The formulation of clinical questions is a critical starting point in the development of Clinical Practice Guidelines (CPGs), directly influencing their scope and recommendations. Although various health organizations have issued numerous guideline development manuals, their guidance on the specific processes and operational methods for formulating clinical questions remains generally insufficiently detailed. This often leads to misunderstandings and operational difficulties for guideline developers in practice.

To compare the methodological content related to the formulation of clinical questions in authoritative guideline development manuals from both domestic and international sources, and to provide insights and references for constructing a more systematic and operational clinical question formulation process.

The system systematically retrieved guidelines and manual development documents published by authoritative domestic and international institutions, with a search period spanning from January 2010 to May 2025. Data were screened based on clearly defined inclusion and exclusion criteria. Using a directed content analysis approach, the study employed the seven-step framework of WHO manuals as an analytical framework to encode, extract, and conduct summary analyses of clinically relevant content identified in the 11 included manuals. Comparative analyses were performed on key elements and processes.

A total of 11 manuals were included, comprising those from the WHO, the National Institute for Health and Care Excellence (NICE) in the UK, the Scottish Interhospital Guidelines Network (SIGN), and the Manual on Acupuncture in Traditional Chinese Medicine [World Federation of Acupuncture Societies (WFAS), National Administration of Traditional Chinese Medicine (NATCM)]. Comparative analysis revealed that all manuals recommended the use of the PICO framework for problem formulation, but differences existed in the definition and application of core concepts such as "scope","issues"and "problems". Only a few manuals provided step-by-step procedural recommendations, while most offered only general guidelines. Regarding the sources of clinical questions, clinical surveys and literature reviews were included. In terms of outcome measure importance evaluation, manuals such as WHO explicitly adopted a 9-point scoring system.

Current guideline manuals provide insufficient guidance in terms of standardization and refinement for the clinical question formulation stage. Future efforts should focus on constructing a systematic, step-by-step operational framework that integrates multi-source clinical question collection, PICO-structured formulation, pre-assessment of evidence quality, and incorporation of patient values. Through systematic comparison, this study clarifies the key components and directions for building such a framework, offering direct methodological references for enhancing the scientific rigor, practicality, and efficiency of guideline development.

临床问题的确定是临床实践指南（CPGs）制订的关键起点，直接影响指南的覆盖范围与推荐意见。尽管各卫生健康组织发布了诸多指南制订手册，但其对临床问题确定的具体流程与操作方法的指导仍普遍不够详尽，导致指南制订者在实际操作中面临理解偏差与操作困难。

比较国内外权威指南研制手册中关于临床问题确定的方法学内容，为构建更系统、可操作的临床问题确定流程提供改进思路。

系统检索国内外权威机构发布的指南研制手册，检索时限为2010年1月—2025年5月，依据明确的纳入与排除标准进行筛选。采用定向内容分析法，以WHO手册的7个步骤为分析框架，对纳入的11份手册中临床问题确定的相关内容进行编码、提取与归纳分析，并对关键要素及流程进行对比。

共纳入包括WHO、英国国家卫生与临床优化研究所（NICE）、苏格兰院际指南网络（SIGN）及中医针灸领域手册[世界针灸学会联合会（WFAS）、国家中医药管理局（NATCM）]等在内的11份手册。比较分析发现：所有手册推荐使用PICO框架构建问题，但在"范围""议题""问题"等核心概念的界定与使用上存在差异；仅少数手册提供步骤化具体流程建议，多数仅提供原则性指导；在临床问题来源上，包含临床调研与文献调研；在结局指标重要性评价上，WHO等手册明确采用9分制评分法。

当前指南手册对临床问题确定环节的指导在规范化和精细化方面力度不够。未来应致力于构建一个整合多源临床问题收集、PICO结构化构建、证据质量前置评估及患者价值观融入的系统化、步骤化操作框架。本研究通过系统比较，明确了该框架构建的关键环节与方向，为提升指南制订的科学性、实用性与效率提供直接方法学参考。