Cliff Wong

Yiqing Xie, Sheng Zhang, Hao Cheng et al. · microsoft-research

Medical text generation aims to assist with administrative work and highlight salient information to support decision-making. To reflect the specific requirements of medical text, in this paper, we propose a set of metrics to evaluate the completeness, conciseness, and attribution of the generated text at a fine-grained level. The metrics can be computed by various types of evaluators including instruction-following (both proprietary and open-source) and supervised entailment models. We demonstrate the effectiveness of the resulting framework, DocLens, with three evaluators on three tasks: clinical note generation, radiology report summarization, and patient question summarization. A comprehensive human study shows that DocLens exhibits substantially higher agreement with the judgments of medical experts than existing metrics. The results also highlight the need to improve open-source evaluators and suggest potential directions.

Chunyuan Li, Cliff Wong, Sheng Zhang et al. · cambridge, microsoft-research

Conversational generative AI has demonstrated remarkable promise for empowering biomedical practitioners, but current investigations focus on unimodal text. Multimodal conversational AI has seen rapid progress by leveraging billions of image-text pairs from the public web, but such general-domain vision-language models still lack sophistication in understanding and conversing about biomedical images. In this paper, we propose a cost-efficient approach for training a vision-language conversational assistant that can answer open-ended research questions of biomedical images. The key idea is to leverage a large-scale, broad-coverage biomedical figure-caption dataset extracted from PubMed Central, use GPT-4 to self-instruct open-ended instruction-following data from the captions, and then fine-tune a large general-domain vision-language model using a novel curriculum learning method. Specifically, the model first learns to align biomedical vocabulary using the figure-caption pairs as is, then learns to master open-ended conversational semantics using GPT-4 generated instruction-following data, broadly mimicking how a layperson gradually acquires biomedical knowledge. This enables us to train a Large Language and Vision Assistant for BioMedicine (LLaVA-Med) in less than 15 hours (with eight A100s). LLaVA-Med exhibits excellent multimodal conversational capability and can follow open-ended instruction to assist with inquiries about a biomedical image. On three standard biomedical visual question answering datasets, LLaVA-Med outperforms previous supervised state-of-the-art on certain metrics. To facilitate biomedical multimodal research, we will release our instruction-following data and the LLaVA-Med model.

Sheng Zhang, Yanbo Xu, Naoto Usuyama et al. · cambridge, microsoft-research

Biomedical data is inherently multimodal, comprising physical measurements and natural language narratives. A generalist biomedical AI model needs to simultaneously process different modalities of data, including text and images. Therefore, training an effective generalist biomedical model requires high-quality multimodal data, such as parallel image-text pairs. Here, we present PMC-15M, a novel dataset that is two orders of magnitude larger than existing biomedical multimodal datasets such as MIMIC-CXR, and spans a diverse range of biomedical image types. PMC-15M contains 15 million biomedical image-text pairs collected from 4.4 million scientific articles. Based on PMC-15M, we have pretrained BiomedCLIP, a multimodal foundation model, with domain-specific adaptations tailored to biomedical vision-language processing. We conducted extensive experiments and ablation studies on standard biomedical imaging tasks from retrieval to classification to visual question-answering (VQA). BiomedCLIP achieved new state-of-the-art results in a wide range of standard datasets, substantially outperforming prior approaches. Intriguingly, by large-scale pretraining on diverse biomedical image types, BiomedCLIP even outperforms state-of-the-art radiology-specific models such as BioViL in radiology-specific tasks such as RSNA pneumonia detection. In summary, BiomedCLIP is a fully open-access foundation model that achieves state-of-the-art performance on various biomedical tasks, paving the way for transformative multimodal biomedical discovery and applications. We release our models at https://aka.ms/biomedclip to facilitate future research in multimodal biomedical AI.

