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Developing a Patient-Focused Study Design for Rare Disease Clinical Trials Open Access


Other title
rare disease
study design
clinical trial
Type of item
Degree grantor
University of Alberta
Author or creator
Yong, Jian
Supervisor and department
Yasui, Yutaka (Public Health Sciences)
Yuan, Yan (Public Health Sciences)
Examining committee member and department
Gian, Jhangri (Public Health Sciences)
Yuan, Yan (Public Health Sciences)
Yasui, Yutaka (Public Health Sciences)
Department of Public Health Sciences
Date accepted
Graduation date
Master of Science
Degree level
Randomized controlled trials for a rare disease face methodological difficulties in evaluating treatment effects due to characteristics of rare diseases such as a small patient population to recruit from, lack of knowledge about the disease itself (i.e., lack of clinically validated endpoints), and heterogeneity of patients. The proposed trial design in this thesis for rare disease controlled trials aims not only efficiency in evaluating treatments compared to the standard parallel-group design of clinical trials, but also incorporates other important aspects in developing rare disease treatments such as providing more opportunities for rare disease patients to access new treatments, evaluating treatment effects where clinically validated endpoints are lacking, and identifying markers for treatment response for use in clinical practice. It is a patient-focused design consisting of two stages. Stage 1 provides all patients the opportunity to access the experimental treatment of the trial and identify patient characteristics that distinguish patients who respond to the experimental treatment and those who do not. Stage 2 is to evaluate treatment effects with a randomization of treatments to patients who had responded to the experimental treatment in Stage 1. To compare the effect of an experimental treatment to that of a standard treatment, Stage 2 uses cross-over design, series of n-of-1 trials design, or response-adaptive design. For both stages, patient-reported outcomes are collected to evaluate treatment effect on rare diseases where clinically validated endpoints may be lacking. Analysis methods and sample size calculations for the proposed two-stage design that uses cross-over design in Stage 2 are explained.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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