Vivek Natarajan

Karan Singhal, Shekoofeh Azizi, Tao Tu et al.

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

Tao Tu, Shekoofeh Azizi, Danny Driess et al.

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

Shekoofeh Azizi, Laura Culp, Jan Freyberg et al.

Recent progress in Medical Artificial Intelligence (AI) has delivered systems that can reach clinical expert level performance. However, such systems tend to demonstrate sub-optimal "out-of-distribution" performance when evaluated in clinical settings different from the training environment. A common mitigation strategy is to develop separate systems for each clinical setting using site-specific data [1]. However, this quickly becomes impractical as medical data is time-consuming to acquire and expensive to annotate [2]. Thus, the problem of "data-efficient generalization" presents an ongoing difficulty for Medical AI development. Although progress in representation learning shows promise, their benefits have not been rigorously studied, specifically for out-of-distribution settings. To meet these challenges, we present REMEDIS, a unified representation learning strategy to improve robustness and data-efficiency of medical imaging AI. REMEDIS uses a generic combination of large-scale supervised transfer learning with self-supervised learning and requires little task-specific customization. We study a diverse range of medical imaging tasks and simulate three realistic application scenarios using retrospective data. REMEDIS exhibits significantly improved in-distribution performance with up to 11.5% relative improvement in diagnostic accuracy over a strong supervised baseline. More importantly, our strategy leads to strong data-efficient generalization of medical imaging AI, matching strong supervised baselines using between 1% to 33% of retraining data across tasks. These results suggest that REMEDIS can significantly accelerate the life-cycle of medical imaging AI development thereby presenting an important step forward for medical imaging AI to deliver broad impact.

Daniel McDuff, Mike Schaekermann, Tao Tu et al.

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.

Ryutaro Tanno, David G. T. Barrett, Andrew Sellergren et al.

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 and delays in report delivery. While recent progress in automated report generation with vision-language models offer clear potential in ameliorating the situation, the path to 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, $\textit{Flamingo-CXR}$, by fine-tuning a well-known vision-language foundation model on radiology data. To evaluate the quality of the AI-generated reports, a group of 16 certified radiologists provide detailed evaluations of AI-generated and human written reports for chest X-rays from an intensive care setting in the United States and an inpatient setting in India. At least one radiologist (out of two per case) preferred the AI report to the ground truth report in over 60$\%$ of cases for both datasets. Amongst the subset of AI-generated reports that contain errors, the most frequently cited reasons were related to the location and finding, whereas for human written reports, most mistakes were related to severity and finding. This disparity suggested potential complementarity between our AI system and human experts, prompting us to develop an assistive scenario in which Flamingo-CXR generates a first-draft report, which is subsequently revised by a clinician. This is the first demonstration of clinician-AI collaboration for report writing, and the resultant reports are assessed to be equivalent or preferred by at least one radiologist to reports written by experts alone in 80$\%$ of in-patient cases and 60$\%$ of intensive care cases.

Isaac R. Galatzer-Levy, Daniel McDuff, Vivek Natarajan et al.

The current work investigates the capability of Large language models (LLMs) that are explicitly trained on large corpuses of medical knowledge (Med-PaLM 2) to predict psychiatric functioning from patient interviews and clinical descriptions without being trained to do so. To assess this, n = 145 depression and n =115 PTSD assessments and n = 46 clinical case studies across high prevalence/high comorbidity disorders (Depressive, Anxiety, Psychotic, trauma and stress, Addictive disorders) were analyzed using prompts to extract estimated clinical scores and diagnoses. Results demonstrate that Med-PaLM 2 is capable of assessing psychiatric functioning across a range of psychiatric conditions with the strongest performance being the prediction of depression scores based on standardized assessments (Accuracy range= 0.80 - 0.84) which were statistically indistinguishable from human clinical raters t(1,144) = 1.20; p = 0.23. Results show the potential for general clinical language models to flexibly predict psychiatric risk based on free descriptions of functioning from both patients and clinicians.

Peter Brodeur, Jacob M. Koshy, Anil Palepu et al.

