基于历史不良事件数据,自动筛选最少且全面的患者报告症状条目。
Automated PRO-CTCAE Symptom Selection based on Prior Adverse Event Profiles
- 用MedDRA术语构建语义空间,量化症状与历史不良事件的关联性。
- 通过谱分析选出兼顾相关性与多样性的核心症状集,覆盖90%以上关键信号。
- 适合临床试验设计者快速优化患者报告症状问卷,降低负担同时不漏风险。
PRO-CTCAE是美国国家癌症研究所开发的肿瘤临床试验中患者报告症状不良事件系统,包含大量源自CTCAE词汇库的条目。传统上,针对特定试验的症状选择依赖于以往毒性谱的判断。项目过多会增加患者负担,影响依从性;过少则可能遗漏重要安全信号。本文提出一种自动化方法,基于历史安全数据筛选最小但全面的PRO-CTCAE子集。每个候选症状首先映射到对应的MedDRA首选术语(PT),再编码至Safeterm——一个高维语义空间,用于捕捉MedDRA术语的临床与上下文多样性。通过结合相关性与发生率构建效用函数,对每个候选项进行评分。进一步采用谱分析处理综合效用与多样性矩阵,识别出一组正交的医学概念,平衡相关性与覆盖范围。症状按重要性排序,依据信息解释率确定截断点。该工具已集成于Safeterm试验安全应用中。通过模拟和真实肿瘤案例研究评估其性能,结果表明该方法可利用MedDRA语义与历史数据,客观、可复现地平衡信号覆盖与患者负担,显著提升PRO-CTCAE设计效率。
原文摘要 · Abstract (English)
The PRO-CTCAE is an NCI-developed patient-reported outcome system for capturing symptomatic adverse events in oncology trials. It comprises a large library drawn from the CTCAE vocabulary, and item selection for a given trial is typically guided by expected toxicity profiles from prior data. Selecting too many PRO-CTCAE items can burden patients and reduce compliance, while too few may miss important safety signals. We present an automated method to select a minimal yet comprehensive PRO-CTCAE subset based on historical safety data. Each candidate PRO-CTCAE symptom term is first mapped to its corresponding MedDRA Preferred Terms (PTs), which are then encoded into Safeterm, a high-dimensional semantic space capturing clinical and contextual diversity in MedDRA terminology. We score each candidate PRO item for relevance to the historical list of adverse event PTs and combine relevance and incidence into a utility function. Spectral analysis is then applied to the combined utility and diversity matrix to identify an orthogonal set of medical concepts that balances relevance and diversity. Symptoms are rank-ordered by importance, and a cut-off is suggested based on the explained information. The tool is implemented as part of the Safeterm trial-safety app. We evaluate its performance using simulations and oncology case studies in which PRO-CTCAE was employed. This automated approach can streamline PRO-CTCAE design by leveraging MedDRA semantics and historical data, providing an objective and reproducible method to balance signal coverage against patient burden.
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