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Article: Bayesian Dose Finding for Combined Drugs with Discrete and Continuous Doses

TitleBayesian Dose Finding for Combined Drugs with Discrete and Continuous Doses
Authors
KeywordsBayesian adaptive design
Combined drugs
Continual reassessment method
Maximum tolerated dose
Phase I trial
Toxicity probability
Two-stage design
Issue Date2012
PublisherInternational Society for Bayesian Analysis. The Journal's web site is located at http://ba.stat.cmu.edu/
Citation
Bayesian Analysis, 2012, v. 7 n. 4, p. 1035-1052 How to Cite?
AbstractThe trend of treating patients with combined drugs has grown in cancer clinical trials. Often, evaluating the synergism of multiple drugs is the primary motivation for such drug-combination studies. To enhance patient response, a new agent is often investigated together with an existing standard of care (SOC) agent. Often, a certain amount of dosage of the SOC is administered in order to maintain at least some therapeutic effects in patients. For clinical trials involving a continuous-dose SOC and a discrete-dose agent, we propose a two-stage Bayesian adaptive dose-finding design. The first stage takes a continual reassessment method to locate the appropriate dose for the discrete-dose agent while fixing the continuous-dose SOC at the minimal therapeutic dose. In the second stage, we make a fine dose adjustment by calibrating the continuous dose to achieve the target toxicity rate as closely as possible. Dose escalation or de-escalation is based on the posterior estimates of the joint toxicity probabilities of combined doses. As the toxicity data accumulate during the trial, we adaptively assign each cohort of patients to the most appropriate dose combination. We conduct extensive simulation studies to examine the operating characteristics of the proposed two-stage design and demonstrate the design’s good performance with practical scenarios.
Persistent Identifierhttp://hdl.handle.net/10722/164644
ISSN
2019 Impact Factor: 2.696
2015 SCImago Journal Rankings: 1.559
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHuo, L-
dc.contributor.authorYuan, Y-
dc.contributor.authorYin, G-
dc.date.accessioned2012-09-20T08:07:21Z-
dc.date.available2012-09-20T08:07:21Z-
dc.date.issued2012-
dc.identifier.citationBayesian Analysis, 2012, v. 7 n. 4, p. 1035-1052-
dc.identifier.issn1931-6690-
dc.identifier.urihttp://hdl.handle.net/10722/164644-
dc.description.abstractThe trend of treating patients with combined drugs has grown in cancer clinical trials. Often, evaluating the synergism of multiple drugs is the primary motivation for such drug-combination studies. To enhance patient response, a new agent is often investigated together with an existing standard of care (SOC) agent. Often, a certain amount of dosage of the SOC is administered in order to maintain at least some therapeutic effects in patients. For clinical trials involving a continuous-dose SOC and a discrete-dose agent, we propose a two-stage Bayesian adaptive dose-finding design. The first stage takes a continual reassessment method to locate the appropriate dose for the discrete-dose agent while fixing the continuous-dose SOC at the minimal therapeutic dose. In the second stage, we make a fine dose adjustment by calibrating the continuous dose to achieve the target toxicity rate as closely as possible. Dose escalation or de-escalation is based on the posterior estimates of the joint toxicity probabilities of combined doses. As the toxicity data accumulate during the trial, we adaptively assign each cohort of patients to the most appropriate dose combination. We conduct extensive simulation studies to examine the operating characteristics of the proposed two-stage design and demonstrate the design’s good performance with practical scenarios.-
dc.languageeng-
dc.publisherInternational Society for Bayesian Analysis. The Journal's web site is located at http://ba.stat.cmu.edu/-
dc.relation.ispartofBayesian Analysis-
dc.rights© 2012 International Society for Bayesian Analysis. This article is available online at https://doi.org/10.1214/12-BA735-
dc.subjectBayesian adaptive design-
dc.subjectCombined drugs-
dc.subjectContinual reassessment method-
dc.subjectMaximum tolerated dose-
dc.subjectPhase I trial-
dc.subjectToxicity probability-
dc.subjectTwo-stage design-
dc.titleBayesian Dose Finding for Combined Drugs with Discrete and Continuous Doses-
dc.typeArticle-
dc.identifier.emailYin, G: gyin@hku.hk-
dc.identifier.authorityYin, G=rp00831-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1214/12-BA735-
dc.identifier.scopuseid_2-s2.0-84872576106-
dc.identifier.hkuros211055-
dc.identifier.volume7-
dc.identifier.issue4-
dc.identifier.spage1035-
dc.identifier.epage1052-
dc.identifier.isiWOS:000311975100013-
dc.publisher.placeUnited States-

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