Staff View
Two-stage clinical trial designs with survival outcomes and adjustment for misclassification in predictive biomarkers

Descriptive

TitleInfo
Title
Two-stage clinical trial designs with survival outcomes and adjustment for misclassification in predictive biomarkers
Name (type = personal)
NamePart (type = family)
Chen
NamePart (type = given)
Yanping
NamePart (type = date)
1972-
DisplayForm
Yanping Chen
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Lin
NamePart (type = given)
Yong
DisplayForm
Yong Lin
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Lu
NamePart (type = given)
Shou-En
DisplayForm
Shou-En Lu
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
co-chair
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (encoding = w3cdtf); (keyDate = yes); (qualifier = exact)
2020
DateOther (encoding = w3cdtf); (qualifier = exact); (type = degree)
2020-05
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
Abstract (type = abstract)
Oncology indispensably leads us to personalized medicine, which allows an individual approach to be taken with each subject. Personalized oncology is based on pharmacogenomics and the effect of genetic differences in individuals. Biomarkers detected using molecular biology tools allow the molecular characterization of cancer signatures and provide information relevant for personalized treatment. The key to success of these targeted therapy is to identify a "predictive biomarker" and validate the "predictive biomarker" through randomized clinical trials. In this dissertation, we focus on biomarker based two-stage clinical trial designs with survival outcomes.

In Part I of this dissertation, we assume that there is no misclassification of biomarker and we design a two-stage adaptive enrichment clinical trial, based on a binary "predictive" biomarker. At the interim analysis, based on the statistics observed from the biomarker negative strata, a decision is made to either continue enrolling both biomarker positive and biomarker negative subjects or enrich the remaining number of subjects only to biomarker positive subjects.
In Part II, we address the issue of misclassification of biomarker which is common in determining the predictive biomarker status. A two-stage stratified study design is proposed and evaluated. We use the information obtained from both marker appeared-positive strata and marker appeared-negative strata, to solve the adjusted log rank statistics for true marker positive and true marker negative group. No additional distributional assumption is needed for this stratified design.

In Part III, we extend the biomarker misclassification adjustment method to the two-stage enrichment designs proposed in Part I. With some additional distributional assumption (exponential distribution assumption for survival times), we can use the information obtained from interim analysis, to help obtain the adjusted log rank statistics for the true marker positive group, even though the marker appeared-negative group was discontinued after interim analysis and no marker appeared-negative subjects are enrolled in Stage II.

Family-wise type I error control is achieved by considering correlation of log rank statistics from the same and/or different stages. R-code is developed to calculate critical values, to achieve specified global power, or specified marginal power, and to calculate sample size as well.
Subject (authority = local)
Topic
Predictive biomarker
Subject (authority = RUETD)
Topic
Public Health
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_10774
PhysicalDescription
Form (authority = gmd)
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xiii, 130 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/t3-xkda-y788
Genre (authority = ExL-Esploro)
ETD doctoral
Back to the top

Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Chen
GivenName
Yanping
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2020-04-19 10:39:12
AssociatedEntity
Name
Yanping Chen
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
Type
Embargo
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2020-05-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2022-05-31
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 31st, 2022.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
Back to the top

Technical

RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
CreatingApplication
Version
1.5
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2020-04-19T10:21:00
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2020-04-19T10:33:58
ApplicationName
pdfTeX-1.40.18
Back to the top
Version 8.5.5
Rutgers University Libraries - Copyright ©2024