Joint TITE-CRM : A Design for Dose Finding Studies for Therapies with Late-Onset Safety and Activity Outcomes

Barnett, Helen and Boix, Oliver and Kontos, Dimitris and Jaki, Thomas (2024) Joint TITE-CRM : A Design for Dose Finding Studies for Therapies with Late-Onset Safety and Activity Outcomes. Statistics in Biopharmaceutical Research. ISSN 1946-6315

[thumbnail of Late_onset_Tox_Eff_paper_TaF_template_unblinded_final]
Text (Late_onset_Tox_Eff_paper_TaF_template_unblinded_final)
Late_onset_Tox_Eff_paper_TaF_template_unblinded_final.pdf - Accepted Version

Download (445kB)

Abstract

In Phase I/II dose-finding trials, the objective is to find the Optimal Biological Dose (OBD), a dose that is both safe and shows sufficient activity that maximizes some optimality criterion based on safety and activity. In cancer, treatment is typically given over several cycles, complicating the identification of the OBD as both toxicity and activity outcomes may occur at any point throughout the follow up of multiple cycles. In this work we present and assess the Joint TITE-CRM, a model-based design for late onset toxicities and activity based on the well-known TITE-CRM. It is found to be superior to the currently available alternative designs that account for late onset bivariate outcomes, as well as being both intuitive and computationally feasible.

Item Type:
Journal Article
Journal or Publication Title:
Statistics in Biopharmaceutical Research
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2600/2613
Subjects:
?? dose-findinglate-onset toxicitieslate-onset activityphase i trialsmodel-basedstatistics and probabilitypharmaceutical science ??
ID Code:
216976
Deposited By:
Deposited On:
25 Mar 2024 15:20
Refereed?:
Yes
Published?:
Published
Last Modified:
27 Nov 2024 02:00