Discovering novel systemic biomarkers in photos of the external eye

Boris Babenko, Ilana Traynis, Christina Chen, Preeti Singh, Akib Uddin, Jorge Cuadros, Lauren P. Daskivich, April Y. Maa, Ramasamy Kim, Eugene Yu-Chuan Kang, Yossi Matias, Greg S. Corrado, Lily Peng, Dale R. Webster, Christopher Semturs, Jonathan Krause, Avinash V. Varadarajan, Naama Hammel, Yun Liu

External eye photos were recently shown to reveal signs of diabetic retinal disease and elevated HbA1c. In this paper, we evaluate if external eye photos contain information about additional systemic medical conditions. We developed a deep learning system (DLS) that takes external eye photos as input and predicts multiple systemic parameters, such as those related to the liver (albumin, AST); kidney (eGFR estimated using the race-free 2021 CKD-EPI creatinine equation, the urine ACR); bone & mineral (calcium); thyroid (TSH); and blood count (Hgb, WBC, platelets). Development leveraged 151,237 images from 49,015 patients with diabetes undergoing diabetic eye screening in 11 sites across Los Angeles county, CA. Evaluation focused on 9 pre-specified systemic parameters and leveraged 3 validation sets (A, B, C) spanning 28,869 patients with and without diabetes undergoing eye screening in 3 independent sites in Los Angeles County, CA, and the greater Atlanta area, GA. We compared against baseline models incorporating available clinicodemographic variables (e.g. age, sex, race/ethnicity, years with diabetes). Relative to the baseline, the DLS achieved statistically significant superior performance at detecting AST>36, calcium<8.6, eGFR<60, Hgb<11, platelets<150, ACR>=300, and WBC<4 on validation set A (a patient population similar to the development sets), where the AUC of DLS exceeded that of the baseline by 5.2-19.4%. On validation sets B and C, with substantial patient population differences compared to the development sets, the DLS outperformed the baseline for ACR>=300 and Hgb<11 by 7.3-13.2%. Our findings provide further evidence that external eye photos contain important biomarkers of systemic health spanning multiple organ systems. Further work is needed to investigate whether and how these biomarkers can be translated into clinical impact.

Large Language Models Encode Clinical Knowledge

Karan Singhal, Shekoofeh Azizi, Tao Tu, S. Sara Mahdavi, Jason Wei, Hyung Won Chung, Nathan Scales, Ajay Tanwani, Heather Cole-Lewis, Stephen Pfohl, Perry Payne, Martin Seneviratne, Paul Gamble, Chris Kelly, Nathaneal Scharli, Aakanksha Chowdhery, Philip Mansfield, Blaise Aguera y Arcas, Dale Webster, Greg S. Corrado, Yossi Matias, Katherine Chou, Juraj Gottweis, Nenad Tomasev, Yun Liu, Alvin Rajkomar, Joelle Barral, Christopher Semturs, Alan Karthikesalingam, Vivek Natarajan

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.

Deep Learning and Glaucoma Specialists: The Relative Importance of Optic Disc Features to Predict Glaucoma Referral in Fundus Photos

Sonia Phene, R. Carter Dunn, Naama Hammel, Yun Liu, Jonathan Krause, Naho Kitade, Mike Schaekermann, Rory Sayres, Derek J. Wu, Ashish Bora, Christopher Semturs, Anita Misra, Abigail E. Huang, Arielle Spitze, Felipe A. Medeiros, April Y. Maa, Monica Gandhi, Greg S. Corrado, Lily Peng, Dale R. Webster

Glaucoma is the leading cause of preventable, irreversible blindness world-wide. The disease can remain asymptomatic until severe, and an estimated 50%-90% of people with glaucoma remain undiagnosed. Glaucoma screening is recommended for early detection and treatment. A cost-effective tool to detect glaucoma could expand screening access to a much larger patient population, but such a tool is currently unavailable. We trained a deep learning algorithm using a retrospective dataset of 86,618 images, assessed for glaucomatous optic nerve head features and referable glaucomatous optic neuropathy (GON). The algorithm was validated using 3 datasets. For referable GON, the algorithm had an AUC of 0.945 (95% CI, 0.929-0.960) in dataset A (1205 images, 1 image/patient; 18.1% referable), images adjudicated by panels of Glaucoma Specialists (GSs); 0.855 (95% CI, 0.841-0.870) in dataset B (9642 images, 1 image/patient; 9.2% referable), images from Atlanta Veterans Affairs Eye Clinic diabetic teleretinal screening program; and 0.881 (95% CI, 0.838-0.918) in dataset C (346 images, 1 image/patient; 81.7% referable), images from Dr. Shroff's Charity Eye Hospital's glaucoma clinic. The algorithm showed significantly higher sensitivity than 7 of 10 graders not involved in determining the reference standard, including 2 of 3 GSs, and showed higher specificity than 3 graders, while remaining comparable to others. For both GSs and the algorithm, the most crucial features related to referable GON were: presence of vertical cup-to-disc ratio of 0.7 or more, neuroretinal rim notching, retinal nerve fiber layer defect, and bared circumlinear vessels. An algorithm trained on fundus images alone can detect referable GON with higher sensitivity than and comparable specificity to eye care providers. The algorithm maintained good performance on an independent dataset with diagnoses based on a full glaucoma workup.

