Advantages of multi-arm non-randomised sequentially allocated cohort designs for Phase II oncology trials

Helen Mossop,Michael J Grayling,James M S Wason,Grant D Stewart,Sarah J Welsh,Ferdia A Gallagher

doi:10.1038/s41416-021-01613-5

Helen Mossop, Michael J Grayling + Show 4 more

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https://doi.org/10.1038/s41416-021-01613-5

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BackgroundEfficient trial designs are required to prioritise promising drugs within Phase II trials. Adaptive designs are examples of such designs, but their efficiency is reduced if there is a delay in assessing patient responses to treatment.MethodsMotivated by the WIRE trial in renal cell carcinoma (NCT03741426), we compare three trial approaches to testing multiple treatment arms: (1) single-arm trials in sequence with interim analyses; (2) a parallel multi-arm multi-stage trial and (3) the design used in WIRE, which we call the Multi-Arm Sequential Trial with Efficient Recruitment (MASTER) design. The MASTER design recruits patients to one arm at a time, pausing recruitment to an arm when it has recruited the required number for an interim analysis. We conduct a simulation study to compare how long the three different trial designs take to evaluate a number of new treatment arms.ResultsThe parallel multi-arm multi-stage and the MASTER design are much more efficient than separate trials. The MASTER design provides extra efficiency when there is endpoint delay, or recruitment is very quick.ConclusionsWe recommend the MASTER design as an efficient way of testing multiple promising cancer treatments in non-comparative Phase II trials.

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Efficient trial designs are required to prioritise promising drugs within Phase II trials
Motivated by the WIRE trial in renal cell carcinoma (NCT03741426), we compare three trial approaches to testing multiple treatment arms: (1) single-arm trials in sequence with interim analyses; (2) a parallel multi-arm multi-stage trial and (3) the design used in WIRE, which we call the Multi-Arm Sequential Trial with Efficient Recruitment (MASTER) design
We conduct a simulation study to compare how long the three different trial designs take to evaluate a number of new treatment arms

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Efficient trial designs are required to prioritise promising drugs within Phase II trials. METHODS: Motivated by the WIRE trial in renal cell carcinoma (NCT03741426), we compare three trial approaches to testing multiple treatment arms: (1) single-arm trials in sequence with interim analyses; (2) a parallel multi-arm multi-stage trial and (3) the design used in WIRE, which we call the Multi-Arm Sequential Trial with Efficient Recruitment (MASTER) design. CONCLUSIONS: We recommend the MASTER design as an efficient way of testing multiple promising cancer treatments in noncomparative Phase II trials. Several Phase II designs are available, including both single-arm and randomised approaches. Traditional methods such as Simon’s two-stage design [1] have been widely used in oncology [2]. Possible options include running multiple single-arm trials successively or using randomised designs. There has been a substantial number of papers on adaptive multi-arm trials where there is a shared control group (see e.g., [4,5,6]), and ones without a control group [7,8,9,10]

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