Show simple item record

dc.contributor.authorSerra, Alessandra
dc.contributor.authorMozgunov, Pavel
dc.contributor.authorJaki, Thomas
dc.date.accessioned2022-01-28T16:37:19Z
dc.date.available2022-01-28T16:37:19Z
dc.date.issued2022-04-30
dc.date.submitted2021-10-05
dc.identifier.issn0277-6715
dc.identifier.othersim9314
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333182
dc.description.abstractOne family of designs that can noticeably improve efficiency in later stages of drug development are multi-arm multi-stage (MAMS) designs. They allow several arms to be studied concurrently and gain efficiency by dropping poorly performing treatment arms during the trial as well as by allowing to stop early for benefit. Conventional MAMS designs were developed for the setting, in which treatment arms are independent and hence can be inefficient when an order in the effects of the arms can be assumed (eg, when considering different treatment durations or different doses). In this work, we extend the MAMS framework to incorporate the order of treatment effects when no parametric dose-response or duration-response model is assumed. The design can identify all promising treatments with high probability. We show that the design provides strong control of the family-wise error rate and illustrate the design in a study of symptomatic asthma. Via simulations we show that the inclusion of the ordering information leads to better decision-making compared to a fixed sample and a MAMS design. Specifically, in the considered settings, reductions in sample size of around 15% were achieved in comparison to a conventional MAMS design.
dc.languageen
dc.publisherWiley
dc.subjectRESEARCH ARTICLE
dc.subjectRESEARCH ARTICLES
dc.subjectadaptive designs
dc.subjectinfectious diseases
dc.subjectmulti‐arm multi‐stage
dc.subjectorder restriction
dc.titleAn order restricted multi-arm multi-stage clinical trial design.
dc.typeArticle
dc.date.updated2022-01-28T16:37:18Z
prism.publicationNameStat Med
dc.identifier.doi10.17863/CAM.80605
dcterms.dateAccepted2021-12-20
rioxxterms.versionofrecord10.1002/sim.9314
rioxxterms.versionAO
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidSerra, Alessandra [0000-0001-8431-5154]
dc.contributor.orcidMozgunov, Pavel [0000-0001-6810-0284]
dc.contributor.orcidJaki, Thomas [0000-0002-1096-188X]
dc.identifier.eissn1097-0258
pubs.funder-project-idNIHR Academy (NIHRDH-SRF-2015-08-001)
pubs.funder-project-idMedical Research Council (MC_UU_00002/14)
pubs.funder-project-idNational Institute for Health Research (NIHRDH-IS-BRC-1215-20014)
cam.issuedOnline2022-01-19


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record