Alan Karthikesalingam

Alan Karthikesalingam

Alan is a clinician and Research Scientist working on Foundation Models for health, most recently including Med-PaLM, Med-PaLM-2, Med-PaLM-Multimodal and AMIE. Prior to this his work at DeepMind and Google explored applications of AI in radiology, ophthalmology, dermatology and electronic health records, resulting in papers published in Nature and Nature Medicine. He is an honorary Lecturer in Vascular Surgery at Imperial College in London. He completed his MA in Neuroscience and Medical Degree (MBBChir) at the University of Cambridge before specialist training in surgery in the London Deanery, where he completed his Membership of the Royal College of Surgeons (MRCS), PhD in Vascular Surgery and was appointed as a NIHR Clinical Lecturer. In 2017 he joined DeepMind's health research team and in 2019 joined Google Health. Prior to joining Google he had published over 150 peer-reviewed articles including first-author studies in the New England Journal of Medicine and The Lancet.
Authored Publications
Google Publications
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    Understanding metric-related pitfalls in image analysis validation
    Annika Reinke
    Lena Maier-Hein
    Paul Jager
    Shravya Shetty
    Understanding Metrics Workgroup
    Nature Methods (2024)
    Preview abstract Validation metrics are key for the reliable tracking of scientific progress and for bridging the current chasm between artificial intelligence (AI) research and its translation into practice. However, increasing evidence shows that particularly in image analysis, metrics are often chosen inadequately in relation to the underlying research problem. This could be attributed to a lack of accessibility of metric-related knowledge: While taking into account the individual strengths, weaknesses, and limitations of validation metrics is a critical prerequisite to making educated choices, the relevant knowledge is currently scattered and poorly accessible to individual researchers. Based on a multi-stage Delphi process conducted by a multidisciplinary expert consortium as well as extensive community feedback, the present work provides the first reliable and comprehensive common point of access to information on pitfalls related to validation metrics in image analysis. Focusing on biomedical image analysis but with the potential of transfer to other fields, the addressed pitfalls generalize across application domains and are categorized according to a newly created, domain-agnostic taxonomy. To facilitate comprehension, illustrations and specific examples accompany each pitfall. As a structured body of information accessible to researchers of all levels of expertise, this work enhances global comprehension of a key topic in image analysis validation. View details
    Generative models improve fairness of medical classifiers under distribution shifts
    Ira Ktena
    Olivia Wiles
    Isabela Albuquerque
    Sylvestre-Alvise Rebuffi
    Ryutaro Tanno
    Danielle Belgrave
    Taylan Cemgil
    Nature Medicine(2024)
    Preview abstract Domain generalization is a ubiquitous challenge for machine learning in healthcare. Model performance in real-world conditions might be lower than expected because of discrepancies between the data encountered during deployment and development. Underrepresentation of some groups or conditions during model development is a common cause of this phenomenon. This challenge is often not readily addressed by targeted data acquisition and ‘labeling’ by expert clinicians, which can be prohibitively expensive or practically impossible because of the rarity of conditions or the available clinical expertise. We hypothesize that advances in generative artificial intelligence can help mitigate this unmet need in a steerable fashion, enriching our training dataset with synthetic examples that address shortfalls of underrepresented conditions or subgroups. We show that diffusion models can automatically learn realistic augmentations from data in a label-efficient manner. We demonstrate that learned augmentations make models more robust and statistically fair in-distribution and out of distribution. To evaluate the generality of our approach, we studied three distinct medical imaging contexts of varying difficulty: (1) histopathology, (2) chest X-ray and (3) dermatology images. Complementing real samples with synthetic ones improved the robustness of models in all three medical tasks and increased fairness by improving the accuracy of clinical diagnosis within underrepresented groups, especially out of distribution. View details
    Towards Generalist Biomedical AI
    Danny Driess
    Andrew Carroll
    Chuck Lau
    Ryutaro Tanno
    Ira Ktena
    Anil Palepu
    Basil Mustafa
    Aakanksha Chowdhery
    Simon Kornblith
    Philip Mansfield
    Sushant Prakash
    Renee Wong
    Sunny Virmani
    Christopher Semturs
    Sara Mahdavi
    Bradley Green
    Ewa Dominowska
    Joelle Barral
    Karan Singhal
    Pete Florence
    NEJM AI(2024)
    Preview abstract BACKGROUND: Medicine is inherently multimodal, requiring the simultaneous interpretation and integration of insights between many data modalities spanning text, imaging, genomics, and more. Generalist biomedical artificial intelligence systems that flexibly encode, integrate, and interpret these data might better enable impactful applications ranging from scientific discovery to care delivery. METHODS: To catalyze development of these models, we curated 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 introduced Med-PaLM Multimodal (Med-PaLM M), our proof of concept for a generalist biomedical AI system that flexibly encodes and interprets biomedical data including clinical language, imaging, and genomics with the same set of model weights. To further probe the capabilities and limitations of Med-PaLM M, we conducted a radiologist evaluation of model-generated (and human) chest x-ray reports. RESULTS: We observed encouraging performance across model scales. Med-PaLM M reached performance competitive with or exceeding the state of the art on all MultiMedBench tasks, often surpassing specialist models by a wide margin. In a side-by-side ranking on 246 retrospective chest x-rays, clinicians expressed a pairwise preference for Med-PaLM Multimodal reports over those produced by radiologists in up to 40.50% of cases, suggesting potential clinical utility. CONCLUSIONS: Although considerable work is needed to validate these models in real-world cases and understand if cross-modality generalization is possible, our results represent a milestone toward the development of generalist biomedical artificial intelligence systems. View details
