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.