Meta-Analyses, Disease Progression Models, and Trial Design and Analyses

• Activity Number: 233
• Type: Contributed
• Date/Time: Monday, August 4, 2014 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Russell Reeve*+
• Companies: Quintiles
• Keywords: adaptive design ; simulation ; functional data ; rheumatoid arthritis ; psoriasis ; Alzheimer's

Abstract

Disease progression models describe the time course of a disease, typically through an endpoint related to clinical manifestation. For example, in rheumatoid arthritis one may relate ACR20, DAS28, or other endpoints, to time. We have constructed models for use in designing clinical trials in the areas of rheumatoid arthritis, plaque psoriasis, Alzheimer's disease, and Parkinson's disease. The models have typically been constructed using publicly available literature, put together in a meta-analysis. These models can then be used in several ways, but the more common is to use these as the basis for trial simulations. The trial simulations are then used to explore design options, with the objective of selecting the best design parameters to maximize some operating characteristic of the design, such as power for a given sample size or minimum sample size for a given power. In this talk, I discuss the construction of the disease progression models for several clinical endpoints, how these disease progression models can be used to make decisions on important trial attributes, such as primary endpoint, interim analysis options, timing of the primary endpoint, and whether an adaptive or f