Impact of study design and patient population on outcomes from cholinesterase inhibitor trials.
The authors conducted a comparative review of study designs and patient populations used in pivotal trials investigating various cholinesterase inhibitors (tacrine, donepezil, rivastigmine, galantamine, controlled-release physostigmine, and metrifionate) and their impact on outcomes reported. Study design parameters that were investigated included patient selection, definitions of adverse dropouts and serious adverse events, effective doses used, dosing flexibility (fixed versus flexible), forced titration, and titration rate. Population characteristics included medical comorbidity and disease severity. Data suggest that differences in study designs and patient populations affect outcomes. Therefore, caution should be taken before making decisions on relative efficacy, safety, and tolerability, because clinical studies are not always directly comparable.
Anand
Ravi
R
ranand9872@aol.com
Hartman
Richard
R
Sohn
Hyesung
H
Danyluk
Jacquiline
J
Graham
Stephen M
SM
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000145:classification / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000175:diagnosis; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006304:Health Status; D006801:Humans; D020714:Maximum Tolerated Dose; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012720:Severity of Illness Index
D002800:Cholinesterase Inhibitors