Ying-Ying Zhu , Wen-Xuan Wang , Shui-Kit Cheuk , Guan-Rui Feng , Xing-Ge Li , Jia-Ying Peng , Ying Liu , Shao-Rui Yu , Jin-Ling Tang , Shein-Chung Chow , Ji-Bin Li
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Descriptive analyses, primarily consisting of frequency and percentage, were employed to analyzed and reported the data.</p></div><div><h3>Results</h3><p>A total of 180 cancer clinical trials with adaptive designs were identified. The first three most common type of adaptive design was the group sequential design (<em>n</em>=114, 63.3 %), adaptive dose-finding design (<em>n</em>=22, 12.2 %), and adaptive platform design (<em>n</em>=16, 8.9 %). The results showed that 4.4 % (<em>n</em>=8) of trials conducted post hoc modifications, and around 29.4 % (<em>n</em>=53) did not provide the methods for controlling type I errors. Among phase II or above trials, 79.9 % (112/140) applied the surrogate endpoint as the primary outcome in these trials. Importantly, 27.2 % (49/180) of trials did not report clear information on the independent data monitoring committee (iDMC), and 13.3 % (<em>n</em>=24) without clear information on interim analyses. 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引用次数: 0
摘要
背景:近年来,随着各种应用指南的发布,适应性设计在癌症试验中的应用在全球范围内大幅增加。本系统综述旨在全面总结适应性设计在癌症临床试验中的主要方法和执行特点:方法:我们对PubMed、EMBASE和Cochrane对照试验中央登记册进行了全面检索,筛选出符合条件的采用适应性设计并在癌症患者中开展的临床试验。适应性设计的方法和执行特征是提取的主要测量指标。采用描述性分析(主要包括频率和百分比)来分析和报告数据:结果:共发现了 180 项采用适应性设计的癌症临床试验。前三种最常见的适应性设计分别是分组序贯设计(n=114,63.3%)、适应性剂量探索设计(n=22,12.2%)和适应性平台设计(n=16,8.9%)。结果显示,4.4%(8 例)的试验进行了事后修改,约 29.4%(53 例)的试验未提供控制 I 型误差的方法。在二期或二期以上的试验中,79.9%(112/140)的试验将替代终点作为主要结果。重要的是,27.2%(49/180)的试验没有明确报告独立数据监测委员会(iDMC)的信息,13.3%(24)的试验没有明确报告中期分析的信息。中期分析表明,34.4%(62/180)的试验因无效而停止,10.6%(19人)因疗效而停止,2.2%(4人)因早期安全性问题而停止:本研究强调,癌症试验中的适应性设计在设计或严格按照方案实施方面面临巨大挑战,可能会严重影响试验的有效性和完整性。因此,研究人员、申办者和政策制定者必须积极监督和指导其应用。
A landscape of methodology and implementation of adaptive designs in cancer clinical trials
Background
The use of adaptive designs in cancer trials has considerably increased worldwide in recent years, along with the release of various guidelines for their application. This systematic review aims to comprehensively summarize the key methodological and executive features of adaptive designs in cancer clinical trials.
Methods
A comprehensive search from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted to screen eligible clinical trials that employed adaptive designs and were conducted in cancer patients. The methodological and executive characteristics of adaptive designs were the main measurements extracted. Descriptive analyses, primarily consisting of frequency and percentage, were employed to analyzed and reported the data.
Results
A total of 180 cancer clinical trials with adaptive designs were identified. The first three most common type of adaptive design was the group sequential design (n=114, 63.3 %), adaptive dose-finding design (n=22, 12.2 %), and adaptive platform design (n=16, 8.9 %). The results showed that 4.4 % (n=8) of trials conducted post hoc modifications, and around 29.4 % (n=53) did not provide the methods for controlling type I errors. Among phase II or above trials, 79.9 % (112/140) applied the surrogate endpoint as the primary outcome in these trials. Importantly, 27.2 % (49/180) of trials did not report clear information on the independent data monitoring committee (iDMC), and 13.3 % (n=24) without clear information on interim analyses. Interim analyses suggested 34.4 % (62/180) of trials being stopped for futility, 10.6 % (n=19) for efficacy, and 2.2 % (n=4) for safety concerns in the early stage.
Conclusions
This study emphasizes adaptive designs in cancer trials face significant challenges in their design or strict implementation according to protocol, which might significantly compromise the validity and integrity of trials. It is thus important for researchers, sponsors, and policymakers to actively oversee and guide their application.
期刊介绍:
Critical Reviews in Oncology/Hematology publishes scholarly, critical reviews in all fields of oncology and hematology written by experts from around the world. Critical Reviews in Oncology/Hematology is the Official Journal of the European School of Oncology (ESO) and the International Society of Liquid Biopsy.