Ivan Lopez

Thomas Savage, Stephen Ma, Abdessalem Boukil et al.

Large Language Model (LLM) fine tuning is underutilized in the field of medicine. Two of the most common methods of fine tuning are Supervised Fine Tuning (SFT) and Direct Preference Optimization (DPO), but there is little guidance informing users when to use either technique. In this investigation, we compare the performance of SFT and DPO for five common natural language tasks in medicine: Classification with text data, Classification with numeric data, Clinical Reasoning, Summarization, and Clinical Triage. We find that SFT alone is sufficient for Classification with text data, whereas DPO improves performance for the more complex tasks of Clinical Reasoning, Summarization and Clinical Triage. Our results establish the role and importance of DPO fine tuning within medicine, and consequently call attention to current software gaps that prevent widespread deployment of this technique.

Alejandro Lozano, Min Woo Sun, James Burgess et al. · stanford

The development of vision-language models (VLMs) is driven by large-scale and diverse multimodal datasets. However, progress toward generalist biomedical VLMs is limited by the lack of annotated, publicly accessible datasets across biology and medicine. Existing efforts are restricted to narrow domains, missing the full diversity of biomedical knowledge encoded in scientific literature. To address this gap, we introduce BIOMEDICA, a scalable, open-source framework to extract, annotate, and serialize the entirety of the PubMed Central Open Access subset into an easy-to-use, publicly accessible dataset. Our framework produces a comprehensive archive with over 24 million unique image-text pairs from over 6 million articles. Metadata and expert-guided annotations are also provided. We demonstrate the utility and accessibility of our resource by releasing BMCA-CLIP, a suite of CLIP-style models continuously pre-trained on the BIOMEDICA dataset via streaming, eliminating the need to download 27 TB of data locally. On average, our models achieve state-of-the-art performance across 40 tasks - spanning pathology, radiology, ophthalmology, dermatology, surgery, molecular biology, parasitology, and cell biology - excelling in zero-shot classification with a 6.56% average improvement (as high as 29.8% and 17.5% in dermatology and ophthalmology, respectively), and stronger image-text retrieval, all while using 10x less compute. To foster reproducibility and collaboration, we release our codebase and dataset for the broader research community.

Alejandro Lozano, Min Woo Sun, James Burgess et al. · stanford

Despite the excitement behind biomedical artificial intelligence (AI), access to high-quality, diverse, and large-scale data - the foundation for modern AI systems - is still a bottleneck to unlocking its full potential. To address this gap, we introduce Biomedica, an open-source dataset derived from the PubMed Central Open Access subset, containing over 6 million scientific articles and 24 million image-text pairs, along with 27 metadata fields (including expert human annotations). To overcome the challenges of accessing our large-scale dataset, we provide scalable streaming and search APIs through a web server, facilitating seamless integration with AI systems. We demonstrate the utility of the Biomedica dataset by building embedding models, chat-style models, and retrieval-augmented chat agents. Notably, all our AI models surpass previous open systems in their respective categories, underscoring the critical role of diverse, high-quality, and large-scale biomedical data.

Ivan Lopez, Selin S. Everett, Bryan J. Bunning et al.

Large language models (LLMs) are entering clinician workflows, yet evaluations rarely measure how clinician reasoning shapes model behavior during clinical interactions. We combined 61 New England Journal of Medicine Case Records with 92 real-world clinician-AI interactions to evaluate 21 reasoning LLM variants across 8 frontier models on differential diagnosis generation and next step recommendations under three conditions: reasoning alone, after expert clinician context, and after adversarial clinician context. LLM-clinician concordance increased substantially after clinician exposure, with simulations sharing >=3 differential diagnosis items rising from 65.8% to 93.5% and >=3 next step recommendations from 20.3% to 53.8%. Expert context significantly improved correct final diagnosis inclusion across all 21 models (mean +20.4 percentage points), reflecting both reasoning improvement and passive content echoing, while adversarial context caused significant diagnostic degradation in 14 models (mean -5.4 percentage points). Multi-turn disagreement probes revealed distinct model phenotypes ranging from highly conformist to dogmatic, with adversarial arguments remaining a persistent vulnerability even for otherwise resilient models. Inference-time scaling reduced harmful echoing of clinician-introduced recommendations across WHO-defined harm severity tiers (relative reductions: 62.7% mild, 57.9% moderate, 76.3% severe, 83.5% death-tier). In GPT-4o experiments, explicit clinician uncertainty signals improved diagnostic performance after adversarial context (final diagnosis inclusion 27% to 42%) and reduced alignment with incorrect arguments by 21%. These findings establish a foundation for evaluating clinician-AI collaboration, introducing interactive metrics and mitigation strategies essential for safety and robustness.