Large language model (LLM)-based AI systems have shown promise for patient-facing diagnostic and management conversations in simulated settings. Translating these systems into clinical practice requires assessment in real-world workflows with rigorous safety oversight. We report a prospective, single-arm feasibility study of an LLM-based conversational AI, the Articulate Medical Intelligence Explorer (AMIE), conducting clinical history taking and presentation of potential diagnoses for patients to discuss with their provider at urgent care appointments at a leading academic medical center. 100 adult patients completed an AMIE text-chat interaction up to 5 days before their appointment. We sought to assess the conversational safety and quality, patient and clinician experience, and clinical reasoning capabilities compared to primary care providers (PCPs). Human safety supervisors monitored all patient-AMIE interactions in real time and did not need to intervene to stop any consultations based on pre-defined criteria. Patients reported high satisfaction and their attitudes towards AI improved after interacting with AMIE (p < 0.001). PCPs found AMIE's output useful with a positive impact on preparedness. AMIE's differential diagnosis (DDx) included the final diagnosis, per chart review 8 weeks post-encounter, in 90% of cases, with 75% top-3 accuracy. Blinded assessment of AMIE and PCP DDx and management (Mx) plans suggested similar overall DDx and Mx plan quality, without significant differences for DDx (p = 0.6) and appropriateness and safety of Mx (p = 0.1 and 1.0, respectively). PCPs outperformed AMIE in the practicality (p = 0.003) and cost effectiveness (p = 0.004) of Mx. While further research is needed, this study demonstrates the initial feasibility, safety, and user acceptance of conversational AI in a real-world setting, representing crucial steps towards clinical translation.

Yubin Kim, Salman Rahman, Samuel Schmidgall et al.

Scientific discovery in digital health requires converting continuous physiological signals from wearable devices into clinically actionable biomarkers. We introduce CoDaS (AI Co-Data-Scientist), a multi-agent system that structures biomarker discovery as an iterative process combining hypothesis generation, statistical analysis, adversarial validation, and literature-grounded reasoning with human oversight using large-scale wearable datasets. Across three cohorts totaling 9,279 participant-observations, CoDaS identified 41 candidate digital biomarkers for mental health and 25 for metabolic outcomes, each subjected to an internal validation battery spanning replication, stability, robustness, and discriminative power. Across two independent depression cohorts, CoDaS surfaced circadian instability-related features in both datasets, reflected in sleep duration variability (DWB, ρ= 0.252, p < 0.001) and sleep onset variability (GLOBEM, ρ= 0.126, p < 0.001). In a metabolic cohort, CoDaS derived a cardiovascular fitness index (steps/resting heart rate; ρ= -0.374, p < 0.001), and recovered established clinical associations, including the hepatic function ratio (AST/ALT; ρ= -0.375, p < 0.001), a known correlate of insulin resistance. Incorporating CoDaS-derived features alongside demographic variables led to modest but consistent improvements in predictive performance, with cross-validated ΔR^2 increases of 0.040 for depression and 0.021 for insulin resistance. These findings suggest that CoDaS enables systematic and traceable hypothesis generation and prioritization for biomarker discovery from large-scale wearable data.

Khaled Saab, Tao Tu, Wei-Hung Weng et al.

Excellence in a wide variety of medical applications poses considerable challenges for AI, requiring advanced reasoning, access to up-to-date medical knowledge and understanding of complex multimodal data. Gemini models, with strong general capabilities in multimodal and long-context reasoning, offer exciting possibilities in medicine. Building on these core strengths of Gemini, we introduce Med-Gemini, a family of highly capable multimodal models that are specialized in medicine with the ability to seamlessly use web search, and that can be efficiently tailored to novel modalities using custom encoders. We evaluate Med-Gemini on 14 medical benchmarks, establishing new state-of-the-art (SoTA) performance on 10 of them, and surpass the GPT-4 model family on every benchmark where a direct comparison is viable, often by a wide margin. On the popular MedQA (USMLE) benchmark, our best-performing Med-Gemini model achieves SoTA performance of 91.1% accuracy, using a novel uncertainty-guided search strategy. On 7 multimodal benchmarks including NEJM Image Challenges and MMMU (health & medicine), Med-Gemini improves over GPT-4V by an average relative margin of 44.5%. We demonstrate the effectiveness of Med-Gemini's long-context capabilities through SoTA performance on a needle-in-a-haystack retrieval task from long de-identified health records and medical video question answering, surpassing prior bespoke methods using only in-context learning. Finally, Med-Gemini's performance suggests real-world utility by surpassing human experts on tasks such as medical text summarization, alongside demonstrations of promising potential for multimodal medical dialogue, medical research and education. Taken together, our results offer compelling evidence for Med-Gemini's potential, although further rigorous evaluation will be crucial before real-world deployment in this safety-critical domain.

