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Placebo-Controlled Trials and Active-Control Trials in the Evaluation of New Treatments. Part 1: Ethical and Scientific Issues
Abstract
In recent years, several authors have argued that placebo-controlled trials are invariably unethical when known effective therapy is available for the condition being studied, regardless of the condition or the consequences of deferring treatment. Some have also disputed the value of placebo-controlled trials in such a setting, asserting that the comparison of new treatment with old treatment is sufficient to establish efficacy and is all that should be of interest. This article considers the ethical concerns about use of placebo controls and describes the limited ability of active-control equivalence (also known as noninferiority) trials to establish efficacy of new therapies in many medical contexts. The authors conclude that placebo-controlled trials are not uniformly unethical when known effective therapies are available; rather, their acceptability is determined by whether the patient will be harmed by deferral of therapy. If patients are not harmed, such trials can ethically be carried out. Furthermore, active-control trials, although valuable, informative, and appropriate in many circumstances, often cannot provide reliable evidence of the effectiveness of a new therapy.
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“On the other hand, the use of current therapies (active controls) can also be controversial.”
From Understanding Equivalence and Noninferiority Testing (2011) · cites this paper as [13]
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“Another reason is that in many instances the use of placebos is unethical.”
From Understanding Equivalence and Noninferiority Testing (2011) · cites this paper as [13]
In the citing paper
“The issues involved in this decision are discussed by Ellenberg and Temple 12 and Temple and Ellenberg 13 .”
From Understanding Equivalence and Noninferiority Testing (2011) · cites this paper as [13]
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Metadata
- Authors
- Temple, R., & Ellenberg, S. S.
- Affiliations
- Center for Biologics Evaluation and Research (US)
- Corresponding author
- Temple, Robert
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2000-09-19
- Volume
- 133
- Issue
- 6
- Pages
- 455-463
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W1987467897
- Cited by
- 871
- References
- 3
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 15 · 2023: 19 · 2022: 21 · 2021: 30 · 2020: 23 · 2019: 21 · 2018: 22 · 2017: 26 · 2016: 17 · 2015: 35 · 2014: 28 · 2013: 32 · 2012: 52
- FWCI
- 70.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- DigitalGeorgetown (Georgetown University Library) (submittedVersion)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
- Health Sciences › Nursing › Issues, ethics and legal aspects › Biomedical Ethics and Regulation
- Keywords
- research ethics, efficacy evaluation, patient harm, new drugs, clinical trial design
- MeSH terms
- Ethics, Medical, Helsinki Declaration, Humans, Informed Consent, Placebos, Sensitivity and Specificity, Therapeutic Equivalency, Controlled Clinical Trials as Topic, Ethics, Research
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