Karan Singhal

A comprehensive differential diagnosis is a cornerstone of medical care that is often reached through an iterative process of interpretation that combines clinical history, physical examination, investigations and procedures. Interactive interfaces powered by large language models present new opportunities to assist and automate aspects of this process¹. Here we introduce the Articulate Medical Intelligence Explorer (AMIE), a large language model that is optimized for diagnostic reasoning, and evaluate its ability to generate a differential diagnosis alone or as an aid to clinicians. Twenty clinicians evaluated 302 challenging, real-world medical cases sourced from published case reports. Each case report was read by two clinicians, who were randomized to one of two assistive conditions: assistance from search engines and standard medical resources; or assistance from AMIE in addition to these tools. All clinicians provided a baseline, unassisted differential diagnosis prior to using the respective assistive tools. AMIE exhibited standalone performance that exceeded that of unassisted clinicians (top-10 accuracy 59.1% versus 33.6%, P = 0.04). Comparing the two assisted study arms, the differential diagnosis quality score was higher for clinicians assisted by AMIE (top-10 accuracy 51.7%) compared with clinicians without its assistance (36.1%; McNemar’s test: 45.7, P < 0.01) and clinicians with search (44.4%; McNemar’s test: 4.75, P = 0.03). Further, clinicians assisted by AMIE arrived at more comprehensive differential lists than those without assistance from AMIE. Our study suggests that AMIE 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.

At the heart of medicine lies physician–patient dialogue, where skillful history-taking enables effective diagnosis, management and enduring trust^1,2. Artificial intelligence (AI) systems capable of diagnostic dialogue could increase accessibility and quality of care. However, approximating clinicians’ expertise is an outstanding challenge. Here we introduce AMIE (Articulate Medical Intelligence Explorer), a large language model (LLM)-based AI system optimized for diagnostic dialogue. AMIE uses a self-play-based³ simulated environment with automated feedback for scaling learning across disease conditions, specialties and contexts. We designed a framework for evaluating clinically meaningful axes of performance, including history-taking, diagnostic accuracy, management, communication skills and empathy. We compared AMIE’s performance to that of primary care physicians in a randomized, double-blind crossover study of text-based consultations with validated patient-actors similar to objective structured clinical examination^4,5. The study included 159 case scenarios from providers in Canada, the United Kingdom and India, 20 primary care physicians compared to AMIE, and evaluations by specialist physicians and patient-actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 30 out of 32 axes according to the specialist physicians and 25 out of 26 axes according to the patient-actors. Our research has several limitations and should be interpreted with caution. Clinicians used synchronous text chat, which permits large-scale LLM–patient interactions, but this is unfamiliar in 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.

Large language models (LLMs) have shown promise in medical question answering, with Med-PaLM being the first to exceed a ‘passing’ score in United States Medical Licensing Examination style questions. However, challenges remain in long-form medical question answering and handling real-world workflows. Here, we present Med-PaLM 2, which bridges these gaps with a combination of base LLM improvements, medical domain fine-tuning and new strategies for improving reasoning and grounding through ensemble refinement and chain of retrieval. Med-PaLM 2 scores up to 86.5% on the MedQA dataset, improving upon Med-PaLM by over 19%, and demonstrates dramatic performance increases across MedMCQA, PubMedQA and MMLU clinical topics datasets. Our detailed human evaluations framework shows that physicians prefer Med-PaLM 2 answers to those from other physicians on eight of nine clinical axes. Med-PaLM 2 also demonstrates significant improvements over its predecessor across all evaluation metrics, particularly on new adversarial datasets designed to probe LLM limitations (P < 0.001). In a pilot study using real-world medical questions, specialists preferred Med-PaLM 2 answers to generalist physician answers 65% of the time. While specialist answers were still preferred overall, both specialists and generalists rated Med-PaLM 2 to be as safe as physician answers, demonstrating its growing potential in real-world medical applications.

Automated radiology report generation has the potential to improve patient care and reduce the workload of radiologists. However, the path toward real-world adoption has been stymied by the challenge of evaluating the clinical quality of artificial intelligence (AI)-generated reports. We build a state-of-the-art report generation system for chest radiographs, called Flamingo-CXR, and perform an expert evaluation of AI-generated reports by engaging a panel of board-certified radiologists. We observe a wide distribution of preferences across the panel and across clinical settings, with 56.1% of Flamingo-CXR intensive care reports evaluated to be preferable or equivalent to clinician reports, by half or more of the panel, rising to 77.7% for in/outpatient X-rays overall and to 94% for the subset of cases with no pertinent abnormal findings. Errors were observed in human-written reports and Flamingo-CXR reports, with 24.8% of in/outpatient cases containing clinically significant errors in both report types, 22.8% in Flamingo-CXR reports only and 14.0% in human reports only. For reports that contain errors we develop an assistive setting, a demonstration of clinician–AI collaboration for radiology report composition, indicating new possibilities for potential clinical utility.

Large language models (LLMs) hold promise to serve complex health information needs but also have the potential to introduce harm and exacerbate health disparities. Reliably evaluating equity-related model failures is a critical step toward developing systems that promote health equity. We present resources and methodologies for surfacing biases with potential to precipitate equity-related harms in long-form, LLM-generated answers to medical questions and conduct a large-scale empirical case study with the Med-PaLM 2 LLM. Our contributions include a multifactorial framework for human assessment of LLM-generated answers for biases and EquityMedQA, a collection of seven datasets enriched for adversarial queries. Both our human assessment framework and our dataset design process are grounded in an iterative participatory approach and review of Med-PaLM 2 answers. Through our empirical study, we find that our approach surfaces biases that may be missed by narrower evaluation approaches. Our experience underscores the importance of using diverse assessment methodologies and involving raters of varying backgrounds and expertise. While our approach is not sufficient to holistically assess whether the deployment of an artificial intelligence (AI) system promotes equitable health outcomes, we hope that it can be leveraged and built upon toward a shared goal of LLMs that promote accessible and equitable healthcare.

Radiology reports are an instrumental part of modern medicine, informing key clinical decisions such as diagnosis and treatment. The worldwide shortage of radiologists, however, restricts access to expert care and imposes heavy workloads, contributing to avoidable errors in report delivery. While recent progress in automated report generation with vision-language models offers clear potential to ameliorate this situation, the path toward real-world adoption has been stymied by the challenge of evaluating the clinical quality of AI-generated reports. In this study, we build a state-of-the-art report generation system for chest radiographs, Flamingo-CXR, by fine-tuning a well-known vision-language foundation model on radiology data. To measure the quality of the AI-generated reports, we perform an expert evaluation, that is largest in scale and diversity to date, by engaging a group of 27 certified radiologists in the United States and India to provide detailed assessment of AI-generated and human written reports from an intensive care setting as well as an inpatient setting. We observe a wide distribution of preferences across the panel, ranging from full consensus to dissensus, across clinical settings and regions, with 55.4% of Flamingo-CXR intensive care reports evaluated to be preferable or equivalent to clinician reports, by half or more of the panel, rising to 77.7% for outpatient x-rays overall and to 94% for the subset of cases with no pertinent abnormal findings. For reports that contain errors we develop an assistive setting, the first demonstration of clinician-AI collaboration for radiology report composition, and we observe a synergistic improvement across all clinical settings. Altogether, these nuanced evaluations reveal disparities between the AI system and radiologists, identify areas for potential clinical utility and pave the way toward a collaborative system that enhances clinical accuracy of radiology reporting.