Juraj Gottweis, Wei-Hung Weng, Alexander Daryin et al.

Scientific discovery relies on scientists generating novel hypotheses that undergo rigorous experimental validation. To augment this process, we introduce an AI co-scientist, a multi-agent system built on Gemini 2.0. The AI co-scientist is intended to help uncover new, original knowledge and to formulate demonstrably novel research hypotheses and proposals, building upon prior evidence and aligned to scientist-provided research objectives and guidance. The system's design incorporates a generate, debate, and evolve approach to hypothesis generation, inspired by the scientific method and accelerated by scaling test-time compute. Key contributions include: (1) a multi-agent architecture with an asynchronous task execution framework for flexible compute scaling; (2) a tournament evolution process for self-improving hypotheses generation. Automated evaluations show continued benefits of test-time compute, improving hypothesis quality. While general purpose, we focus development and validation in three biomedical areas: drug repurposing, novel target discovery, and explaining mechanisms of bacterial evolution and anti-microbial resistance. For drug repurposing, the system proposes candidates with promising validation findings, including candidates for acute myeloid leukemia that show tumor inhibition in vitro at clinically applicable concentrations. For novel target discovery, the AI co-scientist proposed new epigenetic targets for liver fibrosis, validated by anti-fibrotic activity and liver cell regeneration in human hepatic organoids. Finally, the AI co-scientist recapitulated unpublished experimental results via a parallel in silico discovery of a novel gene transfer mechanism in bacterial evolution. These results, detailed in separate, co-timed reports, demonstrate the potential to augment biomedical and scientific discovery and usher an era of AI empowered scientists.

Tao Tu, Anil Palepu, Mike Schaekermann et al.

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.

Meet Shah, Jason Gusdorf, Anil Palepu et al.

The practice of medicine relies not only upon skillful dialogue but also on the nuanced exchange and interpretation of rich auditory and visual cues between doctors and patients. Building on the low-latency voice and video processing capabilities of Gemini, we introduce AI co-clinician, a first-of-its-kind conversational AI system utilizing continuous streams of audio-visual data from live patient conversations to inform real-time clinical decisions. Its dual-agent architecture balances deep clinical reasoning with the low latency required for natural dialogue. To assess this system, we implemented a video-based interface emulating telemedicine consultations. We crafted 20 standardized outpatient scenarios requiring proactive real-time auditory and visual reasoning and designed "TelePACES" evaluation criteria alongside case-specific rubrics. In a randomized, interface-blinded, crossover simulation study (n = 120 encounters) with 10 internal medicine residents as patient actors, we compared AI co-clinician with primary care physicians (PCPs), GPT-Realtime, and a baseline agent. AI co-clinician approached PCPs in key TelePACES dimensions, including management plans and differential diagnosis, while significantly outperforming GPT-Realtime across all general criteria. While our agent demonstrated parity with PCPs in case-specific triage measures, physicians maintained superior overall performance in case-specific assessments. Although AI co-clinician marks a significant advance in real-time telemedical AI, gaps remain in physical examination and disease-specific reasoning. Our work shows that text-only approaches fail to capture the true challenges of medical consultation and suggests that high-stakes real-time diagnostic AI is most safely advanced in collaborative, triadic models where AI can be a supportive co-clinician for doctors and patients.

Yu Jiang, Vivek Natarajan, Xinlei Chen et al.

