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Mar 13

Synthetic Patients: Simulating Difficult Conversations with Multimodal Generative AI for Medical Education

Problem: Effective patient-centered communication is a core competency for physicians. However, both seasoned providers and medical trainees report decreased confidence in leading conversations on sensitive topics such as goals of care or end-of-life discussions. The significant administrative burden and the resources required to provide dedicated training in leading difficult conversations has been a long-standing problem in medical education. Approach: In this work, we present a novel educational tool designed to facilitate interactive, real-time simulations of difficult conversations in a video-based format through the use of multimodal generative artificial intelligence (AI). Leveraging recent advances in language modeling, computer vision, and generative audio, this tool creates realistic, interactive scenarios with avatars, or "synthetic patients." These synthetic patients interact with users throughout various stages of medical care using a custom-built video chat application, offering learners the chance to practice conversations with patients from diverse belief systems, personalities, and ethnic backgrounds. Outcomes: While the development of this platform demanded substantial upfront investment in labor, it offers a highly-realistic simulation experience with minimal financial investment. For medical trainees, this educational tool can be implemented within programs to simulate patient-provider conversations and can be incorporated into existing palliative care curriculum to provide a scalable, high-fidelity simulation environment for mastering difficult conversations. Next Steps: Future developments will explore enhancing the authenticity of these encounters by working with patients to incorporate their histories and personalities, as well as employing the use of AI-generated evaluations to offer immediate, constructive feedback to learners post-simulation.

Exploring the Inquiry-Diagnosis Relationship with Advanced Patient Simulators

Online medical consultation (OMC) restricts doctors to gathering patient information solely through inquiries, making the already complex sequential decision-making process of diagnosis even more challenging. Recently, the rapid advancement of large language models has demonstrated a significant potential to transform OMC. However, most studies have primarily focused on improving diagnostic accuracy under conditions of relatively sufficient information, while paying limited attention to the "inquiry" phase of the consultation process. This lack of focus has left the relationship between "inquiry" and "diagnosis" insufficiently explored. In this paper, we first extract real patient interaction strategies from authentic doctor-patient conversations and use these strategies to guide the training of a patient simulator that closely mirrors real-world behavior. By inputting medical records into our patient simulator to simulate patient responses, we conduct extensive experiments to explore the relationship between "inquiry" and "diagnosis" in the consultation process. Experimental results demonstrate that inquiry and diagnosis adhere to the Liebig's law: poor inquiry quality limits the effectiveness of diagnosis, regardless of diagnostic capability, and vice versa. Furthermore, the experiments reveal significant differences in the inquiry performance of various models. To investigate this phenomenon, we categorize the inquiry process into four types: (1) chief complaint inquiry; (2) specification of known symptoms; (3) inquiry about accompanying symptoms; and (4) gathering family or medical history. We analyze the distribution of inquiries across the four types for different models to explore the reasons behind their significant performance differences. We plan to open-source the weights and related code of our patient simulator at https://github.com/LIO-H-ZEN/PatientSimulator.

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

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

AgentClinic: a multimodal agent benchmark to evaluate AI in simulated clinical environments

Diagnosing and managing a patient is a complex, sequential decision making process that requires physicians to obtain information -- such as which tests to perform -- and to act upon it. Recent advances in artificial intelligence (AI) and large language models (LLMs) promise to profoundly impact clinical care. However, current evaluation schemes overrely on static medical question-answering benchmarks, falling short on interactive decision-making that is required in real-life clinical work. Here, we present AgentClinic: a multimodal benchmark to evaluate LLMs in their ability to operate as agents in simulated clinical environments. In our benchmark, the doctor agent must uncover the patient's diagnosis through dialogue and active data collection. We present two open medical agent benchmarks: a multimodal image and dialogue environment, AgentClinic-NEJM, and a dialogue-only environment, AgentClinic-MedQA. We embed cognitive and implicit biases both in patient and doctor agents to emulate realistic interactions between biased agents. We find that introducing bias leads to large reductions in diagnostic accuracy of the doctor agents, as well as reduced compliance, confidence, and follow-up consultation willingness in patient agents. Evaluating a suite of state-of-the-art LLMs, we find that several models that excel in benchmarks like MedQA are performing poorly in AgentClinic-MedQA. We find that the LLM used in the patient agent is an important factor for performance in the AgentClinic benchmark. We show that both having limited interactions as well as too many interaction reduces diagnostic accuracy in doctor agents. The code and data for this work is publicly available at https://AgentClinic.github.io.

The impact of using an AI chatbot to respond to patient messages

Documentation burden is a major contributor to clinician burnout, which is rising nationally and is an urgent threat to our ability to care for patients. Artificial intelligence (AI) chatbots, such as ChatGPT, could reduce clinician burden by assisting with documentation. Although many hospitals are actively integrating such systems into electronic medical record systems, AI chatbots utility and impact on clinical decision-making have not been studied for this intended use. We are the first to examine the utility of large language models in assisting clinicians draft responses to patient questions. In our two-stage cross-sectional study, 6 oncologists responded to 100 realistic synthetic cancer patient scenarios and portal messages developed to reflect common medical situations, first manually, then with AI assistance. We find AI-assisted responses were longer, less readable, but provided acceptable drafts without edits 58% of time. AI assistance improved efficiency 77% of time, with low harm risk (82% safe). However, 7.7% unedited AI responses could severely harm. In 31% cases, physicians thought AI drafts were human-written. AI assistance led to more patient education recommendations, fewer clinical actions than manual responses. Results show promise for AI to improve clinician efficiency and patient care through assisting documentation, if used judiciously. Monitoring model outputs and human-AI interaction remains crucial for safe implementation.

Unsupervised Pre-Training for Vietnamese Automatic Speech Recognition in the HYKIST Project

In today's interconnected globe, moving abroad is more and more prevalent, whether it's for employment, refugee resettlement, or other causes. Language difficulties between natives and immigrants present a common issue on a daily basis, especially in medical domain. This can make it difficult for patients and doctors to communicate during anamnesis or in the emergency room, which compromises patient care. The goal of the HYKIST Project is to develop a speech translation system to support patient-doctor communication with ASR and MT. ASR systems have recently displayed astounding performance on particular tasks for which enough quantities of training data are available, such as LibriSpeech. Building a good model is still difficult due to a variety of speaking styles, acoustic and recording settings, and a lack of in-domain training data. In this thesis, we describe our efforts to construct ASR systems for a conversational telephone speech recognition task in the medical domain for Vietnamese language to assist emergency room contact between doctors and patients across linguistic barriers. In order to enhance the system's performance, we investigate various training schedules and data combining strategies. We also examine how best to make use of the little data that is available. The use of publicly accessible models like XLSR-53 is compared to the use of customized pre-trained models, and both supervised and unsupervised approaches are utilized using wav2vec 2.0 as architecture.

Towards Conversational Diagnostic AI

At the heart of medicine lies the physician-patient dialogue, where skillful history-taking paves the way for accurate diagnosis, effective management, and enduring trust. Artificial Intelligence (AI) systems capable of diagnostic dialogue could increase accessibility, consistency, and quality of care. However, approximating clinicians' expertise is an outstanding grand challenge. Here, we introduce AMIE (Articulate Medical Intelligence Explorer), a Large Language Model (LLM) based AI system optimized for diagnostic dialogue. AMIE uses a novel self-play based simulated environment with automated feedback mechanisms for scaling learning across diverse disease conditions, specialties, and contexts. We designed a framework for evaluating clinically-meaningful axes of performance including history-taking, diagnostic accuracy, management reasoning, communication skills, and empathy. We compared AMIE's performance to that of primary care physicians (PCPs) in a randomized, double-blind crossover study of text-based consultations with validated patient actors in the style of an Objective Structured Clinical Examination (OSCE). The study included 149 case scenarios from clinical providers in Canada, the UK, and India, 20 PCPs for comparison with AMIE, and evaluations by specialist physicians and patient actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 28 of 32 axes according to specialist physicians and 24 of 26 axes according to patient actors. Our research has several limitations and should be interpreted with appropriate caution. Clinicians were limited to unfamiliar synchronous text-chat which permits large-scale LLM-patient interactions but is not representative of usual clinical practice. While further research is required before AMIE could be translated to real-world settings, the results represent a milestone towards conversational diagnostic AI.

