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Barnett, Helen ; George, Matthew ; Skanji, Donia ; Saint-Hilary, Gaelle ; Jaki, Thomas ; Mozgunov, Pavel

A comparison of model-free phase I dose escalation designs for dual-agent combination therapies

Barnett, Helen, George, Matthew, Skanji, Donia, Saint-Hilary, Gaelle, Jaki, Thomas und Mozgunov, Pavel (2024) A comparison of model-free phase I dose escalation designs for dual-agent combination therapies. Statistical Methods in Medical Research 33 (2), S. 203-226.

Veröffentlichungsdatum dieses Volltextes: 22 Sep 2025 06:41
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.77776


Zusammenfassung

It is increasingly common for therapies in oncology to be given in combination. In some cases, patients can benefit from the interaction between two drugs, although often at the risk of higher toxicity. A large number of designs to conduct phase I trials in this setting are available, where the objective is to select the maximum tolerated dose combination. Recently, a number of model-free (also ...

It is increasingly common for therapies in oncology to be given in combination. In some cases, patients can benefit from the interaction between two drugs, although often at the risk of higher toxicity. A large number of designs to conduct phase I trials in this setting are available, where the objective is to select the maximum tolerated dose combination. Recently, a number of model-free (also called model-assisted) designs have provoked interest, providing several practical advantages over the more conventional approaches of rule-based or model-based designs. In this paper, we demonstrate a novel calibration procedure for model-free designs to determine their most desirable parameters. Under the calibration procedure, we compare the behaviour of model-free designs to model-based designs in a comprehensive simulation study, covering a number of clinically plausible scenarios. It is found that model-free designs are competitive with the model-based designs in terms of the proportion of correct selections of the maximum tolerated dose combination. However, there are a number of scenarios in which model-free designs offer a safer alternative. This is also illustrated in the application of the designs to a case study using data from a phase I oncology trial.



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Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftStatistical Methods in Medical Research
Verlag:Sage
Band:33
Nummer des Zeitschriftenheftes oder des Kapitels:2
Seitenbereich:S. 203-226
Datum24 Januar 2024
InstitutionenInformatik und Data Science > Fachbereich Maschinelles Lernen und Data Science > Chair for Computational Statistics (Prof. Dr. Thomas Jaki)
Identifikationsnummer
WertTyp
10.1177/09622802231220497DOI
Stichwörter / KeywordsDose-finding, combination therapies, model-free designs, phase I trials
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-777767
Dokumenten-ID77776

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