Representation of patients with dementia in clinical trials of donepezil.
OBJECTIVE
To evaluate the representation of frail older adults in randomized controlled trials (RCTs), and to assess consequences of under representation by analyzing drug discontinuation rates.


METHODS
A cohort of older adults newly dispensed donepezil in Ontario between September 2001 and March 2002 was constructed using administrative data. A systematic review of the literature identified RCTs of donepezil. Patients dispensed donepezil were then compared to clinical trial subjects. Discontinuation rates were examined for patients with and without potential contraindications to this drug.


RESULTS
There were 6,424 older adults in the Ontario cohort with new claims for donepezil. Ten RCTs evaluating the use of donepezil were identified (n = 3,423). Between 51% and 78% of the Ontario cohort would have been ineligible for RCT enrollment. Patients dispensed donepezil were older (80.3 vs. 73.7 years, p < 0.001) and more likely to be in long-term care (14.1 vs. 7.1%, p < 0.001) than RCT subjects. Overall, 27.8% of the Ontario cohort discontinued donepezil within seven months of initial prescription. Discontinuation rates were significantly higher for patients with a history of obstructive lung disease, active cardiovascular disease, or Parkinsonism.


CONCLUSIONS
Fewer than half of the older adults dispensed donepezil in Ontario would have been eligible to participate in the RCTs that established the efficacy of this drug. Discontinuation rates were higher among patient groups not represented in the trials. Clinicians should carefully assess the potential risks and benefits of such drug therapies for older patients with dementia.
Gill
Sudeep S
SS
Kunin-Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care, Toronto, Ontario. sudeep.gill@ices.on.ca
Bronskill
Susan E
SE
Mamdani
Muhammad
M
Sykora
Kathy
K
Li
Ping
P
Shulman
Kenneth I
KI
Anderson
Geoffrey M
GM
Hillmer
Michael P
MP
Wodchis
Walter P
WP
Rochon
Paula A
PA
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D015331:Cohort Studies; D003704:Dementia / Q000188:drug therapy*; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009864:Ontario; D010352:Patient Dropouts; D018579:Patient Selection; D010880:Piperidines / Q000627:therapeutic use*; D010818:Practice Patterns, Physicians'; D016032:Randomized Controlled Trials as Topic
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil