Development of gatekeeping strategies in confirmatory clinical trials
Abstract
This paper discusses multiplicity issues arising in confirmatory clinical trials with hierarchically ordered multiple objectives. In order to protect the overall type I error rate, multiple objectives are analyzed using multiple testing procedures. When the objectives are ordered and grouped in multiple families (e.g. families of primary and secondary endpoints), gatekeeping procedures are employed to account for this hierarchical structure. We discuss considerations arising in the process of building gatekeeping procedures, including proper use of relevant trial‐specific information and criteria for selecting gatekeeping procedures. The methods and principles discussed in this paper are illustrated using a clinical trial in patients with type II diabetes mellitus.
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A two-step analysis with a gatekeeping strategy was used to control the family-wise type 1 error rate.
“we utilized two-step analysis with a gatekeeping strategy40 to control the family-wise type 1 error rate.”
From Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial (2016) · cites this paper as [40]
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- Authors
- Dmitrienko, A., Millen, B. A., Brechenmacher, T., & Paux, G.
- Affiliations
- Eli Lilly (United States) (US)
- Sumitomo Dainippon Pharma (Japan) (JP)
- Sanofi (France) (FR)
- Corresponding author
- Dmitrienko, Alex
- Venue
- Biometrical Journal
- Publisher
- Wiley
- Published
- 2011-11
- Volume
- 53
- Issue
- 6
- Pages
- 875-893
- ISSN
- 0323-3847 (ISSN-L)
- 1521-4036
- OpenAlex
- W1975798555
- Cited by
- 43
- References
- 26
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 8 · 2014: 2 · 2013: 5 · 2012: 3
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biometrical Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods and Bayesian Inference
- Physical Sciences › Mathematics › Statistics and Probability › Probability and Statistical Research
- Keywords
- confirmatory trials, multiplicity, multiple comparisons, type I error rate, primary and secondary endpoints, type 2 diabetes
- MeSH terms
- Biometry, Clinical Trials as Topic, Diabetes Mellitus, Type 2, Goals, Humans, Hypoglycemic Agents
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