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Ethical Issues in Stopping Randomized Trials Early Because of Apparent Benefit
- Paul S. Mueller, MD, MPH;
- Victor M. Montori, MD, MSc;
- Dirk Bassler, MD, MSc;
- Barbara A. Koenig, PhD; and
- Gordon H. Guyatt, MD, MSc
- From Mayo Clinic College of Medicine, Rochester, Minnesota; University Children's Hospital, Tuebingen, Germany; and McMaster University, Hamilton, Ontario, Canada.
Abstract
Stopping randomized trials early because of an apparent benefit is becoming more common. To protect and promote the interests of trial participants, investigators may feel obligated to stop a trial early because of the apparent benefit of a study treatment (compared with placebo or other treatment). There are, however, serious ethical problems with doing so. Truncated trials systematically overestimate treatment effects; in cases where the number of accrued outcome events is small, the overestimation may be very large. Generating seriously inflated estimates of treatment effect violates the ethical research requirement of scientific validity. Subsequent use of inflated estimates to inform clinical decision making and practice guidelines violates the ethical requirements of social value and a favorable risk–benefit ratio. Researchers should ensure that a large number of outcome events accrues before stopping a trial and then continue recruitment to assess whether positive trends continue. This can balance the need to protect research participants with the ethical requirements of scientific validity, social value, and a favorable risk–benefit ratio.
Article and Author Information
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Potential Financial Conflicts of Interest: Consultancies: B.A. Koenig (Affymetrix Corporation).
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Requests for Single Reprints: Paul S. Mueller, MD, MPH, Program in Professionalism and Bioethics, Department of Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905; e-mail, mueller.pauls{at}mayo.edu.
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Current Author Addresses: Drs. Mueller, Montori, and Koenig: Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905.
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Dr. Bassler: University Children's Hospital, Department of Neonatology, Calwerstrasse 7, 72076 Tuebingen, Germany.
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Dr. Guyatt: McMaster University, 1200 Main Street West, Room 2C12, Hamilton, L8N 3Z5 Ontario, Canada.
