Supplementary data: The maze of real-world evidence frameworks: from a desert to a jungle! An environmental scan and comparison across regulatory and health technology assessment agencies

These are peer-reviewed supplementary materials for the article 'The maze of real-world evidence frameworks: from a desert to a jungle! An environmental scan and comparison across regulatory and health technology assessment agencies' published in the Journal of Comparative Effectiveness Research.Supplementary Table 1: Search StrategiesSupplementary Table 2: Summary of real-world evidence guidance across regulatory and health technology assessment agencies, and other decision-makersSupplementary Table 3: Real-world evidence guidance references from international organizations or working groupsSupplementary Table 4: International Society for Pharmacoepidemiology-endorsed publications on real-world evidence topicsSupplementary Table 5: List of checklists, templates, and tools referenced by the included RWE guidance documentsAim: Regulatory and health technology assessment (HTA) agencies have increasingly published frameworks, guidelines, and recommendations for the use of real-world evidence (RWE) in healthcare decision-making. Variations in the scope and content of these documents, with updates running in parallel, may create challenges for their implementation especially during the market authorization and reimbursement phases of a medicine’s life cycle. This environmental scan aimed to comprehensively identify and summarize the guidance documents for RWE developed by most well-established regulatory and reimbursement agencies, as well as other organizations focused on healthcare decision-making, and present their similarities and differences. Methods: RWE guidance documents, including white papers from regulatory and HTA agencies, were reviewed in March 2024. Data on scope and recommendations from each body were extracted by two reviewers and similarities and differences were summarized across four topics: study planning, choosing fit-for-purpose data, study conduct, and reporting. Post-authorization or non-pharmacological guidance was excluded. Results: Forty-six documents were identified across multiple agencies; US FDA produced the most RWE-related guidance. All agencies addressed specific and often similar methodological issues related to study design, data fitness-for-purpose, reliability, and reproducibility, although inconsistency in terminologies on these topics was noted. Two HTA bodies (National Institute for Health and Care Excellence [NICE] and Canada’s Drug Agency) each centralized all related RWE guidance under a unified framework. RWE quality tools and checklists were not consistently named and some differences in preferences were noted. European Medicines Agency, NICE, Haute Autorit ´e de Sant´ e, and the Institute for Quality and Efficiency in Health Care included specific recommendations on the use of analytical approaches to address RWE complexities and increase trust in its findings. Conclusion: Similarities in agencies’ expectations on RWE studies design, quality elements, and reporting will facilitate evidence generation strategy and activities for manufacturers facing multiple, including global, regulatory and reimbursement submissions and re-submissions. A strong preference by decision-making bodies for local real-world data generation may hinder opportunities for data sharing and outputs from international federated data networks. Closer collaboration between decision-making agencies towards a harmonized RWE roadmap, which can be centrally preserved in a living mode, will provide manufacturers and researchers clarity on minimum acceptance requirements and expectations, especially as novel methodologies for RWE generation are rapidly emerging.

本数据集为发表于《比较有效性研究杂志》之文章《现实世界证据框架的迷宫：从沙漠到丛林！跨监管和卫生技术评估机构的环境扫描与比较》的同行评审补充材料。补充表1：搜索策略；补充表2：监管和卫生技术评估机构及其他决策者关于现实世界证据（RWE）指导的概要；补充表3：来自国际组织或工作组的现实世界证据指导参考文献；补充表4：国际药理流行病学协会认可的现实世界证据主题出版物；补充表5：包含现实世界证据指导文件的清单、模板和工具列表。目标：随着监管和卫生技术评估（HTA）机构越来越多地发布框架、指南和建议，用于在医疗决策中应用现实世界证据（RWE），这些文件的范畴和内容存在差异，且更新并行进行，可能给其实施带来挑战，尤其是在药物生命周期中的市场授权和报销阶段。此次环境扫描旨在全面识别和总结大多数知名监管和报销机构以及专注于医疗决策的其他组织制定的RWE指导文件，并展示其相似性与差异性。方法：在2024年3月，对RWE指导文件进行了审查，包括监管和HTA机构的白皮书。由两位审查员提取了各机构的范畴和建议数据，并总结了四个主题：研究规划、选择适宜数据、研究执行和报告。排除授权后或非药理学的指导。结果：在多个机构中识别出46个文件；美国食品药品监督管理局（US FDA）产生了最多的RWE相关指导。所有机构都针对与研究设计、数据适宜性、可靠性和可重复性相关的特定且通常相似的方法论问题进行了处理，尽管在这些主题上的术语存在不一致性。两个HTA机构（国家健康与护理卓越研究所[NICE]和加拿大药品管理局）各自将所有相关RWE指导集中在一个统一的框架下。RWE质量工具和清单的命名并不一致，并注意到一些偏好差异。欧洲药品管理局、NICE、Haute Autorité de Santé和卫生保健质量与效率研究所包括针对使用分析方法解决RWE复杂性和提高其发现可信度的具体建议。结论：机构对RWE研究设计、质量要素和报告的期望相似性将促进面对多重，包括全球性监管和报销提交和重新提交的制造商的证据生成策略和活动。决策机构对本地现实世界数据生成的强烈偏好可能会阻碍数据共享和国际联邦数据网络输出的机会。决策机构之间就统一的RWE路线图进行更紧密的合作，该路线图可以集中保存在一种动态模式中，将为制造商和研究人员提供关于最低接受要求和期望的清晰度，尤其是在现实世界证据生成的新方法快速涌现的背景下。