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

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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.

Related collections

Most cited references 80

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Transplantation of embryonic dopamine neurons for severe Parkinson's disease.

C R Freed, P E Greene, R E Breeze … (2001)

Transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson's disease has proved beneficial in open clinical trials. However, whether this intervention would be more effective than sham surgery in a controlled trial is not known. We randomly assigned 40 patients who were 34 to 75 years of age and had severe Parkinson's disease (mean duration, 14 years) to receive a transplant of nerve cells or sham surgery; all were to be followed in a double-blind manner for one year. In the transplant recipients, cultured mesencephalic tissue from four embryos was implanted into the putamen bilaterally. In the patients who received sham surgery, holes were drilled in the skull but the dura was not penetrated. The primary outcome was a subjective global rating of the change in the severity of disease, scored on a scale of -3.0 to 3.0 at one year, with negative scores indicating a worsening of symptoms and positive scores an improvement. The mean (+/-SD) scores on the global rating scale for improvement or deterioration at one year were 0.0+/-2.1 in the transplantation group and -0.4+/-1.7 in the sham-surgery group. Among younger patients (60 years old or younger), standardized tests of Parkinson's disease revealed significant improvement in the transplantation group as compared with the sham-surgery group when patients were tested in the morning before receiving medication (P=0.01 for scores on the Unified Parkinson's Disease Rating Scale; P=0.006 for the Schwab and England score). There was no significant improvement in older patients in the transplantation group. Fiber outgrowth from the transplanted neurons was detected in 17 of the 20 patients in the transplantation group, as indicated by an increase in 18F-fluorodopa uptake on positron-emission tomography or postmortem examination. After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa. Human embryonic dopamine-neuron transplants survive in patients with severe Parkinson's disease and result in some clinical benefit in younger but not in older patients.

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A controlled trial of arthroscopic surgery for osteoarthritis of the knee.

J Bruce Moseley, Kimberly O'malley, Nancy Petersen … (2002)

Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis, but it is unclear how the procedure achieves this result. We conducted a randomized, placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee. A total of 180 patients with osteoarthritis of the knee were randomly assigned to receive arthroscopic débridement, arthroscopic lavage, or placebo surgery. Patients in the placebo group received skin incisions and underwent a simulated débridement without insertion of the arthroscope. Patients and assessors of outcome were blinded to the treatment-group assignment. Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores--three on scales for pain and two on scales for function--and one objective test of walking and stair climbing. A total of 165 patients completed the trial. At no point did either of the intervention groups report less pain or better function than the placebo group. For example, mean (+/-SD) scores on the Knee-Specific Pain Scale (range, 0 to 100, with higher scores indicating more severe pain) were similar in the placebo, lavage, and débridement groups: 48.9+/-21.9, 54.8+/-19.8, and 51.7+/-22.4, respectively, at one year (P=0.14 for the comparison between placebo and lavage; P=0.51 for the comparison between placebo and débridement) and 51.6+/-23.7, 53.7+/-23.7, and 51.4+/-23.2, respectively, at two years (P=0.64 and P=0.96, respectively). Furthermore, the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinically meaningful difference. In this controlled trial involving patients with osteoarthritis of the knee, the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure.

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A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures.

Rachelle Buchbinder, Richard Osborne, Peter R Ebeling … (2009)

Vertebroplasty has become a common treatment for painful osteoporotic vertebral fractures, but there is limited evidence to support its use. We performed a multicenter, randomized, double-blind, placebo-controlled trial in which participants with one or two painful osteoporotic vertebral fractures that were of less than 12 months' duration and unhealed, as confirmed by magnetic resonance imaging, were randomly assigned to undergo vertebroplasty or a sham procedure. Participants were stratified according to treatment center, sex, and duration of symptoms ( or = 6 weeks). Outcomes were assessed at 1 week and at 1, 3, and 6 months. The primary outcome was overall pain (on a scale of 0 to 10, with 10 being the maximum imaginable pain) at 3 months. A total of 78 participants were enrolled, and 71 (35 of 38 in the vertebroplasty group and 36 of 40 in the placebo group) completed the 6-month follow-up (91%). Vertebroplasty did not result in a significant advantage in any measured outcome at any time point. There were significant reductions in overall pain in both study groups at each follow-up assessment. At 3 months, the mean (+/-SD) reductions in the score for pain in the vertebroplasty and control groups were 2.6+/-2.9 and 1.9+/-3.3, respectively (adjusted between-group difference, 0.6; 95% confidence interval, -0.7 to 1.8). Similar improvements were seen in both groups with respect to pain at night and at rest, physical functioning, quality of life, and perceived improvement. Seven incident vertebral fractures (three in the vertebroplasty group and four in the placebo group) occurred during the 6-month follow-up period. We found no beneficial effect of vertebroplasty as compared with a sham procedure in patients with painful osteoporotic vertebral fractures, at 1 week or at 1, 3, or 6 months after treatment. (Australian New Zealand Clinical Trials Registry number, ACTRN012605000079640.) 2009 Massachusetts Medical Society

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Author and article information

Journal

Journal ID (nlm-ta): BMJ Open

Journal ID (iso-abbrev): BMJ Open

Journal ID (hwp): bmjopen

Journal ID (publisher-id): bmjopen

Title: BMJ Open

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2044-6055

Publication date Collection: 2015

Publication date (Electronic): 11 December 2015

Volume: 5

Issue: 12

Electronic Location Identifier: e009655

Affiliations

[1 ]Samueli Institute , Alexandria, Virginia, USA

[2 ]Department of Pain and Translational Symptom Science, School of Nursing, University of Maryland , Baltimore, Maryland, USA

[3 ]Department of Anesthesiology, School of Medicine, University of Maryland , Baltimore, Maryland, USA

[4 ]Program in Placebo Studies, Beth Israel Deaconess Medical Center, Harvard Medical School Boston , Massachusetts, USA

[5 ]The Methodist Hospital , Houston, Texas, USA

[6 ]Department of Bioethics, Clinical Center, National Institutes of Health , Bethesda, Maryland, USA

[7 ]Department of Medical Psychology, University Medical Center Hamburg-Eppendorf , Hamburg-Eppendorf, Hamburg, Germany

[8 ]Institute of General Practice, Technische Universitat Munchen , Munich, Germany

[9 ]Institute of Medical Psychology, Ludwig-Maximilians-University Munich , Munich, Germany

Author notes

[Correspondence to ] Dr Wayne B Jonas; wjonas@ 123456siib.org

Article

Publisher ID: bmjopen-2015-009655

DOI: 10.1136/bmjopen-2015-009655

PMC ID: 4679929

PubMed ID: 26656986

SO-VID: ae96adc2-a597-4df4-a12a-2b12f9d9dcb1

Copyright © 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/

License:

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

History

Date received : 10 August 2015

Date revision received : 28 October 2015

Date accepted : 5 November 2015

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