OBJECTIVES: To investigate outcome measures used in AD Phase III trials for disease modifying interventions, biomarker studies, cognitive enhancement, and symptomatic relief treatments.

METHODS: Advanced search in clinical trials.gov site was undertaken, using the following words; “Alzheimer’s Disease”, “Interventional studies”, “Phase 3”, “recruiting”, “not yet recruiting”, “active”, “not recruiting studies”, 62 studies were identified for inclusion in the analysis.

RESULTS: Across the 62 studies, 38 (61.3%) were disease modifying interventions, 16 (25.8%) were for symptomatic relief, 7 (11.3%) were biomarker studies and 1 (1.6%) was for cognition enhancement. 50 (80.6%) were randomized studies and 12 (19.4%) were non-randomized studies; the total number of patients were 48,104 and the number of patient-years were 94,841. The primary endpoints included cognition, functional, & agitation measures represented by; ADAS-Cog, CDR-SB, MMSE, CDR-GS, ADCS-ADL, ADCS-CGIC, and CMAI. Composite measures represented by iADRS, Severe Impairment Battery, PACC-5. Biomarker measures represented by amyloid plaque clearance, CSF and plasma p-tau181.Total hippocampal volume, safety and tolerability measures were represented by ARIA-E, ARIA-H, anti-drug antibody, AEs, SAEs. Sleep/insomnia measures represented by Epworth Sleepiness Scale and Insomnia Severity Index. Across the 62 studies, the secondary endpoints included all of the primary endpoint measures and additional measures for patient and caregiver inputs (QOL-AD, Dementia QOL, EQ-5D-5L, Resource Utilization for Dementia, Zarit Burden Interview), neuropsychiatric symptoms (NPI, sub-domains of NPI) and time to event measures (time to reach complete amyloid plaque clearance, time to clinical progression, MCI, dementia).

CONCLUSIONS: The heterogeneity of AD measurement, suggests no convergence of a gold standard to employ in both cost and comparative effectiveness. A resulting paucity of cost and comparative effectiveness evidence leads to challenges in performing evaluations as required by payers and HTAs for market access and reimbursement decision making.