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postgraduate thesis: Escalation with overdose control for phase I drug-combination trials

TitleEscalation with overdose control for phase I drug-combination trials
Authors
Issue Date2013
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Shi, Y. [施昀]. (2013). Escalation with overdose control for phase I drug-combination trials. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4979973
AbstractThe escalation with overdose control (EWOC) method is a popular modelbased dose finding design for phase I clinical trials. Dose finding for combined drugs has grown rapidly in oncology drug development. A two-dimensional EWOC design is proposed for dose finding with two agents in combination based on a four-parameter logistic regression model. During trial conduct, the posterior distribution of the maximum tolerated dose (MTD) combination is updated continuously in order to find the appropriate dose combination for each cohort of patients. The probability that the next dose combination exceeds the MTD combination can be controlled by a feasibility bound, which is based on a prespecified quantile for the MTD distribution such as to reduce the possibility of over-dosing. Dose escalation, de-escalation or staying at the same doses is determined by searching the MTD combination along rows and columns in a two-drug combination matrix. Simulation studies are conducted to examine the performance of the design under various practical scenarios, and illustrate it with a trial example.
DegreeMaster of Philosophy
SubjectClinical trials - Statistical methods.
Pharmaceutical arithmetic.
Drugs - Design.
Drug development.
Dept/ProgramStatistics and Actuarial Science
Persistent Identifierhttp://hdl.handle.net/10722/181539

 

DC FieldValueLanguage
dc.contributor.authorShi, Yun-
dc.contributor.author施昀-
dc.date.accessioned2013-03-03T03:21:07Z-
dc.date.available2013-03-03T03:21:07Z-
dc.date.issued2013-
dc.identifier.citationShi, Y. [施昀]. (2013). Escalation with overdose control for phase I drug-combination trials. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4979973-
dc.identifier.urihttp://hdl.handle.net/10722/181539-
dc.description.abstractThe escalation with overdose control (EWOC) method is a popular modelbased dose finding design for phase I clinical trials. Dose finding for combined drugs has grown rapidly in oncology drug development. A two-dimensional EWOC design is proposed for dose finding with two agents in combination based on a four-parameter logistic regression model. During trial conduct, the posterior distribution of the maximum tolerated dose (MTD) combination is updated continuously in order to find the appropriate dose combination for each cohort of patients. The probability that the next dose combination exceeds the MTD combination can be controlled by a feasibility bound, which is based on a prespecified quantile for the MTD distribution such as to reduce the possibility of over-dosing. Dose escalation, de-escalation or staying at the same doses is determined by searching the MTD combination along rows and columns in a two-drug combination matrix. Simulation studies are conducted to examine the performance of the design under various practical scenarios, and illustrate it with a trial example.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.source.urihttp://hub.hku.hk/bib/B49799733-
dc.subject.lcshClinical trials - Statistical methods.-
dc.subject.lcshPharmaceutical arithmetic.-
dc.subject.lcshDrugs - Design.-
dc.subject.lcshDrug development.-
dc.titleEscalation with overdose control for phase I drug-combination trials-
dc.typePG_Thesis-
dc.identifier.hkulb4979973-
dc.description.thesisnameMaster of Philosophy-
dc.description.thesislevelMaster-
dc.description.thesisdisciplineStatistics and Actuarial Science-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b4979973-
dc.date.hkucongregation2013-

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