Using generative AI to investigate medical imagery models and datasets

Oran Lang, Doron Yaya-Stupp, Ilana Traynis, Heather Cole-Lewis, Chloe R. Bennett, Courtney Lyles, Charles Lau, Michal Irani, Christopher Semturs, Dale R. Webster, Greg S. Corrado, Avinatan Hassidim, Yossi Matias, Yun Liu, Naama Hammel, Boris Babenko

AI models have shown promise in many medical imaging tasks. However, our ability to explain what signals these models have learned is severely lacking. Explanations are needed in order to increase the trust in AI-based models, and could enable novel scientific discovery by uncovering signals in the data that are not yet known to experts. In this paper, we present a method for automatic visual explanations leveraging team-based expertise by generating hypotheses of what visual signals in the images are correlated with the task. We propose the following 4 steps: (i) Train a classifier to perform a given task (ii) Train a classifier guided StyleGAN-based image generator (StylEx) (iii) Automatically detect and visualize the top visual attributes that the classifier is sensitive towards (iv) Formulate hypotheses for the underlying mechanisms, to stimulate future research. Specifically, we present the discovered attributes to an interdisciplinary panel of experts so that hypotheses can account for social and structural determinants of health. We demonstrate results on eight prediction tasks across three medical imaging modalities: retinal fundus photographs, external eye photographs, and chest radiographs. We showcase examples of attributes that capture clinically known features, confounders that arise from factors beyond physiological mechanisms, and reveal a number of physiologically plausible novel attributes. Our approach has the potential to enable researchers to better understand, improve their assessment, and extract new knowledge from AI-based models. Importantly, we highlight that attributes generated by our framework can capture phenomena beyond physiology or pathophysiology, reflecting the real world nature of healthcare delivery and socio-cultural factors. Finally, we intend to release code to enable researchers to train their own StylEx models and analyze their predictive tasks.

Tx-LLM: A Large Language Model for Therapeutics

Juan Manuel Zambrano Chaves, Eric Wang, Tao Tu, Eeshit Dhaval Vaishnav, Byron Lee, S. Sara Mahdavi, Christopher Semturs, David Fleet, Vivek Natarajan, Shekoofeh Azizi

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.

Towards Generalist Biomedical AI

Tao Tu, Shekoofeh Azizi, Danny Driess, Mike Schaekermann, Mohamed Amin, Pi-Chuan Chang, Andrew Carroll, Chuck Lau, Ryutaro Tanno, Ira Ktena, Basil Mustafa, Aakanksha Chowdhery, Yun Liu, Simon Kornblith, David Fleet, Philip Mansfield, Sushant Prakash, Renee Wong, Sunny Virmani, Christopher Semturs, S Sara Mahdavi, Bradley Green, Ewa Dominowska, Blaise Aguera y Arcas, Joelle Barral, Dale Webster, Greg S. Corrado, Yossi Matias, Karan Singhal, Pete Florence, Alan Karthikesalingam, Vivek Natarajan

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.

Towards Accurate Differential Diagnosis with Large Language Models

Daniel McDuff, Mike Schaekermann, Tao Tu, Anil Palepu, Amy Wang, Jake Garrison, Karan Singhal, Yash Sharma, Shekoofeh Azizi, Kavita Kulkarni, Le Hou, Yong Cheng, Yun Liu, S Sara Mahdavi, Sushant Prakash, Anupam Pathak, Christopher Semturs, Shwetak Patel, Dale R Webster, Ewa Dominowska, Juraj Gottweis, Joelle Barral, Katherine Chou, Greg S Corrado, Yossi Matias, Jake Sunshine, Alan Karthikesalingam, Vivek Natarajan

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.

