmarks. There is no standard to evaluate model predictions and reasoning across a breadth of tasks. To address this, we present MultiMedQA, a benchmark combining six existing open question answering datasets spanning professional medical exams, research, and consumer queries; and HealthSearchQA, a new free-response dataset of medical questions searched online. We propose a framework for human evaluation of model answers along multiple axes including factuality, precision, possible harm, and bias. In addition, we evaluate PaLM (a 540-billion parameter LLM) and its instruction-tuned variant, Flan-PaLM, on MultiMedQA. Using a combination of prompting strategies, Flan-PaLM achieves state-of-the-art accuracy on every MultiMedQA multiple-choice dataset (MedQA, MedMCQA, PubMedQA, MMLU clinical topics), including 67.6% accuracy on MedQA (US Medical License Exam questions), surpassing prior state-of-the-art by over 17%. However, human evaluation reveals key gaps in Flan-PaLM responses. To resolve this we introduce instruction prompt tuning, a parameter-efficient approach for aligning LLMs to new domains using a few exemplars. The resulting model, Med-PaLM, performs encouragingly, but remains inferior to clinicians. We show that comprehension, recall of knowledge, and medical reasoning improve with model scale and instruction prompt tuning, suggesting the potential utility of LLMs in medicine. Our human evaluations reveal important limitations of today's models, reinforcing the importance of both evaluation frameworks and method development in creating safe, helpful LLM models for clinical applications.

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.

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.

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.

A Paradigm Shift in Machine Translation: Boosting Translation Performance of Large Language Models

Generative Large Language Models (LLMs) have achieved remarkable advancements in various NLP tasks. However, these advances have not been reflected in the translation task, especially those with moderate model sizes (i.e., 7B or 13B parameters), which still lag behind conventional supervised encoder-decoder translation models. Previous studies have attempted to improve the translation capabilities of these moderate LLMs, but their gains have been limited. In this study, we propose a novel fine-tuning approach for LLMs that is specifically designed for the translation task, eliminating the need for the abundant parallel data that traditional translation models usually depend on. Our approach consists of two fine-tuning stages: initial fine-tuning on monolingual data followed by subsequent fine-tuning on a small set of high-quality parallel data. We introduce the LLM developed through this strategy as Advanced Language Model-based trAnslator (ALMA). Based on LLaMA-2 as our underlying model, our results show that the model can achieve an average improvement of more than 12 BLEU and 12 COMET over its zero-shot performance across 10 translation directions from the WMT'21 (2 directions) and WMT'22 (8 directions) test datasets. The performance is significantly better than all prior work and even superior to the NLLB-54B model and GPT-3.5-text-davinci-003, with only 7B or 13B parameters. This method establishes the foundation for a novel training paradigm in machine translation.

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.

Supervised Knowledge Makes Large Language Models Better In-context Learners

Large Language Models (LLMs) exhibit emerging in-context learning abilities through prompt engineering. The recent progress in large-scale generative models has further expanded their use in real-world language applications. However, the critical challenge of improving the generalizability and factuality of LLMs in natural language understanding and question answering remains under-explored. While previous in-context learning research has focused on enhancing models to adhere to users' specific instructions and quality expectations, and to avoid undesired outputs, little to no work has explored the use of task-Specific fine-tuned Language Models (SLMs) to improve LLMs' in-context learning during the inference stage. Our primary contribution is the establishment of a simple yet effective framework that enhances the reliability of LLMs as it: 1) generalizes out-of-distribution data, 2) elucidates how LLMs benefit from discriminative models, and 3) minimizes hallucinations in generative tasks. Using our proposed plug-in method, enhanced versions of Llama 2 and ChatGPT surpass their original versions regarding generalizability and factuality. We offer a comprehensive suite of resources, including 16 curated datasets, prompts, model checkpoints, and LLM outputs across 9 distinct tasks. Our empirical analysis sheds light on the advantages of incorporating discriminative models into LLMs and highlights the potential of our methodology in fostering more reliable LLMs.

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.

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.

PathAsst: A Generative Foundation AI Assistant Towards Artificial General Intelligence of Pathology

As advances in large language models (LLMs) and multimodal techniques continue to mature, the development of general-purpose multimodal large language models (MLLMs) has surged, offering significant applications in interpreting natural images. However, the field of pathology has largely remained untapped, particularly in gathering high-quality data and designing comprehensive model frameworks. To bridge the gap in pathology MLLMs, we present PathAsst, a multimodal generative foundation AI assistant to revolutionize diagnostic and predictive analytics in pathology. The development of PathAsst involves three pivotal steps: data acquisition, CLIP model adaptation, and the training of PathAsst's multimodal generative capabilities. Firstly, we collect over 207K high-quality pathology image-text pairs from authoritative sources. Leveraging the advanced power of ChatGPT, we generate over 180K instruction-following samples. Furthermore, we devise additional instruction-following data specifically tailored for invoking eight pathology-specific sub-models we prepared, allowing the PathAsst to effectively collaborate with these models, enhancing its diagnostic ability. Secondly, by leveraging the collected data, we construct PathCLIP, a pathology-dedicated CLIP, to enhance PathAsst's capabilities in interpreting pathology images. Finally, we integrate PathCLIP with the Vicuna-13b and utilize pathology-specific instruction-tuning data to enhance the multimodal generation capacity of PathAsst and bolster its synergistic interactions with sub-models. The experimental results of PathAsst show the potential of harnessing AI-powered generative foundation model to improve pathology diagnosis and treatment processes.

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.

ChatCAD: Interactive Computer-Aided Diagnosis on Medical Image using Large Language Models

Large language models (LLMs) have recently demonstrated their potential in clinical applications, providing valuable medical knowledge and advice. For example, a large dialog LLM like ChatGPT has successfully passed part of the US medical licensing exam. However, LLMs currently have difficulty processing images, making it challenging to interpret information from medical images, which are rich in information that supports clinical decisions. On the other hand, computer-aided diagnosis (CAD) networks for medical images have seen significant success in the medical field by using advanced deep-learning algorithms to support clinical decision-making. This paper presents a method for integrating LLMs into medical-image CAD networks. The proposed framework uses LLMs to enhance the output of multiple CAD networks, such as diagnosis networks, lesion segmentation networks, and report generation networks, by summarizing and reorganizing the information presented in natural language text format. The goal is to merge the strengths of LLMs' medical domain knowledge and logical reasoning with the vision understanding capability of existing medical-image CAD models to create a more user-friendly and understandable system for patients compared to conventional CAD systems. In the future, LLM's medical knowledge can be also used to improve the performance of vision-based medical-image CAD models.

