Zehao Yu

Zehao Yu, Xi Yang, Chong Dang et al.

Objective: We aim to develop an open-source natural language processing (NLP) package, SODA (i.e., SOcial DeterminAnts), with pre-trained transformer models to extract social determinants of health (SDoH) for cancer patients, examine the generalizability of SODA to a new disease domain (i.e., opioid use), and evaluate the extraction rate of SDoH using cancer populations. Methods: We identified SDoH categories and attributes and developed an SDoH corpus using clinical notes from a general cancer cohort. We compared four transformer-based NLP models to extract SDoH, examined the generalizability of NLP models to a cohort of patients prescribed with opioids, and explored customization strategies to improve performance. We applied the best NLP model to extract 19 categories of SDoH from the breast (n=7,971), lung (n=11,804), and colorectal cancer (n=6,240) cohorts. Results and Conclusion: We developed a corpus of 629 cancer patients notes with annotations of 13,193 SDoH concepts/attributes from 19 categories of SDoH. The Bidirectional Encoder Representations from Transformers (BERT) model achieved the best strict/lenient F1 scores of 0.9216 and 0.9441 for SDoH concept extraction, 0.9617 and 0.9626 for linking attributes to SDoH concepts. Fine-tuning the NLP models using new annotations from opioid use patients improved the strict/lenient F1 scores from 0.8172/0.8502 to 0.8312/0.8679. The extraction rates among 19 categories of SDoH varied greatly, where 10 SDoH could be extracted from >70% of cancer patients, but 9 SDoH had a low extraction rate (<70% of cancer patients). The SODA package with pre-trained transformer models is publicly available at https://github.com/uf-hobiinformatics-lab/SDoH_SODA.

Cheng Peng, Xi Yang, Zehao Yu et al.

Objective: To develop a natural language processing system that solves both clinical concept extraction and relation extraction in a unified prompt-based machine reading comprehension (MRC) architecture with good generalizability for cross-institution applications. Methods: We formulate both clinical concept extraction and relation extraction using a unified prompt-based MRC architecture and explore state-of-the-art transformer models. We compare our MRC models with existing deep learning models for concept extraction and end-to-end relation extraction using two benchmark datasets developed by the 2018 National NLP Clinical Challenges (n2c2) challenge (medications and adverse drug events) and the 2022 n2c2 challenge (relations of social determinants of health [SDoH]). We also evaluate the transfer learning ability of the proposed MRC models in a cross-institution setting. We perform error analyses and examine how different prompting strategies affect the performance of MRC models. Results and Conclusion: The proposed MRC models achieve state-of-the-art performance for clinical concept and relation extraction on the two benchmark datasets, outperforming previous non-MRC transformer models. GatorTron-MRC achieves the best strict and lenient F1-scores for concept extraction, outperforming previous deep learning models on the two datasets by 1%~3% and 0.7%~1.3%, respectively. For end-to-end relation extraction, GatorTron-MRC and BERT-MIMIC-MRC achieve the best F1-scores, outperforming previous deep learning models by 0.9%~2.4% and 10%-11%, respectively. For cross-institution evaluation, GatorTron-MRC outperforms traditional GatorTron by 6.4% and 16% for the two datasets, respectively. The proposed method is better at handling nested/overlapped concepts, extracting relations, and has good portability for cross-institute applications.

Aman Pathak, Zehao Yu, Daniel Paredes et al.

The ultrasound characteristics of thyroid nodules guide the evaluation of thyroid cancer in patients with thyroid nodules. However, the characteristics of thyroid nodules are often documented in clinical narratives such as ultrasound reports. Previous studies have examined natural language processing (NLP) methods in extracting a limited number of characteristics (<9) using rule-based NLP systems. In this study, a multidisciplinary team of NLP experts and thyroid specialists, identified thyroid nodule characteristics that are important for clinical care, composed annotation guidelines, developed a corpus, and compared 5 state-of-the-art transformer-based NLP methods, including BERT, RoBERTa, LongFormer, DeBERTa, and GatorTron, for extraction of thyroid nodule characteristics from ultrasound reports. Our GatorTron model, a transformer-based large language model trained using over 90 billion words of text, achieved the best strict and lenient F1-score of 0.8851 and 0.9495 for the extraction of a total number of 16 thyroid nodule characteristics, and 0.9321 for linking characteristics to nodules, outperforming other clinical transformer models. To the best of our knowledge, this is the first study to systematically categorize and apply transformer-based NLP models to extract a large number of clinical relevant thyroid nodule characteristics from ultrasound reports. This study lays ground for assessing the documentation quality of thyroid ultrasound reports and examining outcomes of patients with thyroid nodules using electronic health records.

Aokun Chen, Zehao Yu, Xi Yang et al.

