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Jul 11

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.

Capabilities of GPT-4 on Medical Challenge Problems

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

GPT Takes the Bar Exam

Nearly all jurisdictions in the United States require a professional license exam, commonly referred to as "the Bar Exam," as a precondition for law practice. To even sit for the exam, most jurisdictions require that an applicant completes at least seven years of post-secondary education, including three years at an accredited law school. In addition, most test-takers also undergo weeks to months of further, exam-specific preparation. Despite this significant investment of time and capital, approximately one in five test-takers still score under the rate required to pass the exam on their first try. In the face of a complex task that requires such depth of knowledge, what, then, should we expect of the state of the art in "AI?" In this research, we document our experimental evaluation of the performance of OpenAI's `text-davinci-003` model, often-referred to as GPT-3.5, on the multistate multiple choice (MBE) section of the exam. While we find no benefit in fine-tuning over GPT-3.5's zero-shot performance at the scale of our training data, we do find that hyperparameter optimization and prompt engineering positively impacted GPT-3.5's zero-shot performance. For best prompt and parameters, GPT-3.5 achieves a headline correct rate of 50.3% on a complete NCBE MBE practice exam, significantly in excess of the 25% baseline guessing rate, and performs at a passing rate for both Evidence and Torts. GPT-3.5's ranking of responses is also highly-correlated with correctness; its top two and top three choices are correct 71% and 88% of the time, respectively, indicating very strong non-entailment performance. While our ability to interpret these results is limited by nascent scientific understanding of LLMs and the proprietary nature of GPT, we believe that these results strongly suggest that an LLM will pass the MBE component of the Bar Exam in the near future.

Small Language Models Learn Enhanced Reasoning Skills from Medical Textbooks

While recent advancements in commercial large language models (LM) have shown promising results in medical tasks, their closed-source nature poses significant privacy and security concerns, hindering their widespread use in the medical field. Despite efforts to create open-source models, their limited parameters often result in insufficient multi-step reasoning capabilities required for solving complex medical problems. To address this, we introduce Meerkat-7B, a novel medical AI system with 7 billion parameters. Meerkat-7B was trained using our new synthetic dataset consisting of high-quality chain-of-thought reasoning paths sourced from 18 medical textbooks, along with diverse instruction-following datasets. Our system achieved remarkable accuracy across seven medical benchmarks, surpassing GPT-3.5 by 13.1%, as well as outperforming the previous best 7B models such as MediTron-7B and BioMistral-7B by 13.4% and 9.8%, respectively. Notably, it surpassed the passing threshold of the United States Medical Licensing Examination (USMLE) for the first time for a 7B-parameter model. Additionally, our system offered more detailed free-form responses to clinical queries compared to existing 7B and 13B models, approaching the performance level of GPT-3.5. This significantly narrows the performance gap with large LMs, showcasing its effectiveness in addressing complex medical challenges.

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.

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

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

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.

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.

Are Large Language Models True Healthcare Jacks-of-All-Trades? Benchmarking Across Health Professions Beyond Physician Exams

Recent advancements in Large Language Models (LLMs) have demonstrated their potential in delivering accurate answers to questions about world knowledge. Despite this, existing benchmarks for evaluating LLMs in healthcare predominantly focus on medical doctors, leaving other critical healthcare professions underrepresented. To fill this research gap, we introduce the Examinations for Medical Personnel in Chinese (EMPEC), a pioneering large-scale healthcare knowledge benchmark in traditional Chinese. EMPEC consists of 157,803 exam questions across 124 subjects and 20 healthcare professions, including underrepresented occupations like Optometrists and Audiologists. Each question is tagged with its release time and source, ensuring relevance and authenticity. We conducted extensive experiments on 17 LLMs, including proprietary, open-source models, general domain models and medical specific models, evaluating their performance under various settings. Our findings reveal that while leading models like GPT-4 achieve over 75\% accuracy, they still struggle with specialized fields and alternative medicine. Surprisingly, general-purpose LLMs outperformed medical-specific models, and incorporating EMPEC's training data significantly enhanced performance. Additionally, the results on questions released after the models' training cutoff date were consistent with overall performance trends, suggesting that the models' performance on the test set can predict their effectiveness in addressing unseen healthcare-related queries. The transition from traditional to simplified Chinese characters had a negligible impact on model performance, indicating robust linguistic versatility. Our study underscores the importance of expanding benchmarks to cover a broader range of healthcare professions to better assess the applicability of LLMs in real-world healthcare scenarios.

Benchmarking Large Language Models on CMExam -- A Comprehensive Chinese Medical Exam Dataset

Recent advancements in large language models (LLMs) have transformed the field of question answering (QA). However, evaluating LLMs in the medical field is challenging due to the lack of standardized and comprehensive datasets. To address this gap, we introduce CMExam, sourced from the Chinese National Medical Licensing Examination. CMExam consists of 60K+ multiple-choice questions for standardized and objective evaluations, as well as solution explanations for model reasoning evaluation in an open-ended manner. For in-depth analyses of LLMs, we invited medical professionals to label five additional question-wise annotations, including disease groups, clinical departments, medical disciplines, areas of competency, and question difficulty levels. Alongside the dataset, we further conducted thorough experiments with representative LLMs and QA algorithms on CMExam. The results show that GPT-4 had the best accuracy of 61.6% and a weighted F1 score of 0.617. These results highlight a great disparity when compared to human accuracy, which stood at 71.6%. For explanation tasks, while LLMs could generate relevant reasoning and demonstrate improved performance after finetuning, they fall short of a desired standard, indicating ample room for improvement. To the best of our knowledge, CMExam is the first Chinese medical exam dataset to provide comprehensive medical annotations. The experiments and findings of LLM evaluation also provide valuable insights into the challenges and potential solutions in developing Chinese medical QA systems and LLM evaluation pipelines. The dataset and relevant code are available at https://github.com/williamliujl/CMExam.

Towards Accurate Differential Diagnosis with Large Language Models

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

ClinBench-HPB: A Clinical Benchmark for Evaluating LLMs in Hepato-Pancreato-Biliary Diseases

Hepato-pancreato-biliary (HPB) disorders represent a global public health challenge due to their high morbidity and mortality. Although large language models (LLMs) have shown promising performance in general medical question-answering tasks, the current evaluation benchmarks are mostly derived from standardized examinations or manually designed questions, lacking HPB coverage and clinical cases. To address these issues, we systematically eatablish an HPB disease evaluation benchmark comprising 3,535 closed-ended multiple-choice questions and 337 open-ended real diagnosis cases, which encompasses all the 33 main categories and 465 subcategories of HPB diseases defined in the International Statistical Classification of Diseases, 10th Revision (ICD-10). The multiple-choice questions are curated from public datasets and synthesized data, and the clinical cases are collected from prestigious medical journals, case-sharing platforms, and collaborating hospitals. By evalauting commercial and open-source general and medical LLMs on our established benchmark, namely ClinBench-HBP, we find that while commercial LLMs perform competently on medical exam questions, they exhibit substantial performance degradation on HPB diagnosis tasks, especially on complex, inpatient clinical cases. Those medical LLMs also show limited generalizability to HPB diseases. Our results reveal the critical limitations of current LLMs in the domain of HPB diseases, underscoring the imperative need for future medical LLMs to handle real, complex clinical diagnostics rather than simple medical exam questions. The benchmark will be released at https://clinbench-hpb.github.io.

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

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

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

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