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.

研究目的：探讨行业资助与独立开展的随机对照试验（randomised controlled trials, RCTs）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应是否存在差异。研究设计：采用固定效应模型对多奈哌齐的认知标准化效应量开展荟萃分析（meta-analysis），认知功能评估指标为简易精神状态检查表（Mini Mental State Examination, MMSE）与阿尔茨海默病评定量表-认知分量表（Alzheimer’s Disease Assessment Scale-cognitive subscale, ADAS-cog）。数据来源：纳入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收录的荟萃分析相关研究，并通过PubMed检索补充新增研究。入选标准：纳入双盲、安慰剂对照的任意时长随机对照试验，受试对象为符合可能阿尔茨海默病诊断标准（依据NINCDS-ADRDA/DSM-III/IV诊断标准）且服用任意剂量多奈哌齐的患者。排除联合治疗研究（如多奈哌齐联合美金刚），以及纳入伴其他疾病的阿尔茨海默病患者的研究（如合并帕金森病、唐氏综合征的患者）。研究结果：本检索策略共筛选出14项符合要求的试验（其中4项为独立研究）。药企资助试验报告的多奈哌齐对标准化认知测试的效应量大于独立研究团队开展的试验：标准化均数差（standardised mean difference, SMD）=0.46，95%置信区间（confidence interval, CI）0.37~0.55；独立研究组SMD=0.33，95%CI 0.18~0.48。当仅分析基线至12周的随访变化数据时，该差异依然存在：药企资助组SMD=0.44，95%CI 0.34~0.53；独立组SMD=0.35，95%CI 0.18~0.52。分析显示，在任一随访时间点，资助类型作为研究异质性调节变量的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研究，且该差异无法用行业资助试验更长的随访时长解释。资助类型未表现出统计学显著的调节效应，这一结果可能提示差异由抽样误差导致，也可能源于研究效力不足。