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dc.contributor.authorBrock, K
dc.contributor.authorBillingham, L
dc.contributor.authorCopland, M
dc.contributor.authorSiddique, S
dc.contributor.authorSirovica, M
dc.contributor.authorYap, C
dc.date.accessioned2019-12-11T14:42:31Z
dc.date.issued2017-07-20
dc.identifier.citationBMC medical research methodology, 2017, 17 (1), pp. 112 - ?
dc.identifier.issn1471-2288
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3461
dc.identifier.eissn1471-2288
dc.identifier.doi10.1186/s12874-017-0381-x
dc.description.abstractBackground The Matchpoint trial aims to identify the optimal dose of ponatinib to give with conventional chemotherapy consisting of fludarabine, cytarabine and idarubicin to chronic myeloid leukaemia patients in blastic transformation phase. The dose should be both tolerable and efficacious. This paper describes our experience implementing EffTox in the Matchpoint trial.Methods EffTox is a Bayesian adaptive dose-finding trial design that jointly scrutinises binary efficacy and toxicity outcomes. We describe a nomenclature for succinctly describing outcomes in phase I/II dose-finding trials. We use dose-transition pathways, where doses are calculated for each feasible set of outcomes in future cohorts. We introduce the phenomenon of dose ambivalence, where EffTox can recommend different doses after observing the same outcomes. We also describe our experiences with outcome ambiguity, where the categorical evaluation of some primary outcomes is temporarily delayed.Results We arrived at an EffTox parameterisation that is simulated to perform well over a range of scenarios. In scenarios where dose ambivalence manifested, we were guided by the dose-transition pathways. This technique facilitates planning, and also helped us overcome short-term outcome ambiguity.Conclusions EffTox is an efficient and powerful design, but not without its challenges. Joint phase I/II clinical trial designs will likely become increasingly important in coming years as we further investigate non-cytotoxic treatments and streamline the drug approval process. We hope this account of the problems we faced and the solutions we used will help others implement this dose-finding clinical trial design.Trial registration Matchpoint was added to the European Clinical Trials Database ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005629-65/GB ) on 2013-12-30.
dc.formatElectronic
dc.format.extent112 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectBlast Crisis
dc.subjectImidazoles
dc.subjectPyridazines
dc.subjectIdarubicin
dc.subjectCytarabine
dc.subjectVidarabine
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectModels, Statistical
dc.subjectBayes Theorem
dc.subjectAlgorithms
dc.subjectResearch Design
dc.subjectOutcome Assessment, Health Care
dc.titleImplementing the EffTox dose-finding design in the Matchpoint trial.
dc.typeJournal Article
dcterms.dateAccepted2017-06-30
rioxxterms.versionofrecord10.1186/s12874-017-0381-x
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-07-20
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBMC medical research methodology
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.volume17
pubs.embargo.termsNot known
pubs.oa-locationhttps://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-017-0381-x
icr.researchteamClinical Trials & Statistics Uniten_US
dc.contributor.icrauthorYap, Christinaen


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