Objective: To develop a natural language processing (NLP) system to extract medications and contextual information that help understand drug changes. This project is part of the 2022 n2c2 challenge. Materials and methods: We developed NLP systems for medication mention extraction, event classification (indicating medication changes discussed or not), and context classification to classify medication changes context into 5 orthogonal dimensions related to drug changes. We explored 6 state-of-the-art pretrained transformer models for the three subtasks, including GatorTron, a large language model pretrained using >90 billion words of text (including >80 billion words from >290 million clinical notes identified at the University of Florida Health). We evaluated our NLP systems using annotated data and evaluation scripts provided by the 2022 n2c2 organizers. Results:Our GatorTron models achieved the best F1-scores of 0.9828 for medication extraction (ranked 3rd), 0.9379 for event classification (ranked 2nd), and the best micro-average accuracy of 0.9126 for context classification. GatorTron outperformed existing transformer models pretrained using smaller general English text and clinical text corpora, indicating the advantage of large language models. Conclusion: This study demonstrated the advantage of using large transformer models for contextual medication information extraction from clinical narratives.

Cheng Peng, Xi Yang, Kaleb E Smith et al.

Objective To develop soft prompt-based learning algorithms for large language models (LLMs), examine the shape of prompts, prompt-tuning using frozen/unfrozen LLMs, transfer learning, and few-shot learning abilities. Methods We developed a soft prompt-based LLM model and compared 4 training strategies including (1) fine-tuning without prompts; (2) hard-prompt with unfrozen LLMs; (3) soft-prompt with unfrozen LLMs; and (4) soft-prompt with frozen LLMs. We evaluated 7 pretrained LLMs using the 4 training strategies for clinical concept and relation extraction on two benchmark datasets. We evaluated the transfer learning ability of the prompt-based learning algorithms in a cross-institution setting. We also assessed the few-shot learning ability. Results and Conclusion When LLMs are unfrozen, GatorTron-3.9B with soft prompting achieves the best strict F1-scores of 0.9118 and 0.8604 for concept extraction, outperforming the traditional fine-tuning and hard prompt-based models by 0.6~3.1% and 1.2~2.9%, respectively; GatorTron-345M with soft prompting achieves the best F1-scores of 0.8332 and 0.7488 for end-to-end relation extraction, outperforming the other two models by 0.2~2% and 0.6~11.7%, respectively. When LLMs are frozen, small (i.e., 345 million parameters) LLMs have a big gap to be competitive with unfrozen models; scaling LLMs up to billions of parameters makes frozen LLMs competitive with unfrozen LLMs. For cross-institute evaluation, soft prompting with a frozen GatorTron-8.9B model achieved the best performance. This study demonstrates that (1) machines can learn soft prompts better than humans, (2) frozen LLMs have better few-shot learning ability and transfer learning ability to facilitate muti-institution applications, and (3) frozen LLMs require large models.

Aokun Chen, Daniel Paredes, Zehao Yu et al.

Delirium is an acute decline or fluctuation in attention, awareness, or other cognitive function that can lead to serious adverse outcomes. Despite the severe outcomes, delirium is frequently unrecognized and uncoded in patients' electronic health records (EHRs) due to its transient and diverse nature. Natural language processing (NLP), a key technology that extracts medical concepts from clinical narratives, has shown great potential in studies of delirium outcomes and symptoms. To assist in the diagnosis and phenotyping of delirium, we formed an expert panel to categorize diverse delirium symptoms, composed annotation guidelines, created a delirium corpus with diverse delirium symptoms, and developed NLP methods to extract delirium symptoms from clinical notes. We compared 5 state-of-the-art transformer models including 2 models (BERT and RoBERTa) from the general domain and 3 models (BERT_MIMIC, RoBERTa_MIMIC, and GatorTron) from the clinical domain. GatorTron achieved the best strict and lenient F1 scores of 0.8055 and 0.8759, respectively. We conducted an error analysis to identify challenges in annotating delirium symptoms and developing NLP systems. To the best of our knowledge, this is the first large language model-based delirium symptom extraction system. Our study lays the foundation for the future development of computable phenotypes and diagnosis methods for delirium.

Xi Yang, Zehao Yu, Yi Guo et al.