    Crowdsourcing Dermatology Images with Google Search Ads: Creating a Diverse and Representative Dataset of Real-World Skin Conditions
    Abbi Ward
    Ashley Carrick
    Christopher Semturs
    Dawn Siegel
    Jay Hartford
    Jimmy Li
    Julie Wang
    Justin Ko
    Pradeep Kumar S
    Renee Wong
    Sriram Lakshminarasimhan
    Steven Lin
    Sunny Virmani
    arXiv(2024)
    Preview abstract 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 solicit contributions of images of dermatology conditions, demographic and symptom information from internet users in the United States (US) over 265 days starting March 2023. With informed contributor consent, we described and released this dataset containing 10,106 images from 5058 contributions, with dermatologist labels as well as Fitzpatrick Skin Type and Monk Skin Tone labels for the images. Results We received 22 ± 14 submissions/day over 265 days. Female contributors (66.04%) and younger individuals (52.3% < age 40) had a higher representation in the dataset compared to the US population, and 36.6% of contributors had a non-White racial or ethnic identity. Over 97.5% of contributions were genuine images of skin conditions. Image quality had no impact on dermatologist confidence in assigning a differential diagnosis. The dataset consists largely of short duration (54% with onset < 7 days ago) allergic, infectious, and inflammatory conditions. Fitzpatrick skin type distribution is well-balanced, considering the geographical origin of the dataset and the absence of enrichment for population groups or skin tones. Interpretation 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. View details
    An intentional approach to managing bias in embedding models
    Atilla P. Kiraly
    Alexander D'Amour
    Jungyeon Park
    Rory Pilgrim
    Charles Lau
    Heather Cole-Lewis
    Shravya Shetty
    Krish Eswaran
    Leo Anthony Celi
    The Lancet Digital Health, 6(2024), E126-E130
    Preview abstract Advances in machine learning for health care have brought concerns about bias from the research community; specifically, the introduction, perpetuation, or exacerbation of care disparities. Reinforcing these concerns is the finding that medical images often reveal signals about sensitive attributes in ways that are hard to pinpoint by both algorithms and people. This finding raises a question about how to best design general purpose pretrained embeddings (GPPEs, defined as embeddings meant to support a broad array of use cases) for building downstream models that are free from particular types of bias. The downstream model should be carefully evaluated for bias, and audited and improved as appropriate. However, in our view, well intentioned attempts to prevent the upstream components—GPPEs—from learning sensitive attributes can have unintended consequences on the downstream models. Despite producing a veneer of technical neutrality, the resultant end-to-end system might still be biased or poorly performing. We present reasons, by building on previously published data, to support the reasoning that GPPEs should ideally contain as much information as the original data contain, and highlight the perils of trying to remove sensitive attributes from a GPPE. We also emphasise that downstream prediction models trained for specific tasks and settings, whether developed using GPPEs or not, should be carefully designed and evaluated to avoid bias that makes models vulnerable to issues such as distributional shift. These evaluations should be done by a diverse team, including social scientists, on a diverse cohort representing the full breadth of the patient population for which the final model is intended. View details
    Conversational AI in health: Design considerations from a Wizard-of-Oz dermatology case study with users, clinicians and a medical LLM
    Brenna Li
    Amy Wang
    Patricia Strachan
    Julie Anne Seguin
    Sami Lachgar
    Karyn Schroeder
    Renee Wong
    Naama Hammel
    Rory Sayres
    Christopher Semturs
    Extended Abstracts of the 2024 CHI Conference on Human Factors in Computing Systems, Association for Computing Machinery, pp. 10
    Preview abstract Although skin concerns are common, access to specialist care is limited. Artificial intelligence (AI)-assisted tools to support medical decisions may provide patients with feedback on their concerns while also helping ensure the most urgent cases are routed to dermatologists. Although AI-based conversational agents have been explored recently, how they are perceived by patients and clinicians is not well understood. We conducted a Wizard-of-Oz study involving 18 participants with real skin concerns. Participants were randomly assigned to interact with either a clinician agent (portrayed by a dermatologist) or an LLM agent (supervised by a dermatologist) via synchronous multimodal chat. In both conditions, participants found the conversation to be helpful in understanding their medical situation and alleviate their concerns. Through qualitative coding of the conversation transcripts, we provide insight on the importance of empathy and effective information-seeking. We conclude with design considerations for future AI-based conversational agents in healthcare settings. View details
    Towards Conversational Diagnostic AI
    Anil Palepu
    Khaled Saab
    Jan Freyberg
    Ryutaro Tanno
    Amy Wang
    Brenna Li
    Nenad Tomašev
    Karan Singhal
    Le Hou
    Albert Webson
    Kavita Kulkarni
    Sara Mahdavi
    Christopher Semturs
    Juro Gottweis
    Joelle Barral
    Kat Chou
    Arxiv(2024) (to appear)
    Preview abstract 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. View details
