BACKGROUND For many disease areas, there are often treatments in different stages of the development process. We consider the design of a two-arm parallel group trial where it is planned to add a new experimental treatment arm during the trial. This could potentially save money, patients, time and resources; however, the addition of a treatment arm creates a multiple comparison problem. Current practice in trials when a new treatment arm has been added is to compare the new treatment only to controls randomised concurrently, and this is the setting we consider here. Furthermore, for standard multi-arm trials, optimal allocation randomises a larger number of patients to the control arm than to each experimental treatment arm. METHODS In this paper we propose an adaptive design, the aim of which is to adapt the sample size of the trial when the new treatment arm is added to control the family-wise error rate (FWER) in the strong sense, whilst maintaining the marginal power of each treatment-to-control comparison at the level of the original study. We explore optimal allocation for designs where a treatment arm is added with the aim of increasing the overall power of the study, where we define the overall power to be the probability of detecting all treatments that are better than the control. RESULTS AND CONCLUSIONS An increase in sample size is required to maintain the marginal power for each pairwise comparison when adding a treatment arm if control of the FWER is required at the level of the type I error in the original study. When control of the FWER is required in a single trial which adds an additional experimental treatment arm, but control of the FWER is not required in separate trials, depending on the design characteristics, it may be better to run a separate trial for each experimental treatment, in terms of the number of patients required. An increase in overall power can be achieved when optimal allocation is used once a treatment arm has been added to the trial, rather than continuing with equal allocation to all treatment arms.

中文翻译：

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在正在进行的临床试验中增加治疗臂的设计。

背景技术对于许多疾病区域，经常在发展过程的不同阶段进行治疗。我们考虑了两臂平行小组试验的设计，计划在试验期间添加新的实验治疗组。这有可能节省金钱，患者，时间和资源。但是，增加治疗臂会产生多重比较问题。在试验中，当添加了新的治疗组时，目前的实践做法是仅将新治疗与同时随机对照进行比较，这就是我们在此处考虑的设置。此外，对于标准的多组试验，与每个实验治疗组相比，最佳分配将更多的患者随机分配到对照组。方法在本文中，我们提出了一种自适应设计，其目的是在增加新的治疗组以严格控制家庭误诊率（FWER）的同时适应试验的样本量，同时保持每次治疗与对照比较的边际功效原始研究的水平。为了增加研究的总体能力，我们探索了添加治疗臂的设计的最佳分配，其中我们将总体能力定义为检测出所有优于对照的治疗的可能性。结果与结论如果在原始研究中需要将FWER控制在I型错误的水平，则在增加治疗组时，需要增加样本量以维持每对配对比较的边际功效。如果在单个试验中需要对FWER进行控制，从而增加了一个额外的实验治疗组，但是在单独的试验中不需要对FWER进行控制，则取决于设计特征，对于每个实验处理，最好进行单独的试验，就所需的患者数量而言。一旦将治疗组添加到试验中，而使用最佳分配，则可以实现整体功效的提高，而不是继续对所有治疗组进行均等的分配。