Large Language Models Struggle in Token-Level Clinical Named Entity Recognition

Large Language Models (LLMs) have revolutionized various sectors, including healthcare where they are employed in diverse applications. Their utility is particularly significant in the context of rare diseases, where data scarcity, complexity, and specificity pose considerable challenges. In the clinical domain, Named Entity Recognition (NER) stands out as an essential task and it plays a crucial role in extracting relevant information from clinical texts. Despite the promise of LLMs, current research mostly concentrates on document-level NER, identifying entities in a more general context across entire documents, without extracting their precise location. Additionally, efforts have been directed towards adapting ChatGPT for token-level NER. However, there is a significant research gap when it comes to employing token-level NER for clinical texts, especially with the use of local open-source LLMs. This study aims to bridge this gap by investigating the effectiveness of both proprietary and local LLMs in token-level clinical NER. Essentially, we delve into the capabilities of these models through a series of experiments involving zero-shot prompting, few-shot prompting, retrieval-augmented generation (RAG), and instruction-fine-tuning. Our exploration reveals the inherent challenges LLMs face in token-level NER, particularly in the context of rare diseases, and suggests possible improvements for their application in healthcare. This research contributes to narrowing a significant gap in healthcare informatics and offers insights that could lead to a more refined application of LLMs in the healthcare sector.

CancerLLM: A Large Language Model in Cancer Domain

Medical Large Language Models (LLMs) such as ClinicalCamel 70B, Llama3-OpenBioLLM 70B have demonstrated impressive performance on a wide variety of medical NLP task.However, there still lacks a large language model (LLM) specifically designed for cancer domain. Moreover, these LLMs typically have billions of parameters, making them computationally expensive for healthcare systems.Thus, in this study, we propose CancerLLM, a model with 7 billion parameters and a Mistral-style architecture, pre-trained on 2,676,642 clinical notes and 515,524 pathology reports covering 17 cancer types, followed by fine-tuning on three cancer-relevant tasks, including cancer phenotypes extraction, cancer diagnosis generation, and cancer treatment plan generation. Our evaluation demonstrated that CancerLLM achieves state-of-the-art results compared to other existing LLMs, with an average F1 score improvement of 8.1\%. Additionally, CancerLLM outperforms other models on two proposed robustness testbeds. This illustrates that CancerLLM can be effectively applied to clinical AI systems, enhancing clinical research and healthcare delivery in the field of cancer.

GRU-D-Weibull: A Novel Real-Time Individualized Endpoint Prediction

Accurate prediction models for individual-level endpoints and time-to-endpoints are crucial in clinical practice. In this study, we propose a novel approach, GRU-D-Weibull, which combines gated recurrent units with decay (GRU-D) to model the Weibull distribution. Our method enables real-time individualized endpoint prediction and population-level risk management. Using a cohort of 6,879 patients with stage 4 chronic kidney disease (CKD4), we evaluated the performance of GRU-D-Weibull in endpoint prediction. The C-index of GRU-D-Weibull was ~0.7 at the index date and increased to ~0.77 after 4.3 years of follow-up, similar to random survival forest. Our approach achieved an absolute L1-loss of ~1.1 years (SD 0.95) at the CKD4 index date and a minimum of ~0.45 years (SD0.3) at 4 years of follow-up, outperforming competing methods significantly. GRU-D-Weibull consistently constrained the predicted survival probability at the time of an event within a smaller and more fixed range compared to other models throughout the follow-up period. We observed significant correlations between the error in point estimates and missing proportions of input features at the index date (correlations from ~0.1 to ~0.3), which diminished within 1 year as more data became available. By post-training recalibration, we successfully aligned the predicted and observed survival probabilities across multiple prediction horizons at different time points during follow-up. Our findings demonstrate the considerable potential of GRU-D-Weibull as the next-generation architecture for endpoint risk management, capable of generating various endpoint estimates for real-time monitoring using clinical data.