Crowdsourcing Dermatology Images with Google Search Ads: Creating a Real-World Skin Condition Dataset

Abbi Ward, Jimmy Li, Julie Wang, Sriram Lakshminarasimhan, Ashley Carrick, Bilson Campana, Jay Hartford, Pradeep Kumar S, Tiya Tiyasirichokchai, Sunny Virmani, Renee Wong, Yossi Matias, Greg S. Corrado, Dale R. Webster, Dawn Siegel, Steven Lin, Justin Ko, Alan Karthikesalingam, Christopher Semturs, Pooja Rao

Background: Health datasets from clinical sources do not reflect the breadth and diversity of disease in the real world, impacting research, medical education, and artificial intelligence (AI) tool development. Dermatology is a suitable area to develop and test a new and scalable method to create representative health datasets. Methods: We used Google Search advertisements to invite contributions to an open access dataset of images of dermatology conditions, demographic and symptom information. With informed contributor consent, we describe and release this dataset containing 10,408 images from 5,033 contributions from internet users in the United States over 8 months starting March 2023. The dataset includes dermatologist condition labels as well as estimated Fitzpatrick Skin Type (eFST) and Monk Skin Tone (eMST) labels for the images. Results: We received a median of 22 submissions/day (IQR 14-30). Female (66.72%) and younger (52% < age 40) contributors had a higher representation in the dataset compared to the US population, and 32.6% of contributors reported a non-White racial or ethnic identity. Over 97.5% of contributions were genuine images of skin conditions. Dermatologist confidence in assigning a differential diagnosis increased with the number of available variables, and showed a weaker correlation with image sharpness (Spearman's P values <0.001 and 0.01 respectively). Most contributions were short-duration (54% with onset < 7 days ago ) and 89% were allergic, infectious, or inflammatory conditions. eFST and eMST distributions reflected the geographical origin of the dataset. The dataset is available at github.com/google-research-datasets/scin . Conclusion: Search ads are effective at crowdsourcing images of health conditions. The SCIN dataset bridges important gaps in the availability of representative images of common skin conditions.

Towards Expert-Level Medical Question Answering with Large Language Models

Karan Singhal, Tao Tu, Juraj Gottweis, Rory Sayres, Ellery Wulczyn, Le Hou, Kevin Clark, Stephen Pfohl, Heather Cole-Lewis, Darlene Neal, Mike Schaekermann, Amy Wang, Mohamed Amin, Sami Lachgar, Philip Mansfield, Sushant Prakash, Bradley Green, Ewa Dominowska, Blaise Aguera y Arcas, Nenad Tomasev, Yun Liu, Renee Wong, Christopher Semturs, S. Sara Mahdavi, Joelle Barral, Dale Webster, Greg S. Corrado, Yossi Matias, Shekoofeh Azizi, Alan Karthikesalingam, Vivek Natarajan

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 Gemini Models in Medicine

Khaled Saab, Tao Tu, Wei-Hung Weng, Ryutaro Tanno, David Stutz, Ellery Wulczyn, Fan Zhang, Tim Strother, Chunjong Park, Elahe Vedadi, Juanma Zambrano Chaves, Szu-Yeu Hu, Mike Schaekermann, Aishwarya Kamath, Yong Cheng, David G. T. Barrett, Cathy Cheung, Basil Mustafa, Anil Palepu, Daniel McDuff, Le Hou, Tomer Golany, Luyang Liu, Jean-baptiste Alayrac, Neil Houlsby, Nenad Tomasev, Jan Freyberg, Charles Lau, Jonas Kemp, Jeremy Lai, Shekoofeh Azizi, Kimberly Kanada, SiWai Man, Kavita Kulkarni, Ruoxi Sun, Siamak Shakeri, Luheng He, Ben Caine, Albert Webson, Natasha Latysheva, Melvin Johnson, Philip Mansfield, Jian Lu, Ehud Rivlin, Jesper Anderson, Bradley Green, Renee Wong, Jonathan Krause, Jonathon Shlens, Ewa Dominowska, S. M. Ali Eslami, Katherine Chou, Claire Cui, Oriol Vinyals, Koray Kavukcuoglu, James Manyika, Jeff Dean, Demis Hassabis, Yossi Matias, Dale Webster, Joelle Barral, Greg Corrado, Christopher Semturs, S. Sara Mahdavi, Juraj Gottweis, Alan Karthikesalingam, Vivek Natarajan

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.