    Preview abstract Large language models (LLMs) hold immense 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. In this work, 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 then conduct an empirical case study with Med-PaLM 2, resulting in the largest human evaluation study in this area to date. Our contributions include a multifactorial framework for human assessment of LLM-generated answers for biases, and EquityMedQA, a collection of seven newly-released datasets comprising both manually-curated and LLM-generated questions enriched for adversarial queries. Both our human assessment framework and dataset design process are grounded in an iterative participatory approach and review of possible biases in Med-PaLM 2 answers to adversarial queries. Through our empirical study, we find that the use of a collection of datasets curated through a variety of methodologies, coupled with a thorough evaluation protocol that leverages multiple assessment rubric designs and diverse rater groups, 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. We emphasize that while our framework can identify specific forms of bias, it is not sufficient to holistically assess whether the deployment of an AI system promotes equitable health outcomes. We hope the broader community leverages and builds on these tools and methods towards realizing a shared goal of LLMs that promote accessible and equitable healthcare for all. View details
    Enhancing diagnostic accuracy of medical AI systems via selective deferral to clinicians
    Dj Dvijotham
    Melih Barsbey
    Sumedh Ghaisas
    Robert Stanforth
    Nick Pawlowski
    Patricia Strachan
    Zahra Ahmed
    Yoram Bachrach
    Laura Culp
    Mayank Daswani
    Jan Freyberg
    Atilla Kiraly
    Timo Kohlberger
    Scott Mayer McKinney
    Basil Mustafa
    Krzysztof Geras
    Jan Witowski
    Zhi Zhen Qin
    Jacob Creswell
    Shravya Shetty
    Terry Spitz
    Taylan Cemgil
    Nature Medicine(2023)
    Preview abstract AI systems trained using deep learning have been shown to achieve expert-level identification of diseases in multiple medical imaging settings1,2. While these results are impressive, they don’t accurately reflect the impact of deployment of such systems in a clinical context. Due to the safety-critical nature of this domain and the fact that AI systems are not perfect and can make inaccurate assessments, they are predominantly deployed as assistive tools for clinical experts3. Although clinicians routinely discuss the diagnostic nuances of medical images with each other, weighing human diagnostic confidence against that of an AI system remains a major unsolved barrier to collaborative decision-making4. Furthermore, it has been observed that diagnostic AI models have complementary strengths and weaknesses compared to clinical experts. Yet, complementarity and the assessment of relative confidence between the members of a diagnostic team has remained largely unexploited in how AI systems are currently used in medical settings5. In this paper, we study the behavior of a team composed of diagnostic AI model(s) and clinician(s) in diagnosing disease. To go beyond the performance level of a standalone AI system, we develop a novel selective deferral algorithm that can learn to decide when to rely on a diagnostic AI model and when to defer to a clinical expert. Using this algorithm, we demonstrate that the composite AI+human system has enhanced accuracy (both sensitivity and specificity) relative to a human-only or an AI-only baseline. We decouple the development of the deferral AI model from training of the underlying diagnostic AI model(s). Development of the deferral AI model only requires i) the predictions of a model(s) on a tuning set of medical images (separate from the diagnostic AI models’ training data), ii) the diagnoses made by clinicians on these images and iii) the ground truth disease labels corresponding to those images. Our extensive analysis shows that the selective deferral (SD) system exceeds the performance of either clinicians or AI alone in multiple clinical settings: breast and lung cancer screening. For breast cancer screening, double-reading with arbitration (two readers interpreting each mammogram invoking an arbitrator if needed) is a “gold standard” for performance, never previously exceeded using AI6. The SD system exceeds the accuracy of double-reading with arbitration in a large representative UK screening program (25% reduction in false positives despite equivalent true-positive detection and 66% reduction in the requirement for clinicians to read an image), as well as exceeding the performance of a standalone state-of-art AI system (40% reduction in false positives with equivalent detection of true positives). In a large US dataset the SD system exceeds the accuracy of single-reading by board-certified radiologists and a standalone state-of-art AI system (32% reduction in false positives despite equivalent detection of true positives and 55% reduction in the clinician workload required). The SD system further outperforms both clinical experts alone, and AI alone for the detection of lung cancer in low-dose Computed Tomography images from a large national screening study, with 11% reduction in false positives while maintaining sensitivity given 93% reduction in clinician workload required. Furthermore, the SD system allows controllable trade-offs between sensitivity and specificity and can be tuned to target either specificity or sensitivity as desired for a particular clinical application, or a combination of both. The system generalizes to multiple distribution shifts, retaining superiority to both the AI system alone and human experts alone. We demonstrate that the SD system retains performance gains even on clinicians not present in the training data for the deferral AI. Furthermore, we test the SD system on a new population where the standalone AI system’s performance significantly degrades. We showcase the few-shot adaptation capability of the SD system by demonstrating that the SD system can obtain superiority to both the standalone AI system and the clinician on the new population after being trained on only 40 cases from the new population. Our comprehensive assessment demonstrates that a selective deferral system could significantly improve clinical outcomes in multiple medical imaging applications, paving the way for higher performance clinical AI systems that can leverage the complementarity between clinical experts and medical AI tools. View details
    Consensus, dissensus and synergy between clinicians and specialist foundation models in radiology report generation
    Ryutaro Tanno
    David Barrett
    Sumedh Ghaisas
    Sumanth Dathathri
    Abi See
    Johannes Welbl
    Karan Singhal
    Rhys May
    Roy Lee
    SiWai Man
    Zahra Ahmed
    Sara Mahdavi
    Joelle Barral
    Ali Eslami
    Danielle Belgrave
    Shravya Shetty
    Po-Sen Huang
    Ira Ktena
    Arxiv(2023)
    Preview abstract 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, 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. View details
    Detecting shortcut learning for fair medical AI using shortcut testing
    Alexander Brown
    Nenad Tomašev