This document describes Pythia v0.1, the winning entry from Facebook AI Research (FAIR)'s A-STAR team to the VQA Challenge 2018. Our starting point is a modular re-implementation of the bottom-up top-down (up-down) model. We demonstrate that by making subtle but important changes to the model architecture and the learning rate schedule, fine-tuning image features, and adding data augmentation, we can significantly improve the performance of the up-down model on VQA v2.0 dataset -- from 65.67% to 70.22%. Furthermore, by using a diverse ensemble of models trained with different features and on different datasets, we are able to significantly improve over the 'standard' way of ensembling (i.e. same model with different random seeds) by 1.31%. Overall, we achieve 72.27% on the test-std split of the VQA v2.0 dataset. Our code in its entirety (training, evaluation, data-augmentation, ensembling) and pre-trained models are publicly available at: https://github.com/facebookresearch/pythia

Soham Chatterjee, Aman Batra, Vivek Natarajan

Consider a non-uniform Euler-Bernoulli beam with a tip-mass at one end and a cantilever joint at the other end. The cantilever joint is not fixed and can itself be moved along an axis perpendicular to the beam. The position of the cantilever joint is the control input to the beam. The dynamics of the beam is governed by a coupled PDE-ODE model with boundary input. On a natural state-space, there exists a unique state trajectory for this beam model for every initial state and each twice continuously differentiable control input which is compatible with the initial state. In this paper, we study the motion planning problem of transferring the beam model from an initial state to a final state over a prescribed time-interval and then employ the results obtained to establish the approximate controllability of this model. We address these problems by extending and applying the generating functions approach to flatness-based control to the beam model. We prove that the transfer described above is feasible if the initial and final states belong to a certain set, which also contains the steady-states of the beam model. We then establish that this set contains all the eigenfunctions of the beam model, which form a Riesz basis for the state-space, and thereby conclude the approximate controllability of the beam model over all time intervals. We illustrate our theoretical results on motion planning using simulations and experiments.

Khaled Saab, Jan Freyberg, Chunjong Park et al.

Large Language Models (LLMs) have demonstrated great potential for conducting diagnostic conversations but evaluation has been largely limited to language-only interactions, deviating from the real-world requirements of remote care delivery. Instant messaging platforms permit clinicians and patients to upload and discuss multimodal medical artifacts seamlessly in medical consultation, but the ability of LLMs to reason over such data while preserving other attributes of competent diagnostic conversation remains unknown. Here we advance the conversational diagnosis and management performance of the Articulate Medical Intelligence Explorer (AMIE) through a new capability to gather and interpret multimodal data, and reason about this precisely during consultations. Leveraging Gemini 2.0 Flash, our system implements a state-aware dialogue framework, where conversation flow is dynamically controlled by intermediate model outputs reflecting patient states and evolving diagnoses. Follow-up questions are strategically directed by uncertainty in such patient states, leading to a more structured multimodal history-taking process that emulates experienced clinicians. We compared AMIE to primary care physicians (PCPs) in a randomized, blinded, OSCE-style study of chat-based consultations with patient actors. We constructed 105 evaluation scenarios using artifacts like smartphone skin photos, ECGs, and PDFs of clinical documents across diverse conditions and demographics. Our rubric assessed multimodal capabilities and other clinically meaningful axes like history-taking, diagnostic accuracy, management reasoning, communication, and empathy. Specialist evaluation showed AMIE to be superior to PCPs on 7/9 multimodal and 29/32 non-multimodal axes (including diagnostic accuracy). The results show clear progress in multimodal conversational diagnostic AI, but real-world translation needs further research.

Anil Palepu, Valentin Liévin, Wei-Hung Weng et al.