Polaris: A Safety-focused LLM Constellation Architecture for Healthcare

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

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.

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.

Rethinking Explainability as a Dialogue: A Practitioner's Perspective

As practitioners increasingly deploy machine learning models in critical domains such as health care, finance, and policy, it becomes vital to ensure that domain experts function effectively alongside these models. Explainability is one way to bridge the gap between human decision-makers and machine learning models. However, most of the existing work on explainability focuses on one-off, static explanations like feature importances or rule lists. These sorts of explanations may not be sufficient for many use cases that require dynamic, continuous discovery from stakeholders. In the literature, few works ask decision-makers about the utility of existing explanations and other desiderata they would like to see in an explanation going forward. In this work, we address this gap and carry out a study where we interview doctors, healthcare professionals, and policymakers about their needs and desires for explanations. Our study indicates that decision-makers would strongly prefer interactive explanations in the form of natural language dialogues. Domain experts wish to treat machine learning models as "another colleague", i.e., one who can be held accountable by asking why they made a particular decision through expressive and accessible natural language interactions. Considering these needs, we outline a set of five principles researchers should follow when designing interactive explanations as a starting place for future work. Further, we show why natural language dialogues satisfy these principles and are a desirable way to build interactive explanations. Next, we provide a design of a dialogue system for explainability and discuss the risks, trade-offs, and research opportunities of building these systems. Overall, we hope our work serves as a starting place for researchers and engineers to design interactive explainability systems.

PATIENT-Ψ: Using Large Language Models to Simulate Patients for Training Mental Health Professionals

Mental illness remains one of the most critical public health issues. Despite its importance, many mental health professionals highlight a disconnect between their training and actual real-world patient practice. To help bridge this gap, we propose PATIENT-{\Psi}, a novel patient simulation framework for cognitive behavior therapy (CBT) training. To build PATIENT-{\Psi}, we construct diverse patient cognitive models based on CBT principles and use large language models (LLMs) programmed with these cognitive models to act as a simulated therapy patient. We propose an interactive training scheme, PATIENT-{\Psi}-TRAINER, for mental health trainees to practice a key skill in CBT -- formulating the cognitive model of the patient -- through role-playing a therapy session with PATIENT-{\Psi}. To evaluate PATIENT-{\Psi}, we conducted a comprehensive user study of 13 mental health trainees and 20 experts. The results demonstrate that practice using PATIENT-{\Psi}-TRAINER enhances the perceived skill acquisition and confidence of the trainees beyond existing forms of training such as textbooks, videos, and role-play with non-patients. Based on the experts' perceptions, PATIENT-{\Psi} is perceived to be closer to real patient interactions than GPT-4, and PATIENT-{\Psi}-TRAINER holds strong promise to improve trainee competencies. Our code and data are released at https://github.com/ruiyiw/patient-psi.

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.

Fidelity and Privacy of Synthetic Medical Data

The digitization of medical records ushered in a new era of big data to clinical science, and with it the possibility that data could be shared, to multiply insights beyond what investigators could abstract from paper records. The need to share individual-level medical data to accelerate innovation in precision medicine continues to grow, and has never been more urgent, as scientists grapple with the COVID-19 pandemic. However, enthusiasm for the use of big data has been tempered by a fully appropriate concern for patient autonomy and privacy. That is, the ability to extract private or confidential information about an individual, in practice, renders it difficult to share data, since significant infrastructure and data governance must be established before data can be shared. Although HIPAA provided de-identification as an approved mechanism for data sharing, linkage attacks were identified as a major vulnerability. A variety of mechanisms have been established to avoid leaking private information, such as field suppression or abstraction, strictly limiting the amount of information that can be shared, or employing mathematical techniques such as differential privacy. Another approach, which we focus on here, is creating synthetic data that mimics the underlying data. For synthetic data to be a useful mechanism in support of medical innovation and a proxy for real-world evidence, one must demonstrate two properties of the synthetic dataset: (1) any analysis on the real data must be matched by analysis of the synthetic data (statistical fidelity) and (2) the synthetic data must preserve privacy, with minimal risk of re-identification (privacy guarantee). In this paper we propose a framework for quantifying the statistical fidelity and privacy preservation properties of synthetic datasets and demonstrate these metrics for synthetic data generated by Syntegra technology.

Voice Cloning for Dysarthric Speech Synthesis: Addressing Data Scarcity in Speech-Language Pathology

This study explores voice cloning to generate synthetic speech replicating the unique patterns of individuals with dysarthria. Using the TORGO dataset, we address data scarcity and privacy challenges in speech-language pathology. Our contributions include demonstrating that voice cloning preserves dysarthric speech characteristics, analyzing differences between real and synthetic data, and discussing implications for diagnostics, rehabilitation, and communication. We cloned voices from dysarthric and control speakers using a commercial platform, ensuring gender-matched synthetic voices. A licensed speech-language pathologist (SLP) evaluated a subset for dysarthria, speaker gender, and synthetic indicators. The SLP correctly identified dysarthria in all cases and speaker gender in 95% but misclassified 30% of synthetic samples as real, indicating high realism. Our results suggest synthetic speech effectively captures disordered characteristics and that voice cloning has advanced to produce high-quality data resembling real speech, even to trained professionals. This has critical implications for healthcare, where synthetic data can mitigate data scarcity, protect privacy, and enhance AI-driven diagnostics. By enabling the creation of diverse, high-quality speech datasets, voice cloning can improve generalizable models, personalize therapy, and advance assistive technologies for dysarthria. We publicly release our synthetic dataset to foster further research and collaboration, aiming to develop robust models that improve patient outcomes in speech-language pathology.

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.

Étude cognitive des processus de construction d'une requête dans un système de gestion de connaissances médicales

This article presents the Cogni-CISMeF project, which aims at improving medical information search in the CISMeF system (Catalog and Index of French-language health resources) by including a conversational agent to interact with the user in natural language. To study the cognitive processes involved during the information search, a bottom-up methodology was adopted. Experimentation has been set up to obtain human dialogs between a user (playing the role of patient) dealing with medical information search and a CISMeF expert refining the request. The analysis of these dialogs underlined the use of discursive evidence: vocabulary, reformulation, implicit or explicit expression of user intentions, conversational sequences, etc. A model of artificial agent is proposed. It leads the user in its information search by proposing to him examples, assistance and choices. This model was implemented and integrated in the CISMeF system. ---- Cet article d\'ecrit le projet Cogni-CISMeF qui propose un module de dialogue Homme-Machine \`a int\'egrer dans le syst\`eme d'indexation de connaissances m\'edicales CISMeF (Catalogue et Index des Sites M\'edicaux Francophones). Nous avons adopt\'e une d\'emarche de mod\'elisation cognitive en proc\'edant \`a un recueil de corpus de dialogues entre un utilisateur (jouant le r\^ole d'un patient) d\'esirant une information m\'edicale et un expert CISMeF af inant cette demande pour construire la requ\^ete. Nous avons analys\'e la structure des dialogues ainsi obtenus et avons \'etudi\'e un certain nombre d'indices discursifs : vocabulaire employ\'e, marques de reformulation, commentaires m\'eta et \'epilinguistiques, expression implicite ou explicite des intentions de l'utilisateur, encha\^inement conversationnel, etc. De cette analyse, nous avons construit un mod\`ele d'agent artificiel dot\'e de capacit\'es cognitives capables d'aider l'utilisateur dans sa t\^ache de recherche d'information. Ce mod\`ele a \'et\'e impl\'ement\'e et int\'egr\'e dans le syst\`eme CISMeF.

