Use of placebo controls in the evaluation of surgery: systematic review.
OBJECTIVE
To investigate whether placebo controls should be used in the evaluation of surgical interventions.


METHODS
Systematic review.


METHODS
We searched Medline, Embase, and the Cochrane Controlled Trials Register from their inception to November 2013.


METHODS
Randomised clinical trials comparing any surgical intervention with placebo. Surgery was defined as any procedure that both changes the anatomy and requires a skin incision or use of endoscopic techniques.


METHODS
Three reviewers (KW, BJFD, IR) independently identified the relevant trials and extracted data on study details, outcomes, and harms from included studies.


RESULTS
In 39 out of 53 (74%) trials there was improvement in the placebo arm and in 27 (51%) trials the effect of placebo did not differ from that of surgery. In 26 (49%) trials, surgery was superior to placebo but the magnitude of the effect of the surgical intervention over that of the placebo was generally small. Serious adverse events were reported in the placebo arm in 18 trials (34%) and in the surgical arm in 22 trials (41.5%); in four trials authors did not specify in which arm the events occurred. However, in many studies adverse events were unrelated to the intervention or associated with the severity of the condition. The existing placebo controlled trials investigated only less invasive procedures that did not involve laparotomy, thoracotomy, craniotomy, or extensive tissue dissection.


CONCLUSIONS
Placebo controlled trial is a powerful, feasible way of showing the efficacy of surgical procedures. The risks of adverse effects associated with the placebo are small. In half of the studies, the results provide evidence against continued use of the investigated surgical procedures. Without well designed placebo controlled trials of surgery, ineffective treatment may continue unchallenged.
National Institute of Health Research Musculoskeletal Biomedical Research Unit, Oxford, UK Botnar Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK karolina.wartolowska@ndorms.ox.ac.uk.
Karolina
K
Wartolowska
National Institute of Health Research Musculoskeletal Biomedical Research Unit, Oxford, UK Botnar Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.
Andrew
A
Judge
Botnar Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
Sally
S
Hopewell
Botnar Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
Gary S
GS
Collins
National Institute of Health Research Musculoskeletal Biomedical Research Unit, Oxford, UK Botnar Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK.
Benjamin J F
BJ
Dean
National Institute of Health Research Musculoskeletal Biomedical Research Unit, Oxford, UK Botnar Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK.
Ines
I
Rombach
National Institute of Health Research Musculoskeletal Biomedical Research Unit, Oxford, UK Botnar Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK The Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation, University of Oxford, Oxford, UK Harvard Stem Cell Institute, Holyoke Centre, Cambridge, MA, USA.
David
D
Brindley
Oxford Uehiro Centre for Practical Ethics, University of Oxford, Oxford, UK.
Julian
J
Savulescu
National Institute of Health Research Musculoskeletal Biomedical Research Unit, Oxford, UK Botnar Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK Surgical Intervention Trials Unit (SITU), RCS Surgical Trials Unit, Botnar Institute of Musculoskeletal Sciences, Oxford, UK.
David J
DJ
Beard
National Institute of Health Research Musculoskeletal Biomedical Research Unit, Oxford, UK Botnar Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK Surgical Intervention Trials Unit (SITU), RCS Surgical Trials Unit, Botnar Institute of Musculoskeletal Sciences, Oxford, UK.
Andrew J
AJ
Carr
D006801:Humans; D010919:Placebos / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D013514:Surgical Procedures, Operative
D010919:Placebos