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A dose-finding design for dual-agent trials with patient-specific doses for one agent with application to an opiate detoxification trial

Title: A dose-finding design for dual-agent trials with patient-specific doses for one agent with application to an opiate detoxification trial
Authors: Mozgunov, P
Cro, S
Lingford-Hughes, A
Paterson, LM
Jaki, T
Item 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.
Issue Date: 1-Mar-2022
Date of Acceptance: 21-Nov-2021
URI: http://hdl.handle.net/10044/1/93122
DOI: 10.1002/pst.2181
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.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: MR/T025557/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Pharmacology & Pharmacy
Statistics & Probability
Mathematics
baclofen
combination trial
dose individualisation
dose-finding
methadone
opiate detoxification
DRUG-COMBINATION
baclofen
combination trial
dose individualisation
dose-finding
methadone
opiate detoxification
baclofen
combination trial
dose individualisation
dose-finding
methadone
opiate detoxification
Statistics & Probability
0104 Statistics
1115 Pharmacology and Pharmaceutical Sciences
Publication Status: Published
Conference Place: England
Online Publication Date: 2021-12-10
Appears in Collections:Faculty of Medicine
School of Public Health
Department of Brain Sciences



This item is licensed under a Creative Commons License Creative Commons