Efficacy of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch on activities of daily living in severe Alzheimer’s disease

Objective: Investigate efficacy of 13.3 mg/24 h rivastigmine patch in patients with severe Alzheimer’s disease on Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale–Severe Impairment Version items and domains. Methods: Retrospective analysis of the 24-week, randomized, double-blind ACTivities of daily living and cognitION (ACTION) study, using factor analysis to establish “best fit” for Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale–Severe Impairment Version items into domains. Treatment differences (13.3 vs 4.6 mg/24 h patch) on items and domains were assessed. Results: Overall, 632 patients provided Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale–Severe Impairment Version data. Factor analysis yielded four domains. The 13.3 versus 4.6 mg/24 h patch demonstrated significantly greater efficacy on “Daily function” ( p  = 0.038), supported by greatest effect sizes on items within this domain, and trend toward greater efficacy on “Communication” ( p  = 0.052). No significant between-group differences were observed on “Independence” ( p  = 0.600) or “Environment” ( p  = 0.261). Conclusion: The 13.3 mg/24 h patch was superior to 4.6 mg/24 h patch on “Daily function” in severe Alzheimer’s disease

Dear Mr. Kingsley:

Enclosed please find the “Risk-Informed Inspection Notebook ” which incorporates the updated Significance Determination Process (SDP) Phase 2 Worksheets that inspectors will be using to characterize and risk-inform inspection findings. This document is one of the key implementation tools of the reactor safety SDP in the reactor oversight process and soon will also be publicly available through the Nuclear Regulatory Commission’s (NRC’s) external website a