Author:
Ouma Luke O.,Wason James M. S.,Zheng Haiyan,Wilson Nina,Grayling Michael
Abstract
BackgroundThe 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.MethodsWe 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.FindingsWe 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.ConclusionsUmbrella 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.
Funder
Cancer Research UK
National Institute for Health and Care Research
Reference80 articles.
1. Master protocols to study multiple therapies, multiple diseases, or both;Woodcock;N Engl J Med,2017
2. New clinical trial designs in the era of precision medicine: an overview of definitions, strengths, weaknesses, and current use in oncology;Janiaud;Cancer Treat Rev,2019
3. Statistical controversies in clinical research: basket trials, umbrella trials, and other master protocols: a review and examples;Renfro;Ann Oncol,2017
4. Biostatistical and logistical considerations in the development of basket and umbrella clinical trials;Yee;Cancer J,2019
5. Master protocol trials in oncology: review and new trial designs;Hirakawa;Contemp Clin Trials Commun,2018
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献