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.

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.

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.

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.

Generalization in Healthcare AI: Evaluation of a Clinical Large Language Model

Advances in large language models (LLMs) provide new opportunities in healthcare for improved patient care, clinical decision-making, and enhancement of physician and administrator workflows. However, the potential of these models importantly depends on their ability to generalize effectively across clinical environments and populations, a challenge often underestimated in early development. To better understand reasons for these challenges and inform mitigation approaches, we evaluated ClinicLLM, an LLM trained on [HOSPITAL]'s clinical notes, analyzing its performance on 30-day all-cause readmission prediction focusing on variability across hospitals and patient characteristics. We found poorer generalization particularly in hospitals with fewer samples, among patients with government and unspecified insurance, the elderly, and those with high comorbidities. To understand reasons for lack of generalization, we investigated sample sizes for fine-tuning, note content (number of words per note), patient characteristics (comorbidity level, age, insurance type, borough), and health system aspects (hospital, all-cause 30-day readmission, and mortality rates). We used descriptive statistics and supervised classification to identify features. We found that, along with sample size, patient age, number of comorbidities, and the number of words in notes are all important factors related to generalization. Finally, we compared local fine-tuning (hospital specific), instance-based augmented fine-tuning and cluster-based fine-tuning for improving generalization. Among these, local fine-tuning proved most effective, increasing AUC by 0.25% to 11.74% (most helpful in settings with limited data). Overall, this study provides new insights for enhancing the deployment of large language models in the societally important domain of healthcare, and improving their performance for broader populations.

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.

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.

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.

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.

LLaVA-Med: Training a Large Language-and-Vision Assistant for Biomedicine in One Day

Conversational generative AI has demonstrated remarkable promise for empowering biomedical practitioners, but current investigations focus on unimodal text. Multimodal conversational AI has seen rapid progress by leveraging billions of image-text pairs from the public web, but such general-domain vision-language models still lack sophistication in understanding and conversing about biomedical images. In this paper, we propose a cost-efficient approach for training a vision-language conversational assistant that can answer open-ended research questions of biomedical images. The key idea is to leverage a large-scale, broad-coverage biomedical figure-caption dataset extracted from PubMed Central, use GPT-4 to self-instruct open-ended instruction-following data from the captions, and then fine-tune a large general-domain vision-language model using a novel curriculum learning method. Specifically, the model first learns to align biomedical vocabulary using the figure-caption pairs as is, then learns to master open-ended conversational semantics using GPT-4 generated instruction-following data, broadly mimicking how a layperson gradually acquires biomedical knowledge. This enables us to train a Large Language and Vision Assistant for BioMedicine (LLaVA-Med) in less than 15 hours (with eight A100s). LLaVA-Med exhibits excellent multimodal conversational capability and can follow open-ended instruction to assist with inquiries about a biomedical image. On three standard biomedical visual question answering datasets, LLaVA-Med outperforms previous supervised state-of-the-art on certain metrics. To facilitate biomedical multimodal research, we will release our instruction-following data and the LLaVA-Med model.

RULE: Reliable Multimodal RAG for Factuality in Medical Vision Language Models

The recent emergence of Medical Large Vision Language Models (Med-LVLMs) has enhanced medical diagnosis. However, current Med-LVLMs frequently encounter factual issues, often generating responses that do not align with established medical facts. Retrieval-Augmented Generation (RAG), which utilizes external knowledge, can improve the factual accuracy of these models but introduces two major challenges. First, limited retrieved contexts might not cover all necessary information, while excessive retrieval can introduce irrelevant and inaccurate references, interfering with the model's generation. Second, in cases where the model originally responds correctly, applying RAG can lead to an over-reliance on retrieved contexts, resulting in incorrect answers. To address these issues, we propose RULE, which consists of two components. First, we introduce a provably effective strategy for controlling factuality risk through the calibrated selection of the number of retrieved contexts. Second, based on samples where over-reliance on retrieved contexts led to errors, we curate a preference dataset to fine-tune the model, balancing its dependence on inherent knowledge and retrieved contexts for generation. We demonstrate the effectiveness of RULE on three medical VQA datasets, achieving an average improvement of 20.8% in factual accuracy. We publicly release our benchmark and code in https://github.com/richard-peng-xia/RULE.

ASTRAL: Automated Safety Testing of Large Language Models

Large Language Models (LLMs) have recently gained attention due to their ability to understand and generate sophisticated human-like content. However, ensuring their safety is paramount as they might provide harmful and unsafe responses. Existing LLM testing frameworks address various safety-related concerns (e.g., drugs, terrorism, animal abuse) but often face challenges due to unbalanced and obsolete datasets. In this paper, we present ASTRAL, a tool that automates the generation and execution of test cases (i.e., prompts) for testing the safety of LLMs. First, we introduce a novel black-box coverage criterion to generate balanced and diverse unsafe test inputs across a diverse set of safety categories as well as linguistic writing characteristics (i.e., different style and persuasive writing techniques). Second, we propose an LLM-based approach that leverages Retrieval Augmented Generation (RAG), few-shot prompting strategies and web browsing to generate up-to-date test inputs. Lastly, similar to current LLM test automation techniques, we leverage LLMs as test oracles to distinguish between safe and unsafe test outputs, allowing a fully automated testing approach. We conduct an extensive evaluation on well-known LLMs, revealing the following key findings: i) GPT3.5 outperforms other LLMs when acting as the test oracle, accurately detecting unsafe responses, and even surpassing more recent LLMs (e.g., GPT-4), as well as LLMs that are specifically tailored to detect unsafe LLM outputs (e.g., LlamaGuard); ii) the results confirm that our approach can uncover nearly twice as many unsafe LLM behaviors with the same number of test inputs compared to currently used static datasets; and iii) our black-box coverage criterion combined with web browsing can effectively guide the LLM on generating up-to-date unsafe test inputs, significantly increasing the number of unsafe LLM behaviors.

