Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Trials. 2024 Sep 12;25(1):608. doi: 10.1186/s13063-024-08400-6.
Multi-Arm, Multi-Stage (MAMS) clinical trial designs allow for multiple therapies to be compared across a spectrum of clinical trial phases. MAMS designs fall under several overarching design groups, including adaptive designs (AD) and multi-arm (MA) designs. Factorial clinical trials designs represent a combination of factorial and MAMS trial designs and can provide increased efficiency relative to fixed, traditional designs. We explore design choices associated with Factorial Adaptive Multi-Arm Multi-Stage (FAST) designs, which represent the combination of factorial and MAMS designs.
Simulation studies were conducted to assess the impact of the type of analyses, the timing of analyses, and the effect size observed across multiple outcomes on trial operating characteristics for a FAST design. Given multiple outcomes types assessed within the hypothetical trial, the primary analysis approach for each assessment varied depending on data type.
The simulation studies demonstrate that the proposed class of FAST trial designs can offer a framework to potentially provide improvements relative to other trial designs, such as a MAMS or factorial trial. Further, we note that the design implementation decisions, such as the timing and type of analyses conducted throughout trial, can have a great impact on trial operating characteristics.
Motivated by a trial currently under design, our work shows that the FAST category of trial can potentially offer benefits similar to both MAMS and factorial designs; however, the chosen design aspects which can be included in a FAST trial need to be thoroughly explored during the planning phase.
多臂、多阶段（MAMS）临床试验设计允许在一系列临床试验阶段对多种疗法进行比较。MAMS 设计属于几种总体设计组，包括适应性设计（AD）和多臂（MA）设计。析因临床试验设计代表了析因和 MAMS 试验设计的结合，可以提供相对于固定、传统设计的更高效率。我们探讨了与析因自适应多臂多阶段（FAST）设计相关的设计选择，该设计代表了析因和 MAMS 设计的结合。
进行了模拟研究，以评估分析类型、分析时机以及多个结局观察到的效应大小对 FAST 设计试验操作特性的影响。鉴于假设试验中评估的多个结局类型，每种评估的主要分析方法取决于数据类型。
模拟研究表明，拟议的 FAST 试验设计类可以提供一个框架，相对于其他试验设计（如 MAMS 或析因试验）可能提供改进。此外，我们注意到设计实施决策，例如整个试验过程中进行的分析类型和时机，对试验操作特性有重大影响。
受当前正在设计的一项试验的启发，我们的工作表明，FAST 类试验可能具有与 MAMS 和析因设计相似的优势；然而，在 FAST 试验中可以包含的选定设计方面需要在规划阶段进行深入探讨。