DDXPlus: A New Dataset For Automatic Medical Diagnosis

There has been a rapidly growing interest in Automatic Symptom Detection (ASD) and Automatic Diagnosis (AD) systems in the machine learning research literature, aiming to assist doctors in telemedicine services. These systems are designed to interact with patients, collect evidence about their symptoms and relevant antecedents, and possibly make predictions about the underlying diseases. Doctors would review the interactions, including the evidence and the predictions, collect if necessary additional information from patients, before deciding on next steps. Despite recent progress in this area, an important piece of doctors' interactions with patients is missing in the design of these systems, namely the differential diagnosis. Its absence is largely due to the lack of datasets that include such information for models to train on. In this work, we present a large-scale synthetic dataset of roughly 1.3 million patients that includes a differential diagnosis, along with the ground truth pathology, symptoms and antecedents for each patient. Unlike existing datasets which only contain binary symptoms and antecedents, this dataset also contains categorical and multi-choice symptoms and antecedents useful for efficient data collection. Moreover, some symptoms are organized in a hierarchy, making it possible to design systems able to interact with patients in a logical way. As a proof-of-concept, we extend two existing AD and ASD systems to incorporate the differential diagnosis, and provide empirical evidence that using differentials as training signals is essential for the efficiency of such systems or for helping doctors better understand the reasoning of those systems.

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.

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

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

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.

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

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

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.

Interactive Dialogue Agents via Reinforcement Learning on Hindsight Regenerations

Recent progress on large language models (LLMs) has enabled dialogue agents to generate highly naturalistic and plausible text. However, current LLM language generation focuses on responding accurately to questions and requests with a single effective response. In reality, many real dialogues are interactive, meaning an agent's utterances will influence their conversational partner, elicit information, or change their opinion. Accounting for how an agent can effectively steer a conversation is a crucial ability in many dialogue tasks, from healthcare to preference elicitation. Existing methods for fine-tuning dialogue agents to accomplish such tasks would rely on curating some amount of expert data. However, doing so often requires understanding the underlying cognitive processes of the conversational partner, which is a skill neither humans nor LLMs trained on human data can reliably do. Our key insight is that while LLMs may not be adept at identifying effective strategies for steering conversations a priori, or in the middle of an ongoing conversation, they can do so post-hoc, or in hindsight, after seeing how their conversational partner responds. We use this fact to rewrite and augment existing suboptimal data, and train via offline reinforcement learning (RL) an agent that outperforms both prompting and learning from unaltered human demonstrations. We apply our approach to two domains that require understanding human mental state, intelligent interaction, and persuasion: mental health support, and soliciting charitable donations. Our results in a user study with real humans show that our approach greatly outperforms existing state-of-the-art dialogue agents.

Evaluation of GPT-3.5 and GPT-4 for supporting real-world information needs in healthcare delivery

Despite growing interest in using large language models (LLMs) in healthcare, current explorations do not assess the real-world utility and safety of LLMs in clinical settings. Our objective was to determine whether two LLMs can serve information needs submitted by physicians as questions to an informatics consultation service in a safe and concordant manner. Sixty six questions from an informatics consult service were submitted to GPT-3.5 and GPT-4 via simple prompts. 12 physicians assessed the LLM responses' possibility of patient harm and concordance with existing reports from an informatics consultation service. Physician assessments were summarized based on majority vote. For no questions did a majority of physicians deem either LLM response as harmful. For GPT-3.5, responses to 8 questions were concordant with the informatics consult report, 20 discordant, and 9 were unable to be assessed. There were 29 responses with no majority on "Agree", "Disagree", and "Unable to assess". For GPT-4, responses to 13 questions were concordant, 15 discordant, and 3 were unable to be assessed. There were 35 responses with no majority. Responses from both LLMs were largely devoid of overt harm, but less than 20% of the responses agreed with an answer from an informatics consultation service, responses contained hallucinated references, and physicians were divided on what constitutes harm. These results suggest that while general purpose LLMs are able to provide safe and credible responses, they often do not meet the specific information need of a given question. A definitive evaluation of the usefulness of LLMs in healthcare settings will likely require additional research on prompt engineering, calibration, and custom-tailoring of general purpose models.

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.

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.

Therapy as an NLP Task: Psychologists' Comparison of LLMs and Human Peers in CBT

Wider access to therapeutic care is one of the biggest challenges in mental health treatment. Due to institutional barriers, some people seeking mental health support have turned to large language models (LLMs) for personalized therapy, even though these models are largely unsanctioned and untested. We investigate the potential and limitations of using LLMs as providers of evidence-based therapy by using mixed methods clinical metrics. Using HELPERT, a prompt run on a large language model using the same process and training as a comparative group of peer counselors, we replicated publicly accessible mental health conversations rooted in Cognitive Behavioral Therapy (CBT) to compare session dynamics and counselor's CBT-based behaviors between original peer support sessions and their reconstructed HELPERT sessions. Two licensed, CBT-trained clinical psychologists evaluated the sessions using the Cognitive Therapy Rating Scale and provided qualitative feedback. Our findings show that the peer sessions are characterized by empathy, small talk, therapeutic alliance, and shared experiences but often exhibit therapist drift. Conversely, HELPERT reconstructed sessions exhibit minimal therapist drift and higher adherence to CBT methods but display a lack of collaboration, empathy, and cultural understanding. Through CTRS ratings and psychologists' feedback, we highlight the importance of human-AI collaboration for scalable mental health. Our work outlines the ethical implication of imparting human-like subjective qualities to LLMs in therapeutic settings, particularly the risk of deceptive empathy, which may lead to unrealistic patient expectations and potential harm.

Addressing cognitive bias in medical language models

There is increasing interest in the application large language models (LLMs) to the medical field, in part because of their impressive performance on medical exam questions. While promising, exam questions do not reflect the complexity of real patient-doctor interactions. In reality, physicians' decisions are shaped by many complex factors, such as patient compliance, personal experience, ethical beliefs, and cognitive bias. Taking a step toward understanding this, our hypothesis posits that when LLMs are confronted with clinical questions containing cognitive biases, they will yield significantly less accurate responses compared to the same questions presented without such biases. In this study, we developed BiasMedQA, a benchmark for evaluating cognitive biases in LLMs applied to medical tasks. Using BiasMedQA we evaluated six LLMs, namely GPT-4, Mixtral-8x70B, GPT-3.5, PaLM-2, Llama 2 70B-chat, and the medically specialized PMC Llama 13B. We tested these models on 1,273 questions from the US Medical Licensing Exam (USMLE) Steps 1, 2, and 3, modified to replicate common clinically-relevant cognitive biases. Our analysis revealed varying effects for biases on these LLMs, with GPT-4 standing out for its resilience to bias, in contrast to Llama 2 70B-chat and PMC Llama 13B, which were disproportionately affected by cognitive bias. Our findings highlight the critical need for bias mitigation in the development of medical LLMs, pointing towards safer and more reliable applications in healthcare.

