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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.

Published version
Peer-reviewed

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Authors

Cro, Suzie 
Lingford-Hughes, Anne 
Paterson, Louise M 

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.

Description

Keywords

baclofen, combination trial, dose individualisation, dose-finding, methadone, opiate detoxification, Computer Simulation, Dose-Response Relationship, Drug, Humans, Maximum Tolerated Dose, Medical Oncology, Neoplasms, Opiate Alkaloids, Research Design

Journal Title

Pharm Stat

Conference Name

Journal ISSN

1539-1604
1539-1612

Volume Title

Publisher

Wiley
Sponsorship
NIHR Academy (SRF-2015-08-001)
Medical Research Council (MC_UU_00002/14)
National Institute for Health and Care Research (IS-BRC-1215-20014)