Benjamin Danek

Zifeng Wang, Hanyin Wang, Benjamin Danek et al.

The integration of Large Language Models (LLMs) into medical applications has sparked widespread interest across the healthcare industry, from drug discovery and development to clinical decision support, assisting telemedicine, medical devices, and healthcare insurance applications. This perspective paper aims to discuss the inner workings of building LLM-powered medical AI applications and introduces a comprehensive framework for their development. We review existing literature and outline the unique challenges of applying LLMs in specialized medical contexts. Additionally, we introduce a three-step framework to organize medical LLM research activities: 1) Modeling: breaking down complex medical workflows into manageable steps for developing medical-specific models; 2) Optimization: optimizing the model performance with crafted prompts and integrating external knowledge and tools, and 3) System engineering: decomposing complex tasks into subtasks and leveraging human expertise for building medical AI applications. Furthermore, we offer a detailed use case playbook that describes various LLM-powered medical AI applications, such as optimizing clinical trial design, enhancing clinical decision support, and advancing medical imaging analysis. Finally, we discuss various challenges and considerations for building medical AI applications with LLMs, such as handling hallucination issues, data ownership and compliance, privacy, intellectual property considerations, compute cost, sustainability issues, and responsible AI requirements.

Zifeng Wang, Benjamin Danek, Jimeng Sun

Validating scientific hypotheses is a central challenge in biomedical research, and remains difficult for artificial intelligence (AI) agents due to the complexity of real-world data analysis and evidence interpretation. In this work, we present BioDSA-1K, a benchmark designed to evaluate AI agents on realistic, data-driven biomedical hypothesis validation tasks. BioDSA-1K consists of 1,029 hypothesis-centric tasks paired with 1,177 analysis plans, curated from over 300 published biomedical studies to reflect the structure and reasoning found in authentic research workflows. Each task includes a structured hypothesis derived from the original study's conclusions, expressed in the affirmative to reflect the language of scientific reporting, and one or more pieces of supporting evidence grounded in empirical data tables. While these hypotheses mirror published claims, they remain testable using standard statistical or machine learning methods. The benchmark enables evaluation along four axes: (1) hypothesis decision accuracy, (2) alignment between evidence and conclusion, (3) correctness of the reasoning process, and (4) executability of the AI-generated analysis code. Importantly, BioDSA-1K includes non-verifiable hypotheses: cases where the available data are insufficient to support or refute a claim, reflecting a common yet underexplored scenario in real-world science. We propose BioDSA-1K as a foundation for building and evaluating generalizable, trustworthy AI agents for biomedical discovery.

Zifeng Wang, Junyi Gao, Benjamin Danek et al.

Leveraging large language models (LLMs) to generate high-stakes documents, such as informed consent forms (ICFs), remains a significant challenge due to the extreme need for regulatory compliance and factual accuracy. Here, we present InformGen, an LLM-driven copilot for accurate and compliant ICF drafting by optimized knowledge document parsing and content generation, with humans in the loop. We further construct a benchmark dataset comprising protocols and ICFs from 900 clinical trials. Experimental results demonstrate that InformGen achieves near 100% compliance with 18 core regulatory rules derived from FDA guidelines, outperforming a vanilla GPT-4o model by up to 30%. Additionally, a user study with five annotators shows that InformGen, when integrated with manual intervention, attains over 90% factual accuracy, significantly surpassing the vanilla GPT-4o model's 57%-82%. Crucially, InformGen ensures traceability by providing inline citations to source protocols, enabling easy verification and maintaining the highest standards of factual integrity.

Zifeng Wang, Qiao Jin, Jiacheng Lin et al.