MentalArena: Self-play Training of Language Models for Diagnosis and Treatment of Mental Health Disorders

Mental health disorders are one of the most serious diseases in the world. Most people with such a disease lack access to adequate care, which highlights the importance of training models for the diagnosis and treatment of mental health disorders. However, in the mental health domain, privacy concerns limit the accessibility of personalized treatment data, making it challenging to build powerful models. In this paper, we introduce MentalArena, a self-play framework to train language models by generating domain-specific personalized data, where we obtain a better model capable of making a personalized diagnosis and treatment (as a therapist) and providing information (as a patient). To accurately model human-like mental health patients, we devise Symptom Encoder, which simulates a real patient from both cognition and behavior perspectives. To address intent bias during patient-therapist interactions, we propose Symptom Decoder to compare diagnosed symptoms with encoded symptoms, and dynamically manage the dialogue between patient and therapist according to the identified deviations. We evaluated MentalArena against 6 benchmarks, including biomedicalQA and mental health tasks, compared to 6 advanced models. Our models, fine-tuned on both GPT-3.5 and Llama-3-8b, significantly outperform their counterparts, including GPT-4o. We hope that our work can inspire future research on personalized care. Code is available in https://github.com/Scarelette/MentalArena/tree/main

Exploring Large Language Models for Specialist-level Oncology Care

Large language models (LLMs) have shown remarkable progress in encoding clinical knowledge and responding to complex medical queries with appropriate clinical reasoning. However, their applicability in subspecialist or complex medical settings remains underexplored. In this work, we probe the performance of AMIE, a research conversational diagnostic AI system, in the subspecialist domain of breast oncology care without specific fine-tuning to this challenging domain. To perform this evaluation, we curated a set of 50 synthetic breast cancer vignettes representing a range of treatment-naive and treatment-refractory cases and mirroring the key information available to a multidisciplinary tumor board for decision-making (openly released with this work). We developed a detailed clinical rubric for evaluating management plans, including axes such as the quality of case summarization, safety of the proposed care plan, and recommendations for chemotherapy, radiotherapy, surgery and hormonal therapy. To improve performance, we enhanced AMIE with the inference-time ability to perform web search retrieval to gather relevant and up-to-date clinical knowledge and refine its responses with a multi-stage self-critique pipeline. We compare response quality of AMIE with internal medicine trainees, oncology fellows, and general oncology attendings under both automated and specialist clinician evaluations. In our evaluations, AMIE outperformed trainees and fellows demonstrating the potential of the system in this challenging and important domain. We further demonstrate through qualitative examples, how systems such as AMIE might facilitate conversational interactions to assist clinicians in their decision making. However, AMIE's performance was overall inferior to attending oncologists suggesting that further research is needed prior to consideration of prospective uses.

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.

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.

TalkToModel: Explaining Machine Learning Models with Interactive Natural Language Conversations

Machine Learning (ML) models are increasingly used to make critical decisions in real-world applications, yet they have become more complex, making them harder to understand. To this end, researchers have proposed several techniques to explain model predictions. However, practitioners struggle to use these explainability techniques because they often do not know which one to choose and how to interpret the results of the explanations. In this work, we address these challenges by introducing TalkToModel: an interactive dialogue system for explaining machine learning models through conversations. Specifically, TalkToModel comprises of three key components: 1) a natural language interface for engaging in conversations, making ML model explainability highly accessible, 2) a dialogue engine that adapts to any tabular model and dataset, interprets natural language, maps it to appropriate explanations, and generates text responses, and 3) an execution component that constructs the explanations. We carried out extensive quantitative and human subject evaluations of TalkToModel. Overall, we found the conversational system understands user inputs on novel datasets and models with high accuracy, demonstrating the system's capacity to generalize to new situations. In real-world evaluations with humans, 73% of healthcare workers (e.g., doctors and nurses) agreed they would use TalkToModel over baseline point-and-click systems for explainability in a disease prediction task, and 85% of ML professionals agreed TalkToModel was easier to use for computing explanations. Our findings demonstrate that TalkToModel is more effective for model explainability than existing systems, introducing a new category of explainability tools for practitioners. Code & demo released here: https://github.com/dylan-slack/TalkToModel.

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.

Two Case Studies of Experience Prototyping Machine Learning Systems in the Wild

Throughout the course of my Ph.D., I have been designing the user experience (UX) of various machine learning (ML) systems. In this workshop, I share two projects as case studies in which people engage with ML in much more complicated and nuanced ways than the technical HCML work might assume. The first case study describes how cardiology teams in three hospitals used a clinical decision-support system that helps them decide whether and when to implant an artificial heart to a heart failure patient. I demonstrate that physicians cannot draw on their decision-making experience by seeing only patient data on paper. They are also confused by some fundamental premises upon which ML operates. For example, physicians asked: Are ML predictions made based on clinicians' best efforts? Is it ethical to make decisions based on previous patients' collective outcomes? In the second case study, my collaborators and I designed an intelligent text editor, with the goal of improving authors' writing experience with NLP (Natural Language Processing) technologies. We prototyped a number of generative functionalities where the system provides phrase-or-sentence-level writing suggestions upon user request. When writing with the prototype, however, authors shared that they need to "see where the sentence is going two paragraphs later" in order to decide whether the suggestion aligns with their writing; Some even considered adopting machine suggestions as plagiarism, therefore "is simply wrong". By sharing these unexpected and intriguing responses from these real-world ML users, I hope to start a discussion about such previously-unknown complexities and nuances of -- as the workshop proposal states -- "putting ML at the service of people in a way that is accessible, useful, and trustworthy to all".

PMC-LLaMA: Towards Building Open-source Language Models for Medicine

Recently, Large Language Models (LLMs) have showcased remarkable capabilities in natural language understanding. While demonstrating proficiency in everyday conversations and question-answering situations, these models frequently struggle in domains that require precision, such as medical applications, due to their lack of domain-specific knowledge. In this paper, we describe the procedure for building a powerful, open-source language model specifically designed for medicine applications, termed as PMC-LLaMA. Our contributions are threefold: (i) we systematically investigate the process of adapting a general-purpose foundation language model towards medical domain, this involves data-centric knowledge injection through the integration of 4.8M biomedical academic papers and 30K medical textbooks, as well as comprehensive fine-tuning for alignment with domain-specific instructions; (ii) we contribute a large-scale, comprehensive dataset for instruction tuning. This dataset encompasses medical question-answering (QA), rationale for reasoning, and conversational dialogues, comprising a total of 202M tokens; (iii) we conduct thorough ablation studies to demonstrate the effectiveness of each proposed component. While evaluating on various public medical question-answering benchmarks, our lightweight PMCLLaMA, which consists of only 13 billion parameters, exhibits superior performance, even surpassing ChatGPT. All models, codes, datasets can be found in https://github.com/chaoyi-wu/PMC-LLaMA.

CasiMedicos-Arg: A Medical Question Answering Dataset Annotated with Explanatory Argumentative Structures

Explaining Artificial Intelligence (AI) decisions is a major challenge nowadays in AI, in particular when applied to sensitive scenarios like medicine and law. However, the need to explain the rationale behind decisions is a main issue also for human-based deliberation as it is important to justify why a certain decision has been taken. Resident medical doctors for instance are required not only to provide a (possibly correct) diagnosis, but also to explain how they reached a certain conclusion. Developing new tools to aid residents to train their explanation skills is therefore a central objective of AI in education. In this paper, we follow this direction, and we present, to the best of our knowledge, the first multilingual dataset for Medical Question Answering where correct and incorrect diagnoses for a clinical case are enriched with a natural language explanation written by doctors. These explanations have been manually annotated with argument components (i.e., premise, claim) and argument relations (i.e., attack, support), resulting in the Multilingual CasiMedicos-Arg dataset which consists of 558 clinical cases in four languages (English, Spanish, French, Italian) with explanations, where we annotated 5021 claims, 2313 premises, 2431 support relations, and 1106 attack relations. We conclude by showing how competitive baselines perform over this challenging dataset for the argument mining task.

