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Jaki, Thomas ; Barnett, Helen ; Titman, Andrew ; Mozgunov, Pavel

A seamless Phase I/II platform design with a time-to-event efficacy endpoint for potential COVID-19 therapies

Jaki, Thomas , Barnett, Helen, Titman, Andrew and Mozgunov, Pavel (2024) A seamless Phase I/II platform design with a time-to-event efficacy endpoint for potential COVID-19 therapies. Statistical Methods in Medical Research 33 (11-12), pp. 2115-2130.

Date of publication of this fulltext: 22 Sep 2025 06:25
Article
DOI to cite this document: 10.5283/epub.77767


Abstract

In the search for effective treatments for COVID-19, the initial emphasis has been on re-purposed treatments. To maximize the chances of finding successful treatments, novel treatments that have been developed for this disease in particular, are needed. In this article, we describe and evaluate the statistical design of the AGILE platform, an adaptive randomized seamless Phase I/II trial platform ...

In the search for effective treatments for COVID-19, the initial emphasis has been on re-purposed treatments. To maximize the chances of finding successful treatments, novel treatments that have been developed for this disease in particular, are needed. In this article, we describe and evaluate the statistical design of the AGILE platform, an adaptive randomized seamless Phase I/II trial platform that seeks to quickly establish a safe range of doses and investigates treatments for potential efficacy. The bespoke Bayesian design (i) utilizes randomization during dose-finding, (ii) shares control arm information across the platform, and (iii) uses a time-to-event endpoint with a formal testing structure and error control for evaluation of potential efficacy. Both single-agent and combination treatments are considered. We find that the design can identify potential treatments that are safe and efficacious reliably with small to moderate sample sizes.



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Details

Item typeArticle
Journal or Publication TitleStatistical Methods in Medical Research
Publisher:Sage
Volume:33
Number of Issue or Book Chapter:11-12
Page Range:pp. 2115-2130
Date14 October 2024
InstitutionsInformatics and Data Science > Department Machine Learning & Data Science > Lehrstuhl für Computational Statistics (Prof. Dr. Thomas Jaki)
Identification Number
ValueType
10.1177/09622802241288348DOI
KeywordsAdaptive platform trial, dose-escalation, COVID-19, randomized, seamless, time-to-improvement
Dewey Decimal Classification000 Computer science, information & general works > 004 Computer science
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgPartially
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-777674
Item ID77767

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