Alzheimer’s Disease Interception: Methods for Evaluating a New Generation of Therapies

In 2011, we began a pilot project to explore the feasibility of developing clinical study design guidance to meet the needs of an international array of health technology assessment (HTA) organizations and coverage bodies. This pilot launched the Green Park Collaborative (at the time, “GPC International”) and led to the creation of a 2013 Evidence Guidance Document (EGD) providing recommendations for design of phase 3 trials of pharmacological therapies for mild to moderate Alzheimer’s disease (AD).  These recommendations were agreed upon by an international assortment of payer and HTA bodies. The collaborative also produced an evaluation of the pilot project exploring the challenges and opportunities of international collaboration on such guidance.

In 2018, CMTP launched an initiative providing updated guidance on methods for evaluating the efficacy of therapies to treat Alzheimer's disease, this time with focus on disease interception: trials of disease modifying agents designed to intervene in disease development very early in the process, even before patients have become symptomatic. The field of Alzheimer’s therapeutics has moved in this direction based on a hypothesis that the most promising opportunity for intervening in the underlying disease process is to act very early in the process of abnormal protein deposition in the brain. This new focus raised issues regarding the types of evidence needed by health plan decision-makers to cover these new therapies. How can study designers assure that patients are correctly identified as candidates for therapy? How long should patients be followed to demonstrate benefit, and which outcomes make a difference in the very early stages of disease development?