Closed Testing Procedures for Group Sequential Clinical Trials with Multiple Endpoints
Abstract
A simple approach is given for conducting closed testing in clinical trials with multiple endpoints in which group sequential monitoring is planned. The approach allows a flexible stopping time; the earliest and latest stopping times are described. The paradigm is applicable both to clinical trials with multiple endpoints and to the one-sided multiple comparison problem of several treatments versus a control. The approach leads to enhancements of previous methods and suggestions for new methods. An example of a respiratory disease trial with four endpoints is given.
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The PERSEUS study used a hierarchical testing procedure proposed by Tang and Geller (1999) to control overall family-wise type I error for the primary and key secondary endpoints.
“A hierarchical testing procedure proposed by Tang and Geller (1999) 3 was used to control overall family-wise type I error for the primary and key secondary endpoints.”
From Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. (2024) · cites this paper as Tang and Geller (1999)
The PERSEUS study used a hierarchical testing procedure proposed by Tang and Geller (1999) to control overall family-wise type I error for the primary and key secondary endpoints.
“A hierarchical testing procedure proposed by Tang and Geller (1999) 3 was used to control overall family-wise type I error for the primary and key secondary endpoints.”
From Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. (2024) · cites this paper as [3]
Cites
Discrete sequential boundaries for clinical trials
GORDON LAN, K. K., & DEMETS, D. L. (1983) · Biometrika · doi:10.1093/biomet/70.3.659 · Cited by 2,310 · see citing works
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Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes
Bakris, G. L., Agarwal, R., Anker, S. D., Pitt, B., Ruilope, L. M., Rossing, P., Kolkhof, P., Nowack, C., Schloemer, P., Joseph, A., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2025845 · Cited by 2,935 · see citing works
Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma
Facon, T., Kumar, S., Plesner, T., Orlowski, R. Z., Moreau, P., Bahlis, N., Basu, S., Nahi, H., Hulin, C., Quach, H., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1817249 · Cited by 1,027 · see citing works
Phase 3 Trial of Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis
Sanyal, A. J., Newsome, P. N., Kliers, I., Østergaard, L. H., Long, M. T., Kjær, M. S., Cali, A. M. G., Bugianesi, E., Rinella, M. E., Roden, M., et al. (2025) · New England Journal of Medicine · doi:10.1056/nejmoa2413258 · Cited by 1,115 · see citing works
Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma.
Sonneveld, P., Dimopoulos, M. A., Boccadoro, M., Quach, H., Ho, P. J., Beksac, M., Hulin, C., Antonioli, E., Leleu, X., Mangiacavalli, S., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2312054 · Cited by 599 · see citing works
Hierarchical testing of multiple endpoints in group‐sequential trials
Glimm, E., Maurer, W., & Bretz, F. (2010) · Statistics in Medicine · doi:10.1002/sim.3748 · Cited by 89 · see citing works
- Authors
- Tang, D., & Geller, N. L.
- Affiliations
- Nathan Kline Institute for Psychiatric Research (US)
- National Heart, Lung, and Blood Institute (US)
- Corresponding author
- Tang, Dei‐In
- ORCID
- Geller, Nancy L.
- Venue
- Biometrics
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-12
- Volume
- 55
- Issue
- 4
- Pages
- 1188-1192
- ISSN
- 0006-341X (ISSN-L)
- 1541-0420
- OpenAlex
- W1993632196
- Cited by
- 81
- References
- 1
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 1 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 4
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biometrics (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Physical Sciences › Mathematics › Statistics and Probability › Probability and Statistical Research
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods and Bayesian Inference
- Keywords
- closed testing procedure, multiple endpoints, multiple comparisons, early stopping, clinical trials
- MeSH terms
- Biometry, Clinical Trials as Topic, Humans, Respiratory Tract Diseases, Time Factors, Cross-Over Studies
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