Explanatory Argument Extraction of Correct Answers in Resident Medical Exams

Developing the required technology to assist medical experts in their everyday activities is currently a hot topic in the Artificial Intelligence research field. Thus, a number of large language models (LLMs) and automated benchmarks have recently been proposed with the aim of facilitating information extraction in Evidence-Based Medicine (EBM) using natural language as a tool for mediating in human-AI interaction. The most representative benchmarks are limited to either multiple-choice or long-form answers and are available only in English. In order to address these shortcomings, in this paper we present a new dataset which, unlike previous work: (i) includes not only explanatory arguments for the correct answer, but also arguments to reason why the incorrect answers are not correct; (ii) the explanations are written originally by medical doctors to answer questions from the Spanish Residency Medical Exams. Furthermore, this new benchmark allows us to setup a novel extractive task which consists of identifying the explanation of the correct answer written by medical doctors. An additional benefit of our setting is that we can leverage the extractive QA paradigm to automatically evaluate performance of LLMs without resorting to costly manual evaluation by medical experts. Comprehensive experimentation with language models for Spanish shows that sometimes multilingual models fare better than monolingual ones, even outperforming models which have been adapted to the medical domain. Furthermore, results across the monolingual models are mixed, with supposedly smaller and inferior models performing competitively. In any case, the obtained results show that our novel dataset and approach can be an effective technique to help medical practitioners in identifying relevant evidence-based explanations for medical questions.

MedSumm: A Multimodal Approach to Summarizing Code-Mixed Hindi-English Clinical Queries

In the healthcare domain, summarizing medical questions posed by patients is critical for improving doctor-patient interactions and medical decision-making. Although medical data has grown in complexity and quantity, the current body of research in this domain has primarily concentrated on text-based methods, overlooking the integration of visual cues. Also prior works in the area of medical question summarisation have been limited to the English language. This work introduces the task of multimodal medical question summarization for codemixed input in a low-resource setting. To address this gap, we introduce the Multimodal Medical Codemixed Question Summarization MMCQS dataset, which combines Hindi-English codemixed medical queries with visual aids. This integration enriches the representation of a patient's medical condition, providing a more comprehensive perspective. We also propose a framework named MedSumm that leverages the power of LLMs and VLMs for this task. By utilizing our MMCQS dataset, we demonstrate the value of integrating visual information from images to improve the creation of medically detailed summaries. This multimodal strategy not only improves healthcare decision-making but also promotes a deeper comprehension of patient queries, paving the way for future exploration in personalized and responsive medical care. Our dataset, code, and pre-trained models will be made publicly available.

Control of Medical Digital Twins with Artificial Neural Networks

The objective of personalized medicine is to tailor interventions to an individual patient's unique characteristics. A key technology for this purpose involves medical digital twins, computational models of human biology that can be personalized and dynamically updated to incorporate patient-specific data collected over time. Certain aspects of human biology, such as the immune system, are not easily captured with physics-based models, such as differential equations. Instead, they are often multi-scale, stochastic, and hybrid. This poses a challenge to existing model-based control and optimization approaches that cannot be readily applied to such models. Recent advances in automatic differentiation and neural-network control methods hold promise in addressing complex control problems. However, the application of these approaches to biomedical systems is still in its early stages. This work introduces dynamics-informed neural-network controllers as an alternative approach to control of medical digital twins. As a first use case for this method, the focus is on agent-based models, a versatile and increasingly common modeling platform in biomedicine. The effectiveness of the proposed neural-network control method is illustrated and benchmarked against other methods with two widely-used agent-based model types. The relevance of the method introduced here extends beyond medical digital twins to other complex dynamical systems.

Towards Expert-Level Medical Question Answering with Large Language Models

Recent artificial intelligence (AI) systems have reached milestones in "grand challenges" ranging from Go to protein-folding. The capability to retrieve medical knowledge, reason over it, and answer medical questions comparably to physicians has long been viewed as one such grand challenge. Large language models (LLMs) have catalyzed significant progress in medical question answering; Med-PaLM was the first model to exceed a "passing" score in US Medical Licensing Examination (USMLE) style questions with a score of 67.2% on the MedQA dataset. However, this and other prior work suggested significant room for improvement, especially when models' answers were compared to clinicians' answers. Here we present Med-PaLM 2, which bridges these gaps by leveraging a combination of base LLM improvements (PaLM 2), medical domain finetuning, and prompting strategies including a novel ensemble refinement approach. Med-PaLM 2 scored up to 86.5% on the MedQA dataset, improving upon Med-PaLM by over 19% and setting a new state-of-the-art. We also observed performance approaching or exceeding state-of-the-art across MedMCQA, PubMedQA, and MMLU clinical topics datasets. We performed detailed human evaluations on long-form questions along multiple axes relevant to clinical applications. In pairwise comparative ranking of 1066 consumer medical questions, physicians preferred Med-PaLM 2 answers to those produced by physicians on eight of nine axes pertaining to clinical utility (p < 0.001). We also observed significant improvements compared to Med-PaLM on every evaluation axis (p < 0.001) on newly introduced datasets of 240 long-form "adversarial" questions to probe LLM limitations. While further studies are necessary to validate the efficacy of these models in real-world settings, these results highlight rapid progress towards physician-level performance in medical question answering.

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

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

Automatic Differential Diagnosis using Transformer-Based Multi-Label Sequence Classification

As the field of artificial intelligence progresses, assistive technologies are becoming more widely used across all industries. The healthcare industry is no different, with numerous studies being done to develop assistive tools for healthcare professionals. Automatic diagnostic systems are one such beneficial tool that can assist with a variety of tasks, including collecting patient information, analyzing test results, and diagnosing patients. However, the idea of developing systems that can provide a differential diagnosis has been largely overlooked in most of these research studies. In this study, we propose a transformer-based approach for providing differential diagnoses based on a patient's age, sex, medical history, and symptoms. We use the DDXPlus dataset, which provides differential diagnosis information for patients based on 49 disease types. Firstly, we propose a method to process the tabular patient data from the dataset and engineer them into patient reports to make them suitable for our research. In addition, we introduce two data modification modules to diversify the training data and consequently improve the robustness of the models. We approach the task as a multi-label classification problem and conduct extensive experiments using four transformer models. All the models displayed promising results by achieving over 97% F1 score on the held-out test set. Moreover, we design additional behavioral tests to get a broader understanding of the models. In particular, for one of our test cases, we prepared a custom test set of 100 samples with the assistance of a doctor. The results on the custom set showed that our proposed data modification modules improved the model's generalization capabilities. We hope our findings will provide future researchers with valuable insights and inspire them to develop reliable systems for automatic differential diagnosis.

