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UBC Theses and Dissertations
Procedures for multiple outcome measures with applications to multiple sclerosis clinical trials Guh, Payhsuan Daphne
Abstract
In planning clinical trials in many subject areas, researchers often find it difficult to designate one single outcome measure as the primary endpoint to describe treatment efficacy. When a disease affects a patient's functions in multiple dimensions, expecting one outcome measure to assess treatment efficacy in a comprehensive way may not be realistic. Multiple sclerosis (MS) is one such complex disease. The topic addressed in this thesis concerns approaches for the design and analysis of clinical trials where a multidimensional outcome measure is used to measure treatment efficacy. The most common approach is to select a single primary endpoint for formal statistical testing with all other outcome measures considered as secondary. This thesis is concerned with the situation where agreement on a single primary endpoint is not possible so that methods based on multiple endpoints are required. Five methods, Bonferroni adjustment, Hotelling's T2, O'Brien's OLS and GLS statistics and disjunctive outcome measures are examined and compared through power and sample size calculations. Our discussion of these methods is focused on two-armed (placebo and treatment) randomized clinical trials based on continuous outcome measures. We assume that the data to be analyzed are the changes in the responses from the baseline to the end of the trial and the underlying distribution of the multiple outcome measures can be approximated as multivariate normal. Our investigation is focused on the features of the configuration of the standardized differences in the underlying population means and the correlation structure among the multiple outcome measures. Specifically, several special cases are examined to highlight the main differences among the statistical properties of these methods. We also apply the methods considered to two MS clinical trial data sets for a more focused comparison of these methods for actual MS patient populations.
Item Metadata
Title |
Procedures for multiple outcome measures with applications to multiple sclerosis clinical trials
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
1997
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Description |
In planning clinical trials in many subject areas, researchers often find it difficult to
designate one single outcome measure as the primary endpoint to describe treatment
efficacy. When a disease affects a patient's functions in multiple dimensions, expecting
one outcome measure to assess treatment efficacy in a comprehensive way may not be
realistic. Multiple sclerosis (MS) is one such complex disease. The topic addressed
in this thesis concerns approaches for the design and analysis of clinical trials where
a multidimensional outcome measure is used to measure treatment efficacy. The most
common approach is to select a single primary endpoint for formal statistical testing with
all other outcome measures considered as secondary. This thesis is concerned with the
situation where agreement on a single primary endpoint is not possible so that methods
based on multiple endpoints are required.
Five methods, Bonferroni adjustment, Hotelling's T2, O'Brien's OLS and GLS statistics
and disjunctive outcome measures are examined and compared through power and
sample size calculations. Our discussion of these methods is focused on two-armed
(placebo and treatment) randomized clinical trials based on continuous outcome measures.
We assume that the data to be analyzed are the changes in the responses from the
baseline to the end of the trial and the underlying distribution of the multiple outcome
measures can be approximated as multivariate normal. Our investigation is focused
on the features of the configuration of the standardized differences in the underlying
population means and the correlation structure among the multiple outcome measures.
Specifically, several special cases are examined to highlight the main differences among
the statistical properties of these methods. We also apply the methods considered to two MS clinical trial data sets for a more focused comparison of these methods for actual MS
patient populations.
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Extent |
5895446 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-04-27
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0088420
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
1998-05
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Item Media
Item Citations and Data
Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.