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.

Adaptive Inference-Time Compute: LLMs Can Predict if They Can Do Better, Even Mid-Generation

Inference-time computation is a powerful paradigm to enhance the performance of large language models (LLMs), with Best-of-N sampling being a widely used technique. However, this method is computationally expensive, requiring both (1) an external reward model and (2) the generation of multiple samples. In this work, we introduce a new generative self-evaluation scheme designed to adaptively reduce the number of generated samples while maintaining or even improving performance. We use a generative reward model formulation, allowing the LLM to predict mid-generation the probability that restarting the generation will yield a better response. These predictions are obtained without an external reward model and can be used to decide whether or not to generate more samples, prune unpromising samples early on, or to pick the best sample. This capability is very inexpensive as it involves generating a single predefined token. Trained using a dataset constructed with real unfiltered LMSYS user prompts, Llama 3.1 8B's win rate against GPT-4 on AlpacaEval increases from 21% to 34% with 16 samples and math performance on GSM8K improves from 84% to 91%. By sampling only when the LLM determines that it is beneficial to do so and adaptively adjusting temperature annealing, we demonstrate that 74% of the improvement from using 16 samples can be achieved with only 1.2 samples on average. We further demonstrate that 50-75% of samples can be pruned early in generation with minimal degradation in performance. Overall, our methods enable more efficient and scalable compute utilization during inference for LLMs.

Tool Calling: Enhancing Medication Consultation via Retrieval-Augmented Large Language Models

Large-scale language models (LLMs) have achieved remarkable success across various language tasks but suffer from hallucinations and temporal misalignment. To mitigate these shortcomings, Retrieval-augmented generation (RAG) has been utilized to provide external knowledge to facilitate the answer generation. However, applying such models to the medical domain faces several challenges due to the lack of domain-specific knowledge and the intricacy of real-world scenarios. In this study, we explore LLMs with RAG framework for knowledge-intensive tasks in the medical field. To evaluate the capabilities of LLMs, we introduce MedicineQA, a multi-round dialogue benchmark that simulates the real-world medication consultation scenario and requires LLMs to answer with retrieved evidence from the medicine database. MedicineQA contains 300 multi-round question-answering pairs, each embedded within a detailed dialogue history, highlighting the challenge posed by this knowledge-intensive task to current LLMs. We further propose a new Distill-Retrieve-Read framework instead of the previous Retrieve-then-Read. Specifically, the distillation and retrieval process utilizes a tool calling mechanism to formulate search queries that emulate the keyword-based inquiries used by search engines. With experimental results, we show that our framework brings notable performance improvements and surpasses the previous counterparts in the evidence retrieval process in terms of evidence retrieval accuracy. This advancement sheds light on applying RAG to the medical domain.

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.

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.

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.

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.

Rare Disease Differential Diagnosis with Large Language Models at Scale: From Abdominal Actinomycosis to Wilson's Disease

Large language models (LLMs) have demonstrated impressive capabilities in disease diagnosis. However, their effectiveness in identifying rarer diseases, which are inherently more challenging to diagnose, remains an open question. Rare disease performance is critical with the increasing use of LLMs in healthcare settings. This is especially true if a primary care physician needs to make a rarer prognosis from only a patient conversation so that they can take the appropriate next step. To that end, several clinical decision support systems are designed to support providers in rare disease identification. Yet their utility is limited due to their lack of knowledge of common disorders and difficulty of use. In this paper, we propose RareScale to combine the knowledge LLMs with expert systems. We use jointly use an expert system and LLM to simulate rare disease chats. This data is used to train a rare disease candidate predictor model. Candidates from this smaller model are then used as additional inputs to black-box LLM to make the final differential diagnosis. Thus, RareScale allows for a balance between rare and common diagnoses. We present results on over 575 rare diseases, beginning with Abdominal Actinomycosis and ending with Wilson's Disease. Our approach significantly improves the baseline performance of black-box LLMs by over 17% in Top-5 accuracy. We also find that our candidate generation performance is high (e.g. 88.8% on gpt-4o generated chats).

M^{2}UGen: Multi-modal Music Understanding and Generation with the Power of Large Language Models

The current landscape of research leveraging large language models (LLMs) is experiencing a surge. Many works harness the powerful reasoning capabilities of these models to comprehend various modalities, such as text, speech, images, videos, etc. They also utilize LLMs to understand human intention and generate desired outputs like images, videos, and music. However, research that combines both understanding and generation using LLMs is still limited and in its nascent stage. To address this gap, we introduce a Multi-modal Music Understanding and Generation (M^{2}UGen) framework that integrates LLM's abilities to comprehend and generate music for different modalities. The M^{2}UGen framework is purpose-built to unlock creative potential from diverse sources of inspiration, encompassing music, image, and video through the use of pretrained MERT, ViT, and ViViT models, respectively. To enable music generation, we explore the use of AudioLDM 2 and MusicGen. Bridging multi-modal understanding and music generation is accomplished through the integration of the LLaMA 2 model. Furthermore, we make use of the MU-LLaMA model to generate extensive datasets that support text/image/video-to-music generation, facilitating the training of our M^{2}UGen framework. We conduct a thorough evaluation of our proposed framework. The experimental results demonstrate that our model achieves or surpasses the performance of the current state-of-the-art models.

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.

