OBJECTIVE: To illustrate controversial issues associated with stopping randomized controlled trials (RCTs) early for apparent benefit. STUDY DESIGN AND SETTING: The article presents our review of prior relevant work and our research group's reflections on early stopping. RESULTS: Compelling evidence suggests that trials stopped early for benefit systematically overestimate treatment effects, sometimes by a large amount. Unresolved controversies in trials stopped early for benefit include ethical and statistical problems in the interpretation of results. CONCLUSIONS: The best strategy to minimize the problems associated with early stopping of RCTs for benefit is not to stop early. As an alternative, we suggest a threefold approach: a low P-value as the threshold for stopping at the time of interim analyses, not to look before a sufficiently large number of events has accrued and continuation of enrollment and follow-up for a further period.
OBJECTIVE: To illustrate controversial issues associated with stopping randomized controlled trials (RCTs) early for apparent benefit. STUDY DESIGN AND SETTING: The article presents our review of prior relevant work and our research group's reflections on early stopping. RESULTS: Compelling evidence suggests that trials stopped early for benefit systematically overestimate treatment effects, sometimes by a large amount. Unresolved controversies in trials stopped early for benefit include ethical and statistical problems in the interpretation of results. CONCLUSIONS: The best strategy to minimize the problems associated with early stopping of RCTs for benefit is not to stop early. As an alternative, we suggest a threefold approach: a low P-value as the threshold for stopping at the time of interim analyses, not to look before a sufficiently large number of events has accrued and continuation of enrollment and follow-up for a further period.
Authors: Katherine S Button; John P A Ioannidis; Claire Mokrysz; Brian A Nosek; Jonathan Flint; Emma S J Robinson; Marcus R Munafò Journal: Nat Rev Neurosci Date: 2013-04-10 Impact factor: 34.870
Authors: Frederik Keus; Jørn Wetterslev; Christian Gluud; Cornelis J H M van Laarhoven Journal: BMC Med Res Methodol Date: 2010-10-01 Impact factor: 4.615
Authors: Matthew R Sydes; Mahesh K B Parmar; Nicholas D James; Noel W Clarke; David P Dearnaley; Malcolm D Mason; Rachel C Morgan; Karen Sanders; Patrick Royston Journal: Trials Date: 2009-06-11 Impact factor: 2.279