The Ethics of ChatGPT in Medicine and Healthcare: A Systematic Review on Large Language Models (LLMs)

With the introduction of ChatGPT, Large Language Models (LLMs) have received enormous attention in healthcare. Despite their potential benefits, researchers have underscored various ethical implications. While individual instances have drawn much attention, the debate lacks a systematic overview of practical applications currently researched and ethical issues connected to them. Against this background, this work aims to map the ethical landscape surrounding the current stage of deployment of LLMs in medicine and healthcare. Electronic databases and preprint servers were queried using a comprehensive search strategy. Studies were screened and extracted following a modified rapid review approach. Methodological quality was assessed using a hybrid approach. For 53 records, a meta-aggregative synthesis was performed. Four fields of applications emerged and testify to a vivid exploration phase. Advantages of using LLMs are attributed to their capacity in data analysis, personalized information provisioning, support in decision-making, mitigating information loss and enhancing information accessibility. However, we also identifies recurrent ethical concerns connected to fairness, bias, non-maleficence, transparency, and privacy. A distinctive concern is the tendency to produce harmful misinformation or convincingly but inaccurate content. A recurrent plea for ethical guidance and human oversight is evident. Given the variety of use cases, it is suggested that the ethical guidance debate be reframed to focus on defining what constitutes acceptable human oversight across the spectrum of applications. This involves considering diverse settings, varying potentials for harm, and different acceptable thresholds for performance and certainty in healthcare. In addition, a critical inquiry is necessary to determine the extent to which the current experimental use of LLMs is necessary and justified.

Faithful Persona-based Conversational Dataset Generation with Large Language Models

High-quality conversational datasets are essential for developing AI models that can communicate with users. One way to foster deeper interactions between a chatbot and its user is through personas, aspects of the user's character that provide insights into their personality, motivations, and behaviors. Training Natural Language Processing (NLP) models on a diverse and comprehensive persona-based dataset can lead to conversational models that create a deeper connection with the user, and maintain their engagement. In this paper, we leverage the power of Large Language Models (LLMs) to create a large, high-quality conversational dataset from a seed dataset. We propose a Generator-Critic architecture framework to expand the initial dataset, while improving the quality of its conversations. The Generator is an LLM prompted to output conversations. The Critic consists of a mixture of expert LLMs that control the quality of the generated conversations. These experts select the best generated conversations, which we then use to improve the Generator. We release Synthetic-Persona-Chat, consisting of 20k conversations seeded from Persona-Chat. We evaluate the quality of Synthetic-Persona-Chat and our generation framework on different dimensions through extensive experiments, and observe that the losing rate of Synthetic-Persona-Chat against Persona-Chat during Turing test decreases from 17.2% to 8.8% over three iterations.

Vision Language Models in Medicine

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

Generative Expressive Conversational Speech Synthesis

Conversational Speech Synthesis (CSS) aims to express a target utterance with the proper speaking style in a user-agent conversation setting. Existing CSS methods employ effective multi-modal context modeling techniques to achieve empathy understanding and expression. However, they often need to design complex network architectures and meticulously optimize the modules within them. In addition, due to the limitations of small-scale datasets containing scripted recording styles, they often fail to simulate real natural conversational styles. To address the above issues, we propose a novel generative expressive CSS system, termed GPT-Talker.We transform the multimodal information of the multi-turn dialogue history into discrete token sequences and seamlessly integrate them to form a comprehensive user-agent dialogue context. Leveraging the power of GPT, we predict the token sequence, that includes both semantic and style knowledge, of response for the agent. After that, the expressive conversational speech is synthesized by the conversation-enriched VITS to deliver feedback to the user.Furthermore, we propose a large-scale Natural CSS Dataset called NCSSD, that includes both naturally recorded conversational speech in improvised styles and dialogues extracted from TV shows. It encompasses both Chinese and English languages, with a total duration of 236 hours.We conducted comprehensive experiments on the reliability of the NCSSD and the effectiveness of our GPT-Talker. Both subjective and objective evaluations demonstrate that our model outperforms other state-of-the-art CSS systems significantly in terms of naturalness and expressiveness. The Code, Dataset, and Pre-trained Model are available at: https://github.com/AI-S2-Lab/GPT-Talker.

BiMediX: Bilingual Medical Mixture of Experts LLM

In this paper, we introduce BiMediX, the first bilingual medical mixture of experts LLM designed for seamless interaction in both English and Arabic. Our model facilitates a wide range of medical interactions in English and Arabic, including multi-turn chats to inquire about additional details such as patient symptoms and medical history, multiple-choice question answering, and open-ended question answering. We propose a semi-automated English-to-Arabic translation pipeline with human refinement to ensure high-quality translations. We also introduce a comprehensive evaluation benchmark for Arabic medical LLMs. Furthermore, we introduce BiMed1.3M, an extensive Arabic-English bilingual instruction set covering 1.3 Million diverse medical interactions, resulting in over 632 million healthcare specialized tokens for instruction tuning. Our BiMed1.3M dataset includes 250k synthesized multi-turn doctor-patient chats and maintains a 1:2 Arabic-to-English ratio. Our model outperforms state-of-the-art Med42 and Meditron by average absolute gains of 2.5% and 4.1%, respectively, computed across multiple medical evaluation benchmarks in English, while operating at 8-times faster inference. Moreover, our BiMediX outperforms the generic Arabic-English bilingual LLM, Jais-30B, by average absolute gains of 10% on our Arabic medical benchmark and 15% on bilingual evaluations across multiple datasets. Our project page with source code and trained model is available at https://github.com/mbzuai-oryx/BiMediX .

Better to Ask in English: Cross-Lingual Evaluation of Large Language Models for Healthcare Queries

Large language models (LLMs) are transforming the ways the general public accesses and consumes information. Their influence is particularly pronounced in pivotal sectors like healthcare, where lay individuals are increasingly appropriating LLMs as conversational agents for everyday queries. While LLMs demonstrate impressive language understanding and generation proficiencies, concerns regarding their safety remain paramount in these high-stake domains. Moreover, the development of LLMs is disproportionately focused on English. It remains unclear how these LLMs perform in the context of non-English languages, a gap that is critical for ensuring equity in the real-world use of these systems.This paper provides a framework to investigate the effectiveness of LLMs as multi-lingual dialogue systems for healthcare queries. Our empirically-derived framework XlingEval focuses on three fundamental criteria for evaluating LLM responses to naturalistic human-authored health-related questions: correctness, consistency, and verifiability. Through extensive experiments on four major global languages, including English, Spanish, Chinese, and Hindi, spanning three expert-annotated large health Q&A datasets, and through an amalgamation of algorithmic and human-evaluation strategies, we found a pronounced disparity in LLM responses across these languages, indicating a need for enhanced cross-lingual capabilities. We further propose XlingHealth, a cross-lingual benchmark for examining the multilingual capabilities of LLMs in the healthcare context. Our findings underscore the pressing need to bolster the cross-lingual capacities of these models, and to provide an equitable information ecosystem accessible to all.

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.

CLIPSyntel: CLIP and LLM Synergy for Multimodal Question Summarization in Healthcare

In the era of modern healthcare, swiftly generating medical question summaries is crucial for informed and timely patient care. Despite the increasing complexity and volume of medical data, existing studies have focused solely on text-based summarization, neglecting the integration of visual information. Recognizing the untapped potential of combining textual queries with visual representations of medical conditions, we introduce the Multimodal Medical Question Summarization (MMQS) Dataset. This dataset, a major contribution to our work, pairs medical queries with visual aids, facilitating a richer and more nuanced understanding of patient needs. We also propose a framework, utilizing the power of Contrastive Language Image Pretraining(CLIP) and Large Language Models(LLMs), consisting of four modules that identify medical disorders, generate relevant context, filter medical concepts, and craft visually aware summaries. Our comprehensive framework harnesses the power of CLIP, a multimodal foundation model, and various general-purpose LLMs, comprising four main modules: the medical disorder identification module, the relevant context generation module, the context filtration module for distilling relevant medical concepts and knowledge, and finally, a general-purpose LLM to generate visually aware medical question summaries. Leveraging our MMQS dataset, we showcase how visual cues from images enhance the generation of medically nuanced summaries. This multimodal approach not only enhances the decision-making process in healthcare but also fosters a more nuanced understanding of patient queries, laying the groundwork for future research in personalized and responsive medical care

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.

