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Ethical issues in stopping randomized trials early because of apparent benefit.
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.
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“The international survey yielded examples of trials that encountered extenuating circumstances including regulatory changes, new standards of care, and security threats (Table).”
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Metadata
- Authors
- Mueller, P. S., Montori, V. M., Bassler, D., Koenig, B. A., & Guyatt, G. H.
- Affiliations
- Mayo Clinic (US)
- From Mayo Clinic College of Medicine, Rochester, Minnesota; University Children's Hospital, Tuebingen, Germany; and McMaster University, Hamilton, Ontario, Canada.
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2007-06-19
- Volume
- 146
- Issue
- 12
- Pages
- 878-881
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W2148390494
- Cited by
- 202
- References
- 20
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 30 · 2023: 10 · 2022: 10 · 2021: 5 · 2020: 13 · 2019: 8 · 2018: 2 · 2017: 9 · 2016: 12 · 2015: 15 · 2014: 5 · 2013: 10 · 2012: 13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- DigitalGeorgetown (Georgetown University Library) (submittedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Health Sciences › Nursing › Issues, ethics and legal aspects › Biomedical Ethics and Regulation
- Keywords
- early trial termination, randomized controlled trials, trial ethics, scientific validity, risk-benefit ratio, social values
- MeSH terms
- Humans, Informed Consent, Social Values, Reproducibility of Results, Bias, Randomized Controlled Trials as Topic, Risk Assessment, Ethics Committees, Research
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