特许药械真实世界研究中外部对照的研究设计要点和统计分析方法

Key Points of Study Design and Statistical Analysis for External Control Application in Real World Study of Special Innovative Medicines and Devices

特许药械由于临床急需的特点而难以设立同期内部对照(IC),其在海南博鳌乐城国际医疗旅游先行区(以下简称乐城先行区)进行的真实世界研究(RWS)常以单臂研究为主,但单臂研究结果解释性有限且不能有效控制偏倚。国际人用药品注册技术协调会(ICH)、美国食品药品监督管理局(FDA)以及我国国家药品监督管理局(NMPA)发布的指导原则中,针对特殊场景均推荐使用外部对照(EC)。本文将以上述国内外指导原则为依据,按照研究设计和统计分析两个阶段,分别介绍针对乐城先行区特许药械RWS场景下EC的研究设计要点和统计分析方法,旨在为开展特许药械相关高质量临床研究、加快国内注册审批提供参考依据。

Due to the urgent clinical needs,it is difficult to establish internal controls(IC)for special innovative medicines and devices.Real world study(RWS)of special innovative medicines and devices conducted in Boao Lecheng of Hainan Province often focuses on single-arm study designs.However,single-arm studies have limitations in interpretability and effective bias control.In the guidelines issued by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH),the Food and Drug Administration(FDA),and the National Medical Products Administration(NMPA),external controls(EC)are recommended for special scenarios.This article,based on the domestic and foreign guidelines above,introduces the key points of study design and statistical analysis methods for EC in the RWS scenario of special innovative medicines and devices in Lecheng.The aim is to provide a basis for conducting high-quality clinical research on special innovative medicines and devices and to accelerate domestic registration and approval.