The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
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 authors interpreted these as extenuating circumstances and implemented mitigating strategies including changes to the statistical analysis plan to mitigate the effects of these changes in the patient population.”
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“Investigators evaluated the effect of small-volume blood collection tubes vs standard tubes to reduce red blood cell transfusion in critical care patients in a pragmatic multicenter, stepped-wedge cluster trial at 25 sites in Canada.”
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“The types of patients admitted to the critical care units (and their corresponding prognoses) may have changed substantially after the start of the COVID-19 pandemic, with variable proportions of COVID-19 and elective surgery patients across sites.”
In the citing paper
“The prevalence of other underlying conditions leading to critical care unit admissions also changed in unanticipated ways.”
In the citing paper
“The investigators modified their analysis plan to mitigate the effect of these changes (Table).”
In the citing paper
“For example, the study by Siegal et al 21 conducted in critical care units encountered changes in the populations and underlying conditions of patients admitted to these settings due to the COVID-19 pandemic.”
In the citing paper
“The COVID-19 pandemic delayed implementation of the intervention at some sites due to clinical workload, pandemic preparedness activities, and infection control precautions, but the trial was ultimately completed.”
In the citing paper
“The international survey yielded examples of trials that encountered extenuating circumstances including regulatory changes, new standards of care, and security threats (Table).”
Citations
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Items 201–202 of 202
Clinical equipoise and ethical challenges in expanding endovascular stroke thrombectomy practice
Wadhwa, A., McNeil, E. P., Bhatt, P. B., Han, K., Purohit, S., Granstein, J. H., Ogilvy, C. S., Ganau, M., & Taussky, P. (2026) · Frontiers in Surgery · doi:10.3389/fsurg.2026.1912229
Yang, Y., Wang, J., Hu, Z., Wang, G., & Li, J. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1915023
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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