To what extent are surgery and invasive procedures effective beyond a placebo response? A systematic review with meta-analysis of randomised, sham controlled trials

Wayne B Jonas, Cindy Crawford, Luana Colloca, Ted J Kaptchuk, Bruce Moseley, Franklin G Miller, Levente Kriston, Klaus Linde, Karin Meissner, Wayne B Jonas, Cindy Crawford, Luana Colloca, Ted J Kaptchuk, Bruce Moseley, Franklin G Miller, Levente Kriston, Klaus Linde, Karin Meissner

Abstract

Objectives: To assess the quantity and quality of randomised, sham-controlled studies of surgery and invasive procedures and estimate the treatment-specific and non-specific effects of those procedures.

Design: Systematic review and meta-analysis.

Data sources: We searched PubMed, EMBASE, CINAHL, CENTRAL (Cochrane Library), PILOTS, PsycInfo, DoD Biomedical Research, clinicaltrials.gov, NLM catalog and NIH Grantee Publications Database from their inception through January 2015.

Study selection: We included randomised controlled trials of surgery and invasive procedures that penetrated the skin or an orifice and had a parallel sham procedure for comparison.

Data extraction and analysis: Three authors independently extracted data and assessed risk of bias. Studies reporting continuous outcomes were pooled and the standardised mean difference (SMD) with 95% CIs was calculated using a random effects model for difference between true and sham groups.

Results: 55 studies (3574 patients) were identified meeting inclusion criteria; 39 provided sufficient data for inclusion in the main analysis (2902 patients). The overall SMD of the continuous primary outcome between treatment/sham-control groups was 0.34 (95% CI 0.20 to 0.49; p<0.00001; I(2)=67%). The SMD for surgery versus sham surgery was non-significant for pain-related conditions (n=15, SMD=0.13, p=0.08), marginally significant for studies on weight loss (n=10, SMD=0.52, p=0.05) and significant for gastroesophageal reflux disorder (GERD) studies (n=5, SMD=0.65, p<0.001) and for other conditions (n=8, SMD=0.44, p=0.004). Mean improvement in sham groups relative to active treatment was larger in pain-related conditions (78%) and obesity (71%) than in GERD (57%) and other conditions (57%), and was smaller in classical-surgery trials (21%) than in endoscopic trials (73%) and those using percutaneous procedures (64%).

Conclusions: The non-specific effects of surgery and other invasive procedures are generally large. Particularly in the field of pain-related conditions, more evidence from randomised placebo-controlled trials is needed to avoid continuation of ineffective treatments.

Keywords: COMPLEMENTARY MEDICINE; INTERNAL MEDICINE; SURGERY.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Figures

Figure 1
Figure 1
Flow chart of included studies. RCT, randomised controlled trial.
Figure 2
Figure 2
The specific effect of invasive procedures and surgery.
Figure 3
Figure 3
Funnel plot using continuous outcomes (effects of active vs sham treatment) of the 39 studies included in the main meta-analysis.
Figure 4
Figure 4
Relative contribution to improvement in the placebo and active treatment groups.

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