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Background. The DURATIONS design has been recently proposed as a practicalalternative to a standard two-arm non-inferiority design when the goal is tooptimise some continuous aspect of treatment administration, e.g. duration orfrequency, preserving efficacy but improving on secondary outcomes such assafety, costs or convenience. The main features of this design are that (i) itrandomises patients to a moderate number of arms across the continuum and (ii)it uses a model to share information across arms. While papers published todate about the design have focused on analysis aspects, here we show how todesign 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 fornon-small cell lung cancer patients. Because the aspect of treatmentadministration to optimise is frequency, rather than duration, we propose torename the design as Multi-Arm Multi-Stage Response Over ContinuousIntervention (MAMS-ROCI). Methods. We show how simulations can be used todesign such a trial. We propose to use the ADEMP framework to plan suchsimulations, 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 anexample. Results. We describe all the choices made while designing theREFINE-Lung trial, and the results of the simulations performed. We justify ourchoice of total sample size based on these results. Conclusions. MAMS-ROCItrials can be designed using simulation studies that have to be carefullyplanned and conducted. REFINE-Lung has been designed using such an approach andwe have shown how researchers could similarly design their own MAMS-ROCI trial.

How to design a MAMS-ROCI (aka DURATIONS) randomised trial: the REFINE-Lung case study