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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 und 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), S. 186-204.
Veröffentlichungsdatum dieses Volltextes: 24 Feb 2026 13:07
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.78730
Zusammenfassung
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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| Dokumentenart | Artikel | ||||
| Titel eines Journals oder einer Zeitschrift | Statistical Methods in Medical Research | ||||
| Verlag: | Sage | ||||
|---|---|---|---|---|---|
| Band: | 35 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 1 | ||||
| Seitenbereich: | S. 186-204 | ||||
| Datum | 5 Dezember 2025 | ||||
| Institutionen | Informatik und Data Science > Fachbereich Maschinelles Lernen und Data Science > Chair for Computational Statistics (Prof. Dr. Thomas Jaki) | ||||
| Identifikationsnummer |
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| Stichwörter / Keywords | dose-finding, late-onset toxicities, late-onset activity, dual agent, phase I trials, model-based | ||||
| Dewey-Dezimal-Klassifikation | 000 Informatik, Informationswissenschaft, allgemeine Werke > 004 Informatik | ||||
| Status | Veröffentlicht | ||||
| Begutachtet | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden | Zum Teil | ||||
| URN der UB Regensburg | urn:nbn:de:bvb:355-epub-787306 | ||||
| Dokumenten-ID | 78730 |
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