在随机临床试验设计中纳入外部控制:实体瘤案例研究。

IF 3.9 3区 医学 Q1 HEALTH CARE SCIENCES & SERVICES BMC Medical Research Methodology Pub Date : 2024-11-01 DOI:10.1186/s12874-024-02383-3
Emily M Damone, Jiawen Zhu, Herbert Pang, Xiao Li, Yinqi Zhao, Evan Kwiatkowski, Lisa A Carey, Joseph G Ibrahim
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引用次数: 0

摘要

背景:在考虑未来试验设计时,临床试验中使用历史外部对照数据的兴趣和需求日益增长。混合对照设计可以更有效地利用更少的患者和有限的资源达到相同的效果。目前有关适当统计方法的文献很少,而这些方法可以解释研究中历史外部对照和对照患者之间的差异。在本文中,我们将说明在确定 RCT 不可行后,如果采用混合对照设计,临床试验的分析框架:方法:我们以之前完成的两项非鳞癌 NSCLC 的 RCT 和一个全国性的电子健康记录衍生去标识数据库为例,比较了每项试验的 5 种分析方法,并进行了一组模拟,以确定此类设计的运行特征:结果:在单一试验估算中,病例加权自适应功率先验法估算出的治疗危险比与原始试验结论一致,但置信区间较窄。模拟研究表明,在研究样本量一致的情况下,病例加权自适应功率先验法在所有 5 种方法中取得了最高的功率(并很好地控制了 1 类误差):通过遵循所提出的混合控制框架,我们可以透明地设计混合控制试验,并考虑到控制组之间的差异,同时控制类型-1 误差,并从外部控制的额外贡献中获得效率收益。
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Incorporating external controls in the design of randomized clinical trials: a case study in solid tumors.

Background: The use of historical external control data in clinical trials has grown in interest and needs when considering the design of future trials. Hybrid control designs can be more efficient to achieve the same power with fewer patients and limited resources. The literature is sparse on appropriate statistical methods which can account for the differences between historical external controls and the control patients in a study. In this article, we illustrate the analysis framework of a clinical trial if a hybrid control design was used after determining an RCT may not be feasible.

Methods: We utilize two previously completed RCTs in nonsquamous NSCLC and a nationwide electronic health record derived de-identified database as examples and compare 5 analysis methods on each trial, as well as a set of simulations to determine operating characteristics of such designs.

Results: In single trial estimation, the Case Weighted Adaptive Power Prior provided estimated treatment hazard ratios consistent with the original trial's conclusions with narrower confidence intervals. The simulation studies showed that the Case Weighted Adaptive Power Prior achieved the highest power (and well controlled type-1 error) across all 5 methods with consistent study sample size.

Conclusions: By following the proposed hybrid control framework, one can design a hybrid control trial transparently and accounting for differences between control groups while controlling type-1 error and still achieving efficiency gains from the additional contribution from external controls.

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来源期刊
BMC Medical Research Methodology
BMC Medical Research Methodology 医学-卫生保健
CiteScore
6.50
自引率
2.50%
发文量
298
审稿时长
3-8 weeks
期刊介绍: BMC Medical Research Methodology is an open access journal publishing original peer-reviewed research articles in methodological approaches to healthcare research. Articles on the methodology of epidemiological research, clinical trials and meta-analysis/systematic review are particularly encouraged, as are empirical studies of the associations between choice of methodology and study outcomes. BMC Medical Research Methodology does not aim to publish articles describing scientific methods or techniques: these should be directed to the BMC journal covering the relevant biomedical subject area.
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