Massachusetts Institute of Technology
Abstract:Background: Large language models (LLMs) are trained to follow directions, but this introduces a vulnerability to blindly comply with user requests even if they generate wrong information. In medicine, this could accelerate the generation of misinformation that impacts human well-being. Objectives/Methods: We analyzed compliance to requests to generate misleading content about medications in settings where models know the request is illogical. We investigated whether in-context directions and instruction-tuning of LLMs to prioritize logical reasoning over compliance reduced misinformation risk. Results: While all frontier LLMs complied with misinformation requests, both prompt-based and parameter-based approaches can improve the detection of logic flaws in requests and prevent the dissemination of medical misinformation. Conclusion: Shifting LLMs to prioritize logic over compliance could reduce risks of exploitation for medical misinformation.
Abstract:Simulated patient systems play a crucial role in modern medical education and research, providing safe, integrative learning environments and enabling clinical decision-making simulations. Large Language Models (LLM) could advance simulated patient systems by replicating medical conditions and patient-doctor interactions with high fidelity and low cost. However, ensuring the effectiveness and trustworthiness of these systems remains a challenge, as they require a large, diverse, and precise patient knowledgebase, along with a robust and stable knowledge diffusion to users. Here, we developed AIPatient, an advanced simulated patient system with AIPatient Knowledge Graph (AIPatient KG) as the input and the Reasoning Retrieval-Augmented Generation (Reasoning RAG) agentic workflow as the generation backbone. AIPatient KG samples data from Electronic Health Records (EHRs) in the Medical Information Mart for Intensive Care (MIMIC)-III database, producing a clinically diverse and relevant cohort of 1,495 patients with high knowledgebase validity (F1 0.89). Reasoning RAG leverages six LLM powered agents spanning tasks including retrieval, KG query generation, abstraction, checker, rewrite, and summarization. This agentic framework reaches an overall accuracy of 94.15% in EHR-based medical Question Answering (QA), outperforming benchmarks that use either no agent or only partial agent integration. Our system also presents high readability (median Flesch Reading Ease 77.23; median Flesch Kincaid Grade 5.6), robustness (ANOVA F-value 0.6126, p<0.1), and stability (ANOVA F-value 0.782, p<0.1). The promising performance of the AIPatient system highlights its potential to support a wide range of applications, including medical education, model evaluation, and system integration.
Abstract:Reproducibility remains a significant challenge in machine learning (ML) for healthcare. In this field, datasets, model pipelines, and even task/cohort definitions are often private, leading to a significant barrier in sharing, iterating, and understanding ML results on electronic health record (EHR) datasets. In this paper, we address a significant part of this problem by introducing the Automatic Cohort Extraction System for Event-Stream Datasets (ACES). This tool is designed to simultaneously simplify the development of task/cohorts for ML in healthcare and enable the reproduction of these cohorts, both at an exact level for single datasets and at a conceptual level across datasets. To accomplish this, ACES provides (1) a highly intuitive and expressive configuration language for defining both dataset-specific concepts and dataset-agnostic inclusion/exclusion criteria, and (2) a pipeline to automatically extract patient records that meet these defined criteria from real-world data. ACES can be automatically applied to any dataset in either the Medical Event Data Standard (MEDS) or EventStreamGPT (ESGPT) formats, or to *any* dataset for which the necessary task-specific predicates can be extracted in an event-stream form. ACES has the potential to significantly lower the barrier to entry for defining ML tasks, redefine the way researchers interact with EHR datasets, and significantly improve the state of reproducibility for ML studies in this modality. ACES is available at https://github.com/justin13601/aces.
Abstract:Electronic health records (EHRs) contain vast amounts of complex data, but harmonizing and processing this information remains a challenging and costly task requiring significant clinical expertise. While large language models (LLMs) have shown promise in various healthcare applications, their potential for abstracting medical concepts from EHRs remains largely unexplored. We introduce EHRmonize, a framework leveraging LLMs to abstract medical concepts from EHR data. Our study uses medication data from two real-world EHR databases to evaluate five LLMs on two free-text extraction and six binary classification tasks across various prompting strategies. GPT-4o's with 10-shot prompting achieved the highest performance in all tasks, accompanied by Claude-3.5-Sonnet in a subset of tasks. GPT-4o achieved an accuracy of 97% in identifying generic route names, 82% for generic drug names, and 100% in performing binary classification of antibiotics. While EHRmonize significantly enhances efficiency, reducing annotation time by an estimated 60%, we emphasize that clinician oversight remains essential. Our framework, available as a Python package, offers a promising tool to assist clinicians in EHR data abstraction, potentially accelerating healthcare research and improving data harmonization processes.