Generating Synthetic Documents for Cross-Encoder Re-Rankers: A Comparative Study of ChatGPT and Human Experts

We investigate the usefulness of generative Large Language Models (LLMs) in generating training data for cross-encoder re-rankers in a novel direction: generating synthetic documents instead of synthetic queries. We introduce a new dataset, ChatGPT-RetrievalQA, and compare the effectiveness of models fine-tuned on LLM-generated and human-generated data. Data generated with generative LLMs can be used to augment training data, especially in domains with smaller amounts of labeled data. We build ChatGPT-RetrievalQA based on an existing dataset, human ChatGPT Comparison Corpus (HC3), consisting of public question collections with human responses and answers from ChatGPT. We fine-tune a range of cross-encoder re-rankers on either human-generated or ChatGPT-generated data. Our evaluation on MS MARCO DEV, TREC DL'19, and TREC DL'20 demonstrates that cross-encoder re-ranking models trained on ChatGPT responses are statistically significantly more effective zero-shot re-rankers than those trained on human responses. In a supervised setting, the human-trained re-rankers outperform the LLM-trained re-rankers. Our novel findings suggest that generative LLMs have high potential in generating training data for neural retrieval models. Further work is needed to determine the effect of factually wrong information in the generated responses and test our findings' generalizability with open-source LLMs. We release our data, code, and cross-encoders checkpoints for future work.

Math Agents: Computational Infrastructure, Mathematical Embedding, and Genomics

The advancement in generative AI could be boosted with more accessible mathematics. Beyond human-AI chat, large language models (LLMs) are emerging in programming, algorithm discovery, and theorem proving, yet their genomics application is limited. This project introduces Math Agents and mathematical embedding as fresh entries to the "Moore's Law of Mathematics", using a GPT-based workflow to convert equations from literature into LaTeX and Python formats. While many digital equation representations exist, there's a lack of automated large-scale evaluation tools. LLMs are pivotal as linguistic user interfaces, providing natural language access for human-AI chat and formal languages for large-scale AI-assisted computational infrastructure. Given the infinite formal possibility spaces, Math Agents, which interact with math, could potentially shift us from "big data" to "big math". Math, unlike the more flexible natural language, has properties subject to proof, enabling its use beyond traditional applications like high-validation math-certified icons for AI alignment aims. This project aims to use Math Agents and mathematical embeddings to address the ageing issue in information systems biology by applying multiscalar physics mathematics to disease models and genomic data. Generative AI with episodic memory could help analyse causal relations in longitudinal health records, using SIR Precision Health models. Genomic data is suggested for addressing the unsolved Alzheimer's disease problem.

Interpretable Bilingual Multimodal Large Language Model for Diverse Biomedical Tasks

Several medical Multimodal Large Languange Models (MLLMs) have been developed to address tasks involving visual images with textual instructions across various medical modalities, achieving impressive results. Most current medical generalist models are region-agnostic, treating the entire image as a holistic representation. However, they struggle to identify which specific regions they are focusing on when generating a sentence. To mimic the behavior of doctors, who typically begin by reviewing the entire image before concentrating on specific regions for a thorough evaluation, we aim to enhance the capability of medical MLLMs in understanding anatomical regions within entire medical scans. To achieve it, we first formulate Region-Centric tasks and construct a large-scale dataset, MedRegInstruct, to incorporate regional information into training. Combining our collected dataset with other medical multimodal corpora for training, we propose a Region-Aware medical MLLM, MedRegA, which is the first bilingual generalist medical AI system to simultaneously handle image-level and region-level medical vision-language tasks across a broad range of modalities. Our MedRegA not only enables three region-centric tasks, but also achieves the best performance for visual question answering, report generation and medical image classification over 8 modalities, showcasing significant versatility. Experiments demonstrate that our model can not only accomplish powerful performance across various medical vision-language tasks in bilingual settings, but also recognize and detect structures in multimodal medical scans, boosting the interpretability and user interactivity of medical MLLMs. Our project page is https://medrega.github.io.

MMed-RAG: Versatile Multimodal RAG System for Medical Vision Language Models

Artificial Intelligence (AI) has demonstrated significant potential in healthcare, particularly in disease diagnosis and treatment planning. Recent progress in Medical Large Vision-Language Models (Med-LVLMs) has opened up new possibilities for interactive diagnostic tools. However, these models often suffer from factual hallucination, which can lead to incorrect diagnoses. Fine-tuning and retrieval-augmented generation (RAG) have emerged as methods to address these issues. However, the amount of high-quality data and distribution shifts between training data and deployment data limit the application of fine-tuning methods. Although RAG is lightweight and effective, existing RAG-based approaches are not sufficiently general to different medical domains and can potentially cause misalignment issues, both between modalities and between the model and the ground truth. In this paper, we propose a versatile multimodal RAG system, MMed-RAG, designed to enhance the factuality of Med-LVLMs. Our approach introduces a domain-aware retrieval mechanism, an adaptive retrieved contexts selection method, and a provable RAG-based preference fine-tuning strategy. These innovations make the RAG process sufficiently general and reliable, significantly improving alignment when introducing retrieved contexts. Experimental results across five medical datasets (involving radiology, ophthalmology, pathology) on medical VQA and report generation demonstrate that MMed-RAG can achieve an average improvement of 43.8% in the factual accuracy of Med-LVLMs. Our data and code are available in https://github.com/richard-peng-xia/MMed-RAG.

On the Compositional Generalization of Multimodal LLMs for Medical Imaging

Multimodal large language models (MLLMs) hold significant potential in the medical field, but their capabilities are often limited by insufficient data in certain medical domains, highlighting the need for understanding what kinds of images can be used by MLLMs for generalization. Current research suggests that multi-task training outperforms single-task as different tasks can benefit each other, but they often overlook the internal relationships within these tasks, providing limited guidance on selecting datasets to enhance specific tasks. To analyze this phenomenon, we attempted to employ compositional generalization (CG)-the ability of models to understand novel combinations by recombining learned elements-as a guiding framework. Since medical images can be precisely defined by Modality, Anatomical area, and Task, naturally providing an environment for exploring CG. Therefore, we assembled 106 medical datasets to create Med-MAT for comprehensive experiments. The experiments confirmed that MLLMs can use CG to understand unseen medical images and identified CG as one of the main drivers of the generalization observed in multi-task training. Additionally, further studies demonstrated that CG effectively supports datasets with limited data and delivers consistent performance across different backbones, highlighting its versatility and broad applicability. Med-MAT is publicly available at https://github.com/FreedomIntelligence/Med-MAT.