Cliff Wong, Sheng Zhang, Yu Gu et al. · cambridge, microsoft-research

Clinical trial matching is a key process in health delivery and discovery. In practice, it is plagued by overwhelming unstructured data and unscalable manual processing. In this paper, we conduct a systematic study on scaling clinical trial matching using large language models (LLMs), with oncology as the focus area. Our study is grounded in a clinical trial matching system currently in test deployment at a large U.S. health network. Initial findings are promising: out of box, cutting-edge LLMs, such as GPT-4, can already structure elaborate eligibility criteria of clinical trials and extract complex matching logic (e.g., nested AND/OR/NOT). While still far from perfect, LLMs substantially outperform prior strong baselines and may serve as a preliminary solution to help triage patient-trial candidates with humans in the loop. Our study also reveals a few significant growth areas for applying LLMs to end-to-end clinical trial matching, such as context limitation and accuracy, especially in structuring patient information from longitudinal medical records.

Yu Gu, Sheng Zhang, Naoto Usuyama et al. · cambridge, microsoft-research

Large language models (LLMs), such as GPT-4, have demonstrated remarkable capabilities across a wide range of tasks, including health applications. In this paper, we study how LLMs can be used to scale biomedical knowledge curation. We find that while LLMs already possess decent competency in structuring biomedical text, by distillation into a task-specific student model through self-supervised learning, substantial gains can be attained over out-of-box LLMs, with additional advantages such as cost, efficiency, and white-box model access. We conduct a case study on adverse drug event (ADE) extraction, which is an important area for improving care. On standard ADE extraction evaluation, a GPT-3.5 distilled PubMedBERT model attained comparable accuracy as supervised state-of-the-art models without using any labeled data. Despite being over 1,000 times smaller, the distilled model outperformed its teacher GPT-3.5 by over 6 absolute points in F1 and GPT-4 by over 5 absolute points. Ablation studies on distillation model choice (e.g., PubMedBERT vs BioGPT) and ADE extraction architecture shed light on best practice for biomedical knowledge extraction. Similar gains were attained by distillation for other standard biomedical knowledge extraction tasks such as gene-disease associations and protected health information, further illustrating the promise of this approach.

Javier González, Risa Ueno, Cliff Wong et al.

The rapid digitization of real-world data presents an unprecedented opportunity to optimize healthcare delivery and accelerate biomedical discovery. However, these data are often found in unstructured forms such as clinical notes in electronic medical records (EMRs), and is typically plagued by confounders, making it challenging to generate robust real-world evidence (RWE). Therefore, we present TRIALSCOPE, a framework designed to distil RWE from population level observational data at scale. TRIALSCOPE leverages biomedical language models to structure clinical text at scale, employs advanced probabilistic modeling for denoising and imputation, and incorporates state-of-the-art causal inference techniques to address common confounders in treatment effect estimation. Extensive experiments were conducted on a large-scale dataset of over one million cancer patients from a single large healthcare network in the United States. TRIALSCOPE was shown to automatically curate high-quality structured patient data, expanding the dataset and incorporating key patient attributes only available in unstructured form. The framework reduces confounding in treatment effect estimation, generating comparable results to randomized controlled lung cancer trials. Additionally, we demonstrate simulations of unconducted clinical trials - including a pancreatic cancer trial with varying eligibility criteria - using a suite of validation tests to ensure robustness. Thorough ablation studies were conducted to better understand key components of TRIALSCOPE and establish best practices for RWE generation from EMRs. TRIALSCOPE was able to extract data cancer treatment data from EMRs, overcoming limitations of manual curation. We were also able to show that TRIALSCOPE could reproduce results of lung and pancreatic cancer clinical trials from the extracted real world data.

Juan Manuel Zambrano Chaves, Shih-Cheng Huang, Yanbo Xu et al. · microsoft-research

The scaling laws and extraordinary performance of large foundation models motivate the development and utilization of such models in biomedicine. However, despite early promising results on some biomedical benchmarks, there are still major challenges that need to be addressed before these models can be used in real-world clinics. Frontier general-domain models such as GPT-4V still have significant performance gaps in multimodal biomedical applications. More importantly, less-acknowledged pragmatic issues, including accessibility, model cost, and tedious manual evaluation make it hard for clinicians to use state-of-the-art large models directly on private patient data. Here, we explore training open-source small multimodal models (SMMs) to bridge competency gaps for unmet clinical needs in radiology. To maximize data efficiency, we adopt a modular approach by incorporating state-of-the-art pre-trained models for image and text modalities, and focusing on training a lightweight adapter to ground each modality to the text embedding space, as exemplified by LLaVA-Med. For training, we assemble a large dataset of over 697 thousand radiology image-text pairs. For evaluation, we propose CheXprompt, a GPT-4-based metric for factuality evaluation, and demonstrate its parity with expert evaluation. For best practice, we conduct a systematic ablation study on various choices in data engineering and multimodal training. The resulting LlaVA-Rad (7B) model attains state-of-the-art results on standard radiology tasks such as report generation and cross-modal retrieval, even outperforming much larger models such as GPT-4V and Med-PaLM M (84B). The inference of LlaVA-Rad is fast and can be performed on a single V100 GPU in private settings, offering a promising state-of-the-art tool for real-world clinical applications.

