Objective

To evaluate the association between the degree of response to placebo in migraine studies and the observed difference between drug and placebo across studies of preventative treatments for migraine.

Methods

A systematic review was performed using MEDLINE and the Cochrane Central Register of Controlled Clinical Trials from January 1988 to June 2019. Randomized, double-blind, parallel-group, placebo-controlled trials on oral or injection preventative treatments for migraine were included. Single- and multi-variable linear regression analyses were performed on the placebo-subtracted response rate (i.e. placebo responders subtracted from active responders), and the proportion of placebo responders. Fisher’s exact tests were performed on the level of placebo response and the success in meeting the study’s primary endpoint.

Results

After adjusting for route of administration and number of randomized subjects, there was a statistically significant association between the proportion of patients who were placebo responders and the placebo-subtracted response rate (b = −0.27, p = 0.02). There was a statistically significant difference in trial success rate (60%) between studies with ≤20% placebo responders and studies with > 30% placebo responders (p = 0.03).

Conclusion

Considering the detrimental impact that high placebo response can have on clinical trials, it is imperative to find effective solutions to decrease the placebo response and increase assay sensitivity.

中文翻译：

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安慰剂反应、观察到的治疗效果和未能达到主要终点之间的关系：预防性偏头痛药物治疗临床试验的系统评价。

客观的

评估偏头痛研究中对安慰剂的反应程度与偏头痛预防性治疗研究中观察到的药物和安慰剂之间的差异之间的关联。

方法

1988 年 1 月至 2019 年 6 月期间，使用 MEDLINE 和 Cochrane 对照临床试验中心登记册进行了系统评价。纳入了关于偏头痛口服或注射预防性治疗的随机、双盲、平行组、安慰剂对照试验。对减去安慰剂的反应率（即从积极反应者中减去安慰剂反应者）和安慰剂反应者的比例进行单变量和多变量线性回归分析。费舍尔的精确测试是在安慰剂反应水平和达到研究主要终点的成功率上进行的。

结果

在调整给药途径和随机受试者数量后，安慰剂响应患者的比例与减去安慰剂的响应率之间存在统计学显着相关性（b = -0.27，p  = 0.02）。≤ 20% 安慰剂反应者的研究和 > 30% 安慰剂反应者的研究之间的试验成功率 (60%) 存在统计学显着差异 ( p  = 0.03)。

结论

考虑到高安慰剂反应可能对临床试验产生不利影响，必须找到有效的解决方案来降低安慰剂反应并提高检测灵敏度。