Ivan Lopez, Fateme Nateghi Haredasht, Kaitlin Caoili et al.

Accurate classification of clinical text often requires fine-tuning pre-trained language models, a process that is costly and time-consuming due to the need for high-quality data and expert annotators. Synthetic data generation offers an alternative, though pre-trained models may not capture the syntactic diversity of clinical notes. We propose an embedding-driven approach that uses diversity sampling from a small set of real clinical notes to guide large language models in few-shot prompting, generating synthetic text that better reflects clinical syntax. We evaluated this method using the CheXpert dataset on a classification task, comparing it to random few-shot and zero-shot approaches. Using cosine similarity and a Turing test, our approach produced synthetic notes that more closely align with real clinical text. Our pipeline reduced the data needed to reach the 0.85 AUC cutoff by 40% for AUROC and 30% for AUPRC, while augmenting models with synthetic data improved AUROC by 57% and AUPRC by 68%. Additionally, our synthetic data was 0.9 times as effective as real data, a 60% improvement in value.

Karthik S. Vedula, Annika Gupta, Akshay Swaminathan et al.

Large language models (LLMs) excel at clinical information extraction but their computational demands limit practical deployment. Knowledge distillation--the process of transferring knowledge from larger to smaller models--offers a potential solution. We evaluate the performance of distilled BERT models, which are approximately 1,000 times smaller than modern LLMs, for clinical named entity recognition (NER) tasks. We leveraged state-of-the-art LLMs (Gemini and OpenAI models) and medical ontologies (RxNorm and SNOMED) as teacher labelers for medication, disease, and symptom extraction. We applied our approach to over 3,300 clinical notes spanning five publicly available datasets, comparing distilled BERT models against both their teacher labelers and BERT models fine-tuned on human labels. External validation was conducted using clinical notes from the MedAlign dataset. For disease extraction, F1 scores were 0.82 (teacher model), 0.89 (BioBERT trained on human labels), and 0.84 (BioBERT-distilled). For medication, F1 scores were 0.84 (teacher model), 0.91 (BioBERT-human), and 0.87 (BioBERT-distilled). For symptoms: F1 score of 0.73 (teacher model) and 0.68 (BioBERT-distilled). Distilled BERT models had faster inference (12x, 4x, 8x faster than GPT-4o, o1-mini, and Gemini Flash respectively) and lower costs (85x, 101x, 2x cheaper than GPT-4o, o1-mini, and Gemini Flash respectively). On the external validation dataset, the distilled BERT model achieved F1 scores of 0.883 (medication), 0.726 (disease), and 0.699 (symptom). Distilled BERT models were up to 101x cheaper and 12x faster than state-of-the-art LLMs while achieving similar performance on NER tasks. Distillation offers a computationally efficient and scalable alternative to large LLMs for clinical information extraction.

Monica Munnangi, Akshay Swaminathan, Jason Alan Fries et al.

Verifying and attributing factual claims is essential for the safe and effective use of large language models (LLMs) in healthcare. A core component of factuality evaluation is fact decomposition, the process of breaking down complex clinical statements into fine-grained atomic facts for verification. Recent work has proposed fact decomposition, which uses LLMs to rewrite source text into concise sentences conveying a single piece of information, to facilitate fine-grained fact verification. However, clinical documentation poses unique challenges for fact decomposition due to dense terminology and diverse note types and remains understudied. To address this gap and explore these challenges, we present FactEHR, an NLI dataset consisting of document fact decompositions for 2,168 clinical notes spanning four types from three hospital systems, resulting in 987,266 entailment pairs. We assess the generated facts on different axes, from entailment evaluation of LLMs to a qualitative analysis. Our evaluation, including review by the clinicians, reveals substantial variability in LLM performance for fact decomposition. For example, Gemini-1.5-Flash consistently generates relevant and accurate facts, while Llama-3 8B produces fewer and less consistent outputs. The results underscore the need for better LLM capabilities to support factual verification in clinical text.