Research has established beyond doubt that Alzheimer’s dementia is a result of multiple disease processes. The hypothesis behind EPAD suggested that early, targeted intervention focused on the very first stages of disease will be more successful than efforts to tackle established disease processes have been. By delaying, preventing or eliminating the pathologies that begin in mid-life, it may be possible to block the cascade of events that, over subsequent decades, culminate in dementia symptoms.
This approach required greater insight into the life of the brain than has ever been achieved before. EPAD has been set up to find the answers.
The EPAD study design addressed the limitations of a traditional Phase II Alzheimer’s dementia trial, delivering a guaranteed trial-ready cohort of pre-screened participants and superior data at a faster rate than ever before.
EPAD aimed to efficiently deliver early, accurate results. Studying new drugs in a well-designed Phase II PoC trial with clinical endpoints prior to Phase III, and continuous evaluation against a shared placebo, EPAD utilised the power of adaptive design and Bayesian statistics to streamline trials, increase knowledge and improve outcomes.
Drug trials in Alzheimer’s research have to date been hampered by uncertainty in which population to test, and which outcome measures to use. EPAD provided one well-characterised cohort, with biomarker evidence of Alzheimer’s disease pathology and a consistent set of outcomes, so intervention owners can expect guaranteed recruitment, fewer screen failures and more accurate results.
The EPAD PoC was ready to use and provided all the major components required to run a clinical trial in Alzheimer’s disease. Interventions owners had to bring their intervention and we aimed to provide the comprehensive infrastructure to deliver the rest.
EPAD also provided supported access to global Alzheimer’s dementia experts and 39 partners ranging from world leading universities, major pharmaceutical companies, digital research organisations and CROs.
Flexible and efficient study design
The EPAD PoC study design provided comprehensive, ongoing assessment and analysis of interventions throughout the study lifecycle, allowing for a flexibility and efficiency not possible in traditional trial formats.
The study design incorporated:
- Use of a cognitive measure as the primary endpoint.
- Frequent evolutionary analyses for success and futility.
- Advancement of compounds that achieve an effect on an intermediate phenotype or biomarker of target engagement to the clinical stage of the study (note: compounds that have already demonstrated target engagement may bypass this step).
- Use of Bayesian statistical models to achieve faster randomisation to doses or interventions that appear more effective overall or in specific subpopulations.
- Efficient use of the accruing data.
- Randomisation to drug or placebo for each intervention, with analysis using combined data from all placebo subjects to increase the power of the analyses.
The PoC master protocol outlined our study design and requirements for all interventions.