论文标题：Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials

期刊：Trials

作者：Jeremy Howick, Rebecca Webster, Nigel Kirby and Kerry Hood

发表时间：2018/12/11

数字识别码：10.1186/s13063-018-3042-4

原文链接：https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-018-3042-4?utm_source=other&utm_medium=other&utm_content=null&utm_campaign=BSCN_2_WX_Trails_Arti_Scinet

微信链接：https://mp.weixin.qq.com/s/dK0FcE8OJj0x44T8emdGgg

Trials 近期发表的文章研究了临床试验中安慰剂可能对参与者带来的不良影响，结果发现，近一半服用安慰剂的参与者表示临床干预给他们带来了副作用。在本篇博客中，该研究的第一作者，Jeremy Howick博士，将与我们探讨该研究的相关发现。

© PavelIvanov / Getty Images / iStock

一项新的研究发现，在临床试验中服用安慰剂的参与者有一半报告自己由于临床干预而出现了不良反应，而这些安慰剂通常只是没有任何作用的片剂，例如糖片。更令人惊讶的是，在服用安慰剂的人群中，每20人中就有1人因为更严重的副作用退出了试验。该研究所用的数据来自1271项随机试验以及250726名试验参与者。所报告的不良反应包括腹痛、厌食、烧灼感、胸痛、疲劳甚至死亡。

但是糖片怎么会产生副作用呢？这一问题的答案关键在于错误的归因（misattribution）及消极的信念（negative expectations）。

参加试验的人可能会因为各种各样与试验无关的原因出现胃痛。因为他们参加了试验，就会错误地认为是试验干预导致了疼痛。这种情况会被报道为副作用，而事实上它本来就会发生。

某些情况下，有关副作用的提醒会让患者相信他们会受副作用影响（比如胃痛），而这种想法会让患者真的表现出相关症状。这种负面预期的影响被称为“反安慰剂”效应。

在本研究中没有关于实验参与者的数据。然而，我们从其他研究中得知，告知患者副作用的方式会影响他们是否报告副作用的产生。例如，去年发表在《柳叶刀》杂志上的一项研究发现，当患者知道他们在服用他汀类药物时，更有可能报告相关副作用。当他们不知道的时候，肌肉相关的副作用并没有增加。

另一项研究发现，在一项通过服用阿司匹林或磺胺吡酮治疗不稳定型心绞痛的随机试验中，如果患者收到可能引起胃肠道副作用的声明，则因产生胃肠道副作用而退出研究的可能性要高出六倍。

寻求减少安慰剂组患者副作用的方法对于提高试验质量很重要，也可能改善临床试验的伦理问题。然而当务之急是了解究竟该如何实现这些目标？

错误的归因是很难避免的，因为在试验中，参与者很难知道像胃痛这样的症状是由试验干预引起的，还是源于最初导致他们参加试验的身体状况。然而，我们似乎可以削弱负面预期带来的损害。

例如，告知患者一种新疗法对90%的患者是安全的，或用另一种方式告知他们10%的患者可能出现头痛等症状，虽然两种表述方式涵盖了同样的信息，但后者会更有可能导致副作用的发生。

不幸的是，目前还没有充分的研究来指导人们如何以一种不会产生反安慰剂效应的方式告知参与者试验干预的相关危害。最近的一项系统评价表明，提供给参与者资料往往不能满足他们的需要，且所用的表达方式有时使他们感到难以理解。

目前，牛津大学与卡迪夫大学的研究人员正在尝试寻找相关方法，希望能够让参与试验的患者以最佳方式获得有关参与试验的均衡的利弊信息。

摘要：

Background

Trial participants in placebo groups report experiencing adverse events (AEs). Existing systematic reviews have not been synthesized, leaving questions about why these events occur as well as their prevalence across different conditions unanswered.

Objectives

(1)

To synthesize the evidence of prevalence of AEs in trial placebo groups across different conditions.

(2)

To compare AEs in trial placebo groups with AEs reported in untreated groups within a subset of randomized trials.

Search methods

We searched PubMed for records with the word “nocebo” in the title and “systematic” in any field. We also contacted experts and hand-searched references of included studies.

Study eligibility

We included any systematic review of randomized trials where nocebo effects were reported. We excluded systematic reviews of non-randomized studies.

Participants and interventions

We included studies in any disease area.

Study appraisal and synthesis methods

We appraised the quality of the studies using a shortened version of the Assessment of Multiple Systematic Reviews tool (AMSTAR) tool. We reported medians and interquartile ranges (IQRs) of AEs. Among the trials within the review that included untreated groups, we compared the prevalence of AEs in untreated groups with the prevalence of AEs in placebo groups.

Results

We identified 20 systematic reviews. These included 1271 randomized trials and 250,726 placebo-treated patients. The median prevalence of AEs in trial placebo groups was 49.1% (IQR 25.7–64.4%). The median rate of dropouts due to AEs was 5% (IQR 2.28–8.4%). Within the 15 of trials that reported AEs in untreated groups, we found that the AE rate in placebo groups (6.51%) was higher than that reported in untreated groups (4.25%).

Limitations

This study was limited by the quality of included reviews and the small number of trials that included untreated groups.

Conclusions and implications of key findings

AEs in trial placebo groups are common and cannot be attributed entirely to natural history. Trial methodologies that reduce AEs in placebo groups while satisfying the requirement of informed consent should be developed and implemented.

阅读论文全文请访问：

https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-018-3042-4?utm_source=other&utm_medium=other&utm_content=null&utm_campaign=BSCN_2_WX_Trails_Arti_Scinet

期刊介绍:

Trials (https://trialsjournal.biomedcentral.com/,2.067 - 2-year Impact Factor, 2.343 - 5-year Impact Factor) encompasses all aspects of the performance and findings of randomized controlled trials in health. We publish articles on general trial methodology and research into trial processes, as well as study protocols and statistical analysis plans for randomised controlled trials, commentaries and traditional results papers - regardless of outcome or significance of findings.

（来源：科学网）