Cameron Po-Hsuan Chen
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Toward a test of medical AI superintelligence
Ethan Goh
David Wu
Chase Walton
Liam McCoy
Anastasia Perez
Laura Wegner
Fateme Nateghi Haredasht
Luyang Luo
Kathleen Lacar
Thomas Buckley
Austin Schoeffler
Peter Brodeur
Kameron C. Black
John Havlik
John Rumsfeld
Daniel Lopez-martinez
Paxton Maeder-York
Karan Singhal
David Gunning
Bon Ku
Haider Warraich
Shantanu Nundy
Vishnu Ravi
Arnold Milstein
Jason Hom
Kevin Schulman
Pranav Rajpurkar
Arjun Manrai
Robert Wachter, MD
Eric Topol
Eric horvitz
Adam Rodman
Jonathan Chen
Nature Medicine (2026)
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Researchers urgently need a rigorous, task-based framework to define and measure medical AI ‘superintelligence’, because existing benchmarks are misleading and insufficient.
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Prospective evidence for conversational medical AI is hard, but non-negotiable
Adam Rodman
Ami Parekh
Ethan Goh
Christina Chen
Joelle Barral
Nature Medicine (2026)
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Trust in clinical artificial intelligence (AI) cannot be benchmarked into existence. It must be earned through rigorous prospective studies in real-world clinical settings, where the hardest lessons often concern the humans and systems around the AI, not the technology itself.
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SymptomAI: Toward a Conversational AI Agent for Everyday Symptom Assessment
Joe Breda
Fadi Yousif
Beszel Hawkins
Marinela Cotoi
Miao Liu
Ray Luo
Sam Schmidgall
Girish Narayanswamy
Samuel Solomon
Max Xu
Longfei Shangguan
Bhavna Daryani
Buddy Herkenham
Cara Tan
Mark Malhotra
Shwetak Patel
Zach Wasson
Dimitrios Antos
Bob Lou
Matthew Thompson
Jonathan Richina
Anupam Pathak
Nichole Young-Lin
Jake Sunshine
Daniel McDuff
Arxiv preprint, 2605.040 (2026) (to appear)
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Language models excel at diagnostic assessments on curated medical case-studies and vignettes, performing on par with, or better than, clinical professionals. However, existing studies focus on complex scenarios with rich context making it difficult to draw conclusions about how these systems perform for patients reporting symptoms in everyday life. We deployed SymptomAI, a set of conversational AI agents for end-to-end patient interviewing and differential diagnosis (DDx), via the Fitbit app in a study that randomized participants (N=13,917) to interact with five AI agents. This corpus captures diverse communication and a realistic distribution of illnesses from a real world population. A subset of 1,228 participants reported a clinician-provided diagnosis, and 517 of these were further evaluated by a panel of clinicians during over 250 hours of annotation. SymptomAI DDx were significantly more accurate (OR = 2.56, p < 0.001) than those from independent clinicians given the same dialogue in a blinded randomized comparison. Moreover, agentic strategies which conduct a dedicated symptom interview that elicit additional symptom information before providing a diagnosis, perform substantially better than baseline, user-guided conversations (p < 0.001). An auxiliary analysis on 1,509 conversations from a general US population panel validated that these results generalize beyond wearable device users. We used SymptomAI diagnoses as labels for all 13,917 participants to analyze over 500,000 days of wearable metrics across nearly 400 unique conditions. We identified strong associations between acute infections and physiological shifts (e.g., OR > 7 for influenza). While limited by self-reported ground truth, these results demonstrate the benefits of a dedicated and complete symptom interview compared to a user-guided symptom discussion, which is the default of most consumer LLMs.
