Use of placebo controls in the evaluation of surgery: systematic reviewBMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g3253 (Published 21 May 2014) Cite this as: BMJ 2014;348:g3253
- Karolina Wartolowska, NDORMS research fellow12,
- Andrew Judge, university research lecturer123,
- Sally Hopewell, senior research fellow24,
- Gary S Collins, NDORMS senior research fellow24,
- Benjamin J F Dean, DPhil student12,
- Ines Rombach, statistician12,
- David Brindley, DPhil student1256,
- Julian Savulescu, Uehiro chair in practical ethics7,
- David J Beard, professor of musculoskeletal sciences128,
- Andrew J Carr, professor of orthopaedic surgery128
- 1National Institute of Health Research Musculoskeletal Biomedical Research Unit, Oxford, UK
- 2Botnar Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK
- 3MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK
- 4Centre for Statistics in Medicine, University of Oxford, Oxford, UK
- 5The Oxford—UCL Centre for the Advancement of Sustainable Medical Innovation, University of Oxford, Oxford, UK
- 6Harvard Stem Cell Institute, Holyoke Centre, Cambridge, MA, USA
- 7Oxford Uehiro Centre for Practical Ethics, University of Oxford, Oxford, UK
- 8Surgical Intervention Trials Unit (SITU), RCS Surgical Trials Unit, Botnar Institute of Musculoskeletal Sciences, Oxford, UK
- Correspondence to: K Wartolowska
- Accepted 5 May 2014
Objective To investigate whether placebo controls should be used in the evaluation of surgical interventions.
Design Systematic review.
Data sources We searched Medline, Embase, and the Cochrane Controlled Trials Register from their inception to November 2013.
Study selection 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.
Data extraction 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.
Contributors: KW, AJC, and DJB conceived and designed the study. KW, AJ, SH, and GSC designed the search strategy and statistical analysis. KW, IR, and BJFD collected and managed the data. KW drafted the manuscript and is the guarantor of the study. KW, AJC, DJB, IR, BJFD, DB, JS, SH, and GSC critically revised the manuscript for important intellectual content. All authors had full access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis, and revised and approved the final version of the article.
Funding: This study was funded by the NIHR Oxford Musculoskeletal Biomedical Research Unit. The funding source had no role in the design and conduct of the study, in the collection, analysis and interpretation of the data, or in the preparation, review, or approval of the manuscript.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: the authors are involved in a placebo controlled surgical trial on shoulder pain (NCT01623011); no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Not required.
Data sharing: No additional data available.
Transparency: The lead author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; no important aspects of the study have been omitted.
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) 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/3.0/.