    Jan Freyberg
    Yuan Liu
    Nature Communications (2023)
    Preview abstract Machine learning (ML) holds great promise for improving healthcare, but it is critical to ensure that its use will not propagate or amplify health disparities. An important step is to characterize the (un)fairness of ML models—their tendency to perform differently across subgroups of the population—and to understand its underlying mechanisms. One potential driver of algorithmic unfairness, shortcut learning, arises when ML models base predictions on improper correlations in the training data. Diagnosing this phenomenon is difficult as sensitive attributes may be causally linked with disease. Using multitask learning, we propose a method to directly test for the presence of shortcut learning in clinical ML systems and demonstrate its application to clinical tasks in radiology and dermatology. Finally, our approach reveals instances when shortcutting is not responsible for unfairness, highlighting the need for a holistic approach to fairness mitigation in medical AI. View details
    Towards Physician-Level Medical Question Answering with Large Language Models
    Karan Singhal
    Juro Gottweis
    Rory Sayres
    Le Hou
    Kevin Clark
    Heather Cole-Lewis
    Amy Wang
    Sami Lachgar
    Philip Mansfield
    Sushant Prakash
    Bradley Green
    Ewa Dominowska
    Nenad Tomašev
    Renee Wong
    Christopher Semturs
    Sara Mahdavi
    Joelle Barral
    Arxiv(2023) (to appear)
    Preview abstract 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. View details
    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
    Boris Babenko
    Megan Zoë Walker
    Aaron Loh
    Cameron Chen
    Yuan Liu
    Scott Mayer McKinney
    Zach William Beaver
    Fiona Keleher Ryan
    Mozziyar Etemadi
    Umesh Telang
    Lily Hao Yi Peng
    Geoffrey Everest Hinton
    Mohammad Norouzi
    Nature Biomedical Engineering(2023)
    Preview abstract 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. View details
    Large Language Models Encode Clinical Knowledge
    Karan Singhal
    Sara Mahdavi
    Jason Wei
    Hyung Won Chung
    Nathan Scales
    Ajay Tanwani
    Heather Cole-Lewis
    Perry Payne
    Martin Seneviratne
    Paul Gamble
    Abubakr Abdelrazig Hassan Babiker
    Nathanael Schaerli
    Aakanksha Chowdhery
    Philip Mansfield
    Dina Demner-Fushman
    Katherine Chou
    Juraj Gottweis
    Nenad Tomašev
    Alvin Rajkomar
    Joelle Barral
    Christopher Semturs
    Nature(2023)
    Preview abstract Large language models (LLMs) have demonstrated impressive capabilities, but the bar for clinical applications is high. Attempts to assess the clinical knowledge of models typically rely on automated evaluations based on limited benchmarks. Here, to address these limitations, we present MultiMedQA, a benchmark combining six existing medical question answering datasets spanning professional medicine, research and consumer queries and a new dataset of medical questions searched online, HealthSearchQA. We propose a human evaluation framework for model answers along multiple axes including factuality, comprehension, reasoning, possible harm and bias. In addition, we evaluate Pathways Language Model (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 and Measuring Massive Multitask Language Understanding (MMLU) clinical topics), including 67.6% accuracy on MedQA (US Medical Licensing Exam-style questions), surpassing the prior state of the art by more than 17%. However, human evaluation reveals key gaps. 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, knowledge recall and reasoning improve with model scale and instruction prompt tuning, suggesting the potential utility of LLMs in medicine. Our human evaluations reveal limitations of today’s models, reinforcing the importance of both evaluation frameworks and method development in creating safe, helpful LLMs for clinical applications. View details
    Towards Accurate Differential Diagnosis with Large Language Models
    Daniel McDuff
    Anil Palepu
    Amy Wang
    Karan Singhal
    Yash Sharma
    Kavita Kulkarni
    Le Hou
    Sara Mahdavi
    Sushant Prakash
    Anupam Pathak
    Christopher Semturs
    Shwetak Patel
    Ewa Dominowska
    Juro Gottweis
    Joelle Barral
    Kat Chou
    Jake Sunshine
    Arxiv(2023)
    Preview abstract 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. View details
    Diagnosing failures of fairness transfer across distribution shift in real-world medical settings
    Sanmi Koyejo
    Eva Schnider
    Krista Opsahl-Ong
    Alex Brown
    Christina Chen
    Yuan Liu
    Silvia Chiappa
    Alexander Nicholas D'Amour
    Proceedings of Neural Information Processing Systems 2022(2022)
    Preview abstract 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. View details
    Supervised Transfer Learning at Scale for Medical Imaging
    Aaron Loh
    Basil Mustafa
    Jan Freyberg
    Patricia MacWilliams
    Megan Wilson
    Scott Mayer McKinney
    Yuan Liu
    Peggy Bui
    Umesh Telang
    ArXiV(2021)
    Preview abstract Transfer learning is a standard building block of successful medical imaging models, yet previous efforts suggest that at limited scale of pre-training data and model capacity, benefits of transfer learning to medical imaging are insubstantial. In this work, we explore whether scaling up pre-training can help improve transfer to medical tasks. In particular, we show that when using the Big Transfer recipe to further scale up pre-training, we can indeed considerably improve transfer performance across three popular yet diverse medical imaging tasks - interpretation of chest radiographs, breast cancer detection from mammograms and skin condition detection from smartphone images. Despite pre-training on unrelated source domains, we show that scaling up the model capacity and pre-training data yields performance improvements regardless of how much downstream medical data is available. In particular, we show suprisingly large improvements to zero-shot generalisation under distribution shift. Probing and quantifying other aspects of model performance relevant to medical imaging and healthcare, we demonstrate that these gains do not come at the expense of model calibration or fairness. View details
    Concept-based model explanations for Electronic Health Records
    Eric Loreaux
    Shaobo Hou
    Sebastien Baur
    Martin G Seneviratne
    Anne Mottram
    Nenad Tomasev
    Association for Computing Machinery, New York, NY, USA(2021), 36–46