Developing artificial intelligence (AI) for vertical domains requires a solid data foundation for both training and evaluation. In this work, we introduce TrialPanorama, a large-scale, structured database comprising 1,657,476 clinical trial records aggregated from 15 global sources. The database captures key aspects of trial design and execution, including trial setups, interventions, conditions, biomarkers, and outcomes, and links them to standard biomedical ontologies such as DrugBank and MedDRA. This structured and ontology-grounded design enables TrialPanorama to serve as a unified, extensible resource for a wide range of clinical trial tasks, including trial planning, design, and summarization. To demonstrate its utility, we derive a suite of benchmark tasks directly from the TrialPanorama database. The benchmark spans eight tasks across two categories: three for systematic review (study search, study screening, and evidence summarization) and five for trial design (arm design, eligibility criteria, endpoint selection, sample size estimation, and trial completion assessment). The experiments using five state-of-the-art large language models (LLMs) show that while general-purpose LLMs exhibit some zero-shot capability, their performance is still inadequate for high-stakes clinical trial workflows. We release TrialPanorama database and the benchmark to facilitate further research on AI for clinical trials.

Zifeng Wang, Benjamin Danek, Ziwei Yang et al.

Data science plays a critical role in biomedical research, but it requires professionals with expertise in coding and medical data analysis. Large language models (LLMs) have shown great potential in supporting medical tasks and performing well in general coding tests. However, existing evaluations fail to assess their capability in biomedical data science, particularly in handling diverse data types such as genomics and clinical datasets. To address this gap, we developed a benchmark of data science coding tasks derived from the analyses of 39 published studies. This benchmark comprises 293 coding tasks (128 in Python and 165 in R) performed on real-world TCGA-type genomics and clinical data. Our findings reveal that the vanilla prompting of LLMs yields suboptimal performances due to drawbacks in following input instructions, understanding target data, and adhering to standard analysis practices. Next, we benchmarked six cutting-edge LLMs and advanced adaptation methods, finding two methods to be particularly effective: chain-of-thought prompting, which provides a step-by-step plan for data analysis, which led to a 21% code accuracy improvement (56.6% versus 35.3%); and self-reflection, enabling LLMs to refine the buggy code iteratively, yielding an 11% code accuracy improvement (45.5% versus 34.3%). Building on these insights, we developed a platform that integrates LLMs into the data science workflow for medical professionals. In a user study with five medical professionals, we found that while LLMs cannot fully automate programming tasks, they significantly streamline the programming process. We found that 80% of their submitted code solutions were incorporated from LLM-generated code, with up to 96% reuse in some cases. Our analysis highlights the potential of LLMs to enhance data science efficiency in biomedical research when integrated into expert workflows.

Zifeng Wang, Lang Cao, Benjamin Danek et al.

Synthesizing clinical evidence largely relies on systematic reviews of clinical trials and retrospective analyses from medical literature. However, the rapid expansion of publications presents challenges in efficiently identifying, summarizing, and updating clinical evidence. Here, we introduce TrialMind, a generative artificial intelligence (AI) pipeline for facilitating human-AI collaboration in three crucial tasks for evidence synthesis: study search, screening, and data extraction. To assess its performance, we chose published systematic reviews to build the benchmark dataset, named TrialReviewBench, which contains 100 systematic reviews and the associated 2,220 clinical studies. Our results show that TrialMind excels across all three tasks. In study search, it generates diverse and comprehensive search queries to achieve high recall rates (Ours 0.711-0.834 v.s. Human baseline 0.138-0.232). For study screening, TrialMind surpasses traditional embedding-based methods by 30% to 160%. In data extraction, it outperforms a GPT-4 baseline by 29.6% to 61.5%. We further conducted user studies to confirm its practical utility. Compared to manual efforts, human-AI collaboration using TrialMind yielded a 71.4% recall lift and 44.2% time savings in study screening and a 23.5% accuracy lift and 63.4% time savings in data extraction. Additionally, when comparing synthesized clinical evidence presented in forest plots, medical experts favored TrialMind's outputs over GPT-4's outputs in 62.5% to 100% of cases. These findings show the promise of LLM-based approaches like TrialMind to accelerate clinical evidence synthesis via streamlining study search, screening, and data extraction from medical literature, with exceptional performance improvement when working with human experts.