GPT4Video: A Unified Multimodal Large Language Model for lnstruction-Followed Understanding and Safety-Aware Generation

While the recent advances in Multimodal Large Language Models (MLLMs) constitute a significant leap forward in the field, these models are predominantly confined to the realm of input-side multimodal comprehension, lacking the capacity for multimodal content generation. To fill this gap, we present GPT4Video, a unified multi-model framework that empowers Large Language Models (LLMs) with the capability of both video understanding and generation. Specifically, we develop an instruction-following-based approach integrated with the stable diffusion generative model, which has demonstrated to effectively and securely handle video generation scenarios. GPT4Video offers the following benefits: 1) It exhibits impressive capabilities in both video understanding and generation scenarios. For example, GPT4Video outperforms Valley by 11.8\% on the Video Question Answering task, and surpasses NExt-GPT by 2.3\% on the Text to Video generation task. 2) it endows the LLM/MLLM with video generation capabilities without requiring additional training parameters and can flexibly interface with a wide range of models to perform video generation. 3) it maintains a safe and healthy conversation not only in output-side but also the input side in an end-to-end manner. Qualitative and qualitative experiments demonstrate that GPT4Video holds the potential to function as a effective, safe and Humanoid-like video assistant that can handle both video understanding and generation scenarios.

SemiHVision: Enhancing Medical Multimodal Models with a Semi-Human Annotated Dataset and Fine-Tuned Instruction Generation

Multimodal large language models (MLLMs) have made significant strides, yet they face challenges in the medical domain due to limited specialized knowledge. While recent medical MLLMs demonstrate strong performance in lab settings, they often struggle in real-world applications, highlighting a substantial gap between research and practice. In this paper, we seek to address this gap at various stages of the end-to-end learning pipeline, including data collection, model fine-tuning, and evaluation. At the data collection stage, we introduce SemiHVision, a dataset that combines human annotations with automated augmentation techniques to improve both medical knowledge representation and diagnostic reasoning. For model fine-tuning, we trained PMC-Cambrian-8B-AN over 2400 H100 GPU hours, resulting in performance that surpasses public medical models like HuatuoGPT-Vision-34B (79.0% vs. 66.7%) and private general models like Claude3-Opus (55.7%) on traditional benchmarks such as SLAKE and VQA-RAD. In the evaluation phase, we observed that traditional benchmarks cannot accurately reflect realistic clinical task capabilities. To overcome this limitation and provide more targeted guidance for model evaluation, we introduce the JAMA Clinical Challenge, a novel benchmark specifically designed to evaluate diagnostic reasoning. On this benchmark, PMC-Cambrian-AN achieves state-of-the-art performance with a GPT-4 score of 1.29, significantly outperforming HuatuoGPT-Vision-34B (1.13) and Claude3-Opus (1.17), demonstrating its superior diagnostic reasoning abilities.

HALoGEN: Fantastic LLM Hallucinations and Where to Find Them

Despite their impressive ability to generate high-quality and fluent text, generative large language models (LLMs) also produce hallucinations: statements that are misaligned with established world knowledge or provided input context. However, measuring hallucination can be challenging, as having humans verify model generations on-the-fly is both expensive and time-consuming. In this work, we release HALoGEN, a comprehensive hallucination benchmark consisting of: (1) 10,923 prompts for generative models spanning nine domains including programming, scientific attribution, and summarization, and (2) automatic high-precision verifiers for each use case that decompose LLM generations into atomic units, and verify each unit against a high-quality knowledge source. We use this framework to evaluate ~150,000 generations from 14 language models, finding that even the best-performing models are riddled with hallucinations (sometimes up to 86% of generated atomic facts depending on the domain). We further define a novel error classification for LLM hallucinations based on whether they likely stem from incorrect recollection of training data (Type A errors), or incorrect knowledge in training data (Type B errors), or are fabrication (Type C errors). We hope our framework provides a foundation to enable the principled study of why generative models hallucinate, and advances the development of trustworthy large language models.

Vi(E)va LLM! A Conceptual Stack for Evaluating and Interpreting Generative AI-based Visualizations

The automatic generation of visualizations is an old task that, through the years, has shown more and more interest from the research and practitioner communities. Recently, large language models (LLM) have become an interesting option for supporting generative tasks related to visualization, demonstrating initial promising results. At the same time, several pitfalls, like the multiple ways of instructing an LLM to generate the desired result, the different perspectives leading the generation (code-based, image-based, grammar-based), and the presence of hallucinations even for the visualization generation task, make their usage less affordable than expected. Following similar initiatives for benchmarking LLMs, this paper copes with the problem of modeling the evaluation of a generated visualization through an LLM. We propose a theoretical evaluation stack, EvaLLM, that decomposes the evaluation effort in its atomic components, characterizes their nature, and provides an overview of how to implement and interpret them. We also designed and implemented an evaluation platform that provides a benchmarking resource for the visualization generation task. The platform supports automatic and manual scoring conducted by multiple assessors to support a fine-grained and semantic evaluation based on the EvaLLM stack. Two case studies on GPT3.5-turbo with Code Interpreter and Llama2-70-b models show the benefits of EvaLLM and illustrate interesting results on the current state-of-the-art LLM-generated visualizations.

Improving Medical Reasoning through Retrieval and Self-Reflection with Retrieval-Augmented Large Language Models

Recent proprietary large language models (LLMs), such as GPT-4, have achieved a milestone in tackling diverse challenges in the biomedical domain, ranging from multiple-choice questions to long-form generations. To address challenges that still cannot be handled with the encoded knowledge of LLMs, various retrieval-augmented generation (RAG) methods have been developed by searching documents from the knowledge corpus and appending them unconditionally or selectively to the input of LLMs for generation. However, when applying existing methods to different domain-specific problems, poor generalization becomes apparent, leading to fetching incorrect documents or making inaccurate judgments. In this paper, we introduce Self-BioRAG, a framework reliable for biomedical text that specializes in generating explanations, retrieving domain-specific documents, and self-reflecting generated responses. We utilize 84k filtered biomedical instruction sets to train Self-BioRAG that can assess its generated explanations with customized reflective tokens. Our work proves that domain-specific components, such as a retriever, domain-related document corpus, and instruction sets are necessary for adhering to domain-related instructions. Using three major medical question-answering benchmark datasets, experimental results of Self-BioRAG demonstrate significant performance gains by achieving a 7.2% absolute improvement on average over the state-of-the-art open-foundation model with a parameter size of 7B or less. Overall, we analyze that Self-BioRAG finds the clues in the question, retrieves relevant documents if needed, and understands how to answer with information from retrieved documents and encoded knowledge as a medical expert does. We release our data and code for training our framework components and model weights (7B and 13B) to enhance capabilities in biomedical and clinical domains.

