Data from: The effect of funding sources on donepezil randomised controlled trial outcome: a meta-analysis

Objective: To investigate whether there is a difference in the treatment
effect of donepezil on cognition in Alzheimer disease between
industry-funded and independent randomised controlled trials. Design:
Fixed effects meta-analysis of standardised effects of donepezil on
cognition as measured by the Mini Mental State Examination and the
Alzheimer’s Disease Assessment Scale-cognitive subscale. Data sources:
Studies included in the meta-analyses reported in the National Institute
for Health and Care Excellence (NICE) technical appraisal 217 updated with
new studies through a PubMed search. Eligibility criteria: Inclusion
criteria were double-blind, placebo-controlled trials of any length
comparing patients diagnosed with probable Alzheimer disease (according to
the NINCDS-ADRDA/DSM-III/IV criteria) taking any dosage of donepezil.
Studies of combination therapies (eg, donepezil and memantine) were
excluded, as were studies that enrolled patients with a diagnosis of
Alzheimer disease associated with other disorders (eg, Parkinson's
disease and Down's syndrome). Results: Our search strategy identified
14 relevant trials (4 independent) with suitable data. Trials sponsored by
pharmaceutical companies reported a larger effect of donepezil on
standardised cognitive tests than trials published by independent research
groups (standardised mean difference (SMD)=0.46, 95% CI 0.37 to 0.55 vs
SMD=0.33, 95% CI 0.18 to 0.48, respectively). This difference remained
when only data representing change up to 12 weeks from baseline were
analysed (industry SMD=0.44, 95% CI 0.34 to 0.53 vs independent SMD=0.35,
95% CI 0.18 to 0.52). Analysis revealed that the effect of funding as a
moderator variable of study heterogeneity was not statistically
significant at either time point. Conclusions: The effect size of
donepezil on cognition is larger in industry-funded than independent
trials and this is not explained by the longer duration of industry-funded
trials. The lack of a statistically significant moderator effect may
indicate that the differences are due to chance, but may also result from
lack of power.

研究目标：探讨由行业资助与独立开展的随机对照试验中，多奈哌齐（donepezil）对阿尔茨海默病（Alzheimer disease）患者认知功能的治疗效果是否存在差异。

研究设计：采用固定效应荟萃分析（fixed effects meta-analysis）方法，分析多奈哌齐对认知功能的标准化效应；认知功能的评估工具为简易精神状态检查表（Mini Mental State Examination）及阿尔茨海默病评估量表-认知分表（Alzheimer’s Disease Assessment Scale-cognitive subscale）。

数据来源：纳入的研究包括英国国家卫生与临床优化研究所（National Institute for Health and Care Excellence, NICE）技术评估报告217中的荟萃分析所涵盖的研究，以及通过PubMed检索补充的最新研究。

纳入与排除标准：纳入标准为采用双盲、安慰剂对照设计的试验（无论时长），研究对象为确诊为可能阿尔茨海默病（依据NINCDS-ADRDA/DSM-III/IV标准）且接受任意剂量多奈哌齐治疗的患者。排除联合治疗研究（如多奈哌齐联合美金刚）及纳入合并其他疾病的阿尔茨海默病患者的研究（如帕金森病、唐氏综合征）。

研究结果：通过检索策略共识别出14项符合要求的相关试验（其中4项为独立试验）。制药公司资助的试验显示，多奈哌齐对标准化认知测试的效应大于独立研究团队开展的试验（标准化均数差（standardised mean difference, SMD）分别为0.46，95%置信区间（confidence interval, CI）0.37至0.55；以及0.33，95% CI 0.18至0.48）。仅分析基线后12周内的变化数据时，这一差异仍然存在（行业资助组SMD=0.44，95% CI 0.34至0.53；独立组SMD=0.35，95% CI 0.18至0.52）。分析表明，在两个时间点上，资助类型作为研究异质性的调节变量，其效应均无统计学意义。

研究结论：行业资助试验中多奈哌齐对认知功能的效应量大于独立试验，且这一差异并非由行业资助试验的时长更长所致。调节效应无统计学意义可能表明差异源于偶然，但也可能是统计效力（power）不足所致。