Ho Hin Lee, Yu Gu, Theodore Zhao et al.

Recent advancements in biomedical image analysis have been significantly driven by the Segment Anything Model (SAM). This transformative technology, originally developed for general-purpose computer vision, has found rapid application in medical image processing. Within the last year, marked by over 100 publications, SAM has demonstrated its prowess in zero-shot learning adaptations for medical imaging. The fundamental premise of SAM lies in its capability to segment or identify objects in images without prior knowledge of the object type or imaging modality. This approach aligns well with tasks achievable by the human visual system, though its application in non-biological vision contexts remains more theoretically challenging. A notable feature of SAM is its ability to adjust segmentation according to a specified resolution scale or area of interest, akin to semantic priming. This adaptability has spurred a wave of creativity and innovation in applying SAM to medical imaging. Our review focuses on the period from April 1, 2023, to September 30, 2023, a critical first six months post-initial publication. We examine the adaptations and integrations of SAM necessary to address longstanding clinical challenges, particularly in the context of 33 open datasets covered in our analysis. While SAM approaches or achieves state-of-the-art performance in numerous applications, it falls short in certain areas, such as segmentation of the carotid artery, adrenal glands, optic nerve, and mandible bone. Our survey delves into the innovative techniques where SAM's foundational approach excels and explores the core concepts in translating and applying these models effectively in diverse medical imaging scenarios.

Shane Waxler, Paul Blazek, Davis White et al.

Realizing personalized medicine at scale calls for methods that distill insights from longitudinal patient journeys, which can be viewed as a sequence of medical events. Foundation models pretrained on large-scale medical event data represent a promising direction for scaling real-world evidence generation and generalizing to diverse downstream tasks. Using Epic Cosmos, a dataset with medical events from de-identified longitudinal health records for 16.3 billion encounters over 300 million unique patient records from 310 health systems, we introduce the Curiosity models, a family of decoder-only transformer models pretrained on 118 million patients representing 115 billion discrete medical events (151 billion tokens). We present the largest scaling-law study of medical event data, establishing a methodology for pretraining and revealing power-law scaling relationships for compute, tokens, and model size. Consequently, we pretrained a series of compute-optimal models with up to 1 billion parameters. Conditioned on a patient's real-world history, Curiosity autoregressively predicts the next medical event to simulate patient health timelines. We studied 78 real-world tasks, including diagnosis prediction, disease prognosis, and healthcare operations. Remarkably for a foundation model with generic pretraining and simulation-based inference, Curiosity generally outperformed or matched task-specific supervised models on these tasks, without requiring task-specific fine-tuning or few-shot examples. Curiosity's predictive power consistently improves as the model and pretraining scale. Our results show that Curiosity, a generative medical event foundation model, can effectively capture complex clinical dynamics, providing an extensible and generalizable framework to support clinical decision-making, streamline healthcare operations, and improve patient outcomes.

