Background. The DURATIONS design has been recently proposed as a practical alternative to a standard two-arm non-inferiority design when the goal is to optimise some continuous aspect of treatment administration, e.g. duration or frequency, preserving efficacy but improving on secondary outcomes such as safety, costs or convenience. The main features of this design are that (i) it randomises patients to a moderate number of arms across the continuum and (ii) it uses a model to share information across arms. While papers published to date about the design have focused on analysis aspects, here we show how to design such a trial in practice. We use the REFINE-Lung trial as an example; this is a trial seeking the optimal frequency of immunotherapy treatment for non-small cell lung cancer patients. Because the aspect of treatment administration to optimise is frequency, rather than duration, we propose to rename the design as Multi-Arm Multi-Stage Response Over Continuous Intervention (MAMS-ROCI). Methods. We show how simulations can be used to design such a trial. We propose to use the ADEMP framework to plan such simulations, clearly specifying aims, data generating mechanisms, estimands, methods and performance measures before coding and analysing the simulations. We discuss the possible choices to be made using the REFINE-Lung trial as an example. Results. We describe all the choices made while designing the REFINE-Lung trial, and the results of the simulations performed. We justify our choice of total sample size based on these results. Conclusions. MAMS-ROCI trials can be designed using simulation studies that have to be carefully planned and conducted. REFINE-Lung has been designed using such an approach and we have shown how researchers could similarly design their own MAMS-ROCI trial.

翻译：背景。DURATIONS设计近期被提出作为一种实用的替代方案，用于标准双臂非劣效性设计，其目标在于优化治疗实施的某一连续维度（如疗程或频率），在保持疗效的同时改善安全性、成本或便利性等次要结局。该设计的主要特征包括：（i）将患者随机分配至连续区间内适度数量的治疗组；（ii）采用模型在组间共享信息。尽管已发表的论文主要聚焦于该设计的分析方法，本文旨在展示如何在实际中设计此类试验。我们以REFINE-Lung试验为例——该试验旨在寻找非小细胞肺癌患者免疫治疗的最佳频率。鉴于优化的治疗实施维度为频率（而非疗程），我们建议将设计更名为“连续干预多臂多阶段响应设计”（Multi-Arm Multi-Stage Response Over Continuous Intervention，MAMS-ROCI）。方法。我们展示了如何利用模拟设计此类试验，并提出采用ADEMP框架规划模拟研究，在编码与执行模拟之前明确指定目标、数据生成机制、估计量、方法及性能指标。通过REFINE-Lung试验案例，我们探讨了需做出的可选决策。结果。我们详细描述了REFINE-Lung试验设计过程中做出的所有选择，以及模拟结果，并基于这些结果论证了总样本量的选择依据。结论。MAMS-ROCI试验可通过精心规划与实施的模拟研究来设计。REFINE-Lung试验已采用该方法完成设计，本研究亦展示了研究者如何类似地设计其自身的MAMS-ROCI试验。