Manuscript: STaRT-RWE: A structured template for planning and reporting on the implementation of real-world evidence studies

Real world evidence (RWE) generated from real world data (RWD) increasingly informs important decisions about the clinical effectiveness and safety of medical products and interventions. Unlike clinical trials, which can leverage the power of randomization, or non-randomized studies with prospective collection of data for a specific research purpose, most RWE studies make secondary use of longitudinal data collected as part of routine healthcare processes, including administrative claims and electronic health records. This involves numerous complex design and analytic choices. The lack of detail and structure in RWE reporting often requires substantial reviewer time for assessment of studies based on secondary healthcare data. Unambiguous reporting on key design and study implementation parameters could not only streamline and increase efficiency of review for stakeholders, but also improve confidence in the ability to judge the quality of evidence. The level of specificity must be balanced against the burdens it imposes on those reporting and those reviewing study details. In alignment with International Council of Harmonization strategic goals, this public-private collaboration developed a structured template to support RWE study planning, implementation and reporting, based on a consensus document from professional societies. The template specifies key study parameters clearly and concisely in tabular and visual formats, to fulfill several aims: 1) serve as a guiding tool for designing and conducting reproducible RWE studies, 2) set clear expectations for transparent communication of RWE methods, 3) reduce misinterpretation of prose that lacks specificity, 4) allow reviewers to orient quickly and find key information, and 5) facilitate reproducibility, validity assessment, and evidence synthesis. The template is focused on RWE on the effectiveness and safety of medical products and interventions and is compatible with multiple study designs, RWD sources, reporting guidelines, checklists and bias assessment tools. While the simplicity of a checklist is excellent for summarizing areas to report on, it leaves room for misinterpretation and ambiguity about important details of study implementation. We complement the checklist approach by developing a study implementation template where methods related items from existing checklists correspond to the main headings in structured tables where critical details are communicated. Template tables are accompanied by a detailed visual summary in the form of a design diagram. The template is intended to support research planning and preparation, then shared with the final study results to facilitate review and replication. A library of examples for different use cases were prepared to enhance usability.

由真实世界数据（Real World Data, RWD）生成的真实世界证据（Real World Evidence, RWE）正日益为医疗产品与干预措施的临床有效性及安全性相关的重要决策提供参考依据。与可借助随机化优势的临床试验，或是为特定研究目的前瞻性采集数据的非随机研究不同，绝大多数真实世界证据研究均会对常规医疗流程中收集的纵向数据进行二次利用，这类数据涵盖行政索赔数据与电子健康档案。这一过程涉及诸多复杂的研究设计与分析决策环节。真实世界证据的报告往往缺乏细节与结构化框架，致使审阅人员需耗费大量时间对基于二次医疗数据开展的研究进行评估。对关键研究设计与研究执行参数进行清晰明确的报告，不仅能够优化并提升利益相关方的审阅效率，还可增强人们对证据质量评判能力的信心。但需在报告的具体程度与报告者、审阅者承担的额外工作负担之间取得平衡。为契合国际人用药品注册技术协调会（International Council of Harmonization, ICH）的战略目标，该公私合作项目基于各专业协会达成的共识文件，开发了一款结构化模板，用于支撑真实世界证据研究的规划、执行与报告工作。该模板以表格与可视化形式，清晰简洁地列明关键研究参数，旨在实现五大目标：1）为可复现的真实世界证据研究的设计与实施提供指导工具；2）为真实世界证据研究方法的透明化沟通明确预期标准；3）减少因描述缺乏具体性而引发的误解；4）帮助审阅人员快速定位并获取关键信息；5）助力研究复现、有效性评估与证据合成。该模板聚焦于医疗产品与干预措施有效性及安全性相关的真实世界证据，可适配多种研究设计、真实世界数据来源、报告指南、核查清单与偏倚评估工具。尽管核查清单的简洁性非常适合汇总需报告的内容范畴，但它仍为研究执行过程中的重要细节留下了被误解或产生歧义的空间。为此，本模板对核查清单方法进行了补充：将现有核查清单中与研究方法相关的条目，对应至结构化表格的主标题栏，以此传递关键细节信息。模板表格还配有以设计示意图形式呈现的详细可视化摘要。该模板旨在支撑研究规划与筹备工作，后续可与最终研究结果一同共享，以方便审阅与重复验证。项目团队还针对不同应用场景编制了示例库，以提升模板的易用性。