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dc.contributor.authorLaw, Martin
dc.contributor.authorGrayling, Michael J
dc.contributor.authorMander, Adrian P
dc.date.accessioned2022-06-21T23:31:28Z
dc.date.available2022-06-21T23:31:28Z
dc.date.issued2021-03
dc.identifier.issn1539-1604
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338288
dc.description.abstractRandomised controlled trials are considered the gold standard in trial design. However, phase II oncology trials with a binary outcome are often single-arm. Although a number of reasons exist for choosing a single-arm trial, the primary reason is that single-arm designs require fewer participants than their randomised equivalents. Therefore, the development of novel methodology that makes randomised designs more efficient is of value to the trials community. This article introduces a randomised two-arm binary outcome trial design that includes stochastic curtailment (SC), allowing for the possibility of stopping a trial before the final conclusions are known with certainty. In addition to SC, the proposed design involves the use of a randomised block design, which allows investigators to control the number of interim analyses. This approach is compared with existing designs that also use early stopping, through the use of a loss function comprised of a weighted sum of design characteristics. Comparisons are also made using an example from a real trial. The comparisons show that for many possible loss functions, the proposed design is superior to existing designs. Further, the proposed design may be more practical, by allowing a flexible number of interim analyses. One existing design produces superior design realisations when the anticipated response rate is low. However, when using this design, the probability of rejecting the null hypothesis is sensitive to misspecification of the null response rate. Therefore, when considering randomised designs in phase II, we recommend the proposed approach be preferred over other sequential designs.
dc.format.mediumPrint-Electronic
dc.publisherWiley
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectadaptive design
dc.subjectcancer
dc.subjectcontinuous monitoring
dc.subjectinterim analysis
dc.subjectoncology
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectResearch Design
dc.titleA stochastically curtailed two-arm randomised phase II trial design for binary outcomes.
dc.typeArticle
dc.publisher.departmentMrc Biostatistics Unit
dc.date.updated2022-06-21T12:15:13Z
prism.endingPage228
prism.issueIdentifier2
prism.publicationDate2021
prism.publicationNamePharm Stat
prism.startingPage212
prism.volume20
dc.identifier.doi10.17863/CAM.85696
dcterms.dateAccepted2020-08-11
rioxxterms.versionofrecord10.1002/pst.2067
rioxxterms.versionVoR
dc.contributor.orcidLaw, Martin [0000-0001-9594-348X]
dc.identifier.eissn1539-1612
rioxxterms.typeJournal Article/Review
cam.issuedOnline2020-08-29
cam.depositDate2022-06-21
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International