BiomedGPT: A Unified and Generalist Biomedical Generative Pre-trained Transformer for Vision, Language, and Multimodal Tasks

In this paper, we introduce a unified and generalist Biomedical Generative Pre-trained Transformer (BiomedGPT) model, which leverages self-supervision on large and diverse datasets to accept multi-modal inputs and perform a range of downstream tasks. Our experiments demonstrate that BiomedGPT delivers expansive and inclusive representations of biomedical data, outperforming the majority of preceding state-of-the-art models across five distinct tasks with 20 public datasets spanning over 15 unique biomedical modalities. Through the ablation study, we also showcase the efficacy of our multi-modal and multi-task pretraining approach in transferring knowledge to previously unseen data. Overall, our work presents a significant step forward in developing unified and generalist models for biomedicine, with far-reaching implications for improving healthcare outcomes.

A Cross-institutional Evaluation on Breast Cancer Phenotyping NLP Algorithms on Electronic Health Records

Objective: The generalizability of clinical large language models is usually ignored during the model development process. This study evaluated the generalizability of BERT-based clinical NLP models across different clinical settings through a breast cancer phenotype extraction task. Materials and Methods: Two clinical corpora of breast cancer patients were collected from the electronic health records from the University of Minnesota and the Mayo Clinic, and annotated following the same guideline. We developed three types of NLP models (i.e., conditional random field, bi-directional long short-term memory and CancerBERT) to extract cancer phenotypes from clinical texts. The models were evaluated for their generalizability on different test sets with different learning strategies (model transfer vs. locally trained). The entity coverage score was assessed with their association with the model performances. Results: We manually annotated 200 and 161 clinical documents at UMN and MC, respectively. The corpora of the two institutes were found to have higher similarity between the target entities than the overall corpora. The CancerBERT models obtained the best performances among the independent test sets from two clinical institutes and the permutation test set. The CancerBERT model developed in one institute and further fine-tuned in another institute achieved reasonable performance compared to the model developed on local data (micro-F1: 0.925 vs 0.932). Conclusions: The results indicate the CancerBERT model has the best learning ability and generalizability among the three types of clinical NLP models. The generalizability of the models was found to be correlated with the similarity of the target entities between the corpora.

Detecting Reddit Users with Depression Using a Hybrid Neural Network

Depression is a widespread mental health issue, affecting an estimated 3.8% of the global population. It is also one of the main contributors to disability worldwide. Recently it is becoming popular for individuals to use social media platforms (e.g., Reddit) to express their difficulties and health issues (e.g., depression) and seek support from other users in online communities. It opens great opportunities to automatically identify social media users with depression by parsing millions of posts for potential interventions. Deep learning methods have begun to dominate in the field of machine learning and natural language processing (NLP) because of their ease of use, efficient processing, and state-of-the-art results on many NLP tasks. In this work, we propose a hybrid deep learning model which combines a pretrained sentence BERT (SBERT) and convolutional neural network (CNN) to detect individuals with depression with their Reddit posts. The sentence BERT is used to learn the meaningful representation of semantic information in each post. CNN enables the further transformation of those embeddings and the temporal identification of behavioral patterns of users. We trained and evaluated the model performance to identify Reddit users with depression by utilizing the Self-reported Mental Health Diagnoses (SMHD) data. The hybrid deep learning model achieved an accuracy of 0.86 and an F1 score of 0.86 and outperformed the state-of-the-art documented result (F1 score of 0.79) by other machine learning models in the literature. The results show the feasibility of the hybrid model to identify individuals with depression. Although the hybrid model is validated to detect depression with Reddit posts, it can be easily tuned and applied to other text classification tasks and different clinical applications.

Discrimination, calibration, and point estimate accuracy of GRU-D-Weibull architecture for real-time individualized endpoint prediction

Real-time individual endpoint prediction has always been a challenging task but of great clinic utility for both patients and healthcare providers. With 6,879 chronic kidney disease stage 4 (CKD4) patients as a use case, we explored the feasibility and performance of gated recurrent units with decay that models Weibull probability density function (GRU-D-Weibull) as a semi-parametric longitudinal model for real-time individual endpoint prediction. GRU-D-Weibull has a maximum C-index of 0.77 at 4.3 years of follow-up, compared to 0.68 achieved by competing models. The L1-loss of GRU-D-Weibull is ~66% of XGB(AFT), ~60% of MTLR, and ~30% of AFT model at CKD4 index date. The average absolute L1-loss of GRU-D-Weibull is around one year, with a minimum of 40% Parkes serious error after index date. GRU-D-Weibull is not calibrated and significantly underestimates true survival probability. Feature importance tests indicate blood pressure becomes increasingly important during follow-up, while eGFR and blood albumin are less important. Most continuous features have non-linear/parabola impact on predicted survival time, and the results are generally consistent with existing knowledge. GRU-D-Weibull as a semi-parametric temporal model shows advantages in built-in parameterization of missing, native support for asynchronously arrived measurement, capability of output both probability and point estimates at arbitrary time point for arbitrary prediction horizon, improved discrimination and point estimate accuracy after incorporating newly arrived data. Further research on its performance with more comprehensive input features, in-process or post-process calibration are warranted to benefit CKD4 or alike terminally-ill patients.

