The American Statistical Association Biopharmaceutical Section (ASA BIOP) working group on real-world evidence (RWE) has been making continuous, extended effort towards a goal of supporting and advancing regulatory science with respect to non-interventional, clinical studies intended to use real-world data for evidence generation for the purpose of medical product development and evaluation (i.e., RWE studies). In 2023, the working group published a manuscript delineating challenges and opportunities in constructing estimands for RWE studies following a framework in ICH E9(R1) guidance on estimand and sensitivity analysis. As a follow-up task, we describe the other issue in RWE studies, sensitivity analysis. Focusing on the issue of unmeasured confounding, we review availability and applicability of sensitivity analysis methods for different types unmeasured confounding. We discuss consideration on the choice and use of sensitivity analysis for RWE studies. Updated version of this article will present how findings from sensitivity analysis could support regulatory decision-making using a real example.

翻译：美国统计协会生物制药分会（ASA BIOP）真实世界证据（RWE）工作组持续致力于推进监管科学，针对旨在利用真实世界数据生成医疗产品开发与评估证据的非干预性临床研究（即RWE研究）。2023年，该工作组发表了一篇手稿，遵循ICH E9(R1)关于估计目标与敏感性分析指南的框架，阐述了构建RWE研究估计目标的挑战与机遇。作为后续任务，我们探讨了RWE研究中的另一问题——敏感性分析。聚焦未测量混杂因素，我们回顾了针对不同类型未测量混杂因素的敏感性分析方法及其可行性与适用性，讨论了RWE研究中敏感性分析的选择与使用考量。本文更新版本将以实际案例展示敏感性分析结果如何支持监管决策。