12: Why Placebo Progression Should Be the Gold Standard for Endpoint Validation for Progressive Diseases

Thomas M. Menino Convention & Exhibition Center 

Endpoint selection for progressive diseases like Alzheimer's disease is often hindered by rigorous regulatory validation requirements, including construct validity, internal consistency, and external responsiveness. Extensive endpoint validation trials are costly and can delay the delivery of effective treatments to patients by leaving sponsors with a choice of sub-optimal outcomes which require larger sample sizes and lead to higher risk of study failure. While traditional metrics are valuable, the mean-to-standard-deviation ratio (MSDR), a standardized ratio of control arm progression, offers a universal evaluation for progressive diseases. It is mathematically demonstrated how a high MSDR inherently indicates that an endpoint fulfills traditional validation criteria such as those mentioned previously. By prioritizing MSDR, regulators and sponsors can identify sensitive outcomes and evaluate investigational products concurrently with the formal validation process. This approach streamlines drug development without compromising statistical rigor, ensuring that the most responsive tools are used for measuring treatment effects.

Alzheimer's Disease

Progressive Diseases

Clinical Endpoints

Endpoint Validation 

Biopharmaceutical Section