NIA-funded Alzheimer centers are more efficient than commercial clinical recruitment sites for conducting secondary prevention trials of dementia.
Study participant dropout compromises clinical trials by reducing statistical power and potentially biasing findings. We use data from a trial of treatments to delay the progression of mild cognitive impairment to Alzheimer disease (AD) [NEJM 2005;352 (23):79 to 88] to determine predictors of study participant dropout and inform the design and implementation of future trials. Time to study discontinuation was modeled by proportional hazards regression with censoring at incident dementia or trial completion. Of 769 participants, 230 (30%) discontinued prematurely. Risk of dropout was higher among nonwhites [hazard ratio (HR) 2.1, P=0.0007], participants with less than college education (HR=1.6, P=0.02), participants with a Hamilton Depression score of 6 or more (HR=1.3, P=0.04), unmarried males (HR=2.1 relative to married males, P=0.003) and participants recruited by commercial clinical sites (HR=2.2 relative to participants recruited by NIA-funded AD research centers, P<0.0001). A trial using commercial sites with the discontinuation rates and incident dementia event rates experienced in this trial would require 80% more participants than a comparably powered trial using NIA-funded AD research center sites. Targeted retention efforts and utilization of academic sites could substantively improve the statistical power and validity of future clinical trials of cognitively impaired elderly.
Edland
Steven D
SD
Department of Neurosciences, University of California San Diego, La Jolla, CA, USA. sedland@ucsd.edu
Emond
Jennifer A
JA
Aisen
Paul S
PS
Petersen
Ronald C
RC
D000046:Academic Medical Centers; D000368:Aged; D000465:Algorithms; D000544:Alzheimer Disease / Q000517:prevention & control*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D015999:Multivariate Analysis; D054561:National Institute on Aging (U.S.); D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010352:Patient Dropouts / Q000706:statistics & numerical data*; D010880:Piperidines / Q000627:therapeutic use*; D055502:Secondary Prevention / Q000379:methods; D014481:United States; D014810:Vitamin E / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use
D002800:Cholinesterase Inhibitors; D007189:Indans; D018696:Neuroprotective Agents; D010880:Piperidines; D014815:Vitamins; D014810:Vitamin E; D000077265:Donepezil