Towards Conversational Diagnostic AI

Tao Tu, Anil Palepu, Mike Schaekermann, Khaled Saab, Jan Freyberg, Ryutaro Tanno, Amy Wang, Brenna Li, Mohamed Amin, Nenad Tomasev, Shekoofeh Azizi, Karan Singhal, Yong Cheng, Le Hou, Albert Webson, Kavita Kulkarni, S Sara Mahdavi, Christopher Semturs, Juraj Gottweis, Joelle Barral, Katherine Chou, Greg S Corrado, Yossi Matias, Alan Karthikesalingam, Vivek Natarajan

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.

Gemini 2.5: Pushing the Frontier with Advanced Reasoning, Multimodality, Long Context, and Next Generation Agentic Capabilities

Gheorghe Comanici, Eric Bieber, Mike Schaekermann, Ice Pasupat, Noveen Sachdeva, Inderjit Dhillon, Marcel Blistein, Ori Ram, Dan Zhang, Evan Rosen, Luke Marris, Sam Petulla, Colin Gaffney, Asaf Aharoni, Nathan Lintz, Tiago Cardal Pais, Henrik Jacobsson, Idan Szpektor, Nan-Jiang Jiang, Krishna Haridasan, Ahmed Omran, Nikunj Saunshi, Dara Bahri, Gaurav Mishra, Eric Chu, Toby Boyd, Brad Hekman, Aaron Parisi, Chaoyi Zhang, Kornraphop Kawintiranon, Tania Bedrax-Weiss, Oliver Wang, Ya Xu, Ollie Purkiss, Uri Mendlovic, Ilaï Deutel, Nam Nguyen, Adam Langley, Flip Korn, Lucia Rossazza, Alexandre Ramé, Sagar Waghmare, Helen Miller, Nathan Byrd, Ashrith Sheshan, Raia Hadsell, Sangnie Bhardwaj, Pawel Janus, Tero Rissa, Dan Horgan, Alvin Abdagic, Lior Belenki, James Allingham, Anima Singh, Theo Guidroz, Srivatsan Srinivasan, Herman Schmit, Kristen Chiafullo, Andre Elisseeff, Nilpa Jha, Prateek Kolhar, Leonard Berrada, Frank Ding, Xiance Si, Shrestha Basu Mallick, Franz Och, Sofia Erell, Eric Ni, Tejasi Latkar, Sherry Yang, Petar Sirkovic, Ziqiang Feng, Robert Leland, Rachel Hornung, Gang Wu, Charles Blundell, Hamidreza Alvari, Po-Sen Huang, Cathy Yip, Sanja Deur, Li Liu, Gabriela Surita, Pablo Duque, Dima Damen, Johnson Jia, Arthur Guez, Markus Mircea, Animesh Sinha, Alberto Magni, Paweł Stradomski, Tal Marian, Vlado Galić, Wenhu Chen, Hisham Husain, Achintya Singhal, Dominik Grewe, François-Xavier Aubet, Shuang Song, Lorenzo Blanco, Leland Rechis, Lewis Ho, Rich Munoz, Kelvin Zheng, Jessica Hamrick, Kevin Mather, Hagai Taitelbaum, Eliza Rutherford, Yun Lei, Kuangyuan Chen, Anand Shukla, Erica Moreira, Eric Doi, Berivan Isik, Nir Shabat, Dominika Rogozińska, Kashyap Kolipaka, Jason Chang, Eugen Vušak, Srinivasan Venkatachary, Shadi Noghabi, Tarun Bharti, Younghoon Jun, Aleksandr Zaks, Simon Green, Jeshwanth Challagundla, William Wong, Muqthar Mohammad, Dean Hirsch, Yong Cheng, Iftekhar Naim, Lev Proleev, Damien Vincent, Aayush Singh, Maxim Krikun, Dilip Krishnan, Zoubin Ghahramani, Aviel Atias, Rajeev Aggarwal, Christo Kirov, Dimitrios Vytiniotis, Christy Koh, Alexandra Chronopoulou, Pawan Dogra, Vlad-Doru Ion, Gladys Tyen, Jason Lee, Felix Weissenberger, Trevor Strohman, Ashwin Balakrishna, Jack Rae, Marko Velic, Raoul de Liedekerke, Oded Elyada, Wentao Yuan, Canoee Liu, Lior Shani, Sergey Kishchenko, Bea Alessio, Yandong Li, Richard Song, Sam Kwei, Orion Jankowski, Aneesh Pappu, Youhei Namiki, Yenai Ma, Nilesh Tripuraneni, Colin Cherry, Marissa Ikonomidis, Yu-Cheng Ling, Colin Ji, Beka Westberg, Auriel Wright, Da Yu, David Parkinson, Swaroop Ramaswamy, Jerome Connor, Soheil Hassas Yeganeh, Snchit