Recognizing the importance of real-world data (RWD) for regulatory purposes, the United States (US) Congress passed the 21st Century Cures Act1 mandating the development of Food and Drug Administration (FDA) guidance on regulatory use of real-world evidence. The Forum on the Integration of Observational and Randomized Data (FIORD) conducted a meeting bringing together various stakeholder groups to build consensus around best practices for the use of RWD to support regulatory science. Our companion paper describes in detail the context and discussion carried out in the meeting, which includes a recommendation to use a causal roadmap for complete pre-specification of study designs using RWD. This article discusses one step of the roadmap: the specification of a procedure for sensitivity analysis, defined as a procedure for testing the robustness of substantive conclusions to violations of assumptions made in the causal roadmap. We include a worked-out example of a sensitivity analysis from a RWD study on the effectiveness of Nifurtimox in treating Chagas disease, as well as an overview of various methods available for sensitivity analysis in causal inference, emphasizing practical considerations on their use for regulatory purposes.

翻译：认识到真实世界数据（RWD）在监管决策中的重要性，美国国会通过了《21世纪治愈法案》，要求制定食品和药物管理局（FDA）关于真实世界证据监管使用的指南。观察性数据与随机数据整合论坛（FIORD）召开了一次会议，汇集了多方利益相关群体，旨在就使用RWD支持监管科学的最佳实践达成共识。我们的配套论文详细描述了该会议的背景与讨论内容，其中包含一项建议：采用因果路线图对使用RWD的研究设计进行完整预指定。本文讨论该路线图的一个步骤：敏感性分析流程的规范定义，即检验实质性结论对因果路线图中假设违背的稳健性的方法。我们以一项关于硝呋莫司治疗恰加斯病有效性的RWD研究为例，展示了敏感性分析的完整实例，并概述了因果推断中可用的多种敏感性分析方法，重点强调其在监管应用中的实践考量。