Chufan Gao

Chufan Gao, Mononito Goswami, Jieshi Chen et al. · cmu

Healthcare providers usually record detailed notes of the clinical care delivered to each patient for clinical, research, and billing purposes. Due to the unstructured nature of these narratives, providers employ dedicated staff to assign diagnostic codes to patients' diagnoses using the International Classification of Diseases (ICD) coding system. This manual process is not only time-consuming but also costly and error-prone. Prior work demonstrated potential utility of Machine Learning (ML) methodology in automating this process, but it has relied on large quantities of manually labeled data to train the models. Additionally, diagnostic coding systems evolve with time, which makes traditional supervised learning strategies unable to generalize beyond local applications. In this work, we introduce a general weakly-supervised text classification framework that learns from class-label descriptions only, without the need to use any human-labeled documents. It leverages the linguistic domain knowledge stored within pre-trained language models and the data programming framework to assign code labels to individual texts. We demonstrate the efficacy and flexibility of our method by comparing it to state-of-the-art weak text classifiers across four real-world text classification datasets, in addition to assigning ICD codes to medical notes in the publicly available MIMIC-III database.

Andrew Sellergren, Chufan Gao, Fereshteh Mahvar et al.

We introduce MedGemma 1.5 4B, the latest model in the MedGemma collection. MedGemma 1.5 expands on MedGemma 1 by integrating additional capabilities: high-dimensional medical imaging (CT/MRI volumes and histopathology whole slide images), anatomical localization via bounding boxes, multi-timepoint chest X-ray analysis, and improved medical document understanding (lab reports, electronic health records). We detail the innovations required to enable these modalities within a single architecture, including new training data, long-context 3D volume slicing, and whole-slide pathology sampling. Compared to MedGemma 1 4B, MedGemma 1.5 4B demonstrates significant gains in these new areas, improving 3D MRI condition classification accuracy by 11% and 3D CT condition classification by 3% (absolute improvements). In whole slide pathology imaging, MedGemma 1.5 4B achieves a 47% macro F1 gain. Additionally, it improves anatomical localization with a 35% increase in Intersection over Union on chest X-rays and achieves a 4% macro accuracy for longitudinal (multi-timepoint) chest x-ray analysis. Beyond its improved multimodal performance over MedGemma 1, MedGemma 1.5 improves on text-based clinical knowledge and reasoning, improving by 5% on MedQA accuracy and 22% on EHRQA accuracy. It also achieves an average of 18% macro F1 on 4 different lab report information extraction datasets (EHR Datasets 2, 3, 4, and Mendeley Clinical Laboratory Test Reports). Taken together, MedGemma 1.5 serves as a robust, open resource for the community, designed as an improved foundation on which developers can create the next generation of medical AI systems. Resources and tutorials for building upon MedGemma 1.5 can be found at https://goo.gle/MedGemma.

Zifeng Wang, Chufan Gao, Lucas M. Glass et al.

A clinical trial is an essential step in drug development, which is often costly and time-consuming. In silico trials are clinical trials conducted digitally through simulation and modeling as an alternative to traditional clinical trials. AI-enabled in silico trials can increase the case group size by creating virtual cohorts as controls. In addition, it also enables automation and optimization of trial design and predicts the trial success rate. This article systematically reviews papers under three main topics: clinical simulation, individualized predictive modeling, and computer-aided trial design. We focus on how machine learning (ML) may be applied in these applications. In particular, we present the machine learning problem formulation and available data sources for each task. We end with discussing the challenges and opportunities of AI for in silico trials in real-world applications.

Hanyin Wang, Chufan Gao, Christopher Dantona et al.