    Preview abstract Recurrent Neural Networks (RNNs) are often used for sequential modeling of adverse outcomes in electronic health records (EHRs) due to their ability to encode past clinical states. These deep, recurrent architectures have displayed increased performance compared to other modeling approaches in a number of tasks, fueling the interest in deploying deep models in clinical settings. One of the key elements in ensuring safe model deployment and building user trust is model explainability. Testing with Concept Activation Vectors (TCAV) has recently been introduced as a way of providing human-understandable explanations by comparing high-level concepts to the network's gradients. While the technique has shown promising results in real-world imaging applications, it has not been applied to structured temporal inputs. To enable an application of TCAV to sequential predictions in the EHR, we propose an extension of the method to time series data. We evaluate the proposed approach on an open EHR benchmark from the intensive care unit, as well as synthetic data where we are able to better isolate individual effects. View details
    Does Your Dermatology Classifier Know What It Doesn't Know? Detecting the Long-Tail of Unseen Conditions
    Aaron Loh
    Basil Mustafa
    Nick Pawlowski
    Jan Freyberg
    Yuan Liu
    Zach William Beaver
    Nam Vo
    Peggy Bui
    Samantha Winter
    Patricia MacWilliams
    Umesh Telang
    Taylan Cemgil
    Medical Imaging Analysis(2021)
    Preview abstract Supervised deep learning models have proven to be highly effective in classification of dermatological conditions. These models rely on the availability of abundant labeled training examples. However, in the real world, many dermatological conditions are individually too infrequent for per-condition classification with supervised learning. Although individually infrequent, these conditions may collectively be common and therefore are clinically significant in aggregate. To avoid models generating erroneous outputs on such examples, there remains a considerable unmet need for deep learning systems that can better detect such infrequent conditions. These infrequent `outlier' conditions are seen very rarely (or not at all) during training. In this paper, we frame this task as an out-of-distribution (OOD) detection problem. We set up a benchmark ensuring that outlier conditions are disjoint between model train, validation, and test sets. Unlike most traditional OOD benchmarks which detect dataset distribution shift, we aim at detecting semantic differences, often referred to as near-OOD detection which is a more difficult task. We propose a novel hierarchical outlier detection (HOD) approach, which 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 that the proposed HOD outperforms existing techniques for outlier exposure based OOD detection. We also use different state-of-the-art representation learning approaches (BiT-JFT, SimCLR, MICLe) to improve OOD performance and demonstrate the effectiveness of HOD loss for them. Further, we explore different ensembling strategies for OOD detection and propose a diverse ensemble selection process for the best result. We also performed a subgroup analysis over conditions of varying risk levels and different skin types to investigate how OOD performance changes over each subgroup and demonstrated the gains of our framework in comparison to baselines. Furthermore, we go beyond traditional performance metrics and introduce a cost metric to approximate downstream clinical impact. We used this cost metric to compare the proposed method against the baseline, thereby making a stronger case for its effectiveness in real-world deployment scenarios. View details
    Validation and Clinical Applicability of Whole-Volume Automated Segmentation of Optical Coherence Tomography in Retinal Disease Using Deep Learning
    Marc Wilson
    Reena Chopra
    Megan Zoë Wilson
    Charlotte Cooper
    Patricia MacWilliams
    Daniela Florea
    Cían Hughes
    Hagar Khalid
    Sandra Vermeirsch
    Luke Nicholson
    Pearse Keane
    Konstantinos Balaskas
    JAMA Ophthalmology(2021)
    Preview abstract Importance Quantitative volumetric measures of retinal disease in optical coherence tomography (OCT) scans are infeasible to perform owing to the time required for manual grading. Expert-level deep learning systems for automatic OCT segmentation have recently been developed. However, the potential clinical applicability of these systems is largely unknown. Objective To evaluate a deep learning model for whole-volume segmentation of 4 clinically important pathological features and assess clinical applicability. Design, Setting, Participants This diagnostic study used OCT data from 173 patients with a total of 15 558 B-scans, treated at Moorfields Eye Hospital. The data set included 2 common OCT devices and 2 macular conditions: wet age-related macular degeneration (107 scans) and diabetic macular edema (66 scans), covering the full range of severity, and from 3 points during treatment. Two expert graders performed pixel-level segmentations of intraretinal fluid, subretinal fluid, subretinal hyperreflective material, and pigment epithelial detachment, including all B-scans in each OCT volume, taking as long as 50 hours per scan. Quantitative evaluation of whole-volume model segmentations was performed. Qualitative evaluation of clinical applicability by 3 retinal experts was also conducted. Data were collected from June 1, 2012, to January 31, 2017, for set 1 and from January 1 to December 31, 2017, for set 2; graded between November 2018 and January 2020; and analyzed from February 2020 to November 2020. Main Outcomes and Measures Rating and stack ranking for clinical applicability by retinal specialists, model-grader agreement for voxelwise segmentations, and total volume evaluated using Dice similarity coefficients, Bland-Altman plots, and intraclass correlation coefficients. Results Among the 173 patients included in the analysis (92 [53%] women), qualitative assessment found that automated whole-volume segmentation ranked better than or comparable to at least 1 expert grader in 127 scans (73%; 95% CI, 66%-79%). A neutral or positive rating was given to 135 model segmentations (78%; 95% CI, 71%-84%) and 309 expert gradings (2 per scan) (89%; 95% CI, 86%-92%). The model was rated neutrally or positively in 86% to 92% of diabetic macular edema scans and 53% to 87% of age-related macular degeneration scans. Intraclass correlations ranged from 0.33 (95% CI, 0.08-0.96) to 0.96 (95% CI, 0.90-0.99). Dice similarity coefficients ranged from 0.43 (95% CI, 0.29-0.66) to 0.78 (95% CI, 0.57-0.85). Conclusions and Relevance This deep learning–based segmentation tool provided clinically useful measures of retinal disease that would otherwise be infeasible to obtain. Qualitative evaluation was additionally important to reveal clinical applicability for both care management and research. View details