The newly emerged transformer technology has a tremendous impact on NLP research. In the general English domain, transformer-based models have achieved state-of-the-art performances on various NLP benchmarks. In the clinical domain, researchers also have investigated transformer models for clinical applications. The goal of this study is to systematically explore three widely used transformer-based models (i.e., BERT, RoBERTa, and XLNet) for clinical relation extraction and develop an open-source package with clinical pre-trained transformer-based models to facilitate information extraction in the clinical domain. We developed a series of clinical RE models based on three transformer architectures, namely BERT, RoBERTa, and XLNet. We evaluated these models using 2 publicly available datasets from 2018 MADE1.0 and 2018 n2c2 challenges. We compared two classification strategies (binary vs. multi-class classification) and investigated two approaches to generate candidate relations in different experimental settings. In this study, we compared three transformer-based (BERT, RoBERTa, and XLNet) models for relation extraction. We demonstrated that the RoBERTa-clinical RE model achieved the best performance on the 2018 MADE1.0 dataset with an F1-score of 0.8958. On the 2018 n2c2 dataset, the XLNet-clinical model achieved the best F1-score of 0.9610. Our results indicated that the binary classification strategy consistently outperformed the multi-class classification strategy for clinical relation extraction. Our methods and models are publicly available at https://github.com/uf-hobi-informatics-lab/ClinicalTransformerRelationExtraction. We believe this work will improve current practice on clinical relation extraction and other related NLP tasks in the biomedical domain.

Cheng Peng, Xi Yang, Aokun Chen et al.

Objective To solve major clinical natural language processing (NLP) tasks using a unified text-to-text learning architecture based on a generative large language model (LLM) via prompt tuning. Methods We formulated 7 key clinical NLP tasks as text-to-text learning and solved them using one unified generative clinical LLM, GatorTronGPT, developed using GPT-3 architecture and trained with up to 20 billion parameters. We adopted soft prompts (i.e., trainable vectors) with frozen LLM, where the LLM parameters were not updated (i.e., frozen) and only the vectors of soft prompts were updated, known as prompt tuning. We added additional soft prompts as a prefix to the input layer, which were optimized during the prompt tuning. We evaluated the proposed method using 7 clinical NLP tasks and compared them with previous task-specific solutions based on Transformer models. Results and Conclusion The proposed approach achieved state-of-the-art performance for 5 out of 7 major clinical NLP tasks using one unified generative LLM. Our approach outperformed previous task-specific transformer models by ~3% for concept extraction and 7% for relation extraction applied to social determinants of health, 3.4% for clinical concept normalization, 3.4~10% for clinical abbreviation disambiguation, and 5.5~9% for natural language inference. Our approach also outperformed a previously developed prompt-based machine reading comprehension (MRC) model, GatorTron-MRC, for clinical concept and relation extraction. The proposed approach can deliver the ``one model for all`` promise from training to deployment using a unified generative LLM.

Cheng Peng, Zehao Yu, Kaleb E Smith et al.

The progress in natural language processing (NLP) using large language models (LLMs) has greatly improved patient information extraction from clinical narratives. However, most methods based on the fine-tuning strategy have limited transfer learning ability for cross-domain applications. This study proposed a novel approach that employs a soft prompt-based learning architecture, which introduces trainable prompts to guide LLMs toward desired outputs. We examined two types of LLM architectures, including encoder-only GatorTron and decoder-only GatorTronGPT, and evaluated their performance for the extraction of social determinants of health (SDoH) using a cross-institution dataset from the 2022 n2c2 challenge and a cross-disease dataset from the University of Florida (UF) Health. The results show that decoder-only LLMs with prompt tuning achieved better performance in cross-domain applications. GatorTronGPT achieved the best F1 scores for both datasets, outperforming traditional fine-tuned GatorTron by 8.9% and 21.8% in a cross-institution setting, and 5.5% and 14.5% in a cross-disease setting.

Zehao Yu, Xi Yang, Chong Dang et al.

Social and behavioral determinants of health (SBDoH) have important roles in shaping people's health. In clinical research studies, especially comparative effectiveness studies, failure to adjust for SBDoH factors will potentially cause confounding issues and misclassification errors in either statistical analyses and machine learning-based models. However, there are limited studies to examine SBDoH factors in clinical outcomes due to the lack of structured SBDoH information in current electronic health record (EHR) systems, while much of the SBDoH information is documented in clinical narratives. Natural language processing (NLP) is thus the key technology to extract such information from unstructured clinical text. However, there is not a mature clinical NLP system focusing on SBDoH. In this study, we examined two state-of-the-art transformer-based NLP models, including BERT and RoBERTa, to extract SBDoH concepts from clinical narratives, applied the best performing model to extract SBDoH concepts on a lung cancer screening patient cohort, and examined the difference of SBDoH information between NLP extracted results and structured EHRs (SBDoH information captured in standard vocabularies such as the International Classification of Diseases codes). The experimental results show that the BERT-based NLP model achieved the best strict/lenient F1-score of 0.8791 and 0.8999, respectively. The comparison between NLP extracted SBDoH information and structured EHRs in the lung cancer patient cohort of 864 patients with 161,933 various types of clinical notes showed that much more detailed information about smoking, education, and employment were only captured in clinical narratives and that it is necessary to use both clinical narratives and structured EHRs to construct a more complete picture of patients' SBDoH factors.