While large language models (LLMs) have shown promise in diagnostic dialogue, their capabilities for effective management reasoning - including disease progression, therapeutic response, and safe medication prescription - remain under-explored. We advance the previously demonstrated diagnostic capabilities of the Articulate Medical Intelligence Explorer (AMIE) through a new LLM-based agentic system optimised for clinical management and dialogue, incorporating reasoning over the evolution of disease and multiple patient visit encounters, response to therapy, and professional competence in medication prescription. To ground its reasoning in authoritative clinical knowledge, AMIE leverages Gemini's long-context capabilities, combining in-context retrieval with structured reasoning to align its output with relevant and up-to-date clinical practice guidelines and drug formularies. In a randomized, blinded virtual Objective Structured Clinical Examination (OSCE) study, AMIE was compared to 21 primary care physicians (PCPs) across 100 multi-visit case scenarios designed to reflect UK NICE Guidance and BMJ Best Practice guidelines. AMIE was non-inferior to PCPs in management reasoning as assessed by specialist physicians and scored better in both preciseness of treatments and investigations, and in its alignment with and grounding of management plans in clinical guidelines. To benchmark medication reasoning, we developed RxQA, a multiple-choice question benchmark derived from two national drug formularies (US, UK) and validated by board-certified pharmacists. While AMIE and PCPs both benefited from the ability to access external drug information, AMIE outperformed PCPs on higher difficulty questions. While further research would be needed before real-world translation, AMIE's strong performance across evaluations marks a significant step towards conversational AI as a tool in disease management.

Anil Palepu, Vikram Dhillon, Polly Niravath et al.

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.

Ayush Noori, Adam Rodman, Alan Karthikesalingam et al.

Modern computer systems often rely on syslog, a simple, universal protocol that records every critical event across heterogeneous infrastructure. However, healthcare's rapidly growing clinical AI stack has no equivalent. As hospitals rush to pilot large language models and other AI-based clinical decision support tools, we still lack a standard way to record how, when, by whom, and for whom these AI models are used. Without that transparency and visibility, it is challenging to measure real-world performance and outcomes, detect adverse events, or correct bias or dataset drift. In the spirit of syslog, we introduce MedLog, a protocol for event-level logging of clinical AI. Any time an AI model is invoked to interact with a human, interface with another algorithm, or act independently, a MedLog record is created. This record consists of nine core fields: header, model, user, target, inputs, artifacts, outputs, outcomes, and feedback, providing a structured and consistent record of model activity. To encourage early adoption, especially in low-resource settings, and minimize the data footprint, MedLog supports risk-based sampling, lifecycle-aware retention policies, and write-behind caching; detailed traces for complex, agentic, or multi-stage workflows can also be captured under MedLog. MedLog can catalyze the development of new databases and software to store and analyze MedLog records. Realizing this vision would enable continuous surveillance, auditing, and iterative improvement of medical AI, laying the foundation for a new form of digital epidemiology.

Elahe Vedadi, David Barrett, Natalie Harris et al.

Recent work has demonstrated the promise of conversational AI systems for diagnostic dialogue. However, real-world assurance of patient safety means that providing individual diagnoses and treatment plans is considered a regulated activity by licensed professionals. Furthermore, physicians commonly oversee other team members in such activities, including nurse practitioners (NPs) or physician assistants/associates (PAs). Inspired by this, we propose a framework for effective, asynchronous oversight of the Articulate Medical Intelligence Explorer (AMIE) AI system. We propose guardrailed-AMIE (g-AMIE), a multi-agent system that performs history taking within guardrails, abstaining from individualized medical advice. Afterwards, g-AMIE conveys assessments to an overseeing primary care physician (PCP) in a clinician cockpit interface. The PCP provides oversight and retains accountability of the clinical decision. This effectively decouples oversight from intake and can thus happen asynchronously. In a randomized, blinded virtual Objective Structured Clinical Examination (OSCE) of text consultations with asynchronous oversight, we compared g-AMIE to NPs/PAs or a group of PCPs under the same guardrails. Across 60 scenarios, g-AMIE outperformed both groups in performing high-quality intake, summarizing cases, and proposing diagnoses and management plans for the overseeing PCP to review. This resulted in higher quality composite decisions. PCP oversight of g-AMIE was also more time-efficient than standalone PCP consultations in prior work. While our study does not replicate existing clinical practices and likely underestimates clinicians' capabilities, our results demonstrate the promise of asynchronous oversight as a feasible paradigm for diagnostic AI systems to operate under expert human oversight for enhancing real-world care.

