Enrichment of clinical trials in MCI due to AD using markers of amyloid and neurodegeneration. (20th September 2016)

• Record Type: Journal Article
• Authors: Wolz, Robin; Schwarz, Adam J.; Gray, Katherine R.; Yu, Peng; Hill, Derek L.G.
• Is Part Of: Neurology. Volume 87:Number 12(2016)
• Publication Date: 2016-09-20
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000003126
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To investigate the effect of enriching mild cognitive impairment (MCI) clinical trials using combined markers of amyloid pathology and neurodegeneration. Methods: We evaluate an implementation of the recent National Institute for Aging–Alzheimer's Association (NIA-AA) diagnostic criteria for MCI due to Alzheimer disease (AD) as inclusion criteria in clinical trials and assess the effect of enrichment with amyloid (A+), neurodegeneration (N+), and their combination (A+N+) on the rate of clinical progression, required sample sizes, and estimates of trial time and cost. Results: Enrichment based on an individual marker (A+ or N+) substantially improves all assessed trial characteristics. Combined enrichment (A+N+) further improves these results with a reduction in required sample sizes by 45% to 60%, depending on the endpoint. Conclusions: Operationalizing the NIA-AA diagnostic criteria for clinical trial screening has the potential to substantially improve the statistical power of trials in MCI due to AD by identifying a more rapidly progressing patient population.