    Preview abstract Interpretability techniques aim to provide the rationale behind a model's decision, typically by explaining either an individual prediction (local explanation, e.g. `why is this patient diagnosed with this condition') or a class of predictions (global explanation, e.g. `why is this set of patients diagnosed with this condition in general'). While there are many methods focused on either one, few frameworks can provide both local and global explanations in a consistent manner. In this work, we combine two powerful existing techniques, one local (Integrated Gradients, IG) and one global (Testing with Concept Activation Vectors), to provide local and global concept-based explanations. We first sanity check our idea using two synthetic datasets with a known ground truth, and further demonstrate with a benchmark natural image dataset. We test our method with various concepts, target classes, model architectures and IG parameters (e.g. baselines). We show that our method improves global explanations over vanilla TCAV when compared to ground truth, and provides useful local insights. Finally, a user study demonstrates the usefulness of the method compared to no or global explanations only. We hope our work provides a step towards building bridges between many existing local and global methods to get the best of both worlds. View details
    Clinically Applicable Segmentation of Head and Neck Anatomy for Radiotherapy: Deep Learning Algorithm Development and Validation Study
    Stanislav Nikolov
    Sam Blackwell
    Alexei Zverovitch
    Ruheena Mendes
    Michelle Livne
    Jeffrey De Fauw
    Yojan Patel
    Clemens Meyer
    Harry Askham
    Bernardino Romera Paredes
    Carlton Chu
    Dawn Carnell
    Cheng Boon
    Derek D'Souza
    Syed Moinuddin
    Yasmin Mcquinlan
    Sarah Ireland
    Kiarna Hampton
    Krystle Fuller
    Hugh Montgomery
    Geraint Rees
    Mustafa Suleyman
    Trevor John Back
    Cían Hughes
    Olaf Ronneberger
    JMIR(2021)
    Preview abstract Background: Over half a million individuals are diagnosed with head and neck cancer each year globally. Radiotherapy is an important curative treatment for this disease, but it requires manual time to delineate radiosensitive organs at risk. This planning process can delay treatment while also introducing interoperator variability, resulting in downstream radiation dose differences. Although auto-segmentation algorithms offer a potentially time-saving solution, the challenges in defining, quantifying, and achieving expert performance remain. Objective: Adopting a deep learning approach, we aim to demonstrate a 3D U-Net architecture that achieves expert-level performance in delineating 21 distinct head and neck organs at risk commonly segmented in clinical practice. Methods: The model was trained on a data set of 663 deidentified computed tomography scans acquired in routine clinical practice and with both segmentations taken from clinical practice and segmentations created by experienced radiographers as part of this research, all in accordance with consensus organ at risk definitions. Results: We demonstrated the model’s clinical applicability by assessing its performance on a test set of 21 computed tomography scans from clinical practice, each with 21 organs at risk segmented by 2 independent experts. We also introduced surface Dice similarity coefficient, a new metric for the comparison of organ delineation, to quantify the deviation between organ at risk surface contours rather than volumes, better reflecting the clinical task of correcting errors in automated organ segmentations. The model’s generalizability was then demonstrated on 2 distinct open-source data sets, reflecting different centers and countries to model training. Conclusions: Deep learning is an effective and clinically applicable technique for the segmentation of the head and neck anatomy for radiotherapy. With appropriate validation studies and regulatory approvals, this system could improve the efficiency, consistency, and safety of radiotherapy pathways. View details
    Big Self-Supervised Models Advance Medical Image Classification
    Basil Mustafa
    Fiona Ryan
    Zachary Beaver
    Jan Freyberg
    Jonathan Deaton
    Aaron Loh
    Simon Kornblith
    Ting Chen
    Mohammad Norouzi
    International Conference on Computer Vision(2021)
    Preview abstract 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. View details
    Multi-task prediction of organ dysfunction in the ICU using sequential sub-network routing
    Eric Loreaux
    Anne Mottram
    Hugh Montgomery
    Ali Connell
    Nenad Tomašev
    Martin Seneviratne
    Journal of the American Medical Informatics Association (JAMIA)(2021)
    Preview abstract Introduction: Multi-task learning (MTL) using electronic health records (EHRs) allows concurrent prediction of multiple endpoints. MTL has shown promise in improving model performance and training efficiency; however it often suffers from negative transfer - impaired learning if tasks are not appropriately selected. We introduce a sequential sub-network routing (SeqSNR) architecture which uses soft parameter sharing to find related tasks and encourage cross-learning between them. Materials and Methods: Using the Medical Information Mart for Intensive Care (MIMIC-III) dataset, we train deep neural network models to predict the onset of six endpoints including specific organ dysfunctions and general clinical outcomes: acute kidney injury, continuous renal replacement therapy, mechanical ventilation, vasoactive medications, mortality, and length of stay. We compare single task models (ST) with naive multi-task (shared bottom, SB) and SeqSNR in terms of discriminative performance and label efficiency. Results: SeqSNR showed a modest yet statistically significant performance boost across at least 4 out of 6 tasks compared to SB and ST. When the size of the training dataset was reduced for a given task, SeqSNR outperformed ST for all cases showing an average AU PRC boost of 2.1%, 2.9%, and 2.1% for tasks using 1%, 5%, and 10% of labels respectively. Discussion and Conclusion: Multi-task learning has variable performance compared to single-task learning, with the possibility for negative transfer. The SeqSNR architecture outperforms SB and ST in discriminative performance and shows superior performance in terms of label efficiency. SeqSNR should be considered for multi-task predictive modeling using EHR data. View details