GMAI-MMBench: A Comprehensive Multimodal Evaluation Benchmark Towards General Medical AI

Large Vision-Language Models (LVLMs) are capable of handling diverse data types such as imaging, text, and physiological signals, and can be applied in various fields. In the medical field, LVLMs have a high potential to offer substantial assistance for diagnosis and treatment. Before that, it is crucial to develop benchmarks to evaluate LVLMs' effectiveness in various medical applications. Current benchmarks are often built upon specific academic literature, mainly focusing on a single domain, and lacking varying perceptual granularities. Thus, they face specific challenges, including limited clinical relevance, incomplete evaluations, and insufficient guidance for interactive LVLMs. To address these limitations, we developed the GMAI-MMBench, the most comprehensive general medical AI benchmark with well-categorized data structure and multi-perceptual granularity to date. It is constructed from 285 datasets across 39 medical image modalities, 18 clinical-related tasks, 18 departments, and 4 perceptual granularities in a Visual Question Answering (VQA) format. Additionally, we implemented a lexical tree structure that allows users to customize evaluation tasks, accommodating various assessment needs and substantially supporting medical AI research and applications. We evaluated 50 LVLMs, and the results show that even the advanced GPT-4o only achieves an accuracy of 52%, indicating significant room for improvement. Moreover, we identified five key insufficiencies in current cutting-edge LVLMs that need to be addressed to advance the development of better medical applications. We believe that GMAI-MMBench will stimulate the community to build the next generation of LVLMs toward GMAI. Project Page: https://uni-medical.github.io/GMAI-MMBench.github.io/

ChiMed-GPT: A Chinese Medical Large Language Model with Full Training Regime and Better Alignment to Human Preferences

Recently, the increasing demand for superior medical services has highlighted the discrepancies in the medical infrastructure. With big data, especially texts, forming the foundation of medical services, there is an exigent need for effective natural language processing (NLP) solutions tailored to the healthcare domain. Conventional approaches leveraging pre-trained models present promising results in this domain and current large language models (LLMs) offer advanced foundation for medical text processing. However, most medical LLMs are trained only with supervised fine-tuning (SFT), even though it efficiently empowers LLMs to understand and respond to medical instructions but is ineffective in learning domain knowledge and aligning with human preference. Another engineering barrier that prevents current medical LLM from better text processing ability is their restricted context length (e.g., 2,048 tokens), making it hard for the LLMs to process long context, which is frequently required in the medical domain. In this work, we propose ChiMed-GPT, a new benchmark LLM designed explicitly for Chinese medical domain, with enlarged context length to 4,096 tokens and undergoes a comprehensive training regime with pre-training, SFT, and RLHF. Evaluations on real-world tasks including information extraction, question answering, and dialogue generation demonstrate ChiMed-GPT's superior performance over general domain LLMs. Furthermore, we analyze possible biases through prompting ChiMed-GPT to perform attitude scales regarding discrimination of patients, so as to contribute to further responsible development of LLMs in the medical domain. The code and model are released at https://github.com/synlp/ChiMed-GPT.

Exploring Multimodal Large Language Models for Radiology Report Error-checking

This paper proposes one of the first clinical applications of multimodal large language models (LLMs) as an assistant for radiologists to check errors in their reports. We created an evaluation dataset from two real-world radiology datasets (MIMIC-CXR and IU-Xray), with 1,000 subsampled reports each. A subset of original reports was modified to contain synthetic errors by introducing various type of mistakes. The evaluation contained two difficulty levels: SIMPLE for binary error-checking and COMPLEX for identifying error types. LLaVA (Large Language and Visual Assistant) variant models, including our instruction-tuned model, were used for the evaluation. Additionally, a domain expert evaluation was conducted on a small test set. At the SIMPLE level, the LLaVA v1.5 model outperformed other publicly available models. Instruction tuning significantly enhanced performance by 47.4% and 25.4% on MIMIC-CXR and IU-Xray data, respectively. The model also surpassed the domain experts accuracy in the MIMIC-CXR dataset by 1.67%. Notably, among the subsets (N=21) of the test set where a clinician did not achieve the correct conclusion, the LLaVA ensemble mode correctly identified 71.4% of these cases. This study marks a promising step toward utilizing multi-modal LLMs to enhance diagnostic accuracy in radiology. The ensemble model demonstrated comparable performance to clinicians, even capturing errors overlooked by humans. Nevertheless, future work is needed to improve the model ability to identify the types of inconsistency.

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.

Interactive Agents: Simulating Counselor-Client Psychological Counseling via Role-Playing LLM-to-LLM Interactions

Virtual counselors powered by large language models (LLMs) aim to create interactive support systems that effectively assist clients struggling with mental health challenges. To replicate counselor-client conversations, researchers have built an online mental health platform that allows professional counselors to provide clients with text-based counseling services for about an hour per session. Notwithstanding its effectiveness, challenges exist as human annotation is time-consuming, cost-intensive, privacy-protected, and not scalable. To address this issue and investigate the applicability of LLMs in psychological counseling conversation simulation, we propose a framework that employs two LLMs via role-playing for simulating counselor-client interactions. Our framework involves two LLMs, one acting as a client equipped with a specific and real-life user profile and the other playing the role of an experienced counselor, generating professional responses using integrative therapy techniques. We implement both the counselor and the client by zero-shot prompting the GPT-4 model. In order to assess the effectiveness of LLMs in simulating counselor-client interactions and understand the disparities between LLM- and human-generated conversations, we evaluate the synthetic data from various perspectives. We begin by assessing the client's performance through automatic evaluations. Next, we analyze and compare the disparities between dialogues generated by the LLM and those generated by professional counselors. Furthermore, we conduct extensive experiments to thoroughly examine the performance of our LLM-based counselor trained with synthetic interactive dialogues by benchmarking against state-of-the-art models for mental health.

