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Daniells, Libby ; Jaki, Thomas ; Dayimu, Alimu ; Demiris, Nikos ; Bristi, Basu ; Symeonides, Stefan ; Mozgunov, Pavel

Seamless monotherapy-combination phase I dose-escalation model-based design

Daniells, Libby , Jaki, Thomas , Dayimu, Alimu , Demiris, Nikos, Bristi, Basu, Symeonides, Stefan und Mozgunov, Pavel (2025) Seamless monotherapy-combination phase I dose-escalation model-based design. Clinical Trials 22 (4), S. 430-441.

Veröffentlichungsdatum dieses Volltextes: 22 Sep 2025 05:09
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.77714


Zusammenfassung

Phase I dose-escalation studies for a single-agent and combination of anti-cancer agents have explored various model-based designs to guide identification of a maximum tolerated dose and recommended phase II dose. This work describes a parallel approach to dose escalation to expedite identification of maximum tolerated doses both for an anti-cancer agent as monotherapy and in combination with ...

Phase I dose-escalation studies for a single-agent and combination of anti-cancer agents have explored various model-based designs to guide identification of a maximum tolerated dose and recommended phase II dose. This work describes a parallel approach to dose escalation to expedite identification of maximum tolerated doses both for an anti-cancer agent as monotherapy and in combination with another agent. We develop a three-parameter Bayesian logistic regression model that allows for more efficient use of information between monotherapy and combination parts of the study. The model allows the monotherapy and combination data to drive dose escalation of the combination of treatments, reflecting the known dose-toxicity relationship between the monotherapy and combination setting. Through a thorough simulation study in which the proposed model is compared to two comparative approaches, the three-parameter Bayesian logistic regression model is shown to accurately select doses in the target toxicity interval, performing similar to comparative approaches in terms of proportion of target dose/combination selection, while more than halving the proportion of doses selected that were greater than the target toxicity, thereby improving safety concerns.



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Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftClinical Trials
Verlag:Sage
Band:22
Nummer des Zeitschriftenheftes oder des Kapitels:4
Seitenbereich:S. 430-441
Datum12 Juli 2025
InstitutionenInformatik und Data Science > Fachbereich Maschinelles Lernen und Data Science > Chair for Computational Statistics (Prof. Dr. Thomas Jaki)
Identifikationsnummer
WertTyp
10.1177/17407745251350604DOI
Stichwörter / KeywordsDose-finding, combination study
Dewey-Dezimal-Klassifikation000 Informatik, Informationswissenschaft, allgemeine Werke > 004 Informatik
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenZum Teil
URN der UB Regensburgurn:nbn:de:bvb:355-epub-777140
Dokumenten-ID77714

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