title: Placebo-Controlled Trials in Surgery: A Systematic Review and Meta-Analysis.
abstract: This systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized placebo-controlled surgical trials.Central, MEDLINE, and EMBASE were systematically searched to identify randomized controlled trials comparing a surgical procedure to a placebo. "Surgical procedure" was defined as a medical procedure involving an incision with instruments. Placebo was defined as a blinded sham operation involving no change to the structural anatomy and without an expectable physiological response in the target body compartment.Ten randomized placebo-controlled controlled surgical trials were included, all of them published in high-ranking medical journals (mean impact factor: 20.1). Eight of 10 failed to show statistical superiority of the experimental intervention. Serious adverse events did not differ between the groups (rate ratio [RR] 1.38, 95% confidence interval [CI]: 0.92-2.06, P = 0.46). None of the trials had a high risk of bias in any domain. The ethical justification for the use of a placebo control remained unclear in 2 trials.Placebo-controlled surgical trials are feasible and provide high-quality data on efficacy of surgical treatments. The surgical placebo entails a considerable risk for study participants. Consequently, a placebo should be used only if justified by the clinical question and by methodological necessity. Based on the current evidence, a pragmatic proposal for the use of placebo controls in future randomized controlled surgical trials is made.
authors.affiliation: From the Department of General, Visceral and Transplantation Surgery (PP, JCH, FJH, AU, MWB, MKD), University of Heidelberg; The Study Center of the German Surgical Society (SDGC); University of Heidelberg (PP, KG, JCH, SB, MKD); and Institute of Medical Biometry and Informatics (KJ, MK), University of Heidelberg, Heidelberg, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Probst
authors.forename: Kathrin
authors.initials: K
authors.lastname: Grummich
authors.forename: Julian C
authors.initials: JC
authors.lastname: Harnoss
authors.forename: Felix J
authors.initials: FJ
authors.lastname: Hüttner
authors.forename: Katrin
authors.initials: K
authors.lastname: Jensen
authors.forename: Silvia
authors.initials: S
authors.lastname: Braun
authors.forename: Meinhard
authors.initials: M
authors.lastname: Kieser
authors.forename: Alexis
authors.initials: A
authors.lastname: Ulrich
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Markus K
authors.initials: MK
authors.lastname: Diener
mesh_terms: D061214:Patient Safety; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic / Q000941:ethics*; D013514:Surgical Procedures, Operative / Q000941:ethics*