Grover, George Kenwright, Lubo Litchev, Chris Apps, Alex Tomala, Felix Halim, Alex Castro-Ros, Zefei Li, Anudhyan Boral, Pauline Sho, Michal Yarom, Eric Malmi, David Klinghoffer, Rebecca Lin, Alan Ansell, Pradeep Kumar S, Shubin Zhao, Siqi Zuo, Adam Santoro, Heng-Tze Cheng, Solomon Demmessie, Yuchi Liu, Nicole Brichtova, Allie Culp, Nathaniel Braun, Dan Graur, Will Ng, Nikhil Mehta, Aaron Phillips, Patrik Sundberg, Varun Godbole, Fangyu Liu, Yash Katariya, David Rim, Mojtaba Seyedhosseini, Sean Ammirati, Jonas Valfridsson, Mahan Malihi, Timothy Knight, Andeep Toor, Thomas Lampe, Abe Ittycheriah, Lewis Chiang, Chak Yeung, Alexandre Fréchette, Jinmeng Rao, Huisheng Wang, Himanshu Srivastava, Richard Zhang, Rocky Rhodes, Ariel Brand, Dean Weesner, Ilya Figotin, Felix Gimeno, Rachana Fellinger, Pierre Marcenac, José Leal, Eyal Marcus, Victor Cotruta, Rodrigo Cabrera, Sheryl Luo, Dan Garrette, Vera Axelrod, Sorin Baltateanu, David Barker, Dongkai Chen, Horia Toma, Ben Ingram, Jason Riesa, Chinmay Kulkarni, Yujing Zhang, Hongbin Liu, Chao Wang, Martin Polacek, Will Wu, Kai Hui, Adrian N Reyes, Yi Su, Megan Barnes, Ishaan Malhi, Anfal Siddiqui, Qixuan Feng, Mihai Damaschin, Daniele Pighin, Andreas Steiner, Samuel Yang, Ramya Sree Boppana, Simeon Ivanov, Arun Kandoor, Aditya Shah, Asier Mujika, Da Huang, Christopher A. Choquette-Choo, Mohak Patel, Tianhe Yu, Toni Creswell, Jerry, Liu, Catarina Barros, Yasaman Razeghi, Aurko Roy, Phil Culliton, Binbin Xiong, Jiaqi Pan, Thomas Strohmann, Tolly Powell, Babi Seal, Doug DeCarlo, Pranav Shyam, Kaan Katircioglu, Xuezhi Wang, Cassidy Hardin, Immanuel Odisho, Josef Broder, Oscar Chang, Arun Nair, Artem Shtefan, Maura O'Brien, Manu Agarwal, Sahitya Potluri, Siddharth Goyal, Amit Jhindal, Saksham Thakur, Yury Stuken, James Lyon, Kristina Toutanova, Fangxiaoyu Feng, Austin Wu, Ben Horn, Alek Wang, Alex Cullum, Gabe Taubman, Disha Shrivastava, Chongyang Shi, Hamish Tomlinson, Roma Patel, Tao Tu, Ada Maksutaj Oflazer, Francesco Pongetti, Mingyao Yang, Adrien Ali Taïga, Vincent Perot, Nuo Wang Pierse, Feng Han, Yoel Drori, Iñaki Iturrate, Ayan Chakrabarti, Legg Yeung, Dave Dopson, Yi-ting Chen, Apoorv Kulshreshtha, Tongfei Guo, Philip Pham, Tal Schuster, Junquan Chen, Alex Polozov, Jinwei Xing, Huanjie Zhou, Praneeth Kacham, Doron Kukliansky, Antoine Miech, Sergey Yaroshenko, Ed Chi, Sholto Douglas, Hongliang Fei, Mathieu Blondel, Preethi Myla, Lior Madmoni, Xing Wu, Daniel Keysers, Kristian Kjems, Isabela Albuquerque, Lijun Yu, Joel D'sa, Michelle Plantan, Vlad Ionescu, Jaume Sanchez Elias, Abhirut Gupta, Manish Reddy Vuyyuru, Fred Alcober, Tong Zhou, Kaiyang Ji, Florian Hartmann, Subha Puttagunta, Hugo Song, Ehsan Amid, Anca Stefanoiu, Andrew Lee, Paul Pucciarelli, Emma Wang, Amit Raul, Slav Petrov, Isaac Tian, Valentin Anklin, Nana Nti, Victor Gomes, Max Schumacher, Grace Vesom, Alex Panagopoulos, Konstantinos Bousmalis, Daniel Andor, Josh Jacob, Yuan Zhang, Bill Rosgen, Matija Kecman, Matthew Tung, Alexandra Belias, Noah Goodman, Paul Covington, Brian Wieder, Nikita Saxena, Elnaz Davoodi, Muhuan Huang, Sharath Maddineni, Vincent Roulet, Folawiyo Campbell-Ajala, Pier Giuseppe Sessa, Xintian, Wu, Guangda Lai, Paul Collins, Alex