Tinklenberg Jared R, Kraemer Helena C, Yaffe Kristine, Ross Leslie, Sheikh Javaid, Ashford John W, Yesavage Jerome A, Taylor Joy L
Sierra Pacific Mental Illness, Research, Education and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
Am J Geriatr Psychiatry. 2007 Nov;15(11):953-60. doi: 10.1097/JGP.0b013e3180986138.
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.
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.
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.
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.
通过比较一项北欧为期一年的多奈哌齐治疗阿尔茨海默病（AD）患者的随机临床试验结果与一项为期一年的AD患者前瞻性观察性研究数据，确定多奈哌齐在AD患者中的随机临床试验结果是否可应用于临床实践中的AD患者。
对来自加利福尼亚州多个研究点联盟的AD患者进行了至少一年的系统随访。他们的治疗方案，包括多奈哌齐的处方，由其个体医生根据其通常标准确定。
148例接受多奈哌齐治疗的加利福尼亚患者在简易精神状态检查中的一年下降值为1.3（标准差3.5）分，而158例未接受抗阿尔茨海默病药物治疗的AD患者下降值为3.3（标准差4.4）分。在北欧样本中，91例接受多奈哌齐治疗的患者简易精神状态检查下降值约为0.25分，98例接受安慰剂治疗的患者约为2.2分。两项研究中的总体效应大小估计约为0.49。使用倾向方法对加利福尼亚的数据进行了进一步分析；在考虑了可能影响处方决策的差异后，服用多奈哌齐的益处依然存在。
多奈哌齐治疗AD患者的随机临床试验与本观察性研究的比较表明，如果采取适当的方法学和统计学预防措施，那么随机临床试验结果可预测临床实践中的AD患者。这项加利福尼亚研究支持多奈哌齐对具有与北欧研究相似临床特征的AD患者有一定疗效。
