Background

Clinical trials in irritable bowel syndrome are associated with high placebo response rates. We aimed to identify the magnitude of the placebo response and the contributing factors to this occurrence.

Methods

We did a systematic review and meta-analysis with a search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials between April 1, 1959, and April 30, 2020. We included all randomised controlled trials that compared an active pharmacotherapeutic agent with placebo and had a dichotomous outcome of response to therapy (in terms of global improvement or improvement in abdominal pain) in adults (aged ≥18 years) with irritable bowel syndrome. Exclusion criteria were trials reporting on treatment satisfaction as a dichotomous outcome of response to therapy or clinician-reported outcomes and a treatment duration of less than 4 weeks. Our main outcome was identification of the magnitude of the pooled placebo response rate for the following endpoints: global improvement, abdominal pain, and US Food and Drug Administration (FDA) endpoints. We extracted information from published reports and pooled proportions through meta-analysis with random effects. The study was registered with PROSPERO, CRD42020170908.

Findings

Of the 6863 publications identified, 70 articles describing 73 randomised controlled trials were included in our analysis. The pooled placebo response rate was 27·3% (95% CI 24·3–30·9) using the global improvement endpoint, 34·4% (31·2–37·8) using the abdominal pain endpoint, and 17·9% (15·2–21·0) using the composite FDA endpoint responder definition, all with substantial heterogeneity between the trials. Studies published before 2006, and those done in Europe, with a parallel design, a run-in period of 2 weeks or less, a dose schedule of three times a day or more, or a smaller sample size of the control group were significantly associated with an increased pooled placebo response rate.

Interpretation

More than a quarter of patients with irritable bowel syndrome had a placebo response in terms of global improvement, with multiple associated moderators. We recommend future trials apply a run-in period of at least 2 weeks and dose once or twice a day to minimise the placebo response rate.

Funding

None.

中文翻译：

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肠易激综合征患者药理试验中安慰剂反应率的系统评价和荟萃分析

背景

肠易激综合征的临床试验与高安慰剂反应率相关。我们的目的是确定安慰剂反应的幅度以及导致这种情况发生的因素。

方法

我们对1959年4月1日至2020年4月30日之间的MEDLINE，EMBASE和Cochrane对照试验中央注册进行了系统的回顾和荟萃分析。在患有肠易激综合症的成年人（≥18岁）中，安慰剂对治疗的反应有二分结果（就总体改善或腹痛改善而言）。排除标准为试验报告治疗满意度为对治疗反应的二分结果或临床医生报告的结果，且治疗时间少于4周。我们的主要结果是确定下列终点的合并安慰剂反应率的幅度：总体改善，腹痛，和美国食品药品监督管理局（FDA）的端点。我们从发表的报告中提取信息，并通过具有随机效应的荟萃分析汇总比例。该研究已在PROSPERO注册，注册号为CRD42020170908。

发现

在所确定的6863篇出版物中，有70篇文章描述了73个随机对照试验，纳入了我们的分析。总体安慰剂汇总安慰剂反应率为27·3％（95％CI 24·3–30·9），腹部疼痛终点为34·4％（31·2–37·8），17· 9％（15·2–21·0）使用复合FDA终点响应者定义，所有试验之间均存在实质性异质性。与2006年之前发表的研究以及在欧洲进行的研究（平行设计，2周或更短的磨合期，一天3次或更多次的给药方案或对照组的样本量较小）密切相关合并安慰剂反应率提高。

解释

就整体改善而言，超过四分之一的肠易激综合症患者有安慰剂反应，并伴有多个相关的主持人。我们建议以后的试验至少要使用2周的磨合期，并每天给药一次或两次，以最大程度地降低安慰剂的应答率。

资金

没有任何。