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To add or not to add a new treatment arm to a multiarm study: A decision-theoretic framework.

Accepted version
Peer-reviewed

Type

Article

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Authors

Wason, James 
Stallard, Nigel 

Abstract

Multiarm clinical trials, which compare several experimental treatments against control, are frequently recommended due to their efficiency gain. In practise, all potential treatments may not be ready to be tested in a phase II/III trial at the same time. It has become appealing to allow new treatment arms to be added into on-going clinical trials using a "platform" trial approach. To the best of our knowledge, many aspects of when to add arms to an existing trial have not been explored in the literature. Most works on adding arm(s) assume that a new arm is opened whenever a new treatment becomes available. This strategy may prolong the overall duration of a study or cause reduction in marginal power for each hypothesis if the adaptation is not well accommodated. Within a two-stage trial setting, we propose a decision-theoretic framework to investigate when to add or not to add a new treatment arm based on the observed stage one treatment responses. To account for different prospect of multiarm studies, we define utility in two different ways; one for a trial that aims to maximise the number of rejected hypotheses; the other for a trial that would declare a success when at least one hypothesis is rejected from the study. Our framework shows that it is not always optimal to add a new treatment arm to an existing trial. We illustrate a case study by considering a completed trial on knee osteoarthritis.

Description

Keywords

adding-arm, disjunctive power, multiarm, number of rejected hypotheses, Adaptive Clinical Trials as Topic, Biostatistics, Clinical Protocols, Controlled Clinical Trials as Topic, Cryotherapy, Decision Theory, Humans, Multivariate Analysis, Nerve Block, Osteoarthritis, Knee

Journal Title

Stat Med

Conference Name

Journal ISSN

0277-6715
1097-0258

Volume Title

38

Publisher

Wiley

Rights

All rights reserved
Sponsorship
Medical Research Council (MR/N028171/1)
MRC (unknown)