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Application of the negative multinomial distribution to comparative Poisson clinical trials of multiple experimental treatments versus a single control

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Title
Application of the negative multinomial distribution to comparative Poisson clinical trials of multiple experimental treatments versus a single control
Name (type = personal)
NamePart (type = family)
Chiarappa
NamePart (type = given)
Joseph A.
DisplayForm
Joseph A. Chiarappa
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Hoover
NamePart (type = given)
Donald R
DisplayForm
Donald R Hoover
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
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School of Graduate Studies
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school
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Text
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theses
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DateCreated (qualifier = exact)
2019
DateOther (qualifier = exact); (type = degree)
2019-01
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2019
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Clinical trials that compare one or more experimental treatments to a control treatment in which event incidence (i.e. incidence of disease or an adverse event) is rare often assume that comparative Poisson methodology is appropriate for modeling the number of events that occur in each treatment group. Clinical studies of multiple Poisson parameters may be conducted under one of two designs: (A) wait until a total number of events occur among all treatment groups before stopping the study, or (B) wait until a specified amount of time has passed before terminating the study. Exact tests under these approaches are based on the multinomial distribution.
In this dissertation, we consider an alternative approach termed “Design C”, which is to wait until the control group accumulates a pre-specified number of events before stopping the study. The joint distribution of the number of events in the experimental treatment groups at the time of study stoppage, conditional on the number of events observed in the control group, follows a negative multinomial distribution (NMD). The minimum (respectively, maximum) number of events among the experimental treatment arms will be shown to be an appropriate test statistic for determining whether one or more of the experimental treatments is superior (respectively, inferior) to the control at a given one-sided overall Type I error; as such, we first determine the distribution of the order statistics of the NMD. We subsequently provide tables of trial design parameters for select values of one-sided overall Type I error and pointwise power and assuming equal allocation of study subjects to the treatment groups. These studies can be improved by applying curtailed stoppage rules; that is, follow-up of the treatment arms can be discontinued prior to the control group reaching its planned number of events once the ultimate decision is known for each arm. Curtailment has substantial practical implications as reduced follow-up implies reduced study costs and more rapid knowledge of the trial results. We provide simple algorithms to estimate the expected amount of subject follow up (presented in terms of person years) that would be needed until trial termination under both uncurtailed and curtailed stopping rules. Finally, we combine the superiority and inferiority test procedures to provide a two-sided test and briefly consider pairwise comparison of the experimental treatments to each other under the Design C framework.
Subject (authority = RUETD)
Topic
Statistics and Biostatistics
Subject (authority = ETD-LCSH)
Topic
Poisson processes
Subject (authority = ETD-LCSH)
Topic
Clinical trials -- Methodology
RelatedItem (type = host)
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Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_9468
PhysicalDescription
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electronic resource
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application/pdf
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text/xml
Extent
1 online resource (152 pages : illustrations)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Joseph A. Chiarappa
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/t3-08av-an44
Genre (authority = ExL-Esploro)
ETD doctoral
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The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Chiarappa
GivenName
Joseph
MiddleName
A.
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2018-12-31 11:53:04
AssociatedEntity
Name
Joseph Chiarappa
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Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
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Author Agreement License
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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.
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Copyright protected
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Open
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Permission or license
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