Drug Development.

Area of Science:

• Neurodegenerative diseases
• Biomarker discovery
• Clinical trial methodology

Background:

• Plasma phosphorylated tau (p-tau) serves as a pre-screening tool in clinical trials.
• Identifying individuals likely to be amyloid-beta PET positive (Aβ-PET+) can reduce the number of scans and recruitment costs.
• This study evaluates the cost-effectiveness of plasma p-tau thresholds for pre-screening across the Alzheimer's disease (AD) spectrum.

Purpose of the Study:

• To assess the cost-effectiveness of plasma p-tau as a pre-screening tool in AD clinical trials.
• To compare liberal, intermediate, and conservative thresholds for plasma p-tau pre-screening.
• To determine the optimal strategy for reducing Aβ-PET scans and recruitment costs.

Main Methods:

• Studied 1,673 individuals (707 cognitively unimpaired, 966 cognitively impaired) with plasma p-tau217 and Aβ-PET data.
• Tested three thresholds: liberal (95% sensitivity), intermediate (Youden index), and conservative (95% specificity).
• Calculated recruitment sample size based on assay performance and Aβ positivity prevalence.

Main Results:

• The intermediate threshold demonstrated the highest cost-effectiveness, followed by the conservative threshold.
• The liberal threshold did not outperform screening with Aβ-PET alone.
• Pre-screening with the intermediate threshold reduced Aβ-PET scans by 64% in cognitively unimpaired and 46% in cognitively impaired individuals, cutting costs by 59% and 39%, respectively.

Conclusions:

• Plasma p-tau217 is an effective pre-screening tool for AD clinical trials.
• The intermediate threshold offers the most cost-effective approach for both cognitively unimpaired and impaired individuals.
• This strategy optimizes recruitment, reduces Aβ-PET scan needs, and enhances clinical trial efficiency within the AD spectrum.