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Considerations and methods for placebo controls in surgical trials (ASPIRE guidelines)

Considerations and methods for placebo controls in surgical trials (ASPIRE guidelines)
Considerations and methods for placebo controls in surgical trials (ASPIRE guidelines)
Placebo comparisons are increasingly being considered for randomised trials assessing the efficacy of surgical interventions. The aim of this Review is to provide a summary of knowledge on placebo controls in surgical trials. A placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. This Review outlines what a placebo control entails and present understanding of this tool in the context of surgery. We consider when placebo controls in surgery are acceptable (and when they are desirable) in terms of ethical arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be done and interpreted. Use of placebo controls is justified in randomised controlled trials of surgical interventions provided there is a strong scientific and ethical rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with high risk of bias, particularly because of the placebo effect. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. This Review forms an outline for best practice and provides guidance, in the form of the Applying Surgical Placebo in Randomised Evaluations (known as ASPIRE) checklist, for those considering the use of a placebo control in a surgical randomised controlled trial.
trial, control, placebo, surgery, evaluation, ethics, efficacy
0140-6736
828-838
Beard, David J.
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Campbell, Marion K
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Blazeby, Jane M
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Carr, Andrew J
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Weijer, Charles
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Cuthbertson, Brian H
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Buchbinder, Rachelle
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Pinkney, Thomas
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Bishop, Felicity L
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Pugh, Jonathan
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Cousins, Sian
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Harris, Ian A
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Lohmander, L Stefan
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Blencowe, Natalie
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Gillies, Katie
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Probst, Pascal
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Brennan, Carol
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Cook, Andrew
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Farrar-Hockley, Dair
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Savulescu, Julian
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Huxtable, Richard
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Rangan, Amar
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Tracey, Irene
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Brocklehurst, Peter
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Ferreira, Manuela L
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Nicholl, Jon
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Reeves, Barnaby C
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Hamdy, Freddie
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Rowley, Samuel Cs
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Cook, Jonathan A
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Beard, David J.
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Campbell, Marion K
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Blazeby, Jane M
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Carr, Andrew J
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Weijer, Charles
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Cuthbertson, Brian H
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Buchbinder, Rachelle
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Pinkney, Thomas
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Bishop, Felicity L
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Pugh, Jonathan
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Cousins, Sian
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Harris, Ian A
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Lohmander, L Stefan
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Blencowe, Natalie
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Gillies, Katie
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Probst, Pascal
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Brennan, Carol
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Cook, Andrew
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Farrar-Hockley, Dair
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Savulescu, Julian
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Huxtable, Richard
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Rangan, Amar
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Tracey, Irene
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Brocklehurst, Peter
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Ferreira, Manuela L
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Nicholl, Jon
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Reeves, Barnaby C
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Hamdy, Freddie
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Rowley, Samuel Cs
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Cook, Jonathan A
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Beard, David J., Campbell, Marion K, Blazeby, Jane M, Carr, Andrew J, Weijer, Charles, Cuthbertson, Brian H, Buchbinder, Rachelle, Pinkney, Thomas, Bishop, Felicity L, Pugh, Jonathan, Cousins, Sian, Harris, Ian A, Lohmander, L Stefan, Blencowe, Natalie, Gillies, Katie, Probst, Pascal, Brennan, Carol, Cook, Andrew, Farrar-Hockley, Dair, Savulescu, Julian, Huxtable, Richard, Rangan, Amar, Tracey, Irene, Brocklehurst, Peter, Ferreira, Manuela L, Nicholl, Jon, Reeves, Barnaby C, Hamdy, Freddie, Rowley, Samuel Cs and Cook, Jonathan A (2020) Considerations and methods for placebo controls in surgical trials (ASPIRE guidelines). The Lancet, 395 (10226), 828-838. (doi:10.1016/S0140-6736(19)33137-X).

Record type: Review

Abstract

Placebo comparisons are increasingly being considered for randomised trials assessing the efficacy of surgical interventions. The aim of this Review is to provide a summary of knowledge on placebo controls in surgical trials. A placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. This Review outlines what a placebo control entails and present understanding of this tool in the context of surgery. We consider when placebo controls in surgery are acceptable (and when they are desirable) in terms of ethical arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be done and interpreted. Use of placebo controls is justified in randomised controlled trials of surgical interventions provided there is a strong scientific and ethical rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with high risk of bias, particularly because of the placebo effect. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. This Review forms an outline for best practice and provides guidance, in the form of the Applying Surgical Placebo in Randomised Evaluations (known as ASPIRE) checklist, for those considering the use of a placebo control in a surgical randomised controlled trial.