Abstract:The deployment of large language models (LLMs) in healthcare has demonstrated substantial potential for enhancing clinical decision-making, administrative efficiency, and patient outcomes. However, the underrepresentation of diverse groups in the development and application of these models can perpetuate biases, leading to inequitable healthcare delivery. This paper presents a comprehensive scientometric analysis of LLM research for healthcare, including data from January 1, 2021, to June 16, 2024. By analyzing metadata from PubMed and Dimensions, including author affiliations, countries, and funding sources, we assess the diversity of contributors to LLM research. Our findings highlight significant gender and geographic disparities, with a predominance of male authors and contributions primarily from high-income countries (HICs). We introduce a novel journal diversity index based on Gini impurity to measure the inclusiveness of scientific publications. Our results underscore the necessity for greater representation in order to ensure the equitable application of LLMs in healthcare. We propose actionable strategies to enhance diversity and inclusivity in artificial intelligence research, with the ultimate goal of fostering a more inclusive and equitable future in healthcare innovation.
Abstract:Medical knowledge is context-dependent and requires consistent reasoning across various natural language expressions of semantically equivalent phrases. This is particularly crucial for drug names, where patients often use brand names like Advil or Tylenol instead of their generic equivalents. To study this, we create a new robustness dataset, RABBITS, to evaluate performance differences on medical benchmarks after swapping brand and generic drug names using physician expert annotations. We assess both open-source and API-based LLMs on MedQA and MedMCQA, revealing a consistent performance drop ranging from 1-10\%. Furthermore, we identify a potential source of this fragility as the contamination of test data in widely used pre-training datasets. All code is accessible at https://github.com/BittermanLab/RABBITS, and a HuggingFace leaderboard is available at https://huggingface.co/spaces/AIM-Harvard/rabbits-leaderboard.
Abstract:Large language models (LLMs) are increasingly essential in processing natural languages, yet their application is frequently compromised by biases and inaccuracies originating in their training data. In this study, we introduce Cross-Care, the first benchmark framework dedicated to assessing biases and real world knowledge in LLMs, specifically focusing on the representation of disease prevalence across diverse demographic groups. We systematically evaluate how demographic biases embedded in pre-training corpora like $ThePile$ influence the outputs of LLMs. We expose and quantify discrepancies by juxtaposing these biases against actual disease prevalences in various U.S. demographic groups. Our results highlight substantial misalignment between LLM representation of disease prevalence and real disease prevalence rates across demographic subgroups, indicating a pronounced risk of bias propagation and a lack of real-world grounding for medical applications of LLMs. Furthermore, we observe that various alignment methods minimally resolve inconsistencies in the models' representation of disease prevalence across different languages. For further exploration and analysis, we make all data and a data visualization tool available at: www.crosscare.net.
Abstract:Background Advancements in Large Language Models (LLMs) hold transformative potential in healthcare, however, recent work has raised concern about the tendency of these models to produce outputs that display racial or gender biases. Although training data is a likely source of such biases, exploration of disease and demographic associations in text data at scale has been limited. Methods We conducted a large-scale textual analysis using a dataset comprising diverse web sources, including Arxiv, Wikipedia, and Common Crawl. The study analyzed the context in which various diseases are discussed alongside markers of race and gender. Given that LLMs are pre-trained on similar datasets, this approach allowed us to examine the potential biases that LLMs may learn and internalize. We compared these findings with actual demographic disease prevalence as well as GPT-4 outputs in order to evaluate the extent of bias representation. Results Our findings indicate that demographic terms are disproportionately associated with specific disease concepts in online texts. gender terms are prominently associated with disease concepts, while racial terms are much less frequently associated. We find widespread disparities in the associations of specific racial and gender terms with the 18 diseases analyzed. Most prominently, we see an overall significant overrepresentation of Black race mentions in comparison to population proportions. Conclusions Our results highlight the need for critical examination and transparent reporting of biases in LLM pretraining datasets. Our study suggests the need to develop mitigation strategies to counteract the influence of biased training data in LLMs, particularly in sensitive domains such as healthcare.
Abstract:Generative models have been showing potential for producing data in mass. This study explores the enhancement of clinical natural language processing performance by utilizing synthetic data generated from advanced language models. Promising results show feasible applications in such a high-stakes domain.
Abstract:In machine learning (ML), a widespread adage is that the area under the precision-recall curve (AUPRC) is a superior metric for model comparison to the area under the receiver operating characteristic (AUROC) for binary classification tasks with class imbalance. This paper challenges this notion through novel mathematical analysis, illustrating that AUROC and AUPRC can be concisely related in probabilistic terms. We demonstrate that AUPRC, contrary to popular belief, is not superior in cases of class imbalance and might even be a harmful metric, given its inclination to unduly favor model improvements in subpopulations with more frequent positive labels. This bias can inadvertently heighten algorithmic disparities. Prompted by these insights, a thorough review of existing ML literature was conducted, utilizing large language models to analyze over 1.5 million papers from arXiv. Our investigation focused on the prevalence and substantiation of the purported AUPRC superiority. The results expose a significant deficit in empirical backing and a trend of misattributions that have fuelled the widespread acceptance of AUPRC's supposed advantages. Our findings represent a dual contribution: a significant technical advancement in understanding metric behaviors and a stark warning about unchecked assumptions in the ML community. All experiments are accessible at https://github.com/mmcdermott/AUC_is_all_you_need.