The NLP Sandbox: an efficient model-to-data system to enable federated and unbiased evaluation of clinical NLP models

Objective The evaluation of natural language processing (NLP) models for clinical text de-identification relies on the availability of clinical notes, which is often restricted due to privacy concerns. The NLP Sandbox is an approach for alleviating the lack of data and evaluation frameworks for NLP models by adopting a federated, model-to-data approach. This enables unbiased federated model evaluation without the need for sharing sensitive data from multiple institutions. Materials and Methods We leveraged the Synapse collaborative framework, containerization software, and OpenAPI generator to build the NLP Sandbox (nlpsandbox.io). We evaluated two state-of-the-art NLP de-identification focused annotation models, Philter and NeuroNER, using data from three institutions. We further validated model performance using data from an external validation site. Results We demonstrated the usefulness of the NLP Sandbox through de-identification clinical model evaluation. The external developer was able to incorporate their model into the NLP Sandbox template and provide user experience feedback. Discussion We demonstrated the feasibility of using the NLP Sandbox to conduct a multi-site evaluation of clinical text de-identification models without the sharing of data. Standardized model and data schemas enable smooth model transfer and implementation. To generalize the NLP Sandbox, work is required on the part of data owners and model developers to develop suitable and standardized schemas and to adapt their data or model to fit the schemas. Conclusions The NLP Sandbox lowers the barrier to utilizing clinical data for NLP model evaluation and facilitates federated, multi-site, unbiased evaluation of NLP models.

RxWhyQA: a clinical question-answering dataset with the challenge of multi-answer questions

Objectives Create a dataset for the development and evaluation of clinical question-answering (QA) systems that can handle multi-answer questions. Materials and Methods We leveraged the annotated relations from the 2018 National NLP Clinical Challenges (n2c2) corpus to generate a QA dataset. The 1-to-0 and 1-to-N drug-reason relations formed the unanswerable and multi-answer entries, which represent challenging scenarios lacking in the existing clinical QA datasets. Results The result RxWhyQA dataset contains 91,440 QA entries, of which half are unanswerable, and 21% (n=19,269) of the answerable ones require multiple answers. The dataset conforms to the community-vetted Stanford Question Answering Dataset (SQuAD) format. Discussion The RxWhyQA is useful for comparing different systems that need to handle the zero- and multi-answer challenges, demanding dual mitigation of both false positive and false negative answers. Conclusion We created and shared a clinical QA dataset with a focus on multi-answer questions to represent real-world scenarios.

An Open Natural Language Processing Development Framework for EHR-based Clinical Research: A case demonstration using the National COVID Cohort Collaborative (N3C)

While we pay attention to the latest advances in clinical natural language processing (NLP), we can notice some resistance in the clinical and translational research community to adopt NLP models due to limited transparency, Interpretability and usability. Built upon our previous work, in this study, we proposed an open natural language processing development framework and evaluated it through the implementation of NLP algorithms for the National COVID Cohort Collaborative (N3C). Based on the interests in information extraction from COVID-19 related clinical notes, our work includes 1) an open data annotation process using COVID-19 signs and symptoms as the use case, 2) a community-driven ruleset composing platform, and 3) a synthetic text data generation workflow to generate texts for information extraction tasks without involving human subjects. The generated corpora derived out of the texts from multiple intuitions and gold standard annotation are tested on a single institution's rule set has the performances in F1 score of 0.876, 0.706 and 0.694, respectively. The study as a consortium effort of the N3C NLP subgroup demonstrates the feasibility of creating a federated NLP algorithm development and benchmarking platform to enhance multi-institution clinical NLP study.