Aligned with LLM: a new multi-modal training paradigm for encoding fMRI activity in visual cortex

Recently, there has been a surge in the popularity of pre trained large language models (LLMs) (such as GPT-4), sweeping across the entire Natural Language Processing (NLP) and Computer Vision (CV) communities. These LLMs have demonstrated advanced multi-modal understanding capabilities and showcased strong performance across various benchmarks. The LLM has started to embody traits of artificial general intelligence, which holds vital guidance for enhancing brain-like characteristics within visual encoding models. Hence, This paper proposes a new multi-modal training paradigm, aligning with LLM, for encoding fMRI activity in visual cortex. Based on this paradigm, we trained an encoding model in fMRI data named the LLM-Visual Encoding Model (LLM-VEM). Specifically, we utilize LLM (miniGPT4) to generate descriptive text for all stimulus images, forming a high-quality textual description set. Moreover, we use the pre-trained text encoder (CLIP) to process these detailed descriptions, obtaining the text embedding features. Next, we use the contrast loss function to minimize the distance between the image embedding features and the text embedding features to complete the alignment operation of the stimulus image and text information. With the assistance of the pre-trained LLM, this alignment process facilitates better learning of the visual encoding model, resulting in higher precision. The final experimental results indicate that our training paradigm has significantly aided in enhancing the performance of the visual encoding model.

Zhongjing: Enhancing the Chinese Medical Capabilities of Large Language Model through Expert Feedback and Real-world Multi-turn Dialogue

Recent advances in Large Language Models (LLMs) have achieved remarkable breakthroughs in understanding and responding to user intents. However, their performance lag behind general use cases in some expertise domains, such as Chinese medicine. Existing efforts to incorporate Chinese medicine into LLMs rely on Supervised Fine-Tuning (SFT) with single-turn and distilled dialogue data. These models lack the ability for doctor-like proactive inquiry and multi-turn comprehension and cannot align responses with experts' intentions. In this work, we introduce Zhongjing, the first Chinese medical LLaMA-based LLM that implements an entire training pipeline from continuous pre-training, SFT, to Reinforcement Learning from Human Feedback (RLHF). Additionally, we construct a Chinese multi-turn medical dialogue dataset of 70,000 authentic doctor-patient dialogues, CMtMedQA, which significantly enhances the model's capability for complex dialogue and proactive inquiry initiation. We also define a refined annotation rule and evaluation criteria given the unique characteristics of the biomedical domain. Extensive experimental results show that Zhongjing outperforms baselines in various capacities and matches the performance of ChatGPT in some abilities, despite the 100x parameters. Ablation studies also demonstrate the contributions of each component: pre-training enhances medical knowledge, and RLHF further improves instruction-following ability and safety. Our code, datasets, and models are available at https://github.com/SupritYoung/Zhongjing.

Do Large Language Models Align with Core Mental Health Counseling Competencies?

The rapid evolution of Large Language Models (LLMs) offers promising potential to alleviate the global scarcity of mental health professionals. However, LLMs' alignment with essential mental health counseling competencies remains understudied. We introduce CounselingBench, a novel NCMHCE-based benchmark evaluating LLMs across five key mental health counseling competencies. Testing 22 general-purpose and medical-finetuned LLMs, we find frontier models exceed minimum thresholds but fall short of expert-level performance, with significant variations: they excel in Intake, Assessment & Diagnosis yet struggle with Core Counseling Attributes and Professional Practice & Ethics. Medical LLMs surprisingly underperform generalist models accuracy-wise, while at the same time producing slightly higher-quality justifications but making more context-related errors. Our findings highlight the complexities of developing AI systems for mental health counseling, particularly for competencies requiring empathy and contextual understanding. We found that frontier LLMs perform at a level exceeding the minimal required level of aptitude for all key mental health counseling competencies, but fall short of expert-level performance, and that current medical LLMs do not significantly improve upon generalist models in mental health counseling competencies. This underscores the critical need for specialized, mental health counseling-specific fine-tuned LLMs that rigorously aligns with core competencies combined with appropriate human supervision before any responsible real-world deployment can be considered.

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.

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.

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.

Improve LLM-as-a-Judge Ability as a General Ability

LLM-as-a-Judge leverages the generative and reasoning capabilities of large language models (LLMs) to evaluate LLM responses across diverse scenarios, providing accurate preference signals. This approach plays a vital role in aligning LLMs with human values, ensuring ethical and reliable AI outputs that align with societal norms. Recent studies have raised many methods to train LLM as generative judges, but most of them are data consuming or lack accuracy, and only focus on LLM's judge ability. In this work, we regard judge ability as a general ability of LLM and implement a two-stage training approach, comprising supervised fine-tuning (SFT) warm-up and direct preference optimization (DPO) enhancement, to achieve judge style adaptation and improve judgment accuracy. Additionally, we introduce an efficient data synthesis method to generate judgmental content. Experimental results demonstrate that our approach, utilizing only about 2% to 40% of the data required by other methods, achieves SOTA performance on RewardBench. Furthermore, our training method enhances the general capabilities of the model by constructing complicated judge task, and the judge signals provided by our model have significantly enhanced the downstream DPO training performance of our internal models in our test to optimize policy model with Judge Model. We also open-source our model weights and training data to facilitate further research.

GPT-4 passes most of the 297 written Polish Board Certification Examinations

Introduction: Recently, the effectiveness of Large Language Models (LLMs) has increased rapidly, allowing them to be used in a great number of applications. However, the risks posed by the generation of false information through LLMs significantly limit their applications in sensitive areas such as healthcare, highlighting the necessity for rigorous validations to determine their utility and reliability. To date, no study has extensively compared the performance of LLMs on Polish medical examinations across a broad spectrum of specialties on a very large dataset. Objectives: This study evaluated the performance of three Generative Pretrained Transformer (GPT) models on the Polish Board Certification Exam (Pa\'nstwowy Egzamin Specjalizacyjny, PES) dataset, which consists of 297 tests. Methods: We developed a software program to download and process PES exams and tested the performance of GPT models using OpenAI Application Programming Interface. Results: Our findings reveal that GPT-3.5 did not pass any of the analyzed exams. In contrast, the GPT-4 models demonstrated the capability to pass the majority of the exams evaluated, with the most recent model, gpt-4-0125, successfully passing 222 (75%) of them. The performance of the GPT models varied significantly, displaying excellence in exams related to certain specialties while completely failing others. Conclusions: The significant progress and impressive performance of LLM models hold great promise for the increased application of AI in the field of medicine in Poland. For instance, this advancement could lead to the development of AI-based medical assistants for healthcare professionals, enhancing the efficiency and accuracy of medical services.