Haig, Vytenis Sakenas, Xiaowei Xu, Marissa Giustina, Laurent El Shafey, Pichi Charoenpanit, Shefali Garg, Joshua 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Alban Rrustemi, Hao Xiong, Hao Liu, Arpi Vezer, Nolan Ramsden, Shuo-yiin Chang, Sidharth Mudgal, Yan Li, Nino Vieillard, Yedid Hoshen, Farooq Ahmad, Ambrose Slone, Amy Hua, Natan Potikha, Mirko Rossini, Jon Stritar, Sushant Prakash, Zifeng Wang, Xuanyi Dong, Alireza Nazari, Efrat Nehoran, Kaan Tekelioglu, Yinxiao Li, Kartikeya Badola, Tom Funkhouser, Yuanzhen Li, Varun Yerram, Ramya Ganeshan, Daniel Formoso, Karol Langner, Tian Shi, Huijian Li, Yumeya Yamamori, Amayika Panda, Alaa Saade, Angelo Scorza Scarpati, Chris Breaux, CJ Carey, Zongwei Zhou, Cho-Jui Hsieh, Sophie Bridgers, Alena Butryna, Nishesh Gupta, Vaibhav Tulsyan, Sanghyun Woo, Evgenii Eltyshev, Will Grathwohl, Chanel Parks, Seth Benjamin, Rina Panigrahy, Shenil Dodhia, Daniel De Freitas, Chris Sauer, Will Song, Ferran Alet, Jackson Tolins, Cosmin Paduraru, Xingyi Zhou, Brian Albert, Zizhao Zhang, Lei Shu, Mudit Bansal, Sarah Nguyen, Amir Globerson, Owen Xiao, James Manyika, Tom Hennigan, Rong Rong, Josip Matak, Anton Bakalov, Ankur Sharma, Danila Sinopalnikov, Andrew Pierson, Stephen Roller, Geoff Brown, Mingcen Gao, Toshiyuki Fukuzawa, Amin Ghafouri, Kenny Vassigh, Iain Barr, Zhicheng Wang, Anna Korsun, Rajesh Jayaram, Lijie Ren, Tim Zaman, Samira Khan, Yana Lunts, Dan Deutsch, Dave Uthus, Nitzan Katz, Masha Samsikova, Amr Khalifa, Nikhil Sethi, Jiao Sun, Luming Tang, Uri Alon, Xianghong Luo, Dian Yu, Abhishek Nayyar, Bryce Petrini, Will Truong, Vincent Hellendoorn, Nikolai Chinaev, Chris Alberti, Wei Wang, Jingcao Hu, Vahab Mirrokni, Ananth Balashankar, Avia Aharon, Aahil Mehta, Ahmet Iscen, Joseph Kready, Lucas Manning, Anhad Mohananey, Yuankai Chen, Anshuman Tripathi, Allen Wu, Igor Petrovski, Dawsen Hwang, Martin Baeuml, Shreyas Chandrakaladharan, Yuan Liu, Rey Coaguila, Maxwell Chen, Sally Ma, Pouya Tafti, Susheel Tatineni, Terry Spitz, Jiayu Ye, Paul Vicol, Mihaela Rosca, Adrià Puigdomènech, Zohar Yahav, Sanjay Ghemawat, Hanzhao Lin, Phoebe Kirk, Zaid Nabulsi, Sergey Brin, Bernd Bohnet, Ken Caluwaerts, Aditya Srikanth Veerubhotla, Dan Zheng, Zihang Dai, Petre Petrov, Yichong Xu, Ramin Mehran, Zhuo Xu, Luisa Zintgraf, Jiho Choi, Spurthi Amba Hombaiah, Romal Thoppilan, Sashank Reddi, Lukasz Lew, Li Li, Kellie Webster, KP Sawhney, Lampros Lamprou, Siamak Shakeri, Mayank Lunayach, Jianmin Chen, Sumit Bagri, Alex Salcianu, Ying Chen, Yani Donchev, Charlotte Magister, Signe Nørly, Vitor Rodrigues, Tomas Izo, Hila Noga, Joe Zou, Thomas Köppe, Wenxuan Zhou, Kenton Lee, Xiangzhu Long, Danielle Eisenbud, Anthony Chen, Connor Schenck, Chi Ming To, Peilin Zhong, Emanuel Taropa, Minh Truong, Omer Levy, Danilo Martins, Zhiyuan Zhang, Christopher Semturs, Kelvin Zhang, Alex Yakubovich, Pol Moreno, Lara McConnaughey, Di Lu, Sam Redmond, Lotte Weerts, Yonatan Bitton, Tiziana Refice, Nicolas Lacasse, Arthur Conmy, Corentin Tallec, Julian Odell, Hannah Forbes-Pollard, Arkadiusz Socala, Jonathan Hoech, Pushmeet Kohli, Alanna Walton, Rui Wang, Mikita Sazanovich, Kexin Zhu, Andrei Kapishnikov, Rich Galt, Matthew Denton, Ben Murdoch, Caitlin Sikora, Kareem