A dose-finding design for dual-agent trials with patient-specific doses for one agent with application to an opiate detoxification trial
Author(s)
Mozgunov, Pavel
Cro, Suzie
Lingford-Hughes, Anne
Paterson, Louise M
Jaki, Thomas
Type
Journal Article
Abstract
There is a growing interest in early phase dose-finding clinical trials studying combinations of several treatments. While the majority of dose finding designs for such setting were proposed for oncology trials, the corresponding designs are also essential in other therapeutic areas. Furthermore, there is increased recognition of recommending the patient-specific doses/combinations, rather than a single target one that would be recommended to all patients in later phases regardless of their characteristics. In this paper, we propose a dose-finding design for a dual-agent combination trial motivated by an opiate detoxification trial. The distinguishing feature of the trial is that the (continuous) dose of one compound is defined externally by the clinicians and is individual for every patient. The objective of the trial is to define the dosing function that for each patient would recommend the optimal dosage of the second compound. Via a simulation study, we have found that the proposed design results in high accuracy of individual dose recommendation and is robust to the model misspecification and assumptions on the distribution of externally defined doses.
Date Issued
2022-03-01
Date Acceptance
2021-11-21
Citation
Pharmaceutical Statistics: the journal of applied statistics in the pharmaceutical industry, 2022, 21 (2), pp.476-495
ISSN
1539-1604
Publisher
John Wiley and Sons
Start Page
476
End Page
495
Journal / Book Title
Pharmaceutical Statistics: the journal of applied statistics in the pharmaceutical industry
Volume
21
Issue
2
Copyright Statement
© 2021 The Authors. Pharmaceutical Statistics published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Medical Research Council (MRC)
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/34891221
Grant Number
MR/T025557/1
Subjects
baclofen
combination trial
dose individualisation
dose-finding
methadone
opiate detoxification
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2021-12-10