Alzheimer's Imaging Consortium.

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.
• Utilizing plasma p-tau can identify individuals likely to be amyloid-beta positron emission tomography (Aβ-PET) positive.
• This reduces the number of PET scans and recruitment costs.

Purpose of the Study:

• To evaluate the cost-effectiveness of plasma p-tau thresholds (liberal, intermediate, conservative) for pre-screening in Alzheimer's disease (AD) clinical trials.
• To assess the impact on Aβ-PET scan reduction and overall trial costs.

Main Methods:

• Studied 1,673 individuals across the AD spectrum with plasma p-tau217 and Aβ-PET data.
• Tested liberal (95% sensitivity), intermediate (Youden index), and conservative (95% specificity) thresholds.
• 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.
• Pre-screening with the intermediate threshold reduced Aβ-PET scans by 64% in cognitively unimpaired (CU) and 46% in cognitively impaired (CI) individuals.
• Significant cost reductions were observed: 59% in CU and 39% in CI, with similar findings across different p-tau assays.

Conclusions:

• Plasma p-tau217 is an effective pre-screening tool for AD clinical trials.
• The intermediate threshold offers the most cost-effective strategy, reducing Aβ-PET scans and optimizing recruitment.
• This approach enhances clinical trial efficiency for individuals across the AD spectrum.