Three sub-working groups have been formed based on the most timely and critical topics and represent the current focuses of the Alzheimer's Disease (AD) SWG.
1. Primary Analysis / Missing Data / Estimands in AD
The primary objective of a clinical trial should be clearly defined with regard to the target of estimation (estimand) for the efficacy of an investigational drug. An ICH E9 Addendum on estimands has been developed to provide regulatory guidance and promote harmonized standards on the process of estimand determination. The AD SWG strives to align with the estimand framework defined in the regulatory guidance, and to make recommendations to the AD field regarding the appropriate determination of estimands and the implications for statistical estimation methods for clinical trials in Alzheimer’s disease.
2. Endpoints in Early AD
There is increased interest in moving to earlier AD for testing investigational drugs. Early AD represents a promising yet challenging stage of the disease. Concerted efforts are needed to review the different approaches of primary endpoints for phase 3 trials for Early AD and develop synergy in utilizing existing and developing new novel endpoint measures in this space.
3. Disease Modification: Trial Designs and Analytical Methods
The pharmaceutical development in AD is expanding from a focus on symptomatic treatments to investigation of treatments with the potential for modification of the underlying disease. One of the important questions is how to determine disease modifying effect by utilizing clinical trial design and analytical approaches. Research on this topic may provide guidelines for future clinical trial design and support for regulatory reviews of new potentially disease modifying treatments. This work will likely have wide-reaching impacts beyond AD and could be applicable more broadly to other neurodegenerative diseases.