Flexible trial design in practice: Dropping and adding arms in STAMPEDE (MRC PR08, CRUK/06/019)-A multiarm, multistage randomized controlled trial.

27 Background: STAMPEDE (NCT00268476) is a multi-centre, RCT using novel multi‐arm, multi‐stage (MAMS) methods. We describe the methodological and practical issues arising with early stopping of recruitment to some arms following an intermediate analysis and the issues in adding new research arms during the trial. Methods: The trial recruits men with locally advanced or metastatic prostate cancer starting standard long-term hormone therapy. There are 5 research and 1 control arm assessed over 3 intermediate activity stages I-III [outcome measure: failure-free survival (FFS)] and a final efficacy stage IV [outcome measure: overall survival]. At the end of each stage, research arms are formally compared to the control arm. Accrual of further patients is discontinued early for research arms not showing sufficient evidence of activity or with adverse safety considerations; accrual continues to the other arms; this interim hurdle is increasingly stringent at each stage. The addition of new research arm(s) can ...