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一项预先计划的多阶段平台试验,用于发现多种具有控制家族性错误率(FWER)和检验功效的优势治疗方法。

A Preplanned Multi-Stage Platform Trial for Discovering Multiple Superior Treatments With Control of FWER and Power.

作者信息

Greenstreet Peter, Jaki Thomas, Bedding Alun, Mozgunov Pavel

机构信息

Department of Mathematics and Statistics, Lancaster University, Lancaster, UK.

Exeter Clinical Trials Unit, University of Exeter, Exeter, UK.

出版信息

Biom J. 2025 Feb;67(1):e70025. doi: 10.1002/bimj.70025.

Abstract

There is a growing interest in the implementation of platform trials, which provide the flexibility to incorporate new treatment arms during the trial and the ability to halt treatments early based on lack of benefit or observed superiority. In such trials, it can be important to ensure that error rates are controlled. This paper introduces a multi-stage design that enables the addition of new treatment arms, at any point, in a preplanned manner within a platform trial, while still maintaining control over the family-wise error rate. This paper focuses on finding the required sample size to achieve a desired level of statistical power when treatments are continued to be tested even after a superior treatment has already been found. This may be of interest if there are treatments from different sponsors which are also superior to the current control or multiple doses being tested. The calculations to determine the expected sample size is given. A motivating trial is presented in which the sample size of different configurations is studied. In addition, the approach is compared to running multiple separate trials and it is shown that in many scenarios if family-wise error rate control is needed there may not be benefit in using a platform trial when comparing the sample size of the trial.

摘要

平台试验的实施正引发越来越多的关注,这种试验能在试验期间灵活纳入新的治疗组,并能基于缺乏疗效或观察到的优越性提前终止治疗。在这类试验中,确保控制错误率可能很重要。本文介绍了一种多阶段设计,该设计能在平台试验中以预先规划的方式在任何时间点添加新的治疗组,同时仍能控制族系错误率。本文着重探讨当即使已经发现了一种更优治疗方法后仍继续对其他治疗方法进行测试时,为达到期望的统计功效所需的样本量。如果存在来自不同申办方且也优于当前对照的治疗方法或正在测试多种剂量,这可能会是一个值得关注的问题。给出了确定预期样本量的计算方法。文中呈现了一个具有启发性的试验,其中研究了不同配置的样本量。此外,还将该方法与进行多个单独试验进行了比较,结果表明,在许多情况下,如果需要控制族系错误率,那么在比较试验样本量时,使用平台试验可能并无益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/432b/11664203/b4ab145a8e5e/BIMJ-67-e70025-g001.jpg

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