DERA: Enhancing Large Language Model Completions with Dialog-Enabled Resolving Agents

Large language models (LLMs) have emerged as valuable tools for many natural language understanding tasks. In safety-critical applications such as healthcare, the utility of these models is governed by their ability to generate outputs that are factually accurate and complete. In this work, we present dialog-enabled resolving agents (DERA). DERA is a paradigm made possible by the increased conversational abilities of LLMs, namely GPT-4. It provides a simple, interpretable forum for models to communicate feedback and iteratively improve output. We frame our dialog as a discussion between two agent types - a Researcher, who processes information and identifies crucial problem components, and a Decider, who has the autonomy to integrate the Researcher's information and makes judgments on the final output. We test DERA against three clinically-focused tasks. For medical conversation summarization and care plan generation, DERA shows significant improvement over the base GPT-4 performance in both human expert preference evaluations and quantitative metrics. In a new finding, we also show that GPT-4's performance (70%) on an open-ended version of the MedQA question-answering (QA) dataset (Jin et al. 2021, USMLE) is well above the passing level (60%), with DERA showing similar performance. We release the open-ended MEDQA dataset at https://github.com/curai/curai-research/tree/main/DERA.

Automating Feedback Analysis in Surgical Training: Detection, Categorization, and Assessment

This work introduces the first framework for reconstructing surgical dialogue from unstructured real-world recordings, which is crucial for characterizing teaching tasks. In surgical training, the formative verbal feedback that trainers provide to trainees during live surgeries is crucial for ensuring safety, correcting behavior immediately, and facilitating long-term skill acquisition. However, analyzing and quantifying this feedback is challenging due to its unstructured and specialized nature. Automated systems are essential to manage these complexities at scale, allowing for the creation of structured datasets that enhance feedback analysis and improve surgical education. Our framework integrates voice activity detection, speaker diarization, and automated speech recaognition, with a novel enhancement that 1) removes hallucinations (non-existent utterances generated during speech recognition fueled by noise in the operating room) and 2) separates speech from trainers and trainees using few-shot voice samples. These aspects are vital for reconstructing accurate surgical dialogues and understanding the roles of operating room participants. Using data from 33 real-world surgeries, we demonstrated the system's capability to reconstruct surgical teaching dialogues and detect feedback instances effectively (F1 score of 0.79+/-0.07). Moreover, our hallucination removal step improves feedback detection performance by ~14%. Evaluation on downstream clinically relevant tasks of predicting Behavioral Adjustment of trainees and classifying Technical feedback, showed performances comparable to manual annotations with F1 scores of 0.82+/0.03 and 0.81+/0.03 respectively. These results highlight the effectiveness of our framework in supporting clinically relevant tasks and improving over manual methods.

BioMedGPT: Open Multimodal Generative Pre-trained Transformer for BioMedicine

Foundation models (FMs) have exhibited remarkable performance across a wide range of downstream tasks in many domains. Nevertheless, general-purpose FMs often face challenges when confronted with domain-specific problems, due to their limited access to the proprietary training data in a particular domain. In biomedicine, there are various biological modalities, such as molecules, proteins, and cells, which are encoded by the language of life and exhibit significant modality gaps with human natural language. In this paper, we introduce BioMedGPT, an open multimodal generative pre-trained transformer (GPT) for biomedicine, to bridge the gap between the language of life and human natural language. BioMedGPT allows users to easily ``communicate'' with diverse biological modalities through free text, which is the first of its kind. BioMedGPT aligns different biological modalities with natural language via a large generative language model, namely, BioMedGPT-LM. We publish BioMedGPT-10B, which unifies the feature spaces of molecules, proteins, and natural language via encoding and alignment. Through fine-tuning, BioMedGPT-10B outperforms or is on par with human and significantly larger general-purpose foundation models on the biomedical QA task. It also demonstrates promising performance in the molecule QA and protein QA tasks, which could greatly accelerate the discovery of new drugs and therapeutic targets. In addition, BioMedGPT-LM-7B is the first large generative language model based on Llama2 in the biomedical domain, therefore is commercial friendly. Both BioMedGPT-10B and BioMedGPT-LM-7B are open-sourced to the research community. In addition, we publish the datasets that are meticulously curated for the alignment of multi-modalities, i.e., PubChemQA and UniProtQA. All the models, codes, and datasets are available at https://github.com/PharMolix/OpenBioMed.

Citrus: Leveraging Expert Cognitive Pathways in a Medical Language Model for Advanced Medical Decision Support

Large language models (LLMs), particularly those with reasoning capabilities, have rapidly advanced in recent years, demonstrating significant potential across a wide range of applications. However, their deployment in healthcare, especially in disease reasoning tasks, is hindered by the challenge of acquiring expert-level cognitive data. In this paper, we introduce Citrus, a medical language model that bridges the gap between clinical expertise and AI reasoning by emulating the cognitive processes of medical experts. The model is trained on a large corpus of simulated expert disease reasoning data, synthesized using a novel approach that accurately captures the decision-making pathways of clinicians. This approach enables Citrus to better simulate the complex reasoning processes involved in diagnosing and treating medical conditions.To further address the lack of publicly available datasets for medical reasoning tasks, we release the last-stage training data, including a custom-built medical diagnostic dialogue dataset. This open-source contribution aims to support further research and development in the field. Evaluations using authoritative benchmarks such as MedQA, covering tasks in medical reasoning and language understanding, show that Citrus achieves superior performance compared to other models of similar size. These results highlight Citrus potential to significantly enhance medical decision support systems, providing a more accurate and efficient tool for clinical decision-making.

Can large language models democratize access to dual-use biotechnology?

Large language models (LLMs) such as those embedded in 'chatbots' are accelerating and democratizing research by providing comprehensible information and expertise from many different fields. However, these models may also confer easy access to dual-use technologies capable of inflicting great harm. To evaluate this risk, the 'Safeguarding the Future' course at MIT tasked non-scientist students with investigating whether LLM chatbots could be prompted to assist non-experts in causing a pandemic. In one hour, the chatbots suggested four potential pandemic pathogens, explained how they can be generated from synthetic DNA using reverse genetics, supplied the names of DNA synthesis companies unlikely to screen orders, identified detailed protocols and how to troubleshoot them, and recommended that anyone lacking the skills to perform reverse genetics engage a core facility or contract research organization. Collectively, these results suggest that LLMs will make pandemic-class agents widely accessible as soon as they are credibly identified, even to people with little or no laboratory training. Promising nonproliferation measures include pre-release evaluations of LLMs by third parties, curating training datasets to remove harmful concepts, and verifiably screening all DNA generated by synthesis providers or used by contract research organizations and robotic cloud laboratories to engineer organisms or viruses.

Bt-GAN: Generating Fair Synthetic Healthdata via Bias-transforming Generative Adversarial Networks

Synthetic data generation offers a promising solution to enhance the usefulness of Electronic Healthcare Records (EHR) by generating realistic de-identified data. However, the existing literature primarily focuses on the quality of synthetic health data, neglecting the crucial aspect of fairness in downstream predictions. Consequently, models trained on synthetic EHR have faced criticism for producing biased outcomes in target tasks. These biases can arise from either spurious correlations between features or the failure of models to accurately represent sub-groups. To address these concerns, we present Bias-transforming Generative Adversarial Networks (Bt-GAN), a GAN-based synthetic data generator specifically designed for the healthcare domain. In order to tackle spurious correlations (i), we propose an information-constrained Data Generation Process that enables the generator to learn a fair deterministic transformation based on a well-defined notion of algorithmic fairness. To overcome the challenge of capturing exact sub-group representations (ii), we incentivize the generator to preserve sub-group densities through score-based weighted sampling. This approach compels the generator to learn from underrepresented regions of the data manifold. We conduct extensive experiments using the MIMIC-III database. Our results demonstrate that Bt-GAN achieves SOTA accuracy while significantly improving fairness and minimizing bias amplification. We also perform an in-depth explainability analysis to provide additional evidence supporting the validity of our study. In conclusion, our research introduces a novel and professional approach to addressing the limitations of synthetic data generation in the healthcare domain. By incorporating fairness considerations and leveraging advanced techniques such as GANs, we pave the way for more reliable and unbiased predictions in healthcare applications.

