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Title: Optimising the design of phase II studies in cancer
Author: Brown, Sarah Rose
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2012
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Phase 11 trials are a key element of the drug development process and the transition from phase 11 to III is associated with the highest risk in the development pathway. This thesis considers methods to optimise the design of phase 11 trials in cancer. It addresses one of the most important issues in designing such trials - choosing the most appropriate outcome measure to reflect clinical activity. The first step to optimising phase 11 trial design addresses the process behind identifying appropriate designs, allowing researchers to understand the key elements of phase 11 trial design. A guidance document providing researchers with clear points for consideration throughout the design process is developed, to aid researchers to make informed decisions throughout the design process. Successful phase 11 trial design hinges on choosing an outcome measure that best reflects the expected mechanism of action of the treatment under investigation and that acts as a screen for potential long-term benefit. This research considers the novel application of surrogacy methodology to identifying optimal outcome measures for phase 11 trials in advanced colorectal cancer (aCRC). Typically response is used as the primary endpoint in such trials; however this has been shown to be a poor surrogate for survival in aCRC. This thesis evaluates the relationship between response and overall survival in aCRC trials, and explores alternative phase 11 outcome measures in order to identify those most strongly associated with survival. The output of this research will aid trialists in the design of future phase II trials, providing a structured approach to trial design, and recommendations regarding a novel methodological approach to identifying optimal outcome measures. Specifically in aCRC, the research makes recommendations regarding the use of alternative outcome measures to response, providing a basis for the design of future phase 11 trials in this disease area.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available