Text
Considerations and Methods for Placebo Controls in Surgical Trials: State of the Art Review and ASPIRE Guidance - Accepted Manuscript
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Accepted/In Press date: 6 December 2019
e-pub ahead of print date: 5 March 2020
Published date: 7 March 2020
Additional Information: Funding Information: There are no competing interests for any author for the work under consideration. No author received payment or services from a third party for any aspect of the work. DJB has institutional research grants from Zimmer Biomet, the National Institute for Health Research, Versus Arthritis, and Action Research (including the Medical Research Council and the National Institute for Health Research grant for the workshop), declares institutional support from the Rosetrees Trust and The Royal College of Surgeons of England, outside of the submitted work, and is a non-executive director of an unrelated Oxford University spin out company, Pro-mapp. AC is employed by the University of Southampton to work at the National Institute for Health Research Evaluation Trials and Studies Coordinating Centre, which receives funding from the National Institute for Health Research to run several research programmes. AR has educational grants from DePuy J&J and research grants from the National Institute for Health Research and Orthopaedic Research UK. CW receives personal fees from Eli Lilly and Company, Canada. FH has unrelated grant income from the National Institute for Health Research and Cancer Research UK. JAC was joint lead applicant with DJB on the grant that funded the workshop that underpinned this Review. JP received grant funds from the Wellcome Trust. JS receives grant income from the Uehiro Foundation on Ethics and Education, Oxford Martin School, and the Wellcome Trust, and receives salary support and research centre funding from the Murdoch Children's Research Institute and the Melbourne Law School. MLF reports grant income funds from the National Health and Medical Research Council of Australia. PB reports grant income from the Medical Research Council, National Institute for Health Research, and the Wellcome Trust and consultancy from AG Biotest. RB reports multiple grants from the National Health and Medical Research Council of Australia, grant funding from Arthritis Australia, travel expenses for speaking at conferences from the professional organisations hosting the conferences, and has been a member of the Australian Medical Services Advisory Committee since May, 2016. RB has previously published a placebo-controlled trial of vertebroplasty for acute osteoporotic spinal fractures. SCSR reports personal fees from the Medical Research Council and UK Research and Innovation, during the conduct of this Review, and personal fees from the Medical Research Council and UK Research and Innovation, outside of the submitted work. All other authors declare no competing interests. Funding Information: The work was co-commissioned and jointly funded by the Medical Research Council UK and the National Institute for Health Research UK Methodology Research Programme in response to a commissioned call for a workshop on this topic. The NIHR Biomedical Research Centres at the University Hospitals Bristol National Health Service Foundation Trust, the University of Bristol, Oxford Health National Health Service Foundation Trust, and the University of Oxford also funded this work. Applicants for the commission were: David Beard, Jonathan Cook, Marion Campbell, Jane Blazeby, Andrew Carr, Thomas Pinkney, Brian Cuthbertson, Irene Tracey, Rachelle Buchbinder, Julian Savulescu, Dair Farrar-Hockley, and Natalie Blencowe. As part of the process of developing the guidance, a two-day workshop was held in St Anne's College, Oxford in December, 2018. In addition to the applicants, the academic workshop participants were: Jonathan Pugh, Felicity Bishop, Sian Cousins, Charles Weijer, Richard Huxtable, Jon Nicholl, Pascal Probst, Peter Brocklehurst, Andrew Cook, Katie Gillies, Freddie Hamdy, Ian Harris, Naomi Lee, Stefan Lohmander, Amar Rangan, Barnaby Reeves, and Samual Rowley. Carol Brennan and Dair Farrar-Hockley kindly participated and contributed as patient representatives. Dair Farrar-Hockley was also a co-applicant on the workshop grant application. Sian Cousins and Natalie Blencowe kindly took detailed cross-referenced notes throughout and recorded the workshop discussions. Katie Chegwin was responsible for administration and organisation. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, the MRC, or the Department of Health and Social Care. AC, FH, and JMB are NIHR senior investigators. Publisher Copyright: © 2020 Elsevier Ltd
Keywords: trial, control, placebo, surgery, evaluation, ethics, efficacy

Identifiers

Local EPrints ID: 436530
URI: http://eprints.soton.ac.uk/id/eprint/436530
ISSN: 0140-6736
PURE UUID: 2bed3400-6e37-4054-b450-30aa6ed9ec1d
ORCID for Felicity L Bishop: ORCID iD orcid.org/0000-0002-8737-6662

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Date deposited: 12 Dec 2019 17:30
Last modified: 17 Nov 2022 05:02

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Contributors

Author: David J. Beard
Author: Marion K Campbell
Author: Jane M Blazeby
Author: Andrew J Carr
Author: Charles Weijer
Author: Brian H Cuthbertson
Author: Rachelle Buchbinder
Author: Thomas Pinkney
Author: Jonathan Pugh
Author: Sian Cousins
Author: Ian A Harris
Author: L Stefan Lohmander
Author: Natalie Blencowe
Author: Katie Gillies
Author: Pascal Probst
Author: Carol Brennan
Author: Andrew Cook
Author: Dair Farrar-Hockley
Author: Julian Savulescu
Author: Richard Huxtable
Author: Amar Rangan
Author: Irene Tracey
Author: Peter Brocklehurst
Author: Manuela L Ferreira
Author: Jon Nicholl
Author: Barnaby C Reeves
Author: Freddie Hamdy
Author: Samuel Cs Rowley
Author: Jonathan A Cook

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