Cliff Wong, Sam Preston, Qianchu Liu et al. · microsoft-research

A significant fraction of real-world patient information resides in unstructured clinical text. Medical abstraction extracts and normalizes key structured attributes from free-text clinical notes, which is the prerequisite for a variety of important downstream applications, including registry curation, clinical trial operations, and real-world evidence generation. Prior medical abstraction methods typically resort to building attribute-specific models, each of which requires extensive manual effort such as rule creation or supervised label annotation for the individual attribute, thus limiting scalability. In this paper, we show that existing frontier models already possess the universal abstraction capability for scaling medical abstraction to a wide range of clinical attributes. We present UniMedAbstractor (UMA), a unifying framework for zero-shot medical abstraction with a modular, customizable prompt template and the selection of any frontier large language models. Given a new attribute for abstraction, users only need to conduct lightweight prompt adaptation in UMA to adjust the specification in natural languages. Compared to traditional methods, UMA eliminates the need for attribute-specific training labels or handcrafted rules, thus substantially reducing the development time and cost. We conducted a comprehensive evaluation of UMA in oncology using a wide range of marquee attributes representing the cancer patient journey. These include relatively simple attributes typically specified within a single clinical note (e.g. performance status), as well as complex attributes requiring sophisticated reasoning across multiple notes at various time points (e.g. tumor staging). Based on a single frontier model such as GPT-4o, UMA matched or even exceeded the performance of state-of-the-art attribute-specific methods, each of which was tailored to the individual attribute.

Yu Gu, Jingjing Fu, Xiaodong Liu et al.

Large frontier models like GPT-5 now achieve top scores on medical benchmarks. But our stress tests tell a different story. Leading systems often guess correctly even when key inputs like images are removed, flip answers under trivial prompt changes, and fabricate convincing yet flawed reasoning. These aren't glitches; they expose how today's benchmarks reward test-taking tricks over medical understanding. We evaluate six flagship models across six widely used benchmarks and find that high leaderboard scores hide brittleness and shortcut learning. Through clinician-guided rubric evaluation, we show that benchmarks vary widely in what they truly measure yet are treated interchangeably, masking failure modes. We caution that medical benchmark scores do not directly reflect real-world readiness. If we want AI to earn trust in healthcare, we must demand more than leaderboard wins and must hold systems accountable for robustness, sound reasoning, and alignment with real medical demands.

Alyssa Unell, Noel C. F. Codella, Sam Preston et al.

The National Comprehensive Cancer Network (NCCN) provides evidence-based guidelines for cancer treatment. Translating complex patient presentations into guideline-compliant treatment recommendations is time-intensive, requires specialized expertise, and is prone to error. Advances in large language model (LLM) capabilities promise to reduce the time required to generate treatment recommendations and improve accuracy. We present an LLM agent-based approach to automatically generate guideline-concordant treatment trajectories for patients with non-small cell lung cancer (NSCLC). Our contributions are threefold. First, we construct a novel longitudinal dataset of 121 cases of NSCLC patients that includes clinical encounters, diagnostic results, and medical histories, each expertly annotated with the corresponding NCCN guideline trajectories by board-certified oncologists. Second, we demonstrate that existing LLMs possess domain-specific knowledge that enables high-quality proxy benchmark generation for both model development and evaluation, achieving strong correlation (Spearman coefficient r=0.88, RMSE = 0.08) with expert-annotated benchmarks. Third, we develop a hybrid approach combining expensive human annotations with model consistency information to create both the agent framework that predicts the relevant guidelines for a patient, as well as a meta-classifier that verifies prediction accuracy with calibrated confidence scores for treatment recommendations (AUROC=0.800), a critical capability for communicating the accuracy of outputs, custom-tailoring tradeoffs in performance, and supporting regulatory compliance. This work establishes a framework for clinically viable LLM-based guideline adherence systems that balance accuracy, interpretability, and regulatory requirements while reducing annotation costs, providing a scalable pathway toward automated clinical decision support.

Sheng Zhang, Qin Liu, Naoto Usuyama et al. · microsoft-research

The emergence of scaling laws has profoundly shaped the development of large language models (LLMs), enabling predictable performance gains through systematic increases in model size, dataset volume, and compute. Yet, these principles remain largely unexplored in the context of electronic health records (EHRs) -- a rich, sequential, and globally abundant data source that differs structurally from natural language. In this work, we present the first empirical investigation of scaling laws for EHR foundation models. By training transformer architectures on patient timeline data from the MIMIC-IV database across varying model sizes and compute budgets, we identify consistent scaling patterns, including parabolic IsoFLOPs curves and power-law relationships between compute, model parameters, data size, and clinical utility. These findings demonstrate that EHR models exhibit scaling behavior analogous to LLMs, offering predictive insights into resource-efficient training strategies. Our results lay the groundwork for developing powerful EHR foundation models capable of transforming clinical prediction tasks and advancing personalized healthcare.

Sheng Zhang, Hao Cheng, Shikhar Vashishth et al.

Entity linking faces significant challenges such as prolific variations and prevalent ambiguities, especially in high-value domains with myriad entities. Standard classification approaches suffer from the annotation bottleneck and cannot effectively handle unseen entities. Zero-shot entity linking has emerged as a promising direction for generalizing to new entities, but it still requires example gold entity mentions during training and canonical descriptions for all entities, both of which are rarely available outside of Wikipedia. In this paper, we explore Knowledge-RIch Self-Supervision ($\tt KRISS$) for biomedical entity linking, by leveraging readily available domain knowledge. In training, it generates self-supervised mention examples on unlabeled text using a domain ontology and trains a contextual encoder using contrastive learning. For inference, it samples self-supervised mentions as prototypes for each entity and conducts linking by mapping the test mention to the most similar prototype. Our approach can easily incorporate entity descriptions and gold mention labels if available. We conducted extensive experiments on seven standard datasets spanning biomedical literature and clinical notes. Without using any labeled information, our method produces $\tt KRISSBERT$, a universal entity linker for four million UMLS entities that attains new state of the art, outperforming prior self-supervised methods by as much as 20 absolute points in accuracy.

Sheng Zhang, Cliff Wong, Naoto Usuyama et al.

Extracting relations across large text spans has been relatively underexplored in NLP, but it is particularly important for high-value domains such as biomedicine, where obtaining high recall of the latest findings is crucial for practical applications. Compared to conventional information extraction confined to short text spans, document-level relation extraction faces additional challenges in both inference and learning. Given longer text spans, state-of-the-art neural architectures are less effective and task-specific self-supervision such as distant supervision becomes very noisy. In this paper, we propose decomposing document-level relation extraction into relation detection and argument resolution, taking inspiration from Davidsonian semantics. This enables us to incorporate explicit discourse modeling and leverage modular self-supervision for each sub-problem, which is less noise-prone and can be further refined end-to-end via variational EM. We conduct a thorough evaluation in biomedical machine reading for precision oncology, where cross-paragraph relation mentions are prevalent. Our method outperforms prior state of the art, such as multi-scale learning and graph neural networks, by over 20 absolute F1 points. The gain is particularly pronounced among the most challenging relation instances whose arguments never co-occur in a paragraph.

Yu Wang, Jinchao Li, Tristan Naumann et al.

Information overload is a prevalent challenge in many high-value domains. A prominent case in point is the explosion of the biomedical literature on COVID-19, which swelled to hundreds of thousands of papers in a matter of months. In general, biomedical literature expands by two papers every minute, totalling over a million new papers every year. Search in the biomedical realm, and many other vertical domains is challenging due to the scarcity of direct supervision from click logs. Self-supervised learning has emerged as a promising direction to overcome the annotation bottleneck. We propose a general approach for vertical search based on domain-specific pretraining and present a case study for the biomedical domain. Despite being substantially simpler and not using any relevance labels for training or development, our method performs comparably or better than the best systems in the official TREC-COVID evaluation, a COVID-related biomedical search competition. Using distributed computing in modern cloud infrastructure, our system can scale to tens of millions of articles on PubMed and has been deployed as Microsoft Biomedical Search, a new search experience for biomedical literature: https://aka.ms/biomedsearch.

Robin Jia, Cliff Wong, Hoifung Poon

Most information extraction methods focus on binary relations expressed within single sentences. In high-value domains, however, $n$-ary relations are of great demand (e.g., drug-gene-mutation interactions in precision oncology). Such relations often involve entity mentions that are far apart in the document, yet existing work on cross-sentence relation extraction is generally confined to small text spans (e.g., three consecutive sentences), which severely limits recall. In this paper, we propose a novel multiscale neural architecture for document-level $n$-ary relation extraction. Our system combines representations learned over various text spans throughout the document and across the subrelation hierarchy. Widening the system's purview to the entire document maximizes potential recall. Moreover, by integrating weak signals across the document, multiscale modeling increases precision, even in the presence of noisy labels from distant supervision. Experiments on biomedical machine reading show that our approach substantially outperforms previous $n$-ary relation extraction methods.