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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 type | Article | ||||
| Journal or Publication Title | Statistical Methods in Medical Research | ||||
| Publisher: | Sage | ||||
|---|---|---|---|---|---|
| Volume: | 33 | ||||
| Number of Issue or Book Chapter: | 11-12 | ||||
| Page Range: | pp. 2115-2130 | ||||
| Date | 14 October 2024 | ||||
| Institutions | Informatics and Data Science > Department Machine Learning & Data Science > Lehrstuhl für Computational Statistics (Prof. Dr. Thomas Jaki) | ||||
| Identification Number |
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| Keywords | Adaptive platform trial, dose-escalation, COVID-19, randomized, seamless, time-to-improvement | ||||
| Dewey Decimal Classification | 000 Computer science, information & general works > 004 Computer science | ||||
| Status | Published | ||||
| Refereed | Yes, this version has been refereed | ||||
| Created at the University of Regensburg | Partially | ||||
| URN of the UB Regensburg | urn:nbn:de:bvb:355-epub-777674 | ||||
| Item ID | 77767 |
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