the clinical relevant doses if the dose response followed U-shaped curve (Bornkamp 2007). The focus will be on applying the dose response to support future development of GSK654321 by understanding the design issues and developing a better statistical methodology. The third objective of the dissertation is to develop a statistical method to predict the late time point outcome data using outcome data collected earlier to address the issue of prolonged time to interim decision-making. The method of using outcome data collected at early time points to inform the adaptation decisions will help to make quicker decisions. Lastly, based on what are learned from the Phase 2a trial of GSK123456, a recommendation is made for the Phase 2a study design of the follow-on compound GSK654321 which is in the same drug class and currently under-development for arthritis treatment. Outline of Dissertation This section introduces the background of RA disease. It starts with the definition of the disease, followed by the disease symptoms, disease disposition, and research questions and objectives of the dissertation. The beginning of Chapter 2 briefly discusses the epidemiology of RA in the context of recent observational studies. The chapter discusses the assessment of disease activity including biomarkers, clinical activity score, patient assessment, and a physician assessment. The chapter discusses the limitations of the current drug treatments and the need for developing safer and more effective drugs for treating RA.
the clinical relevant doses if the dose response followed U-shaped curve (Bornkamp 2007). The focus will be on applying the dose response to support future development of GSK654321 by understanding the design issues and developing a better statistical methodology. The third objective of the dissertation is to develop a statistical method to predict the late time point outcome data using outcome data collected earlier to address the issue of prolonged time to interim decision-making. The method of using outcome data collected at early time points to inform the adaptation decisions will help to make quicker decisions. Lastly, based on what are learned from the Phase 2a trial of GSK123456, a recommendation is made for the Phase 2a study design of the follow-on compound GSK654321 which is in the same drug class and currently under-development for arthritis treatment. Outline of Dissertation This section introduces the background of RA disease. It starts with the definition of the disease, followed by the disease symptoms, disease disposition, and research questions and objectives of the dissertation. The beginning of Chapter 2 briefly discusses the epidemiology of RA in the context of recent observational studies. The chapter discusses the assessment of disease activity including biomarkers, clinical activity score, patient assessment, and a physician assessment. The chapter discusses the limitations of the current drug treatments and the need for developing safer and more effective drugs for treating RA.