Review Article| Volume 61, ISSUE 3, P241-246, March 2008

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Early stopping of randomized clinical trials for overt efficacy is problematic

  • Dirk Bassler
    Department of Neonatology, University Children's Hospital, Tübingen, Germany
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  • Victor M. Montori
    Knowledge and Encounter Research Unit, Division of Endocrinology and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA
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  • Matthias Briel
    CLARITY Research Group, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada

    Basel Institute for Clinical Epidemiology, University Hospital, Basel, Switzerland
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  • Paul Glasziou
    Centre for Evidence-Based Medicine, Department of Primary Health Care, University of Oxford, Oxford, UK
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  • Gordon Guyatt
    Corresponding author. Department of Clinical Epidemiology and Biostatistics, Health Sciences Centre, Room 2C12, McMaster University, Hamilton, Ontario, Canada. Tel.: +905-525-9140 ext. 22900; fax: +905-524-3841.
    CLARITY Research Group, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
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      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.


      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.


      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.


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