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dc.contributor.authorCole, M
dc.contributor.authorYap, C
dc.contributor.authorBuckley, C
dc.contributor.authorNg, WF
dc.contributor.authorMcInnes, I
dc.contributor.authorFiler, A
dc.contributor.authorSiebert, S
dc.contributor.authorPratt, A
dc.contributor.authorIsaacs, JD
dc.contributor.authorStocken, DD
dc.date.accessioned2021-07-27T08:08:06Z
dc.date.available2021-07-27T08:08:06Z
dc.date.issued2021-07-06
dc.identifier.citationTrials, 2021, 22 (1), pp. 433 - ?
dc.identifier.issn1745-6215
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4700
dc.identifier.eissn1745-6215
dc.identifier.eissn1745-6215en_US
dc.identifier.doi10.1186/s13063-021-05384-5
dc.identifier.doi10.1186/s13063-021-05384-5en_US
dc.description.abstractBackground Adaptive model-based dose-finding designs have demonstrated advantages over traditional rule-based designs but have increased statistical complexity but uptake has been slow especially outside of cancer trials. TRAFIC is a multi-centre, early phase trial in rheumatoid arthritis incorporating a model-based design.Methods A Bayesian adaptive dose-finding phase I trial rolling into a single-arm, single-stage phase II trial. Model parameters for phase I were chosen via Monte Carlo simulation evaluating objective performance measures under clinically relevant scenarios and incorporated stopping rules for early termination. Potential designs were further calibrated utilising dose transition pathways.Discussion TRAFIC is an MRC-funded trial of a re-purposed treatment demonstrating that it is possible to design, fund and implement a model-based phase I trial in a non-cancer population within conventional research funding tracks and regulatory constraints. The phase I design allows borrowing of information from previous trials, all accumulated data to be utilised in decision-making, verification of operating characteristics through simulation, improved understanding for management and oversight teams through dose transition pathways. The rolling phase II design brings efficiencies in trial conduct including site and monitoring activities and cost. TRAFIC is the first funded model-based dose-finding trial in inflammatory disease demonstrating that small phase I/II trials can have an underlying statistical basis for decision-making and interpretation.Trial registration Trials Registration: ISRCTN, ISRCTN36667085 . Registered on September 26, 2014.
dc.formatElectronic
dc.format.extent433 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectArthritis, Rheumatoid
dc.subjectBayes Theorem
dc.subjectDose-Response Relationship, Drug
dc.subjectResearch Design
dc.subjectComputer Simulation
dc.titleTRAFIC: statistical design and analysis plan for a pragmatic early phase 1/2 Bayesian adaptive dose escalation trial in rheumatoid arthritis.
dc.typeJournal Article
dcterms.dateAccepted2021-06-17
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1186/s13063-021-05384-5
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2021-07-06
rioxxterms.licenseref.startdate2021-07-06en_US
dc.relation.isPartOfTrials
pubs.issue1
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit
pubs.publication-statusPublished
pubs.volume22en_US
pubs.embargo.termsNot known
icr.researchteamClinical Trials & Statistics Unit
icr.researchteamClinical Trials & Statistics Uniten_US
dc.contributor.icrauthorYap, Christinaen


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