Defining treatment response to donepezil in Alzheimer's disease: responder analysis of patient-level data from randomized, placebo-controlled studies.
BACKGROUND
Defining treatment success in progressive diseases, such as Alzheimer's disease (AD), can be challenging.


OBJECTIVE
To explore the impact of employing different criteria to define a treatment 'responder' using analyses of patient-level data from randomized, placebo-controlled studies of donepezil in AD.


METHODS
Trials were included in the analysis if they met several criteria, including the following: randomized, placebo-controlled trial of donepezil 10 mg/day in mild-to-moderate AD; cognition measured by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) or Mini-Mental State Examination (MMSE); and a 24-week endpoint and outcomes that included global assessments. Definitions of response were: improvements in cognition plus one other domain; improvement in cognition only; improvement or improvement/no change in global response; and improvement/stabilization/less than expected decline by < or = 2 or < or = 4 or < or = 6 points on the ADAS-cog.


RESULTS
Five studies identified from the literature search met the specified criteria for inclusion. The response to donepezil measured by ADAS-cog varied from 26% to 63% and that of placebo from 14% to 47%, depending on the definition of improvement used. For definitions that included a less than expected decline on ADAS-cog, the more modest the effect defined, the less the drug versus placebo difference and the higher the percentage of patients meeting this definition.


CONCLUSIONS
The definition of treatment 'response' in a progressive neurodegenerative disease can encompass a variety of outcomes, including short-term improvement, longer-term stabilization and a slowed decline in one or more clinically relevant symptoms or symptom domains. The ability to identify groups of people who respond to donepezil underscores the clinical utility of the medication and may contribute to more focused assessments of the cost effectiveness of cholinesterase inhibitors.
Burns
Alistair
A
University of Manchester, Wythenshawe Hospital, Manchester, UK. alistair.burns@manchester.ac.uk
Yeates
Andrew
A
Akintade
Latif
L
Del Valle
Megan
M
Zhang
Richard Y
RY
Schwam
Elias M
EM
Perdomo
Carlos A
CA
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil