Abstract：
OBJECTIVE: Outcomes of clinical trials of treatment in patients with Parkinson\'s disease (PD) may be influenced by placebo effects. The aim of this study was to determine the factors associated with placebo effects in Parkinson\'s disease (PD) for guidance with design of future clinical trials.
METHODS: Factors associated with placebo effects in PD were examined in a meta-analysis using a random effects model with pooling of placebo effects on the Unified Parkinson\'s Disease Rating Scale part III (UPDRS III) or Movement Disorder Society sponsored revision of UPDRS III (MDS-UPDRS III). The following prespecified variables were included in the analyses: with or without drug at baseline, with or without a placebo run-in phase, with or without motor fluctuation, published year, number of study sites, placebo administration period, age, sex, disease duration, and daily levodopa dose. Publication bias was assessed by visual inspection of funnel plots and adjusted using the trim-and-fill method.
RESULTS: Thirty-eight articles with a total of 4828 subjects satisfied the inclusion criteria. There was a significant placebo effect using UPDRS III or MDS-UPDRS III (SMD = - 0.25; 95% CI - 0.35 to - 0.14; p < 0.001, I2 = 92%). Subgroup and/or multivariate meta-regression analyses revealed that placebo effects were associated with advanced PD (p = 0.04), drug exposure at baseline (p < 0.001), placebo administration period (p < 0.001), and disease duration (p < 0.01).
CONCLUSIONS: The results of this study are important as guidance in design of future clinical trials in which the influence of placebo effects is minimized.
METHODS: Factors associated with placebo effects in PD were examined in a meta-analysis using a random effects model with pooling of placebo effects on the Unified Parkinson\'s Disease Rating Scale part III (UPDRS III) or Movement Disorder Society sponsored revision of UPDRS III (MDS-UPDRS III). The following prespecified variables were included in the analyses: with or without drug at baseline, with or without a placebo run-in phase, with or without motor fluctuation, published year, number of study sites, placebo administration period, age, sex, disease duration, and daily levodopa dose. Publication bias was assessed by visual inspection of funnel plots and adjusted using the trim-and-fill method.
RESULTS: Thirty-eight articles with a total of 4828 subjects satisfied the inclusion criteria. There was a significant placebo effect using UPDRS III or MDS-UPDRS III (SMD = - 0.25; 95% CI - 0.35 to - 0.14; p < 0.001, I2 = 92%). Subgroup and/or multivariate meta-regression analyses revealed that placebo effects were associated with advanced PD (p = 0.04), drug exposure at baseline (p < 0.001), placebo administration period (p < 0.001), and disease duration (p < 0.01).
CONCLUSIONS: The results of this study are important as guidance in design of future clinical trials in which the influence of placebo effects is minimized.
摘要：
目的：治疗帕金森病（PD）患者的临床试验结果可能受安慰剂效应的影响。这项研究的目的是确定与帕金森病（PD）安慰剂效应相关的因素，以指导未来临床试验的设计。
方法：在一项荟萃分析中，使用随机效应模型对帕金森病患者中与安慰剂效应相关的因素进行了研究，该模型汇集了统一帕金森病评定量表第三部分（UPDRSIII）或运动障碍协会赞助的UPDRSIII修订版（MDS-UPDRSIII）的安慰剂效应。分析中包括以下预先指定的变量：基线有或没有药物，有或没有安慰剂磨合期，有或没有电机波动，发表年,研究地点的数量，安慰剂给药期间，年龄,性别,疾病持续时间,和每日左旋多巴剂量。通过目视检查漏斗图评估出版偏差，并使用修剪和填充方法进行调整。
结果：38篇，共4828名受试者符合纳入标准。使用UPDRSIII或MDS-UPDRSIII有显著的安慰剂效应(SMD=-0.25;95%CI-0.35至-0.14;p<0.001,I2=92%)。亚组和/或多变量荟萃回归分析显示，安慰剂效应与晚期PD相关（p=0.04），基线时的药物暴露（p<0.001），安慰剂给药期（p<0.001），和病程(p<0.01)。
结论：这项研究的结果对于未来临床试验的设计具有重要的指导意义，在这些临床试验中，安慰剂效应的影响将被最小化。
方法：在一项荟萃分析中，使用随机效应模型对帕金森病患者中与安慰剂效应相关的因素进行了研究，该模型汇集了统一帕金森病评定量表第三部分（UPDRSIII）或运动障碍协会赞助的UPDRSIII修订版（MDS-UPDRSIII）的安慰剂效应。分析中包括以下预先指定的变量：基线有或没有药物，有或没有安慰剂磨合期，有或没有电机波动，发表年,研究地点的数量，安慰剂给药期间，年龄,性别,疾病持续时间,和每日左旋多巴剂量。通过目视检查漏斗图评估出版偏差，并使用修剪和填充方法进行调整。
结果：38篇，共4828名受试者符合纳入标准。使用UPDRSIII或MDS-UPDRSIII有显著的安慰剂效应(SMD=-0.25;95%CI-0.35至-0.14;p<0.001,I2=92%)。亚组和/或多变量荟萃回归分析显示，安慰剂效应与晚期PD相关（p=0.04），基线时的药物暴露（p<0.001），安慰剂给药期（p<0.001），和病程(p<0.01)。
结论：这项研究的结果对于未来临床试验的设计具有重要的指导意义，在这些临床试验中，安慰剂效应的影响将被最小化。
