The Inherent Meaningfulness of a Novel Time Component Test (TCT): Combining Evidence Across Outcomes to Measure the Impact of Treatment on Progression Rate in Degenerative Diseases

• Activity Number: 518 - Estimand, Causal Inference, and Other Statistical Considerations in Clinical Trials
• Type: Contributed
• Date/Time: Thursday, August 11, 2022 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Nathaniel Hogan and Jessie Johnson and Newman Knowlton and Sean Hennessey and Suzanne Hendrix and Samuel Dickson*
• Companies: Pentara and Pentara and Pentara and Pentara Corporation and Pentara and Pentara
• Keywords: Global Statistical Test (GST); Time Component Test (TCT); Progressive Diseases; Rare Diseases; Alzheimer's Disease; Composite Outcomes

Abstract

Degenerative diseases like Alzheimer's Disease and other progressive diseases present unique measurement challenges. Multiple components of disease occur over time like cognitive, functional, and global aspects which change at varying rates during different stages of disease partially due to ceiling and floor effects. These challenges make it difficult to create a single outcome for all stages of disease. But requiring significance on multiple primary outcomes imposes an unusually high standard for approval of treatments for under-treated diseases that often have relatively small populations. We propose the Time Component Test (TCT), a global statistical test that combines outcomes to obtain an estimate of the impact of treatment on progression rate of the disease. We demonstrate how it can be performed asymptotically using summary statistics and using subject level data. Using the TCT improves power without inflating type-I error and estimates time savings which is inherently meaningful and the primary objective of disease modifying treatments of degenerative diseases.