General guidance on exploratory and confirmatory subgroup analysis in late-stage clinical trials
Abstract
This article focuses on a broad class of statistical and clinical considerations related to the assessment of treatment effects across patient subgroups in late-stage clinical trials. This article begins with a comprehensive review of clinical trial literature and regulatory guidelines to help define scientifically sound approaches to evaluating subgroup effects in clinical trials. All commonly used types of subgroup analysis are considered in the article, including different variations of prospectively defined and post-hoc subgroup investigations. In the context of confirmatory subgroup analysis, key design and analysis options are presented, which includes conventional and innovative trial designs that support multi-population tailoring approaches. A detailed summary of exploratory subgroup analysis (with the purpose of either consistency assessment or subgroup identification) is also provided. The article promotes a more disciplined approach to post-hoc subgroup identification and formulates key principles that support reliable evaluation of subgroup effects in this setting.
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Interaction analyses between subgroups may be underpowered to detect significant treatment effect differences between groups.
“Finally, interaction analyses between subgroups may be underpowered to detect significant treatment effect differences between groups. 12”
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Tutorial in biostatistics: data‐driven subgroup identification and analysis in clinical trials
Lipkovich, I., Dmitrienko, A., & B., R. (2017) · Statistics in Medicine · doi:10.1002/sim.7064 · Cited by 291 · see citing works
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- Authors
- Dmitrienko, A., Muysers, C., Fritsch, A., & Lipkovich, I.
- Affiliations
- IQVIA (United Kingdom) (GB)
- Bayer (Germany) (DE)
- Corresponding author
- Dmitrienko, Alex
- Venue
- Journal of Biopharmaceutical Statistics
- Publisher
- Informa UK Limited
- Published
- 2015-09-14
- Volume
- 26
- Issue
- 1
- Pages
- 71-98
- ISSN
- 1054-3406 (ISSN-L)
- 1520-5711
- OpenAlex
- W2258475544
- Cited by
- 51
- References
- 61
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 7 · 2021: 10 · 2020: 7 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 2
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Biopharmaceutical Statistics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Physical Sciences › Mathematics › Statistics and Probability › Advanced Causal Inference Techniques
- Keywords
- subgroup analysis, late-stage clinical trials, consistency analysis, trial design, regulatory guidelines, treatment effect heterogeneity
- MeSH terms
- Clinical Trials as Topic, Data Interpretation, Statistical, Humans, Research Design, Biomarkers
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