Donepezil treatment and Alzheimer disease: can the results of randomized clinical trials be applied to Alzheimer disease patients in clinical practice?
OBJECTIVE
To determine if results from randomized clinical trials of donepezil in Alzheimer disease (AD) patients can be applied to AD patients in clinical practice by comparing the findings from a Nordic one-year randomized AD donepezil trial with data from a one-year prospective, observational study of AD patients.


METHODS
AD patients from a consortium of California sites were systematically followed for at least one year. Their treatment regimens, including prescription of donepezil, were determined by their individual physician according to his or her usual criteria.


RESULTS
The 148 California patients treated with donepezil had a one-year decline of 1.3 (3.5 SD) points on the Mini-Mental State Exam compared to a decline of 3.3 (4.4 SD) in the 158 AD patients who received no anti-Alzheimer drugs. The Mini-Mental State Exam decline in Nordic sample was approximately 0.25 points for the 91 patients receiving donepezil and approximately 2.2 for the 98 placebo patients. The overall effect sizes were estimated at about 0.49 in both studies. The California data were further analyzed using propensity methods; after taking into account differences that could bias prescribing decisions, benefits associated with taking donepezil remained.


CONCLUSIONS
A comparison of a randomized clinical trial of donepezil in AD patients and this observational study indicates that if appropriate methodological and statistical precautions are undertaken, then results from randomized clinical trials can be predictive with AD patients in clinical practice. This California study supports the modest effectiveness of donepezil in AD patients having clinical characteristics similar to those of the Nordic study.
Tinklenberg
Jared R
JR
Sierra Pacific Mental Illness, Research, Education and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA. jerytink@stanford.edu
Kraemer
Helena C
HC
Yaffe
Kristine
K
Ross
Leslie
L
Sheikh
Javaid
J
Ashford
John W
JW
Yesavage
Jerome A
JA
Taylor
Joy L
JL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D002140:California; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D002985:Clinical Protocols; D000077265:Donepezil; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D004363:Drug Utilization; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D010880:Piperidines / Q000627:therapeutic use*; D010818:Practice Patterns, Physicians'; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil