METHODOLOGY Open Access

Impact of lack-of-benefit stopping rules on treatment effect estimates of two-arm multi-stage (TAMS) trials with time to event outcome Babak Choodari-Oskooei*, Mahesh KB Parmar, Patrick Royston and Jack Bowden Background: In 2011, Royston et al. described technical details of a two-arm, multi-stage (TAMS) design. The design enables a trial to be stopped part-way through recruitment if the accumulating data suggests a lack of benefit of the experimental arm. Such interim decisions can be made using data on an available ‘intermediate ’ outcome. At the conclusion of the trial, the definitive outcome is analyzed. Typical intermediate and definitive outcomes in cancer might be progression-free and overall survival, respectively. In TAMS designs, the stopping rule applied at the interim stage(s) affects the sampling distribution of the treatment effect estimator, potentially inducing bias that needs addressing. Methods: We quantified the bias in the treatment effect estimator in TAMS trials according to the size of the treatment effect and for different designs. We also retrospectively ‘redesigned ’ completed cancer trials as TAMS trial