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dc.contributor.authorSilva, RB
dc.contributor.authorYap, C
dc.contributor.authorCarvajal, R
dc.contributor.authorLee, SM
dc.date.accessioned2021-06-22T10:12:48Z
dc.date.available2021-06-22T10:12:48Z
dc.date.issued2021-06-15
dc.identifier.citationJCO Precision Oncology, 2021, (5), pp. 1024 - 1034
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4643
dc.identifier.eissn2473-4284
dc.identifier.doi10.1200/po.21.00136
dc.description.abstractPURPOSE Simulation studies have shown that novel designs such as the continual reassessment method and the Bayesian optimal interval (BOIN) design outperform the 3 + 3 design by recommending the maximum tolerated dose (MTD) more often, using less patients, and allotting more patients to the MTD. However, it is not clear whether these novel designs would have yielded different results in the context of real-world dose-finding trials. This is a commonly mentioned reason for the continuous use of 3 + 3 designs for oncology trials, with investigators considering simulation studies not sufficiently convincing to warrant the additional design complexity of novel designs. METHODS We randomly sampled 60 published dose-finding trials to obtain 22 that used the 3 + 3 design, identified an MTD, published toxicity data, and had more than two dose levels. We compared the published MTD with the estimated MTD using the continual reassessment method and BOIN using target toxicity rates of 25% and 30% and toxicity data from the trial. Moreover, we compared patient allocation and sample size assuming that these novel designs had been implemented. RESULTS Model-based designs chose dose levels higher than the published MTD in about 40% of the trials, with estimated and observed toxicity rates closer to the target toxicity rates of 25% and 30%. They also assigned less patients to suboptimal doses and permitted faster dose escalation. CONCLUSION This study using published dose-finding trials shows that novel designs would recommend different MTDs and confirms the advantages of these designs compared with the 3 + 3 design, which were demonstrated by simulation studies.
dc.format.extent1024 - 1034
dc.languageeng
dc.language.isoeng
dc.publisherAmerican Society of Clinical Oncology (ASCO)
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.titleWould the Recommended Dose Have Been Different Using Novel Dose-Finding Designs? Comparing Dose-Finding Designs in Published Trials
dc.typeJournal Article
dcterms.dateAccepted2021-05-06
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1200/po.21.00136
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJCO Precision Oncology
pubs.issue5
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.embargo.termsNot known
icr.researchteamClinical Trials & Statistics Unit
icr.researchteamClinical Trials & Statistics Uniten_US
dc.contributor.icrauthorYap, Christinaen


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