Department of Surgery, Hospital Nova Central Finland, Jyvaskyla, Finland.
Monash Department of Clinical Epidemiology, Cabrini Institute, Malvern, Australia.
JAMA Netw Open. 2022 Jul 1;5(7):e2223903. doi: 10.1001/jamanetworkopen.2022.23903.
Nonspecific effects, particularly placebo effects, are thought to contribute significantly to the observed effect in surgical trials.
To estimate the proportion of the observed effect of surgical treatment that is due to nonspecific effects (including the placebo effect).
Published Cochrane reviews and updated, extended search of MEDLINE, Embase, and CENTRAL until March 2019.
Published randomized placebo-controlled surgical trials and trials comparing the effect of the same surgical interventions with nonoperative controls (ie, no treatment, usual care, or exercise program).
Pairs of authors independently screened the search results, assessed full texts to identify eligible studies and the risk of bias of included studies, and extracted data. The proportion of all nonspecific effects was calculated as the change in the placebo control divided by the change in the active surgery and pooled in a random-effect meta-analysis. To estimate the magnitude of the placebo effect, we pooled the difference in outcome between placebo and nonoperative controls and used metaregression to estimate the association between the type of control group and the treatment effect (difference between the groups), adjusting for risk of bias, sample size, and type of outcome.
Between- and within-group effect sizes expressed as Hedges g.
In this review, 100 trials were included comprising data from 62 trials with placebo controls (3 also included nonoperative controls), and 38 trials with nonoperative controls (32 interventions; 10 699 participants). Risk of bias across trials was comparable except for performance and detection bias, which was high in trials with nonoperative controls. The mean nonspecific effects accounted for 67% (95% CI, 61% to 73%) of the observed change after surgery; however, this varied widely between different procedures. The estimated surgical placebo effect had a standardized mean difference (SMD) of 0.13 (95% CI, -0.26 to 0.51). Trials with placebo and nonoperative controls found comparable treatment effects (SMD, -0.09 [95% CI, -0.35 to 0.18]; 15 interventions; 73 between-group effects; adjusted analysis: SMD, -0.11 [95% CI, -0.37 to 0.15]).
In this review, the change in health state after surgery was composed largely of nonspecific effects, but no evidence supported a large placebo effect. Placebo-controlled surgical trials may be redundant when trials with nonoperative controls consistently report no substantial association from surgery compared with nonoperative treatment.
非特异性效应（包括安慰剂效应）被认为对手术试验中观察到的效应有重要贡献。
估计手术治疗观察到的效果中归因于非特异性效应（包括安慰剂效应）的比例。
已发表的 Cochrane 综述和更新的、对 MEDLINE、Embase 和 CENTRAL 的扩展搜索，截至 2019 年 3 月。
已发表的随机安慰剂对照手术试验和比较相同手术干预与非手术对照（即无治疗、常规护理或运动方案）效果的试验。
两位作者独立筛选搜索结果，评估全文以确定合格的研究和纳入研究的偏倚风险，并提取数据。所有非特异性效应的比例计算为安慰剂对照的变化除以活性手术的变化，并在随机效应荟萃分析中汇总。为了估计安慰剂效应的大小，我们汇总了安慰剂和非手术对照组之间的结果差异，并使用元回归估计对照组类型与治疗效果（组间差异）之间的关联，同时调整偏倚风险、样本量和结果类型。
表示为 Hedges g 的组间和组内效应大小。
在本次综述中，纳入了 100 项试验，其中包括 62 项安慰剂对照试验的数据（其中 3 项还包括非手术对照）和 38 项非手术对照试验的数据（32 项干预措施；10699 名参与者）。除了与非手术对照试验相关的实施和检测偏倚较高外，各试验的偏倚风险相当。平均非特异性效应占手术后观察到的变化的 67%（95%CI，61%至 73%）；然而，不同手术之间差异很大。估计的手术安慰剂效应的标准化均数差（SMD）为 0.13（95%CI，-0.26 至 0.51）。有安慰剂和非手术对照组的试验发现了可比的治疗效果（SMD，-0.09 [95%CI，-0.35 至 0.18]；15 项干预措施；73 个组间效应；调整分析：SMD，-0.11 [95%CI，-0.37 至 0.15]）。
在本次综述中，手术后健康状况的变化主要归因于非特异性效应，但没有证据支持手术的安慰剂效应很大。当非手术对照组的试验始终报告手术与非手术治疗相比没有实质性关联时，安慰剂对照手术试验可能是多余的。
