REPRESENTATION OF PATIENTS WITH DEMENTIA IN CLINICAL TRIALS OF DONEPEZIL

Main Article Content

Sudeep S. Gill
Susan E. Bronskill
Muhammad Mamdani Mamdani
Kathy Sykora
Ping Li
Kenneth I Shulman
Geoffrey M. Anderson
Michael P. Hillmer
Walter P. Wodchis
Paula A. Rochon

Keywords

Dementia, cholinesterase inhibitors, donepezil, clinical trials

Abstract

Objectives


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  enrolment. Patient’s 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 this drug’s efficacy. 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

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