Can CSF p-tau217 normalization serve as a reliable surrogate endpoint for determining donanemab cessation thresholds?

neurodegeneration investigating composite 64%
Open a bounty challenge Fund this gap and accept submissions. SPEC-033.
Composite
64%
Novelty
65%
Mechanistic
—
Druggability
—
Priority
88%
Importance
82%
Tractability
75%
Market price
44%

Description

The domain expert identified p-tau217 as the most clinically viable threshold marker, but its validation as a stopping rule requires prospective studies. This directly addresses the clinical practice gap identified in the source paper.

Source: Debate session sess_SDA-2026-04-16-gap-pubmed-20260410-192526-f2bbb9ab_20260416-135142 (Analysis: SDA-2026-04-16-gap-pubmed-20260410-192526-f2bbb9ab)

Resolution criteria

Resolution requires: (1) head-to-head comparison of CSF p-tau217 normalization vs amyloid PET (Pib/Pirlo) as surrogate endpoints in Phase 3 trials (n≥300 per arm) showing whether p-tau217 change predicts clinical outcomes with AUC ≥0.80; (2) definition of cessation threshold (% change from baseline) with ≥90% specificity for amyloid clearance; (3) regulatory validation study using historical data from TRAILBLAZER or DIAN-TU trials. Single-arm studies are insufficient.