Increasing placebo responses over time in US clinical trials of neuropathic pain
Increasing placebo responses over time in US clinical trials of neuropathic pain
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DOI：
10.1097/j.pain.0000000000000333
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发表时间：
2015-12-01
期刊：
影响因子：
7.4
通讯作者：
Mogil, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Tuttle, Alexander H.;Tohyama, Sarasa;Mogil, Jeffrey S.
旨在治疗神经性疼痛的新型镇痛药的临床试验的最新失败导致人们对潜在原因进行了很多猜测。经常讨论的可能性是，近年来，这些试验中的安慰剂反应增加了，导致药物和安慰剂臂之间的分离降低。是否确实发生这种情况尚未得到充分解决。在这里，我们从1990年至2013年的慢性神经性疼痛的药物中提取了已发表的随机对照试验（RCT）的数据。治疗优势降低。这种趋势是由在美国进行的研究驱动的。对参与者和研究特征的考虑表明，在美国但没有其他地方，RCT的研究规模和长度有所增加。这些变化与更大的安慰剂反应有关。对单个RCT时间课程的分析显示，治疗与安慰剂反应的动力学不同，前者的发展速度比后者和高原的速度更快，因此在4周内实现了最大的治疗优势。
Recent failures of clinical trials of novel analgesics designed to treat neuropathic pain have led to much speculation about the underlying reasons. One often discussed possibility is that the placebo response in these trials has increased in recent years, leading to lower separation between the drug and placebo arms. Whether this has indeed occurred has not yet been adequately addressed. Here, we extracted data from published randomized controlled trials (RCTs) of drugs for the treatment of chronic neuropathic pain over the years 1990 to 2013. We find that placebo responses have increased considerably over this period, but drug responses have remained stable, leading to diminished treatment advantage. This trend has been driven by studies conducted in the United States. Consideration of participant and study characteristics revealed that in the United States but not elsewhere, RCTs have increased in study size and length. These changes are associated with larger placebo response. Analysis of individual RCT time courses showed different kinetics for the treatment vs placebo responses, with the former evolving more quickly than the latter and plateauing, such that maximum treatment advantage was achieved within 4 weeks.