    Use of deep learning to develop continuous-risk models for adverse event prediction from electronic health records
    Nenad Tomašev
    Sebastien Baur
    Anne Mottram
    Xavier Glorot
    Jack William Rae
    Michal Zielinski
    Harry Askham
    Andre Saraiva
    Valerio Magliulo
    Clemens Meyer
    Suman Venkatesh Ravuri
    Alistair Connell
    Cían Hughes
    Julien Cornebise
    Hugh Montgomery
    Geraint Rees
    Christopher Laing
    Clifton R. Baker
    Thomas Osborne
    Ruth Reeves
    Demis Hassabis
    Dominic King
    Mustafa Suleyman
    Trevor John Back
    Christopher Nielsen
    Martin Gamunu Seneviratne
    Shakir Mohamad
    Nature Protocols(2021)
    Preview abstract Early prediction of patient outcomes is important for targeting preventive care. This protocol describes a practical workflow for developing deep-learning risk models that can predict various clinical and operational outcomes from structured electronic health record (EHR) data. The protocol comprises five main stages: formal problem definition, data pre-processing, architecture selection, calibration and uncertainty, and generalizability evaluation. We have applied the workflow to four endpoints (acute kidney injury, mortality, length of stay and 30-day hospital readmission). The workflow can enable continuous (e.g., triggered every 6 h) and static (e.g., triggered at 24 h after admission) predictions. We also provide an open-source codebase that illustrates some key principles in EHR modeling. This protocol can be used by interdisciplinary teams with programming and clinical expertise to build deep-learning prediction models with alternate data sources and prediction tasks. View details
    Underspecification Presents Challenges for Credibility in Modern Machine Learning
    Alexander Nicholas D'Amour
    Dan Moldovan
    Babak Alipanahi
    Alex Beutel
    Christina Chen
    Jon Deaton
    Jacob Eisenstein
    Shaobo Hou
    Ghassen Jerfel
    Yian Ma
    Akinori Mitani
    Andrea Montanari
    Christopher Nielsen
    Thomas Osborne
    Rajiv Raman
    Kim Ramasamy
    Rory Abbott Sayres
    Martin Gamunu Seneviratne
    Shannon Sequeira
    Harini Suresh
    Victor Veitch
    Journal of Machine Learning Research(2020)
    Preview abstract 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. View details
    International evaluation of an AI system for breast cancer screening
    Scott Mayer McKinney
    Varun Yatindra Godbole
    Jonathan Godwin
    Natasha Antropova
    Hutan Ashrafian
    Trevor John Back
    Mary Chesus
    Ara Darzi
    Mozziyar Etemadi
    Florencia Garcia-Vicente
    Fiona J Gilbert
    Mark D Halling-Brown
    Demis Hassabis
    Sunny Jansen
    Dominic King
    David Melnick
    Hormuz Mostofi
    Lily Hao Yi Peng
    Joshua Reicher
    Bernardino Romera Paredes
    Richard Sidebottom
    Mustafa Suleyman
    Kenneth C. Young
    Jeffrey De Fauw
    Shravya Ramesh Shetty
    Nature(2020)
    Preview abstract Screening mammography aims to identify breast cancer at earlier stages of the disease, when treatment can be more successful. Despite the existence of screening programmes worldwide, the interpretation of mammograms is affected by high rates of false positives and false negatives. Here we present an artificial intelligence (AI) system that is capable of surpassing human experts in breast cancer prediction. To assess its performance in the clinical setting, we curated a large representative dataset from the UK and a large enriched dataset from the USA. We show an absolute reduction of 5.7% and 1.2% (USA and UK) in false positives and 9.4% and 2.7% in false negatives. We provide evidence of the ability of the system to generalize from the UK to the USA. In an independent study of six radiologists, the AI system outperformed all of the human readers: the area under the receiver operating characteristic curve (AUC-ROC) for the AI system was greater than the AUC-ROC for the average radiologist by an absolute margin of 11.5%. We ran a simulation in which the AI system participated in the double-reading process that is used in the UK, and found that the AI system maintained non-inferior performance and reduced the workload of the second reader by 88%. This robust assessment of the AI system paves the way for clinical trials to improve the accuracy and efficiency of breast cancer screening. View details
    Predicting conversion to wet age-related macular degeneration using deep learning
    Jason Yim
    Reena Chopra
    Terry Spitz
    Annette Obika
    Harry Askham
    Marko Lukic
    Josef Huemer
    Katrin Fasler
    Gabriella Moraes
    Clemens Meyer
    Marc Wilson
    Jonathan Mark Dixon
    Cían Hughes
    Geraint Rees
    Peng Khaw
    Dominic King
    Demis Hassabis
    Mustafa Suleyman
    Trevor John Back
    Pearse Keane
    Jeffrey De Fauw
    Nature Medicine(2020)
    Preview abstract Progression to exudative ‘wet’ age-related macular degeneration (exAMD) is a major cause of visual deterioration. In patients diagnosed with exAMD in one eye, we introduce an artificial intelligence (AI) system to predict progression to exAMD in the second eye. By combining models based on three-dimensional (3D) optical coherence tomography images and corresponding automatic tissue maps, our system predicts conversion to exAMD within a clinically actionable 6-month time window, achieving a per-volumetric-scan sensitivity of 80% at 55% specificity, and 34% sensitivity at 90% specificity. This level of performance corresponds to true positives in 78% and 41% of individual eyes, and false positives in 56% and 17% of individual eyes at the high sensitivity and high specificity points, respectively. Moreover, we show that automatic tissue segmentation can identify anatomical changes before conversion and high-risk subgroups. This AI system overcomes substantial interobserver variability in expert predictions, performing better than five out of six experts, and demonstrates the potential of using AI to predict disease progression. View details
    A clinically applicable approach to continuous prediction of future acute kidney injury
    Nenad Tomašev
    Xavier Glorot
    Jack W Rae
