Early stopping of clinical trials.
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.
Cuzick
Jack
J
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
Howell
Anthony
A
Forbes
John
J
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