In the U.S. inpatient payment system, the Diagnosis-Related Group (DRG) is pivotal, but its assignment process is inefficient. The study introduces DRG-LLaMA, an advanced large language model (LLM) fine-tuned on clinical notes to enhance DRGs assignment. Utilizing LLaMA as the foundational model and optimizing it through Low-Rank Adaptation (LoRA) on 236,192 MIMIC-IV discharge summaries, our DRG-LLaMA-7B model exhibited a noteworthy macro-averaged F1 score of 0.327, a top-1 prediction accuracy of 52.0%, and a macro-averaged Area Under the Curve (AUC) of 0.986, with a maximum input token length of 512. This model surpassed the performance of prior leading models in DRG prediction, showing a relative improvement of 40.3% and 35.7% in macro-averaged F1 score compared to ClinicalBERT and CAML, respectively. Applied to base DRG and complication or comorbidity (CC)/major complication or comorbidity (MCC) prediction, DRG-LLaMA achieved a top-1 prediction accuracy of 67.8% and 67.5%, respectively. Additionally, our findings indicate that DRG-LLaMA's performance correlates with increased model parameters and input context lengths.

Chufan Gao, Xulin Fan, Jimeng Sun et al.

Relation extraction aims to classify the relationships between two entities into pre-defined categories. While previous research has mainly focused on sentence-level relation extraction, recent studies have expanded the scope to document-level relation extraction. Traditional relation extraction methods heavily rely on human-annotated training data, which is time-consuming and labor-intensive. To mitigate the need for manual annotation, recent weakly-supervised approaches have been developed for sentence-level relation extraction while limited work has been done on document-level relation extraction. Weakly-supervised document-level relation extraction faces significant challenges due to an imbalanced number "no relation" instances and the failure of directly probing pretrained large language models for document relation extraction. To address these challenges, we propose PromptRE, a novel weakly-supervised document-level relation extraction method that combines prompting-based techniques with data programming. Furthermore, PromptRE incorporates the label distribution and entity types as prior knowledge to improve the performance. By leveraging the strengths of both prompting and data programming, PromptRE achieves improved performance in relation classification and effectively handles the "no relation" problem. Experimental results on ReDocRED, a benchmark dataset for document-level relation extraction, demonstrate the superiority of PromptRE over baseline approaches.

Chufan Gao, Mandis Beigi, Afrah Shafquat et al.

Analyzing data from past clinical trials is part of the ongoing effort to optimize the design, implementation, and execution of new clinical trials and more efficiently bring life-saving interventions to market. While there have been recent advances in the generation of static context synthetic clinical trial data, due to both limited patient availability and constraints imposed by patient privacy needs, the generation of fine-grained synthetic time-sequential clinical trial data has been challenging. Given that patient trajectories over an entire clinical trial are of high importance for optimizing trial design and efforts to prevent harmful adverse events, there is a significant need for the generation of high-fidelity time-sequence clinical trial data. Here we introduce TrialSynth, a Variational Autoencoder (VAE) designed to address the specific challenges of generating synthetic time-sequence clinical trial data. Distinct from related clinical data VAE methods, the core of our method leverages Hawkes Processes (HP), which are particularly well-suited for modeling event-type and time gap prediction needed to capture the structure of sequential clinical trial data. Our experiments demonstrate that TrialSynth surpasses the performance of other comparable methods that can generate sequential clinical trial data at varying levels of fidelity / privacy tradeoff, enabling the generation of highly accurate event sequences across multiple real-world sequential event datasets with small patient source populations. Notably, our empirical findings highlight that TrialSynth not only outperforms existing clinical sequence-generating methods but also produces data with superior utility while empirically preserving patient privacy.

Hanyin Wang, Chufan Gao, Bolun Liu et al.