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Towards expert-level medical AI for real-time video consultations
Mahvish Nagda
Jihyeon Lee
Matthew Thompson
CJ Park
Tim Strother
Roma Ruparel
Teya Bergamaschi
Suhana Bedi
Meet Shah
Pavel Dubov
Toshiyuki Fukuzawa
Sam Schmidgall
Craig Schiff
Joseph Xu
Aliya Rysbek
Yana Lunts
Jan Freyberg
Rebecca Hemenway
David Racz
Carey Radebaugh
Joelle Barral
Kavi Goel
Kat Chou
James Manyika
Gregory Wayne
Yun Liu
Ethan Goh
Christina Chen
Ryutaro Tanno
arXiv (2026)
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Audio-visual interaction is the standard for patient-physician consultations, enabling natural communication and effective assessment of illness through non-verbal cues. While text-based AI has shown promise, it discards essential perceptual dimensions and limits patients who cannot articulate symptoms in writing. Early efforts to extend medical AI to audio-visual interaction have demonstrated feasibility, but not reached clinician-level performance. Here, we provide the first demonstration of expert-level AI in real-time clinical video consultations using AMIE (Articulate Medical Intelligence Explorer) in a video configuration. AMIE (Video) is a Gemini-based multi-agent system integrating low-latency dialogue, clinical reasoning, and real-time audio-visual perception. To guide development, we established a taxonomy and automated evaluations for clinical audio-visual cues in telehealth settings. In a randomized Objective Structured Clinical Examination (OSCE) study with 30 primary care physicians (PCPs), 15 patient actors and 100 clinical scenarios, we compared AMIE (Video), its text-only counterpart AMIE (Text), and PCPs consulting via video. Clinical evaluators rated AMIE (Video) on par or better than PCPs in history-taking, diagnosis, management, and physical observation and examination. Patient actors preferred AMIE's approach to assessing and explaining conditions, while PCPs were preferred for rapport and partnership building. In modality ablation, patient actors preferred AMIE (Video)'s interface over text chat for communicative effectiveness, convenience, and feeling understood. Limitations remain in fine anatomical precision, subtle affective nuances, and high-frequency movements. While further research is needed before real-world translation, these results mark an important milestone toward AI systems capable of augmenting care across the sensory complexity of clinical practice.
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Health equity assessment of machine learning performance (HEAL): a framework and dermatology AI model case study
Terry Spitz
Malcolm Chelliah
Heather Cole-Lewis
Donald Martin
Tiam Jaroensri
Geoff Keeling
Stephanie Farquhar
Qinghan Xue
Jenna Lester
Cían Hughes
Patricia Strachan
Fraser Tan
Peggy Bui
Craig Mermel
Lily Peng
Ivor Horn
The Lancet eClinicalMedicine (2024)
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Background
Artificial intelligence (AI) has repeatedly been shown to encode historical inequities in healthcare. We aimed to develop a framework to quantitatively assess the performance equity of health AI technologies and to illustrate its utility via a case study.
Methods
Here, we propose a methodology to assess whether health AI technologies prioritise performance for patient populations experiencing worse outcomes, that is complementary to existing fairness metrics. We developed the Health Equity Assessment of machine Learning performance (HEAL) framework designed to quantitatively assess the performance equity of health AI technologies via a four-step interdisciplinary process to understand and quantify domain-specific criteria, and the resulting HEAL metric. As an illustrative case study (analysis conducted between October 2022 and January 2023), we applied the HEAL framework to a dermatology AI model. A set of 5420 teledermatology cases (store-and-forward cases from patients of 20 years or older, submitted from primary care providers in the USA and skin cancer clinics in Australia), enriched for diversity in age, sex and race/ethnicity, was used to retrospectively evaluate the AI model's HEAL metric, defined as the likelihood that the AI model performs better for subpopulations with worse average health outcomes as compared to others. The likelihood that AI performance was anticorrelated to pre-existing health outcomes was estimated using bootstrap methods as the probability that the negated Spearman's rank correlation coefficient (i.e., “R”) was greater than zero. Positive values of R suggest that subpopulations with poorer health outcomes have better AI model performance. Thus, the HEAL metric, defined as p (R >0), measures how likely the AI technology is to prioritise performance for subpopulations with worse average health outcomes as compared to others (presented as a percentage below). Health outcomes were quantified as disability-adjusted life years (DALYs) when grouping by sex and age, and years of life lost (YLLs) when grouping by race/ethnicity. AI performance was measured as top-3 agreement with the reference diagnosis from a panel of 3 dermatologists per case.
Findings
Across all dermatologic conditions, the HEAL metric was 80.5% for prioritizing AI performance of racial/ethnic subpopulations based on YLLs, and 92.1% and 0.0% respectively for prioritizing AI performance of sex and age subpopulations based on DALYs. Certain dermatologic conditions were significantly associated with greater AI model performance compared to a reference category of less common conditions. For skin cancer conditions, the HEAL metric was 73.8% for prioritizing AI performance of age subpopulations based on DALYs.
Interpretation
Analysis using the proposed HEAL framework showed that the dermatology AI model prioritised performance for race/ethnicity, sex (all conditions) and age (cancer conditions) subpopulations with respect to pre-existing health disparities. More work is needed to investigate ways of promoting equitable AI performance across age for non-cancer conditions and to better understand how AI models can contribute towards improving equity in health outcomes.
