A Study of the Minimum p-value and Related Methods for the Identification of Treatment-Sensitive Groups
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Authors
Li, Na
Date
Type
thesis
Language
eng
Keyword
predictive classification , cutpoint , minimum p-value method , bootstrap , profile method
Alternative Title
Abstract
In clinical practices, a fundamentally important problem is to identify a subgroup of patients who may benefit more in terms of a clinical outcome from a certain treatment based on a specific clinical variable or biomarker, which is referred as predictive classification in this thesis. The clinical variable or biomarker used for predictive classification is usually continuous and, therefore, a cutpoint needs to be determined for the definition of the subgroup. The commonly adopted methods, the minimum p-value method and the profile method, suffer from the type I error inflation and/or the identifiability issue. In this thesis research, we first propose bootstrap-based methods for the adjustment of the minimum p-value method for predictive classifications with respect to a continuous clinical outcome in both identifiable and non-identifiable cases under random designs and fixed designs, respectively. Since the minimum p-value test statistics diverge at a rate sqrt(n) (n is the sample size) under the framework of the generalized linear model with non-identity link function and the Cox model for respectively categorical and time to event clinical outcomes, bootstrap-based methods are proposed to adjust the profile methods for predictive classifications in both identifiable and non-identifiable cases. The theoretical properties of the proposed adjustments are investigated and simulation studies are conducted to evaluate their fixed sample size performance. In addition, the proposed methods are applied to analyze the data from a cancer clinical trial.
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Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
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Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.