Proprietary Large Language Models (LLMs) such as GPT-4 and Gemini have demonstrated promising capabilities in clinical text summarization tasks. However, due to patient data privacy concerns and computational costs, many healthcare providers prefer using small, locally-hosted models over external generic LLMs. This study presents a comprehensive domain- and task-specific adaptation process for the open-source LLaMA-2 13 billion parameter model, enabling it to generate high-quality clinical notes from outpatient patient-doctor dialogues. Our process incorporates continued pretraining, supervised fine-tuning, and reinforcement learning from both AI and human feedback. We introduced a new approach, DistillDirect, for performing on-policy reinforcement learning with Gemini 1.0 Pro as the teacher model. Our resulting model, LLaMA-Clinic, can generate clinical notes comparable in quality to those authored by physicians. In a blinded physician reader study, the majority (92.8%) of individual evaluations rated the notes generated by LLaMA-Clinic as "acceptable" or higher across three criteria: real-world readiness, completeness, and accuracy. In the more challenging "Assessment and Plan" section, LLaMA-Clinic matched physician-authored notes in real-world readiness score. We highlight key considerations for future clinical note-generation tasks, emphasizing the importance of pre-defining a "best practice" note format, rather than relying on LLMs to determine this for clinical practice.

Chufan Gao, Nicholas Gisolfi, Artur Dubrawski

Signal quality assessment (SQA) is required for monitoring the reliability of data acquisition systems, especially in AI-driven Predictive Maintenance (PMx) application contexts. SQA is vital for addressing "silent failures" of data acquisition hardware and software, which when unnoticed, misinform the users of data, creating the risk for incorrect decisions with unintended or even catastrophic consequences. We have developed an open-source software implementation of signal quality indices (SQIs) for the analysis of time-series data. We codify a range of SQIs, demonstrate them using established benchmark data, and show that they can be effective for signal quality assessment. We also study alternative approaches to denoising time-series data in an attempt to improve the quality of the already degraded signal, and evaluate them empirically on relevant real-world data. To our knowledge, our software toolkit is the first to provide an open source implementation of a broad range of signal quality assessment and improvement techniques validated on publicly available benchmark data for ease of reproducibility. The generality of our framework can be easily extended to assessing reliability of arbitrary time-series measurements in complex systems, especially when morphological patterns of the waveform shapes and signal periodicity are of key interest in downstream analyses.

Hanyin Wang, Chufan Gao, Qiping Xu et al.

Process-supervised reward models (PRMs) excel at providing step-by-step verification for large language model (LLM) outputs in domains like mathematics and coding. However, their application to fields lacking ground-truth answers, such as clinical note generation, poses significant challenges. We introduce a novel framework for training PRMs to deliver step-level reward signals for LLM-generated clinical notes. By precisely defining meaningful "steps," injecting realistic "errors" informed by domain expertise, and leveraging LLMs to generate process supervision data at scale, we overcome previous limitations. Our PRM, built on LLaMA-3.1 8B, consistently outperforms proprietary reasoning and non-reasoning models, achieving state-of-the-art performance on two key evaluations: (1) distinguishing gold-standard from error-containing samples with 98.8% accuracy, and (2) selecting physician-preferred clinical notes with 56.2% accuracy. We investigate critical components for effective PRM training, including optimal loss functions and data selection strategies, and present a comprehensive physician reader study identifying predictors of downstream Best-of-N performance. Our study sheds light on unlocking the potential of PRMs for diverse generative tasks across domains.

Chufan Gao, Tianfan Fu, Jimeng Sun

Clinical trial outcome prediction seeks to estimate the likelihood that a clinical trial will successfully reach its intended endpoint. This process predominantly involves the development of machine learning models that utilize a variety of data sources such as descriptions of the clinical trials, characteristics of the drug molecules, and specific disease conditions being targeted. Accurate predictions of trial outcomes are crucial for optimizing trial planning and prioritizing investments in a drug portfolio. While previous research has largely concentrated on small-molecule drugs, there is a growing need to focus on biologics-a rapidly expanding category of therapeutic agents that often lack the well-defined molecular properties associated with traditional drugs. Additionally, applying conventional methods like graph neural networks to biologics data proves challenging due to their complex nature. To address these challenges, we introduce the Language Interaction Network (LINT), a novel approach that predicts trial outcomes using only the free-text descriptions of the trials. We have rigorously tested the effectiveness of LINT across three phases of clinical trials, where it achieved ROC-AUC scores of 0.770, 0.740, and 0.748 for phases I, II, and III, respectively, specifically concerning trials involving biologic interventions.

