Hohenschurz-Schmidt David, Phalip Jules, Chan Jessica, Gauhe Greta, Soliman Nadia, Vollert Jan, Lunde Sigrid Juhl, Vase Lene
Pain Research, Department of Surgery and Cancer, Imperial College London, London, UK.
Research Department, University College of Osteopathy, London, UK.
Eur J Pain. 2024 Apr;28(4):513-531. doi: 10.1002/ejp.2205. Epub 2023 Nov 20.
The magnitude of placebo effects from physical and psychological 'sham' is unknown but could impact efficacy trials and treatment understanding. To quantify placebo effects, this systematic review of three-armed randomised controlled trials (RCTs) of physical and psychological interventions for pain compared outcomes in 'sham' control intervention and non-exposure arms.
RCTs with treatment, 'sham' control intervention, and non-exposure groups were included, enrolling adults with any pain. A protocol was pre-registered (PROSPERO: CRD42023413324), and twelve databases searched from 2008 to July 2023. Trial methods and blinding were analysed descriptively and risk of bias assessed. Meta-analysis of pain measures at short-, medium- and long-term was performed with random-effects models of standardised mean differences (SMD).Studies were sub-grouped according to control intervention type.
Seventeen RCTs were included. The average short-term placebo effect was small (0.21 SMD, 0.1-0.33 95% CI, p = 0.0002, 1440 participants). It showed no heterogeneity (Tau = 0.1, I = 11%, p = 0.3), preventing meta-regression analyses of effect modifiers. However, sub-group analyses revealed larger placebo effects in manual control interventions compared to disabled devices and miscellaneous control interventions. Overall, placebo analgesia accounted for 39% of treatments' short-term effectiveness. No placebo effects were found at medium-term (7 RCTs, 381 participants) or long-term follow-up (3 RCTs, 173 participants).
The observed placebo analgesia has mechanistic and methodological implications, though its clinical importance may be limited. Control intervention design affects placebo effects, highlighting the importance of considering methodology in RCT interpretation. Review limitations include a small number of long-term studies and sample heterogeneity.
This systematic review directly quantifies placebo effects from physical and psychological 'sham' control interventions and compares them to treatments' overall effectiveness. By doing so, the review enhances our understanding of placebo effects, their relative contribution in clinical trials, and their susceptibly to trial design. It poses further questions regarding the influence of blinding, participant expectations, and features of the therapeutic context. Overall, the insights provided by this review carry methodological significance and are important for the interpretation and synthesis of efficacy trials in this field.
身体和心理“假干预”的安慰剂效应大小尚不清楚，但可能会影响疗效试验和对治疗的理解。为了量化安慰剂效应，本系统评价对针对疼痛的身体和心理干预的三臂随机对照试验（RCT）进行了比较，分析了“假”对照干预组和无暴露组的结果。
纳入有治疗组、“假”对照干预组和无暴露组的RCT，受试者为患有任何疼痛的成年人。预先注册了一项方案（PROSPERO：CRD42023413324），并检索了2008年至2023年7月的12个数据库。对试验方法和盲法进行描述性分析，并评估偏倚风险。采用标准化均数差（SMD）的随机效应模型对短期、中期和长期的疼痛测量指标进行荟萃分析。研究根据对照干预类型进行亚组划分。
纳入17项RCT。短期安慰剂效应平均较小（SMD为0.21，95%CI为0.1 - 0.33，p = 0.0002，1440名参与者）。未显示异质性（Tau = 0.1，I² = 11%，p = 0.3），无法对效应修饰因素进行meta回归分析。然而，亚组分析显示，与残疾设备和其他对照干预相比，手动对照干预中的安慰剂效应更大。总体而言，安慰剂镇痛占治疗短期有效性的39%。在中期（7项RCT，381名参与者）或长期随访（3项RCT，173名参与者）中未发现安慰剂效应。
观察到的安慰剂镇痛具有机制和方法学意义，但其临床重要性可能有限。对照干预设计会影响安慰剂效应，突出了在RCT解释中考虑方法学的重要性。综述的局限性包括长期研究数量少和样本异质性。
本系统评价直接量化了身体和心理“假”对照干预的安慰剂效应，并将其与治疗的总体有效性进行比较。通过这样做，该综述增进了我们对安慰剂效应、它们在临床试验中的相对贡献以及它们对试验设计的敏感性的理解。它提出了关于盲法、参与者期望和治疗背景特征影响的进一步问题。总体而言，本综述提供的见解具有方法学意义，对于该领域疗效试验的解释和综合非常重要。
