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

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; I2=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.