Chufan Gao, Jintai Chen, Jimeng Sun

Automated tabular understanding and reasoning are essential tasks for data scientists. Recently, Large language models (LLMs) have become increasingly prevalent in tabular reasoning tasks. Previous work focuses on (1) finetuning LLMs using labeled data or (2) Training-free prompting LLM agents using chain-of-thought (CoT). Finetuning offers dataset-specific learning at the cost of generalizability. Training-free prompting is highly generalizable but does not take full advantage of training data. In this paper, we propose a novel prompting-based reasoning approach, Learn then Retrieve: LRTab, which integrates the benefits of both by retrieving relevant information learned from training data. We first use prompting to obtain CoT responses over the training data. For incorrect CoTs, we prompt the LLM to predict Prompt Conditions to avoid the error, learning insights from the data. We validate the effectiveness of Prompt Conditions using validation data. Finally, at inference time, we retrieve the most relevant Prompt Conditions for additional context for table understanding. We provide comprehensive experiments on WikiTQ and Tabfact, showing that LRTab is interpretable, cost-efficient, and can outperform previous baselines in tabular reasoning.

Chufan Gao, Jathurshan Pradeepkumar, Trisha Das et al.

Background The cost of drug discovery and development is substantial, with clinical trial outcomes playing a critical role in regulatory approval and patient care. However, access to large-scale, high-quality clinical trial outcome data remains limited, hindering advancements in predictive modeling and evidence-based decision-making. Methods We present the Clinical Trial Outcome (CTO) benchmark, a fully reproducible, large-scale repository encompassing approximately 125,000 drug and biologics trials. CTO integrates large language model (LLM) interpretations of publications, trial phase progression tracking, sentiment analysis from news sources, stock price movements of trial sponsors, and additional trial-related metrics. Furthermore, we manually annotated a dataset of clinical trials conducted between 2020 and 2024 to enhance the quality and reliability of outcome labels. Results The trial outcome labels in the CTO benchmark agree strongly with expert annotations, achieving an F1 score of 94 for Phase 3 trials and 91 across all phases. Additionally, benchmarking standard machine learning models on our manually annotated dataset revealed distribution shifts in recent trials, underscoring the necessity of continuously updated labeling approaches. Conclusions By analyzing CTO's performance on recent clinical trials, we demonstrate the ongoing need for high-quality, up-to-date trial outcome labels. We publicly release the CTO knowledge base and annotated labels at https://chufangao.github.io/CTOD, with regular updates to support research on clinical trial outcomes and inform data-driven improvements in drug development.

Chufan Gao, Xuan Wang, Jimeng Sun

Document-level relation extraction aims to categorize the association between any two entities within a document. We find that previous methods for document-level relation extraction are ineffective in exploiting the full potential of large amounts of training data with varied noise levels. For example, in the ReDocRED benchmark dataset, state-of-the-art methods trained on the large-scale, lower-quality, distantly supervised training data generally do not perform better than those trained solely on the smaller, high-quality, human-annotated training data. To unlock the full potential of large-scale noisy training data for document-level relation extraction, we propose TTM-RE, a novel approach that integrates a trainable memory module, known as the Token Turing Machine, with a noisy-robust loss function that accounts for the positive-unlabeled setting. Extensive experiments on ReDocRED, a benchmark dataset for document-level relation extraction, reveal that TTM-RE achieves state-of-the-art performance (with an absolute F1 score improvement of over 3%). Ablation studies further illustrate the superiority of TTM-RE in other domains (the ChemDisGene dataset in the biomedical domain) and under highly unlabeled settings.