Juan Manuel Zambrano Chaves, Eric Wang, Tao Tu et al.

Developing therapeutics is a lengthy and expensive process that requires the satisfaction of many different criteria, and AI models capable of expediting the process would be invaluable. However, the majority of current AI approaches address only a narrowly defined set of tasks, often circumscribed within a particular domain. To bridge this gap, we introduce Tx-LLM, a generalist large language model (LLM) fine-tuned from PaLM-2 which encodes knowledge about diverse therapeutic modalities. Tx-LLM is trained using a collection of 709 datasets that target 66 tasks spanning various stages of the drug discovery pipeline. Using a single set of weights, Tx-LLM simultaneously processes a wide variety of chemical or biological entities(small molecules, proteins, nucleic acids, cell lines, diseases) interleaved with free-text, allowing it to predict a broad range of associated properties, achieving competitive with state-of-the-art (SOTA) performance on 43 out of 66 tasks and exceeding SOTA on 22. Among these, Tx-LLM is particularly powerful and exceeds best-in-class performance on average for tasks combining molecular SMILES representations with text such as cell line names or disease names, likely due to context learned during pretraining. We observe evidence of positive transfer between tasks with diverse drug types (e.g.,tasks involving small molecules and tasks involving proteins), and we study the impact of model size, domain finetuning, and prompting strategies on performance. We believe Tx-LLM represents an important step towards LLMs encoding biochemical knowledge and could have a future role as an end-to-end tool across the drug discovery development pipeline.

Karan Singhal, Tao Tu, Juraj Gottweis et al.

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.

Jessica Schrouff, Natalie Harris, Oluwasanmi Koyejo et al.

Diagnosing and mitigating changes in model fairness under distribution shift is an important component of the safe deployment of machine learning in healthcare settings. Importantly, the success of any mitigation strategy strongly depends on the structure of the shift. Despite this, there has been little discussion of how to empirically assess the structure of a distribution shift that one is encountering in practice. In this work, we adopt a causal framing to motivate conditional independence tests as a key tool for characterizing distribution shifts. Using our approach in two medical applications, we show that this knowledge can help diagnose failures of fairness transfer, including cases where real-world shifts are more complex than is often assumed in the literature. Based on these results, we discuss potential remedies at each step of the machine learning pipeline.

Alexandros Karargyris, Renato Umeton, Micah J. Sheller et al.

Medical AI has tremendous potential to advance healthcare by supporting the evidence-based practice of medicine, personalizing patient treatment, reducing costs, and improving provider and patient experience. We argue that unlocking this potential requires a systematic way to measure the performance of medical AI models on large-scale heterogeneous data. To meet this need, we are building MedPerf, an open framework for benchmarking machine learning in the medical domain. MedPerf will enable federated evaluation in which models are securely distributed to different facilities for evaluation, thereby empowering healthcare organizations to assess and verify the performance of AI models in an efficient and human-supervised process, while prioritizing privacy. We describe the current challenges healthcare and AI communities face, the need for an open platform, the design philosophy of MedPerf, its current implementation status, and our roadmap. We call for researchers and organizations to join us in creating the MedPerf open benchmarking platform.

Abhijit Guha Roy, Jie Ren, Shekoofeh Azizi et al.

We develop and rigorously evaluate a deep learning based system that can accurately classify skin conditions while detecting rare conditions for which there is not enough data available for training a confident classifier. We frame this task as an out-of-distribution (OOD) detection problem. Our novel approach, hierarchical outlier detection (HOD) assigns multiple abstention classes for each training outlier class and jointly performs a coarse classification of inliers vs. outliers, along with fine-grained classification of the individual classes. We demonstrate the effectiveness of the HOD loss in conjunction with modern representation learning approaches (BiT, SimCLR, MICLe) and explore different ensembling strategies for further improving the results. We perform an extensive subgroup analysis over conditions of varying risk levels and different skin types to investigate how the OOD detection performance changes over each subgroup and demonstrate the gains of our framework in comparison to baselines. Finally, we introduce a cost metric to approximate downstream clinical impact. We use this cost metric to compare the proposed method against a baseline system, thereby making a stronger case for the overall system effectiveness in a real-world deployment scenario.

