等离子体的潜在效用P-Tau和神经丝轻链作为预防临床试验替代生物标志物

Cost-Effectiveness of Plasma Biomarkers as Surrogate for Preventive Clinical Trials in CU Individuals (A) Sample sizes required for hypothetical clinical trials powered to use plasma biomarkers to monitor drug effects in CU older individuals. (B) Estimated cost with surrogate neuroimaging¹³ and plasma biomarkers only for clinical trials powered to use changes in these biomarkers to monitor drug effects. (C) Estimated cost of biomarkers plus the costs with some of the other necessary tests that are influenced by total sample sizes, such as costs with the definition of Aβ positivity (using PET) for population enrichment and a standard clinical evaluation for each participant. The costs of clinical trials using changes in tau-PET (¹⁸F-flortaucipir uptake in the temporal lobe) or structural MRI (tensor-based morphology cortical volume) as surrogate were estimated based on the mean and SD of a 12-month change in these biomarkers previously reported.¹³ For the calculations presented in the figure, we used the following hypothesized costs: MRI = $500; PET = $3,000; plasma marker = $200; recruitment/consenting/clinical assessment = $1,000. Assessments (except for biomarker of enrichment) were calculated to 2 time points (baseline and follow-up). Biomarker and procedure costs were estimations based on research assessments in the United States. These costs are simplified estimations for the sake of analysis and can vary highly depending on several factors. We estimated an attrition rate of 10% in the calculations. Δ = longitudinal change. Reduction in the sample size was calculated in relation to the whole population. Aβ = β-amyloid; CU = cognitively unimpaired; NfL = neurofilament light chain; p-tau181 = phosphorylated tau 181.