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.

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

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

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

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

Effective Transfer Learning for Identifying Similar Questions: Matching User Questions to COVID-19 FAQs

People increasingly search online for answers to their medical questions but the rate at which medical questions are asked online significantly exceeds the capacity of qualified people to answer them. This leaves many questions unanswered or inadequately answered. Many of these questions are not unique, and reliable identification of similar questions would enable more efficient and effective question answering schema. COVID-19 has only exacerbated this problem. Almost every government agency and healthcare organization has tried to meet the informational need of users by building online FAQs, but there is no way for people to ask their question and know if it is answered on one of these pages. While many research efforts have focused on the problem of general question similarity, these approaches do not generalize well to domains that require expert knowledge to determine semantic similarity, such as the medical domain. In this paper, we show how a double fine-tuning approach of pretraining a neural network on medical question-answer pairs followed by fine-tuning on medical question-question pairs is a particularly useful intermediate task for the ultimate goal of determining medical question similarity. While other pretraining tasks yield an accuracy below 78.7% on this task, our model achieves an accuracy of 82.6% with the same number of training examples, an accuracy of 80.0% with a much smaller training set, and an accuracy of 84.5% when the full corpus of medical question-answer data is used. We also describe a currently live system that uses the trained model to match user questions to COVID-related FAQs.

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.

Synthetic Observational Health Data with GANs: from slow adoption to a boom in medical research and ultimately digital twins?

After being collected for patient care, Observational Health Data (OHD) can further benefit patient well-being by sustaining the development of health informatics and medical research. Vast potential is unexploited because of the fiercely private nature of patient-related data and regulations to protect it. Generative Adversarial Networks (GANs) have recently emerged as a groundbreaking way to learn generative models that produce realistic synthetic data. They have revolutionized practices in multiple domains such as self-driving cars, fraud detection, digital twin simulations in industrial sectors, and medical imaging. The digital twin concept could readily apply to modelling and quantifying disease progression. In addition, GANs posses many capabilities relevant to common problems in healthcare: lack of data, class imbalance, rare diseases, and preserving privacy. Unlocking open access to privacy-preserving OHD could be transformative for scientific research. In the midst of COVID-19, the healthcare system is facing unprecedented challenges, many of which of are data related for the reasons stated above. Considering these facts, publications concerning GAN applied to OHD seemed to be severely lacking. To uncover the reasons for this slow adoption, we broadly reviewed the published literature on the subject. Our findings show that the properties of OHD were initially challenging for the existing GAN algorithms (unlike medical imaging, for which state-of-the-art model were directly transferable) and the evaluation synthetic data lacked clear metrics. We find more publications on the subject than expected, starting slowly in 2017, and since then at an increasing rate. The difficulties of OHD remain, and we discuss issues relating to evaluation, consistency, benchmarking, data modelling, and reproducibility.

Automatic Prompt Optimization Techniques: Exploring the Potential for Synthetic Data Generation

Artificial Intelligence (AI) advancement is heavily dependent on access to large-scale, high-quality training data. However, in specialized domains such as healthcare, data acquisition faces significant constraints due to privacy regulations, ethical considerations, and limited availability. While synthetic data generation offers a promising solution, conventional approaches typically require substantial real data for training generative models. The emergence of large-scale prompt-based models presents new opportunities for synthetic data generation without direct access to protected data. However, crafting effective prompts for domain-specific data generation remains challenging, and manual prompt engineering proves insufficient for achieving output with sufficient precision and authenticity. We review recent developments in automatic prompt optimization, following PRISMA guidelines. We analyze six peer-reviewed studies published between 2020 and 2024 that focus on automatic data-free prompt optimization methods. Our analysis reveals three approaches: feedback-driven, error-based, and control-theoretic. Although all approaches demonstrate promising capabilities in prompt refinement and adaptation, our findings suggest the need for an integrated framework that combines complementary optimization techniques to enhance synthetic data generation while minimizing manual intervention. We propose future research directions toward developing robust, iterative prompt optimization frameworks capable of improving the quality of synthetic data. This advancement can be particularly crucial for sensitive fields and in specialized domains where data access is restricted, potentially transforming how we approach synthetic data generation for AI development.

DiaSynth -- Synthetic Dialogue Generation Framework

The scarcity of domain specific dialogue datasets across various domains, from academic topics to everyday conversations, limits the development of dialogue systems for various applications. Existing research is often constrained either by dialogue datasets that are too general or by niche domain dialogue datasets whose scale does not match the required scale for training dialogue systems. To address this gap, we introduce DiaSynth - a synthetic dialogue generation framework capable of generating high quality, contextually rich dialogues across a wide range of domains. Our approach differs from existing frameworks by dynamically generating dialogues that incorporate simulated personas, subtopics, and diverse conversational characteristics, using a Large Language Model (LLM) with Chain of Thought (CoT) reasoning to create contextually rich, domain-specific dialogues that closely mimic natural human interactions. DiaSynth produces tailored dialogues that emulate realistic conversations. We perform our experiments by generating synthetic data using different LLMs and few-shot examples from DialogSum and SAMSum. The pretrained language models fine-tuned on the synthetic data outperform the base models by 16.47%, while the comparison between models fine-tuned on in-domain data and synthetic data shows that the synthetic data is able to capture 90.48% of the distribution of the in-domain data. The quality of the data generated also scales with the size of LLMs. These results validate DiaSynth's potential as a robust alternative to traditional data collection methods.

Cross-Modality Jailbreak and Mismatched Attacks on Medical Multimodal Large Language Models

Security concerns related to Large Language Models (LLMs) have been extensively explored, yet the safety implications for Multimodal Large Language Models (MLLMs), particularly in medical contexts (MedMLLMs), remain insufficiently studied. This paper delves into the underexplored security vulnerabilities of MedMLLMs, especially when deployed in clinical environments where the accuracy and relevance of question-and-answer interactions are critically tested against complex medical challenges. By combining existing clinical medical data with atypical natural phenomena, we redefine two types of attacks: mismatched malicious attack (2M-attack) and optimized mismatched malicious attack (O2M-attack). Using our own constructed voluminous 3MAD dataset, which covers a wide range of medical image modalities and harmful medical scenarios, we conduct a comprehensive analysis and propose the MCM optimization method, which significantly enhances the attack success rate on MedMLLMs. Evaluations with this dataset and novel attack methods, including white-box attacks on LLaVA-Med and transfer attacks on four other state-of-the-art models, indicate that even MedMLLMs designed with enhanced security features are vulnerable to security breaches. Our work underscores the urgent need for a concerted effort to implement robust security measures and enhance the safety and efficacy of open-source MedMLLMs, particularly given the potential severity of jailbreak attacks and other malicious or clinically significant exploits in medical settings. For further research and replication, anonymous access to our code is available at https://github.com/dirtycomputer/O2M_attack. Warning: Medical large model jailbreaking may generate content that includes unverified diagnoses and treatment recommendations. Always consult professional medical advice.