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Pathologist Validation of a Machine Learning–Derived Feature for Colon Cancer Risk Stratification
Vincenzo L’Imperio
Markus Plass
Heimo Müller
Nicolò Tamini
Luca Gianotti
Nicola Zucchini
Robert Reihs
Lily Peng
Marialuisa Lavitrano
David F. Steiner
Kurt Zatloukal
Fabio Pagni
JAMA Network Open (2023)
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Importance: Identifying new prognostic features in colon cancer has the potential to refine histopathologic review and inform patient care. Although prognostic artificial intelligence systems have recently demonstrated significant risk stratification for several cancer types, studies have not yet shown that the machine learning–derived features associated with these prognostic artificial intelligence systems are both interpretable and usable by pathologists.
Objective: To evaluate whether pathologist scoring of a histopathologic feature previously identified by machine learning is associated with survival among patients with colon cancer.
Design, Setting, and Participants: This prognostic study used deidentified, archived colorectal cancer cases from January 2013 to December 2015 from the University of Milano-Bicocca. All available histologic slides from 258 consecutive colon adenocarcinoma cases were reviewed from December 2021 to February 2022 by 2 pathologists, who conducted semiquantitative scoring for tumor adipose feature (TAF), which was previously identified via a prognostic deep learning model developed with an independent colorectal cancer cohort.
Main Outcomes and Measures: Prognostic value of TAF for overall survival and disease-specific survival as measured by univariable and multivariable regression analyses. Interpathologist agreement in TAF scoring was also evaluated.
Results: A total of 258 colon adenocarcinoma histopathologic cases from 258 patients (138 men [53%]; median age, 67 years [IQR, 65-81 years]) with stage II (n = 119) or stage III (n = 139) cancer were included. Tumor adipose feature was identified in 120 cases (widespread in 63 cases, multifocal in 31, and unifocal in 26). For overall survival analysis after adjustment for tumor stage, TAF was independently prognostic in 2 ways: TAF as a binary feature (presence vs absence: hazard ratio [HR] for presence of TAF, 1.55 [95% CI, 1.07-2.25]; P = .02) and TAF as a semiquantitative categorical feature (HR for widespread TAF, 1.87 [95% CI, 1.23-2.85]; P = .004). Interpathologist agreement for widespread TAF vs lower categories (absent, unifocal, or multifocal) was 90%, corresponding to a κ metric at this threshold of 0.69 (95% CI, 0.58-0.80).
Conclusions and Relevance: In this prognostic study, pathologists were able to learn and reproducibly score for TAF, providing significant risk stratification on this independent data set. Although additional work is warranted to understand the biological significance of this feature and to establish broadly reproducible TAF scoring, this work represents the first validation to date of human expert learning from machine learning in pathology. Specifically, this validation demonstrates that a computationally identified histologic feature can represent a human-identifiable, prognostic feature with the potential for integration into pathology practice.
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Domain-specific optimization and diverse evaluation of self-supervised models for histopathology
Jeremy Lai
Faruk Ahmed
Supriya Vijay
Tiam Jaroensri
Jessica Loo
Saurabh Vyawahare
Saloni Agarwal
Fayaz Jamil
arXiv (2023)
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Task-specific deep learning models in histopathology offer promising opportunities for improving diagnosis, clinical research, and precision medicine. However, development of such models is often limited by availability of high-quality data. Foundation models in histopathology that learn general representations across a wide range of tissue types, diagnoses, and magnifications offer the potential to reduce the data, compute, and technical expertise necessary to develop task-specific deep learning models with the required level of model performance. In this work, we describe the development and evaluation of foundation models for histopathology via self-supervised learning (SSL). We first establish a diverse set of benchmark tasks involving 17 unique tissue types and 12 unique cancer types and spanning different optimal magnifications and task types. Next, we use this benchmark to explore and evaluate histopathology-specific SSL methods followed by further evaluation on held out patch-level and weakly supervised tasks. We found that standard SSL methods thoughtfully applied to histopathology images are performant across our benchmark tasks and that domain-specific methodological improvements can further increase performance. Our findings reinforce the value of using domain-specific SSL methods in pathology, and establish a set of high quality foundation models to enable further research across diverse applications.
