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Lookup NU author(s): Luke Ouma, Professor James WasonORCiD, Dr Haiyan ZhengORCiD, Dr Nina WilsonORCiD, Dr Michael GraylingORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Copyright © 2022 Ouma, Wason, Zheng, Wilson and Grayling.Background: The efficiencies that master protocol designs can bring to modern drug development have seen their increased utilization in oncology. Growing interest has also resulted in their consideration in non-oncology settings. Umbrella trials are one class of master protocol design that evaluates multiple targeted therapies in a single disease setting. Despite the existence of several reviews of master protocols, the statistical considerations of umbrella trials have received more limited attention. Methods: We conduct a systematic review of the literature on umbrella trials, examining both the statistical methods that are available for their design and analysis, and also their use in practice. We pay particular attention to considerations for umbrella designs applied outside of oncology. Findings: We identified 38 umbrella trials. To date, most umbrella trials have been conducted in early phase settings (73.7%, 28/38) and in oncology (92.1%, 35/38). The quality of statistical information available about conducted umbrella trials to date is poor; for example, it was impossible to ascertain how sample size was determined in the majority of trials (55.3%, 21/38). The literature on statistical methods for umbrella trials is currently sparse. Conclusions: Umbrella trials have potentially great utility to expedite drug development, including outside of oncology. However, to enable lessons to be effectively learned from early use of such designs, there is a need for higher-quality reporting of umbrella trials. Furthermore, if the potential of umbrella trials is to be realized, further methodological research is required.
Author(s): Ouma LO, Wason JMS, Zheng H, Wilson N, Grayling M
Publication type: Review
Publication status: Published
Journal: Frontiers in Medicine
Year: 2022
Volume: 9
Online publication date: 12/10/2022
Acceptance date: 26/09/2022
ISSN (electronic): 2296-858X
Publisher: Frontiers Media S.A.
URL: https://doi.org/10.3389/fmed.2022.1037439
DOI: 10.3389/fmed.2022.1037439
Data Access Statement: The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author/s.