MediConfusion: Can you trust your AI radiologist? Probing the reliability of multimodal medical foundation models

Multimodal Large Language Models (MLLMs) have tremendous potential to improve the accuracy, availability, and cost-effectiveness of healthcare by providing automated solutions or serving as aids to medical professionals. Despite promising first steps in developing medical MLLMs in the past few years, their capabilities and limitations are not well-understood. Recently, many benchmark datasets have been proposed that test the general medical knowledge of such models across a variety of medical areas. However, the systematic failure modes and vulnerabilities of such models are severely underexplored with most medical benchmarks failing to expose the shortcomings of existing models in this safety-critical domain. In this paper, we introduce MediConfusion, a challenging medical Visual Question Answering (VQA) benchmark dataset, that probes the failure modes of medical MLLMs from a vision perspective. We reveal that state-of-the-art models are easily confused by image pairs that are otherwise visually dissimilar and clearly distinct for medical experts. Strikingly, all available models (open-source or proprietary) achieve performance below random guessing on MediConfusion, raising serious concerns about the reliability of existing medical MLLMs for healthcare deployment. We also extract common patterns of model failure that may help the design of a new generation of more trustworthy and reliable MLLMs in healthcare.

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%

MEDEC: A Benchmark for Medical Error Detection and Correction in Clinical Notes

Several studies showed that Large Language Models (LLMs) can answer medical questions correctly, even outperforming the average human score in some medical exams. However, to our knowledge, no study has been conducted to assess the ability of language models to validate existing or generated medical text for correctness and consistency. In this paper, we introduce MEDEC (https://github.com/abachaa/MEDEC), the first publicly available benchmark for medical error detection and correction in clinical notes, covering five types of errors (Diagnosis, Management, Treatment, Pharmacotherapy, and Causal Organism). MEDEC consists of 3,848 clinical texts, including 488 clinical notes from three US hospital systems that were not previously seen by any LLM. The dataset has been used for the MEDIQA-CORR shared task to evaluate seventeen participating systems [Ben Abacha et al., 2024]. In this paper, we describe the data creation methods and we evaluate recent LLMs (e.g., o1-preview, GPT-4, Claude 3.5 Sonnet, and Gemini 2.0 Flash) for the tasks of detecting and correcting medical errors requiring both medical knowledge and reasoning capabilities. We also conducted a comparative study where two medical doctors performed the same task on the MEDEC test set. The results showed that MEDEC is a sufficiently challenging benchmark to assess the ability of models to validate existing or generated notes and to correct medical errors. We also found that although recent LLMs have a good performance in error detection and correction, they are still outperformed by medical doctors in these tasks. We discuss the potential factors behind this gap, the insights from our experiments, the limitations of current evaluation metrics, and share potential pointers for future research.

A Survey of Medical Vision-and-Language Applications and Their Techniques

Medical vision-and-language models (MVLMs) have attracted substantial interest due to their capability to offer a natural language interface for interpreting complex medical data. Their applications are versatile and have the potential to improve diagnostic accuracy and decision-making for individual patients while also contributing to enhanced public health monitoring, disease surveillance, and policy-making through more efficient analysis of large data sets. MVLMS integrate natural language processing with medical images to enable a more comprehensive and contextual understanding of medical images alongside their corresponding textual information. Unlike general vision-and-language models trained on diverse, non-specialized datasets, MVLMs are purpose-built for the medical domain, automatically extracting and interpreting critical information from medical images and textual reports to support clinical decision-making. Popular clinical applications of MVLMs include automated medical report generation, medical visual question answering, medical multimodal segmentation, diagnosis and prognosis and medical image-text retrieval. Here, we provide a comprehensive overview of MVLMs and the various medical tasks to which they have been applied. We conduct a detailed analysis of various vision-and-language model architectures, focusing on their distinct strategies for cross-modal integration/exploitation of medical visual and textual features. We also examine the datasets used for these tasks and compare the performance of different models based on standardized evaluation metrics. Furthermore, we highlight potential challenges and summarize future research trends and directions. The full collection of papers and codes is available at: https://github.com/YtongXie/Medical-Vision-and-Language-Tasks-and-Methodologies-A-Survey.

Assessing Translation capabilities of Large Language Models involving English and Indian Languages

Generative Large Language Models (LLMs) have achieved remarkable advancements in various NLP tasks. In this work, our aim is to explore the multilingual capabilities of large language models by using machine translation as a task involving English and 22 Indian languages. We first investigate the translation capabilities of raw large language models, followed by exploring the in-context learning capabilities of the same raw models. We fine-tune these large language models using parameter efficient fine-tuning methods such as LoRA and additionally with full fine-tuning. Through our study, we have identified the best performing large language model for the translation task involving LLMs, which is based on LLaMA. Our results demonstrate significant progress, with average BLEU scores of 13.42, 15.93, 12.13, 12.30, and 12.07, as well as CHRF scores of 43.98, 46.99, 42.55, 42.42, and 45.39, respectively, using 2-stage fine-tuned LLaMA-13b for English to Indian languages on IN22 (conversational), IN22 (general), flores200-dev, flores200-devtest, and newstest2019 testsets. Similarly, for Indian languages to English, we achieved average BLEU scores of 14.03, 16.65, 16.17, 15.35 and 12.55 along with chrF scores of 36.71, 40.44, 40.26, 39.51, and 36.20, respectively, using fine-tuned LLaMA-13b on IN22 (conversational), IN22 (general), flores200-dev, flores200-devtest, and newstest2019 testsets. Overall, our findings highlight the potential and strength of large language models for machine translation capabilities, including for languages that are currently underrepresented in LLMs.