|FEASIBILITY1||SCOPING2||RESEARCH3||SUBMITTED4||ENDORSED/ FIT FOR PURPOSE5|
U.S. Food & Drug Administration (FDA)
European Medicines Agency (EMA)
A quantitative model that describes the natural history of cognitive change in Alzheimer disease (AD) can be an enormously valuable tool in the development of novel therapies. Utilizing the extensive historical data available in the literature and from participating members, CPAD has developed such a model which can be used to simulate and test relevant characteristics of clinical trial designs for different hypothesized expected effects of a drug. On June 12, 2013, the FDA issued a determination that CPAD’s drug development tool is fit-for-purpose, which means that it is scientifically supported and is suitable for the purpose of aiding in the design of future clinical trials in patients with mild to moderate AD. This model can be used to explore the effect of important design features such as trial duration, patient evaluation frequency, endpoint selection, and sample size. Clinical trial simulations relying on this model can provide support for the choice of trial design features, and can facilitate protocol review by CDER staff. End-of-Phase 2A meeting requests can be supported through the use of trial simulations based on this model or a modified version when clearly described. On September 19, 2013, the EMA issued a qualification opinion stating that “The proposed disease progression and trial evaluation model, as defined in this document, is suitable for qualification for use in drug development as a longitudinal model for describing changes in cognition in patients with mild and moderate AD, and for use in assisting in trial designs in mild and moderate AD, as defined by the context-of-use.