Basil Mustafa, Aaron Loh, Jan Freyberg et al.

Transfer learning is a standard technique to improve performance on tasks with limited data. However, for medical imaging, the value of transfer learning is less clear. This is likely due to the large domain mismatch between the usual natural-image pre-training (e.g. ImageNet) and medical images. However, recent advances in transfer learning have shown substantial improvements from scale. We investigate whether modern methods can change the fortune of transfer learning for medical imaging. For this, we study the class of large-scale pre-trained networks presented by Kolesnikov et al. on three diverse imaging tasks: chest radiography, mammography, and dermatology. We study both transfer performance and critical properties for the deployment in the medical domain, including: out-of-distribution generalization, data-efficiency, sub-group fairness, and uncertainty estimation. Interestingly, we find that for some of these properties transfer from natural to medical images is indeed extremely effective, but only when performed at sufficient scale.

Shekoofeh Azizi, Basil Mustafa, Fiona Ryan et al.

Self-supervised pretraining followed by supervised fine-tuning has seen success in image recognition, especially when labeled examples are scarce, but has received limited attention in medical image analysis. This paper studies the effectiveness of self-supervised learning as a pretraining strategy for medical image classification. We conduct experiments on two distinct tasks: dermatology skin condition classification from digital camera images and multi-label chest X-ray classification, and demonstrate that self-supervised learning on ImageNet, followed by additional self-supervised learning on unlabeled domain-specific medical images significantly improves the accuracy of medical image classifiers. We introduce a novel Multi-Instance Contrastive Learning (MICLe) method that uses multiple images of the underlying pathology per patient case, when available, to construct more informative positive pairs for self-supervised learning. Combining our contributions, we achieve an improvement of 6.7% in top-1 accuracy and an improvement of 1.1% in mean AUC on dermatology and chest X-ray classification respectively, outperforming strong supervised baselines pretrained on ImageNet. In addition, we show that big self-supervised models are robust to distribution shift and can learn efficiently with a small number of labeled medical images.

Alexander D'Amour, Katherine Heller, Dan Moldovan et al.

ML models often exhibit unexpectedly poor behavior when they are deployed in real-world domains. We identify underspecification as a key reason for these failures. An ML pipeline is underspecified when it can return many predictors with equivalently strong held-out performance in the training domain. Underspecification is common in modern ML pipelines, such as those based on deep learning. Predictors returned by underspecified pipelines are often treated as equivalent based on their training domain performance, but we show here that such predictors can behave very differently in deployment domains. This ambiguity can lead to instability and poor model behavior in practice, and is a distinct failure mode from previously identified issues arising from structural mismatch between training and deployment domains. We show that this problem appears in a wide variety of practical ML pipelines, using examples from computer vision, medical imaging, natural language processing, clinical risk prediction based on electronic health records, and medical genomics. Our results show the need to explicitly account for underspecification in modeling pipelines that are intended for real-world deployment in any domain.

Wei-Hung Weng, Jonathan Deaton, Vivek Natarajan et al.

Class imbalance is a common problem in medical diagnosis, causing a standard classifier to be biased towards the common classes and perform poorly on the rare classes. This is especially true for dermatology, a specialty with thousands of skin conditions but many of which have low prevalence in the real world. Motivated by recent advances, we explore few-shot learning methods as well as conventional class imbalance techniques for the skin condition recognition problem and propose an evaluation setup to fairly assess the real-world utility of such approaches. We find the performance of few-show learning methods does not reach that of conventional class imbalance techniques, but combining the two approaches using a novel ensemble improves model performance, especially for rare classes. We conclude that ensembling can be useful to address the class imbalance problem, yet progress can further be accelerated by real-world evaluation setups for benchmarking new methods.

Jim Winkens, Rudy Bunel, Abhijit Guha Roy et al.

