“希望区域”框架样本量重估在适应性设计临床试验中的应用

doi:10.3969/j.issn.1006-7795.2025.02.004

首都医科大学学报 ›› 2025, Vol. 46 ›› Issue (2): 197-201.doi: 10.3969/j.issn.1006-7795.2025.02.004

• 临床研究与方法学应用进展 • 上一篇下一篇

“希望区域”框架样本量重估在适应性设计临床试验中的应用

杨笑^1，2，3，夏雪^1，2，3，周全¹，郝允逸^1，2，3，王安心^1，2，3*

1.首都医科大学附属北京天坛医院北京市神经外科研究所流行病学研究室，北京 100070; 2.首都医科大学附属北京天坛医院国家神经系统疾病临床医学研究中心，北京 100070;3.首都医科大学临床流行病与临床试验学系北京 100070

收稿日期:2024-11-19 出版日期:2025-04-21 发布日期:2025-04-14
通讯作者: 王安心 E-mail:wanganxin@bjtth.org
基金资助:
北京市高层次公共卫生技术人才建设项目（学科骨干-02-47）。

Application of sample size re-estimation within the “promising zone” framework in adaptive design clinical trials

Yang Xiao^1,2,3, Xia Xue^1,2,3, Zhou Quan¹, Hao Yunyi^1,2,3, Wang Anxin^1,2,3*

1.Department of Epidemiology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China;2.China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China;3.Department of Clinical Epidemiology and Clinical Trial, Capital Medical University, Beijing 100070, China

Received:2024-11-19 Online:2025-04-21 Published:2025-04-14
Supported by:
This study was supported by the High-level Public Health Talents (xuekegugan-02-47).

摘要/Abstract

摘要： “希望区域”法是在非盲状态下对适应性设计临床试验的期中数据进行分析，进而根据期中分析对样本量进行调整，以提高试验成功的概率或减少非必要样本量投入的一种样本量重估方法。Mehta和Pocock基于“希望区域”的概念提出了根据期中分析结果增加样本量的规则（MP设计）。进一步地，MP设计与成组序贯相结合可以为试验设定提前停止边界，允许在有利/不利条件下减少样本量投入。临床试验设计则在“希望区域”框架下进行了进一步优化，通过将样本量与条件效能组合考虑，实现以最小样本量达到最高条件效能的目的。本文将概述“希望区域”法的原理，介绍“希望区域”的确定及样本量重新估计的方法，并结合实际案例进一步说明该方法在临床试验中的可行性。

关键词: 希望区域法, 样本量重估, 适应性设计, 期中分析, 条件效能

Abstract: The “promising zone” is a method used to analyze interim data from adaptive design clinical trials in an unblinded state. It allows for the adjustment of sample size based on interim results to enhance the trial's probability of success or minimize investment in unnecessary sample size. Mehta and Pocock proposed rules for increasing sample size based on interim analysis results using the concept of the “promising zone” (MP design). Furthermore, combination of the MP design with group sequential design can set up early stopping boundaries in trials, allowing for a reduction in sample size under favorable or unfavorable zone. The combination test (CT) design further optimizes the framework of the “promising zone”, by considering sample size and conditional power in combination to achieve the highest conditional power with the smallest sample size. This review summarizes the principles of the “promising zone”, introduces the method of determining the “promising zone” and re-estimating sample size, and further illustrates the feasibility of this method in clinical trials with a practical case.

Key words: promising zone, sample size re-estimate, adaptive design, interim analysis, conditional power

中图分类号:

杨笑, 夏雪, 周全, 郝允逸, 王安心. “希望区域”框架样本量重估在适应性设计临床试验中的应用[J]. 首都医科大学学报, 2025, 46(2): 197-201.

Yang Xiao, Xia Xue, Zhou Quan, Hao Yunyi, Wang Anxin. Application of sample size re-estimation within the “promising zone” framework in adaptive design clinical trials[J]. Journal of Capital Medical University, 2025, 46(2): 197-201.

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“希望区域”框架样本量重估在适应性设计临床试验中的应用

Application of sample size re-estimation within the “promising zone” framework in adaptive design clinical trials

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