Mohamed, Wei Wei, Uri First, Tim McConnell, Luis C. Cobo, James Qin, Thi Avrahami, Daniel Balle, Yu Watanabe, Annie Louis, Adam Kraft, Setareh Ariafar, Yiming Gu, Eugénie Rives, Charles Yoon, Andrei Rusu, James Cobon-Kerr, Chris Hahn, Jiaming Luo, Yuvein, Zhu, Niharika Ahuja, Rodrigo Benenson, Raphaël Lopez Kaufman, Honglin Yu, Lloyd Hightower, Junlin Zhang, Darren Ni, Lisa Anne Hendricks, Gabby Wang, Gal Yona, Lalit Jain, Pablo Barrio, Surya Bhupatiraju, Siva Velusamy, Allan Dafoe, Sebastian Riedel, Tara Thomas, Zhe Yuan, Mathias Bellaiche, Sheena Panthaplackel, Klemen Kloboves, Sarthak Jauhari, Canfer Akbulut, Todor Davchev, Evgeny Gladchenko, David Madras, Aleksandr Chuklin, Tyrone Hill, Quan Yuan, Mukundan Madhavan, Luke Leonhard, Dylan Scandinaro, Qihang Chen, Ning Niu, Arthur Douillard, Bogdan Damoc, Yasumasa Onoe, Fabian Pedregosa, Fred Bertsch, Chas Leichner, Joseph Pagadora, Jonathan Malmaud, Sameera Ponda, Andy Twigg, Oleksii Duzhyi, Jingwei Shen, Miaosen Wang, Roopal Garg, Jing Chen, Utku Evci, Jonathan Lee, Leon Liu, Koji Kojima, Masa Yamaguchi, Arunkumar Rajendran, AJ Piergiovanni, Vinodh Kumar Rajendran, Marco Fornoni, Gabriel Ibagon, Harry Ragan, Sadh MNM Khan, John Blitzer, Andrew Bunner, Guan Sun, Takahiro Kosakai, Scott Lundberg, Ndidi Elue, Kelvin Guu, SK Park, Jane Park, Arunachalam Narayanaswamy, Chengda Wu, Jayaram Mudigonda, Trevor Cohn, Hairong Mu, Ravi Kumar, Laura Graesser, Yichi Zhang, Richard Killam, Vincent Zhuang, Mai Giménez, Wael Al Jishi, Ruy Ley-Wild, Alex Zhai, Kazuki Osawa, Diego Cedillo, Jialu Liu, Mayank Upadhyay, Marcin Sieniek, Roshan Sharma, Tom Paine, Anelia Angelova, Sravanti Addepalli, Carolina Parada, Kingshuk Majumder, Avery Lamp, Sanjiv Kumar, Xiang Deng, Artiom Myaskovsky, Tea Sabolić, Jeffrey Dudek, Sarah York, Félix de Chaumont Quitry, Jiazhong Nie, Dee Cattle, Alok Gunjan, Bilal Piot, Waleed Khawaja, Seojin Bang, Simon Wang, Siavash Khodadadeh, Raghavender R, Praynaa Rawlani, Richard Powell, Kevin Lee, Johannes Griesser, GS Oh, Cesar Magalhaes, Yujia Li, Simon Tokumine, Hadas Natalie Vogel, Dennis Hsu, Arturo BC, Disha Jindal, Matan Cohen, Zi Yang, Junwei Yuan, Dario de Cesare, Tony Bruguier, Jun Xu, Monica Roy, Alon Jacovi, Dan Belov, Rahul Arya, Phoenix Meadowlark, Shlomi Cohen-Ganor, Wenting Ye, Patrick Morris-Suzuki, Praseem Banzal, Gan Song, Pranavaraj Ponnuramu, Fred Zhang, George Scrivener, Salah Zaiem, Alif Raditya Rochman, Kehang Han, Badih Ghazi, Kate Lee, Shahar Drath, Daniel Suo, Antonious Girgis, Pradeep Shenoy, Duy Nguyen, Douglas Eck, Somit Gupta, Le Yan, Joao Carreira, Anmol Gulati, Ruoxin Sang, Daniil Mirylenka, Emma Cooney, Edward Chou, Mingyang Ling, Cindy Fan, Ben Coleman, Guilherme Tubone, Ravin Kumar, Jason Baldridge, Felix Hernandez-Campos, Angeliki Lazaridou, James Besley, Itay Yona, Neslihan Bulut, Quentin Wellens, AJ Pierigiovanni, Jasmine George, Richard Green, Pu Han, Connie Tao, Geoff Clark, Chong You, Abbas Abdolmaleki, Justin Fu, Tongzhou Chen, Ashwin Chaugule, Angad Chandorkar, Altaf Rahman, Will Thompson, Penporn Koanantakool, Mike Bernico, Jie Ren, Andrey Vlasov, Sergei Vassilvitskii, Maciej Kula, Yizhong Liang, Dahun Kim, Yangsibo Huang, Chengxi Ye, Dmitry Lepikhin, Wesley Helmholz

