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Joint time-to-event partial order continual reassessment method and Joint time-to-event Bayesian logistic regression model: Statistical designs for dual agent phase I/II dose finding studies with late-onset toxicity and activity outcomes
Barnett, Helen, Boix, Oliver, Kontos, Dimitris and Jaki, Thomas
(2025)
Joint time-to-event partial order continual reassessment method and Joint time-to-event Bayesian logistic regression model: Statistical designs for dual agent phase I/II dose finding studies with late-onset toxicity and activity outcomes.
Statistical Methods in Medical Research 35 (1), pp. 186-204.
Date of publication of this fulltext: 24 Feb 2026 13:07
Article
DOI to cite this document: 10.5283/epub.78730
Abstract
Dual agent dose-finding trials study the effect of a combination of more than one agent, where the objective is to find the Maximum Tolerated Dose Combination, the combination of doses of the two agents that is associated with a pre-specified risk of being unsafe. In a Phase I/II setting, the objective is to find a dose combination that is both safe and active, the Optimal Biological Dose, that ...
Dual agent dose-finding trials study the effect of a combination of more than one agent, where the objective is to find the Maximum Tolerated Dose Combination, the combination of doses of the two agents that is associated with a pre-specified risk of being unsafe. In a Phase I/II setting, the objective is to find a dose combination that is both safe and active, the Optimal Biological Dose, that optimises a criterion based on both safety and activity. Since Oncology treatments are typically given over multiple cycles, both the safety and activity outcome can be considered as late-onset, potentially occurring in the later cycles of treatment. This work proposes two model-based designs for dual-agent dose finding studies with late-onset activity and late-onset toxicity outcomes, the Joint time-to-event (TITE) partial order continual reassessment method and the Joint TITE Bayesian logistic regression model. Their performance is compared alongside a model-assisted comparator in a comprehensive simulation study motivated by a real trial example, with an extension to consider alternative sized dosing grids. It is found that both model-based methods outperform the model-assisted design. Whilst on average the two model-based designs are comparable, this comparability is not consistent across scenarios.
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Details
| Item type | Article | ||||
| Journal or Publication Title | Statistical Methods in Medical Research | ||||
| Publisher: | Sage | ||||
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| Open Access Type: | CC-License | ||||
| Volume: | 35 | ||||
| Number of Issue or Book Chapter: | 1 | ||||
| Page Range: | pp. 186-204 | ||||
| Date | 5 December 2025 | ||||
| Institutions | Informatics and Data Science > Department Machine Learning & Data Science > Lehrstuhl für Computational Statistics (Prof. Dr. Thomas Jaki) | ||||
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| Keywords | dose-finding, late-onset toxicities, late-onset activity, dual agent, phase I trials, model-based | ||||
| 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-787306 | ||||
| Item ID | 78730 |
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