Reliable detection of out-of-distribution (OOD) inputs is increasingly understood to be a precondition for deployment of machine learning systems. This paper proposes and investigates the use of contrastive training to boost OOD detection performance. Unlike leading methods for OOD detection, our approach does not require access to examples labeled explicitly as OOD, which can be difficult to collect in practice. We show in extensive experiments that contrastive training significantly helps OOD detection performance on a number of common benchmarks. By introducing and employing the Confusion Log Probability (CLP) score, which quantifies the difficulty of the OOD detection task by capturing the similarity of inlier and outlier datasets, we show that our method especially improves performance in the `near OOD' classes -- a particularly challenging setting for previous methods.

Amirata Ghorbani, Vivek Natarajan, David Coz et al.

Despite the recent success in applying supervised deep learning to medical imaging tasks, the problem of obtaining large and diverse expert-annotated datasets required for the development of high performant models remains particularly challenging. In this work, we explore the possibility of using Generative Adverserial Networks (GAN) to synthesize clinical images with skin condition. We propose DermGAN, an adaptation of the popular Pix2Pix architecture, to create synthetic images for a pre-specified skin condition while being able to vary its size, location and the underlying skin color. We demonstrate that the generated images are of high fidelity using objective GAN evaluation metrics. In a Human Turing test, we note that the synthetic images are not only visually similar to real images, but also embody the respective skin condition in dermatologists' eyes. Finally, when using the synthetic images as a data augmentation technique for training a skin condition classifier, we observe that the model performs comparably to the baseline model overall while improving on rare but malignant conditions.

Yuan Liu, Ayush Jain, Clara Eng et al.

Skin conditions affect an estimated 1.9 billion people worldwide. A shortage of dermatologists causes long wait times and leads patients to seek dermatologic care from general practitioners. However, the diagnostic accuracy of general practitioners has been reported to be only 0.24-0.70 (compared to 0.77-0.96 for dermatologists), resulting in referral errors, delays in care, and errors in diagnosis and treatment. In this paper, we developed a deep learning system (DLS) to provide a differential diagnosis of skin conditions for clinical cases (skin photographs and associated medical histories). The DLS distinguishes between 26 skin conditions that represent roughly 80% of the volume of skin conditions seen in primary care. The DLS was developed and validated using de-identified cases from a teledermatology practice serving 17 clinical sites via a temporal split: the first 14,021 cases for development and the last 3,756 cases for validation. On the validation set, where a panel of three board-certified dermatologists defined the reference standard for every case, the DLS achieved 0.71 and 0.93 top-1 and top-3 accuracies respectively. For a random subset of the validation set (n=963 cases), 18 clinicians reviewed the cases for comparison. On this subset, the DLS achieved a 0.67 top-1 accuracy, non-inferior to board-certified dermatologists (0.63, p<0.001), and higher than primary care physicians (PCPs, 0.45) and nurse practitioners (NPs, 0.41). The top-3 accuracy showed a similar trend: 0.90 DLS, 0.75 dermatologists, 0.60 PCPs, and 0.55 NPs. These results highlight the potential of the DLS to augment general practitioners to accurately diagnose skin conditions by suggesting differential diagnoses that may not have been considered. Future work will be needed to prospectively assess the clinical impact of using this tool in actual clinical workflows.

Amanpreet Singh, Vivek Natarajan, Meet Shah et al.

Studies have shown that a dominant class of questions asked by visually impaired users on images of their surroundings involves reading text in the image. But today's VQA models can not read! Our paper takes a first step towards addressing this problem. First, we introduce a new "TextVQA" dataset to facilitate progress on this important problem. Existing datasets either have a small proportion of questions about text (e.g., the VQA dataset) or are too small (e.g., the VizWiz dataset). TextVQA contains 45,336 questions on 28,408 images that require reasoning about text to answer. Second, we introduce a novel model architecture that reads text in the image, reasons about it in the context of the image and the question, and predicts an answer which might be a deduction based on the text and the image or composed of the strings found in the image. Consequently, we call our approach Look, Read, Reason & Answer (LoRRA). We show that LoRRA outperforms existing state-of-the-art VQA models on our TextVQA dataset. We find that the gap between human performance and machine performance is significantly larger on TextVQA than on VQA 2.0, suggesting that TextVQA is well-suited to benchmark progress along directions complementary to VQA 2.0.