A Toolbox for Surfacing Health Equity Harms and Biases in Large Language Models

Stephen R. Pfohl, Heather Cole-Lewis, Rory Sayres, Darlene Neal, Mercy Asiedu, Awa Dieng, Nenad Tomasev, Qazi Mamunur Rashid, Shekoofeh Azizi, Negar Rostamzadeh, Liam G. McCoy, Leo Anthony Celi, Yun Liu, Mike Schaekermann, Alanna Walton, Alicia Parrish, Chirag Nagpal, Preeti Singh, Akeiylah Dewitt, Philip Mansfield, Sushant Prakash, Katherine Heller, Alan Karthikesalingam, Christopher Semturs, Joelle Barral, Greg Corrado, Yossi Matias, Jamila Smith-Loud, Ivor Horn, Karan Singhal

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 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 via 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 AI system promotes equitable health outcomes, we hope that it can be leveraged and built upon towards a shared goal of LLMs that promote accessible and equitable healthcare.

A prospective clinical feasibility study of a conversational diagnostic AI in an ambulatory primary care clinic

Peter Brodeur, Jacob M. Koshy, Anil Palepu, Khaled Saab, Ava Homiar, Roma Ruparel, Charles Wu, Ryutaro Tanno, Joseph Xu, Amy Wang, David Stutz, Wei-Hung Weng, Hannah M. Ferrera, David Barrett, Lindsey Crowley, Jihyeon Lee, Spencer E. Rittner, Ellery Wulczyn, Selena K. Zhang, Elahe Vedadi, Christine G. Kohn, Kavita Kulkarni, Vinay Kadiyala, Sara Mahdavi, Wendy Du, Jessica M. Williams, David Feinbloom, Renee Wong, Tao Tu, Petar Sirkovic, Alessio Orlandi, Christopher Semturs, Yun Liu, Juraj Gottweis, Dale R. Webster, Joëlle Barral, Katherine Chou, Pushmeet Kohli, Avinatan Hassidim, Yossi Matias, James Manyika, Rob Fields, Jonathan X. Li, Marc L. Cohen, Vivek Natarajan, Mike Schaekermann, Alan Karthikesalingam, Adam Rodman

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.