    Michal Zielinski
    Harry Askham
    Andre Saraiva
    Anne Mottram
    Clemens Meyer
    Suman Ravuri
    Alistair Connell
    Cían O Hughes
    Julien Cornebise
    Hugh Montgomery
    Geraint Rees
    Chris Laing
    Clifton R Baker
    Kelly Peterson
    Ruth Reeves
    Demis Hassabis
    Dominic King
    Mustafa Suleyman
    Trevor Back
    Christopher Nielson
    Shakir Mohamed
    Nature, 572(2019), pp. 116-119
    Preview abstract The early prediction of deterioration could have an important role in supporting healthcare professionals, as an estimated 11% of deaths in hospital follow a failure to promptly recognize and treat deteriorating patients. To achieve this goal requires predictions of patient risk that are continuously updated and accurate, and delivered at an individual level with sufficient context and enough time to act. Here we develop a deep learning approach for the continuous risk prediction of future deterioration in patients, building on recent work that models adverse events from electronic health records and using acute kidney injury—a common and potentially life-threatening condition—as an exemplar. Our model was developed on a large, longitudinal dataset of electronic health records that cover diverse clinical environments, comprising 703,782 adult patients across 172 inpatient and 1,062 outpatient sites. Our model predicts 55.8% of all inpatient episodes of acute kidney injury, and 90.2% of all acute kidney injuries that required subsequent administration of dialysis, with a lead time of up to 48 h and a ratio of 2 false alerts for every true alert. In addition to predicting future acute kidney injury, our model provides confidence assessments and a list of the clinical features that are most salient to each prediction, alongside predicted future trajectories for clinically relevant blood tests. Although the recognition and prompt treatment of acute kidney injury is known to be challenging, our approach may offer opportunities for identifying patients at risk within a time window that enables early treatment. View details
    Preview abstract Background Artificial intelligence (AI) research in healthcare is accelerating rapidly with potential applications being demonstrated across many different domains of medicine. However, there are currently limited examples of such techniques being successfully deployed into clinical practice. This article explores the main challenges and limitations of AI in healthcare, and considers steps required to translate these potentially transformative technologies from research to clinical practice. Main body Key challenges for the translation of AI systems in healthcare include those intrinsic to the science of machine learning, logistical difficulties in implementation, and consideration of barriers to adoption or necessary sociocultural or pathway change. Robust peer-reviewed clinical evaluation as part of randomised controlled trials should be viewed as the gold standard for evidence generation, but conducting these in practice may not always be appropriate or feasible. Performance metrics should aim to capture real clinical applicability, and be understandable to intended users. Regulation that balances pace of innovation with potential for harm, alongside thoughtful postmarket surveillance, is required to ensure that patients are not exposed to dangerous interventions, nor deprived of access to beneficial innovations. Mechanisms to enable direct comparisons of AI systems must be developed, including the use of independent, local and representative test sets. Developers of AI algorithms must be vigilant to potential dangers including dataset shift, accidental fitting of confounders, unintended discriminatory bias, the challenges of generalisation to new populations, and unintended negative consequences of new algorithms on health outcomes. Conclusions The safe and timely translation of AI research into clinically validated tools that can benefit everyone is challenging. Further work is required to continue developing robust clinical evaluation and regulatory frameworks using metrics that are intuitive to clinicians, identifying themes of algorithmic bias and unfairness while developing mitigations to address this, reducing brittleness and improving generalisability, and developing methods for improved interpretability of machine learning models. If these goals can be achieved, the benefits for patients are likely to be transformational. View details
    Clinically applicable deep learning for diagnosis and referral in retinal optical coherence tomography
    Jeffrey De Fauw
    Bernardino Romera Paredes
    Stanislav Nikolov Nikolov
    Nenad Tomašev
    Sam Julian Blackwell
    Harry Askham
    Xavier Glorot
    Brendan O'Donoghue
    Daniel James Visentin
    George van den Driessche
    Clemens Meyer
    Faith Mackinder
    Simon Bouton
    Kareem Ayoub
    Reena Chopra
    Dominic King
    Cían Hughes
    Rosalind Raine
    Julian Hughes
    Dawn Sim
    Catherine Egan
    Adnan Tufail
    Hugh Montgomery
    Demis Hassabis
    Geraint Rees
    Trevor John Back
    Peng Khaw
    Mustafa Suleyman
    Julien Cornebise
    Pearse Keane
    Olaf Ronneberger
    Nature(2018)
    Preview abstract The volume and complexity of diagnostic imaging is increasing at a pace faster than the availability of human expertise to interpret it. Artificial intelligence has shown great promise in classifying two-dimensional photographs of some common diseases and typically relies on databases of millions of annotated images. Until now, the challenge of reaching the performance of expert clinicians in a real-world clinical pathway with three-dimensional diagnostic scans has remained unsolved. Here, we apply a novel deep learning architecture to a clinically heterogeneous set of three-dimensional optical coherence tomography scans from patients referred to a major eye hospital. We demonstrate performance in making a referral recommendation that reaches or exceeds that of experts on a range of sight-threatening retinal diseases after training on only 14,884 scans. Moreover, we demonstrate that the tissue segmentations produced by our architecture act as a device-independent representation; referral accuracy is maintained when using tissue segmentations from a different type of device. Our work removes previous barriers to wider clinical use without prohibitive training data requirements across multiple pathologies in a real-world setting. View details
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