Abstract

BackgroundThe multi-arm multi-stage (MAMS) trial is a new paradigm for conducting randomised controlled trials that allows the simultaneous assessment of a number of research treatments against a single control arm. MAMS trials provide earlier answers and are potentially more cost-effective than a series of traditionally designed trials. Prostate cancer is the most common tumour in men and there is a need to improve outcomes for men with hormone-sensitive, advanced disease as quickly as possible. The MAMS design will potentially facilitate evaluation and testing of new therapies in this and other diseases.MethodsSTAMPEDE is an open-label, 5-stage, 6-arm randomised controlled trial using MAMS methodology for men with prostate cancer. It is the first trial of this design to use multiple arms and stages synchronously.ResultsThe practical and statistical issues faced by STAMPEDE in implementing MAMS methodology are discussed and contrasted with those for traditional trials. These issues include the choice of intermediate and final outcome measures, sample size calculations and the impact of varying the assumptions, the process for moving between trial stages, stopping accrual to each trial arm and overall, and issues around perceived trial complexity.ConclusionIt is possible to use the MAMS design to initiate and undertake large scale cancer trials. The results from STAMPEDE will not be known for some years but the lessons learned from running a MAMS trial are shared in the hope that other researchers will use this exciting and efficient method to perform further randomised controlled trials.Trial registrationISRCTN78818544, NCT00268476

Highlights

  • The multi-arm multi-stage (MAMS) trial is a new paradigm for conducting randomised controlled trials that allows the simultaneous assessment of a number of research treatments against a single control arm

  • The purpose of this paper is to describe the methodology of the STAMPEDE trial in order to illustrate and discuss the MAMS trial design and implementation in to practice

  • The variable factors have been chosen such that no arms are stopped early for lack-of-efficacy; the accrual rate is set at 500 patients/year; the median progression-free survival (PFS) and overall survival are estimated to be 24 months and 48 months, respectively; and accrual is uncapped ie recruitment continues to the point of overall maturity

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Summary

Methodology

Issues in applying multi-arm multi-stage methodology to a clinical trial in prostate cancer: the MRC STAMPEDE trial. Address: 1MRC Clinical Trials Unit, London, UK, 2Queen Elizabeth Medical Centre, Birmingham, UK, 3Christie and Salford Royal Foundation Trusts, Manchester, UK, 4Institute of Cancer Research and Royal Marsden Hospitals, Sutton, UK and 5Cardiff University School of Medicine, Cardiff, Wales, UK

Results
Conclusion
Background
D: Overall survival
Prentice RL
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