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Robust and data-efficient generalization of self-supervised machine learning for diagnostic imaging
Laura Anne Culp
Jan Freyberg
Basil Mustafa
Sebastien Baur
Simon Kornblith
Ting Chen
Patricia MacWilliams
Sara Mahdavi
Megan Zoë Walker
Aaron Loh
Scott Mayer McKinney
Jim Winkens
Zach William Beaver
Fiona Keleher Ryan
Justin David Krogue
Mozziyar Etemadi
Umesh Telang
Lily Hao Yi Peng
Geoffrey Everest Hinton
Neil Houlsby
Mohammad Norouzi
Nature Biomedical Engineering (2023)
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Machine-learning models for medical tasks can match or surpass the performance of clinical experts. However, in settings differing from those of the training dataset, the performance of a model can deteriorate substantially. Here we report a representation-learning strategy for machine-learning models applied to medical-imaging tasks that mitigates such ‘out of distribution’ performance problem and that improves model robustness and training efficiency. The strategy, which we named REMEDIS (for ‘Robust and Efficient Medical Imaging with Self-supervision’), combines large-scale supervised transfer learning on natural images and intermediate contrastive self-supervised learning on medical images and requires minimal task-specific customization. We show the utility of REMEDIS in a range of diagnostic-imaging tasks covering six imaging domains and 15 test datasets, and by simulating three realistic out-of-distribution scenarios. REMEDIS improved in-distribution diagnostic accuracies up to 11.5% with respect to strong supervised baseline models, and in out-of-distribution settings required only 1–33% of the data for retraining to match the performance of supervised models retrained using all available data. REMEDIS may accelerate the development lifecycle of machine-learning models for medical imaging.
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Deep learning models for histologic grading of breast cancer and association with disease prognosis
Tiam Jaroensri
Trissia Brown
Isabelle Flament
Fraser Tan
Yuannan Cai
Kunal Nagpal
Emad Rakha
David J. Dabbs
Niels Olson
James H. Wren
Elaine E. Thompson
Erik Seetao
Carrie Robinson
Melissa Miao
Fabien Beckers
Lily Hao Yi Peng
Craig Mermel
npj Breast Cancer (2022)
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Histologic grading of breast cancer involves review and scoring of three well-established morphologic features: mitotic count, nuclear pleomorphism, and tubule formation. Taken together, these features form the basis of the Nottingham Grading System which is used to inform breast cancer characterization and prognosis. In this study, we developed deep learning models to perform histologic scoring of all three components using digitized hematoxylin and eosin-stained slides containing invasive breast carcinoma. We then evaluated the prognostic potential of these models using an external test set and progression free interval as the primary outcome. The individual component models performed at or above published benchmarks for algorithm-based grading approaches and achieved high concordance rates in comparison to pathologist grading. Prognostic performance of histologic scoring provided by the deep learning-based grading was on par with that of pathologists performing review of matched slides. Additionally, by providing scores for each component feature, the deep-learning based approach provided the potential to identify the grading components contributing most to prognostic value. This may enable optimized prognostic models as well as opportunities to improve access to consistent grading and better understand the links between histologic features and clinical outcomes in breast cancer.
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Artificial intelligence for diagnosis and Gleason grading of prostate cancer: the PANDA challenge
Wouter Bulten
Kimmo Kartasalo
Peter Ström
Hans Pinckaers
Kunal Nagpal
Yuannan Cai
Hester van Boven
Robert Vink
Christina Hulsbergen-van de Kaa
Jeroen van der Laak
Mahul B. Amin
Andrew J. Evans
Theodorus van der Kwast
Robert Allan
Peter A. Humphrey
Henrik Grönberg
Hemamali Samaratunga
Brett Delahunt
Toyonori Tsuzuki
Tomi Häkkinen
Lars Egevad
Maggie Demkin
Sohier Dane
Fraser Tan
Masi Valkonen
Lily Peng
Craig H. Mermel
Pekka Ruusuvuori
Geert Litjens
Martin Eklund
the PANDA challenge consortium
Nature Medicine, 28 (2022), pp. 154-163
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Artificial intelligence (AI) has shown promise for diagnosing prostate cancer in biopsies. However, results have been limited to individual studies, lacking validation in multinational settings. Competitions have been shown to be accelerators for medical imaging innovations, but their impact is hindered by lack of reproducibility and independent validation. With this in mind, we organized the PANDA challenge—the largest histopathology competition to date, joined by 1,290 developers—to catalyze development of reproducible AI algorithms for Gleason grading using 10,616 digitized prostate biopsies. We validated that a diverse set of submitted algorithms reached pathologist-level performance on independent cross-continental cohorts, fully blinded to the algorithm developers. On United States and European external validation sets, the algorithms achieved agreements of 0.862 (quadratically weighted κ, 95% confidence interval (CI), 0.840–0.884) and 0.868 (95% CI, 0.835–0.900) with expert uropathologists. Successful generalization across different patient populations, laboratories and reference standards, achieved by a variety of algorithmic approaches, warrants evaluating AI-based Gleason grading in prospective clinical trials.
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