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

• Author / Creator

  Yong, Jian

• 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.

• Subjects / Keywords

  • Rare disease
  • Study design
  • Clinical trial
  • Analysis

• Graduation date

  Fall 2014

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3TD4Z

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.