title: Early stopping of clinical trials.
abstract: Early stopping of clinical trials in favour of a new treatment creates ethical and scientific difficulties, which are different from those associated with early stopping due to toxicity or futility. Two major breast cancer trials have recently taken such a decision, and the problem is relevant for several ongoing trials. Here we argue that such a decision should be taken with the utmost gravity and should be based on a clear overall clinical benefit for the new treatment, and not as an automatic response to crossing a predefined threshold. Predefined rules can be used to trigger a debate within the Independent Data Monitoring and Safety Committee (IDMC) about early stopping, but the IDMC should retain the responsibility of assessing overall clinical benefit in making its recommendation.
authors.affiliation: Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary, University of London, London, UK. jack.cuzick@cancer.org.uk
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
authors.forename: Anthony
authors.initials: A
authors.lastname: Howell
authors.forename: John
authors.initials: J
authors.lastname: Forbes
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy*; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D015914:Estrogen Replacement Therapy / Q000592:standards; D005260:Female; D006801:Humans; D015203:Reproducibility of Results; D012107:Research Design; D012449:Safety; D013997:Time Factors