Zifeng Wang, Chufan Gao, Cao Xiao et al.

Tabular data prediction has been employed in medical applications such as patient health risk prediction. However, existing methods usually revolve around the algorithm design while overlooking the significance of data engineering. Medical tabular datasets frequently exhibit significant heterogeneity across different sources, with limited sample sizes per source. As such, previous predictors are often trained on manually curated small datasets that struggle to generalize across different tabular datasets during inference. This paper proposes to scale medical tabular data predictors (MediTab) to various tabular inputs with varying features. The method uses a data engine that leverages large language models (LLMs) to consolidate tabular samples to overcome the barrier across tables with distinct schema. It also aligns out-domain data with the target task using a "learn, annotate, and refinement" pipeline. The expanded training data then enables the pre-trained MediTab to infer for arbitrary tabular input in the domain without fine-tuning, resulting in significant improvements over supervised baselines: it reaches an average ranking of 1.57 and 1.00 on 7 patient outcome prediction datasets and 3 trial outcome prediction datasets, respectively. In addition, MediTab exhibits impressive zero-shot performances: it outperforms supervised XGBoost models by 8.9% and 17.2% on average in two prediction tasks, respectively.

Saswati Ray, Sana Lakdawala, Mononito Goswami et al.

In this work, we propose GLUE (Graph Deviation Network with Local Uncertainty Estimation), building on the recently proposed Graph Deviation Network (GDN). GLUE not only automatically learns complex dependencies between variables and uses them to better identify anomalous behavior, but also quantifies its predictive uncertainty, allowing us to account for the variation in the data as well to have more interpretable anomaly detection thresholds. Results on two real world datasets tell us that optimizing the negative Gaussian log likelihood is reasonable because GLUE's forecasting results are at par with GDN and in fact better than the vector autoregressor baseline, which is significant given that GDN directly optimizes the MSE loss. In summary, our experiments demonstrate that GLUE is competitive with GDN at anomaly detection, with the added benefit of uncertainty estimations. We also show that GLUE learns meaningful sensor embeddings which clusters similar sensors together.

Chufan Gao, Mononito Goswami

Most advanced supervised Machine Learning (ML) models rely on vast amounts of point-by-point labelled training examples. Hand-labelling vast amounts of data may be tedious, expensive, and error-prone. Recently, some studies have explored the use of diverse sources of weak supervision to produce competitive end model classifiers. In this paper, we survey recent work on weak supervision, and in particular, we investigate the Data Programming (DP) framework. Taking a set of potentially noisy heuristics as input, DP assigns denoised probabilistic labels to each data point in a dataset using a probabilistic graphical model of heuristics. We analyze the math fundamentals behind DP and demonstrate the power of it by applying it on two real-world text classification tasks. Furthermore, we compare DP with pointillistic active and semi-supervised learning techniques traditionally applied in data-sparse settings.

Chufan Gao, Fabian Falck, Mononito Goswami et al.

Monitoring physiological responses to hemodynamic stress can help in determining appropriate treatment and ensuring good patient outcomes. Physicians' intuition suggests that the human body has a number of physiological response patterns to hemorrhage which escalate as blood loss continues, however the exact etiology and phenotypes of such responses are not well known or understood only at a coarse level. Although previous research has shown that machine learning models can perform well in hemorrhage detection and survival prediction, it is unclear whether machine learning could help to identify and characterize the underlying physiological responses in raw vital sign data. We approach this problem by first transforming the high-dimensional vital sign time series into a tractable, lower-dimensional latent space using a dilated, causal convolutional encoder model trained purely unsupervised. Second, we identify informative clusters in the embeddings. By analyzing the clusters of latent embeddings and visualizing them over time, we hypothesize that the clusters correspond to the physiological response patterns that match physicians' intuition. Furthermore, we attempt to evaluate the latent embeddings using a variety of methods, such as predicting the cluster labels using explainable features.