Bio-creep in non-inferiority clinical trials
Abstract
After a non‐inferiority clinical trial, a new therapy may be accepted as effective, even if its treatment effect is slightly smaller than the current standard. It is therefore possible that, after a series of trials where the new therapy is slightly worse than the preceding drugs, an ineffective or harmful therapy might be incorrectly declared efficacious; this is known as ‘bio‐creep’. Several factors may influence the rate at which bio‐creep occurs, including the distribution of the effects of the new agents being tested and how that changes over time, the choice of active comparator, the method used to account for the variability of the estimate of the effect of the active comparator, and changes in the effect of the active comparator from one trial to the next (violations of the constancy assumption). We performed a simulation study to examine which of these factors might lead to bio‐creep and found that bio‐creep was rare, except when the constancy assumption was violated. Copyright © 2010 John Wiley & Sons, Ltd.
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The fact that the TBS arm performed better than the standard measure on all measures and outcomes argues against bio-creep occurring in this trial.
“Bio-creep has been raised as a concern in serial noninferiority trials38; the fact that the TBS arm performed better than the standard measure on all measures and outcomes argues against this phenomenon occurring here.”
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- Authors
- Everson‐Stewart, S., & Emerson, S. S.
- Affiliations
- University of Washington (US)
- Corresponding author
- Everson‐Stewart, Siobhan
- ORCID
- Emerson, Scott S.
- Venue
- Statistics in Medicine
- Publisher
- Wiley
- Published
- 2010-08-30
- Volume
- 29
- Issue
- 27
- Pages
- 2769-2780
- ISSN
- 0277-6715 (ISSN-L)
- 1097-0258
- OpenAlex
- W2111363763
- Cited by
- 64
- References
- 15
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 8 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 2 · 2014: 1 · 2013: 4 · 2012: 2
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Statistics in Medicine (publishedVersion)
- PubMed (publishedVersion)
- Collection of Biostatistics Research Archive (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T32HL007183)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods and Bayesian Inference
- Keywords
- active comparator, simulation study, drug approval
- MeSH terms
- Algorithms, Computer Simulation, Humans, Models, Statistical, Bias, Confidence Intervals, Proportional Hazards Models, Treatment Outcome, Controlled Clinical Trials as Topic
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