Cited by 51Statistical Methods in Clinical TrialsPharmaceutical studies and practicesAdvanced Causal Inference Techniques

General guidance on exploratory and confirmatory subgroup analysis in late-stage clinical trials

Dmitrienko, Alex, Muysers, Christoph, Fritsch, Arno, Lipkovich, Ilya·2016·Journal of Biopharmaceutical Statistics

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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Crossref · 10.1080/10543406.2015.1092033

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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
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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