Grayling, M.J., Dimairo, M. orcid.org/0000-0002-9311-6920, Mander, A.P. et al. (1 more author) (2019) A review of perspectives on the use of randomization in phase II oncology trials. JNCI: Journal of the National Cancer Institute, 111 (12). pp. 1255-1262. ISSN 0027-8874
Abstract
Historically, phase II oncology trials assessed a treatment’s efficacy by examining its tumor response rate in a single-arm trial. Then, approximately 25 years ago, certain statistical and pharmacological considerations ignited a debate around whether randomized designs should be utilized instead. Here, based upon an extensive literature review, we review the arguments on either side of this debate. In particular, we describe the numerous factors that relate to the reliance of single-arm trials on historical control data, and detail the trial scenarios in which there was general agreement on preferential utilization of single-arm or randomized design frameworks, such as the use of single-arm designs when investigating treatments for rare cancers. We then summarize the latest figures on phase II oncology trial design, contrasting current design choices against historical recommendations on best practice. Ultimately, we find several ways in which the design of recently completed phase II trials does not appear to align with said recommendations. For example, despite advice to the contrary, only 66.2% of the assessed trials that employed progression-free survival as a primary or co-primary outcome used a randomized comparative design. In addition, we identify that just 28.2% of the considered randomized comparative trials came to a positive conclusion, as opposed to 72.7% of the single-arm trials. We conclude by describing a selection of important issues influencing contemporary design, framing this discourse in light of current trends in phase II, such as the increased use of biomarkers and recent interest in novel adaptive designs.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 The Author(s). Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Cancer; Progression-free survival; Screening; Selection; Single-arm; Tumor response |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Health and Related Research (Sheffield) > ScHARR - Sheffield Centre for Health and Related Research |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 10 Jul 2019 09:22 |
Last Modified: | 08 Dec 2021 08:56 |
Status: | Published |
Publisher: | Oxford University Press (OUP) |
Refereed: | Yes |
Identification Number: | 10.1093/jnci/djz126 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:148314 |