PO.BCS02.01 · 生物信息与计算
使用自适应LLM智能体系统从真实世界肿瘤学数据中自动化提取队列,用于临床试验可行性与患者选择
Automated cohort extraction from real-world oncology data using adaptive LLM-based agentic systems for clinical trial feasibility and patient selection
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
临床可行性分析和队列识别在精准肿瘤学中具有重要应用,包括针对临床试验及其他研究设计的可行性评估、用于数字孪生建模和虚拟试验模拟的队列提取,以及用于监管申报和比较效果研究的真实世界证据生成。然而,真实世界肿瘤学数据集因其异构、非标准的数据格式以及复杂、相互关联的入组标准而带来重大挑战。这些技术障碍又因技术理解、数据访问和代码执行等功能性难题而进一步加剧。传统方法依赖缓慢、不可扩展的人工查询构建,即便是近期最先进的大语言模型(LLM)也难以进行多步推理并适应多样的数据结构。
为解决这些问题,我们开发了一个自适应的、基于LLM的智能体平台,它能自主学习数据结构、生成并执行代码,并迭代优化分析以提取满足复杂标准的患者队列。与仅生成静态代码、不具备执行能力或数据集适应能力的传统LLM不同,我们平台的智能体架构能动态探索数据模式、验证中间输出并自我纠正错误。它还可接受专家指导,并在流程的每一步实现完全可审计、可编辑和可导出的输出。该系统接受指定复杂标准(如特定诊断、基因组特征、治疗史和时间关系)的自然语言查询,然后自主处理任意形态、规模和格式的真实世界数据(RWD)以识别符合条件的患者。
我们通过复现来自GuardantINFORM™数据库的15项历史可行性分析来评估性能,该数据库整合了来自超过55万名患者的基因组和表观基因组RWD,以及跨多种肿瘤适应症和数据表的去标识化行政理赔数据。我们的验证研究发现,该平台成功地为12项请求提取了精确队列,并为另外2项提供了临床上可接受的近似结果。最后一项分析因临床理解错误而失败,但在改进指导后可事后纠正。相比之下,未经调优智能体能力的最先进LLM无法适应数据集特定结构,任务完成率较低,凸显了基于任务的设计、迭代执行和自我纠正的关键重要性。这一性能使复杂数据分析的访问变得普及,解决了将RWD转化为可操作临床洞见的关键瓶颈,并为能够加速肿瘤学研究的自主、自适应AI系统奠定了基础。
查看英文原文 English abstract
Clinical feasibility analysis and cohort identification have essential applications in precision oncology, including feasibility assessment for clinical trial and other study designs, cohort extraction for digital twin modeling and virtual trial simulation, and real-world evidence generation for regulatory submission and comparative effectiveness research. However, real-world oncology datasets pose significant challenges due to heterogeneous, nonstandard data formats and complex, interconnected inclusion criteria. These technical barriers are compounded by functional hurdles like technical understanding, data access, and code execution. Traditional approaches rely on slow, unscalable manual query construction, and even recent state-of-the-art large language models (LLMs) struggle with multi-step reasoning and adaptation to diverse data structures.
To address these issues, we developed an adaptive LLM-based agentic platform that autonomously learns data structures, generates and executes code, and iteratively refines analyses to extract patient cohorts meeting complex criteria. Unlike conventional LLMs that generate static code without execution capabilities or dataset adaptation, our platform's agentic architecture dynamically explores data schemas, validates intermediate outputs, and self-corrects errors. It also accepts expert guidance and allows fully auditable, editable, and exportable outputs at each step of the process. The system accepts natural language queries specifying complex criteria such as specific diagnoses, genomic profiles, treatment histories, and temporal relationships, then autonomously navigates real-world data (RWD) of any shape, size, and format to identify qualifying patients.
We evaluated performance by replicating 15 historical feasibility analyses from the GuardantINFORM™ database, which integrates genomic and epigenomic RWD from >550K patients with de-identified administrative claims data across multiple oncology indications and data tables. Our validation study found that the platform successfully extracted exact cohorts for 12 requests and delivered clinically acceptable approximations for 2 more. The final analysis failed due to a clinical misunderstanding but was correctable post hoc with improved guidance. In contrast, state-of-the-art LLMs without tuned agentic capabilities failed to adapt to dataset-specific structures and had low task completion rates, highlighting the critical importance of the task-based design, iterative execution, and self-correction. This performance democratizes access to sophisticated data analysis, addressing a critical bottleneck in translating RWD into actionable clinical insights and establishing a foundation for autonomous, adaptive AI systems that can accelerate oncology research.
利益披露 Disclosure
B. Theodorou,
Guardant Health ).
T. Schmitt,
Guardant Health Employment.
Z. Wang,
Guardant Health ).
V. Thati,
Guardant Health ).
A. Watkins,
Guardant Health Employment.
K. Banks,
Guardant Health Employment.
J. Sun,
Guardant Health ).
A. Das,
Guardant Health Employment.