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

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

doi:10.1016/S0140-6736(19)33137-X

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

David J Beard^* (Corresponding Author), Marion K Campbell, Jane M. Blazeby, Andrew J. Carr, Charles Weijer, Brian H. Cuthbertson, Rachelle Buchbinder, Thomas Pinkney, Felicity Bishop, Jonathan Pugh, Sian Cousins, Ian Harris, L. Stefan Lohmander, Natalie Blencowe, Katie Gillies, Pascal Probst , Carol Brennan, Andrew Cook, Dair Farrah-Hockley, Julian SavulescuRichard Huxtable, Amar Rangan, Irene Tracey, Peter Brocklehurst, Manuela L. Ferreira, Jon Nicholl, Barnaby C. Reeves, Freddie Hamdy, Samuel C. S. Rowley, Jonathan A. Cook

^*Corresponding author for this work

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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.

Original language	English
Pages (from-to)	828-838
Number of pages	11
Journal	The Lancet
Volume	395
Issue number	10226
Early online date	5 Mar 2020
DOIs	https://doi.org/10.1016/S0140-6736(19)33137-X
Publication status	Published - 7 Mar 2020

Bibliographical note

The work was co-commissioned and jointly funded by The Medical Research Council UK (MRC) & The National Institute for Health Research UK (NIHR) Methodology Research Programme in response to a commissioned call for a State-of-the-Art workshop on this topic. It was also funded by the NIHR Biomedical Research Centres at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol (BRC-1215-20011) and Oxford Health NHS Foundation Trust and the University of Oxford. Applicants for the commission were; Professor David Beard, Associate Professor Jonathan Cook, Professor Marion Campbell, Professor Jane Blazeby, Professor Andrew Carr, Associate Professor Thomas Pinkney, Professor Brian Cuthbertson, Professor Irene Tracey, Professor Rachelle Buchbinder, Professor Julian Savulescu, Mr Dair Farrar-Hockley and Dr 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: Dr Jonathan Pugh, Dr Felicity Bishop, Dr Sian Cousins, Professor Charles Weijer, Prof Richard Huxtable, Professor Jon Nicholl, Dr Pascal Probst, Professor Peter Brocklehurst, Dr Andrew Cook, Dr Katie Gillies, Professor Freddie Hamdy, Professor Ian Harris, Dr Naomi Lee, Professor Stefan Lohmander, Professor Amar Rangan, Professor Barnaby Reeves, Dr Samual Rowley.

Dr Carol Brennan and Mr Dair Farrar-Hockley kindly participated and contributed as patient representatives. Mr Dair Farrar-Hockley was also a co-applicant on the workshop grant application.

Dr Sian Cousins and Dr Natalie Blencowe kindly took detailed cross referenced notes throughout and recorded the workshop discussions.

Ms Katie Chegwin was responsible for administration and organisation.

The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the MRC or the Department of Health and Social Care. AC and JMB are NIHR Senior Investigators.

Keywords

Guidelines as Topic
Humans
Placebos
Randomized Controlled Trials as Topic/ethics
Research Design
Surgical Procedures, Operative

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Cite this

Beard, D. J., Campbell, M. K., Blazeby, J. M., Carr, A. J., Weijer, C., Cuthbertson, B. H., Buchbinder, R., Pinkney, T., Bishop, F., Pugh, J., Cousins, S., Harris, I., Lohmander, L. S., Blencowe, N., Gillies, K., Probst , P., Brennan, C., Cook, A., Farrah-Hockley, D., ... Cook, J. A. (2020). Considerations and methods for placebo controls in surgical trials (ASPIRE guidelines). The Lancet, 395(10226), 828-838. https://doi.org/10.1016/S0140-6736(19)33137-X

Beard, DJ, Campbell, MK, Blazeby, JM, Carr, AJ, Weijer, C, Cuthbertson, BH, Buchbinder, R, Pinkney, T, Bishop, F, Pugh, J, Cousins, S, Harris, I, Lohmander, LS, Blencowe, N, Gillies, K, Probst , P, Brennan, C, Cook, A, Farrah-Hockley, D, Savulescu, J, Huxtable, R, Rangan, A, Tracey, I, Brocklehurst, P, Ferreira, ML, Nicholl, J, Reeves, BC, Hamdy, F, Rowley, SCS & Cook, JA 2020, 'Considerations and methods for placebo controls in surgical trials (ASPIRE guidelines)', The Lancet, vol. 395, no. 10226, pp. 828-838. https://doi.org/10.1016/S0140-6736(19)33137-X

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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.",

keywords = "Guidelines as Topic, Humans, Placebos, Randomized Controlled Trials as Topic/ethics, Research Design, Surgical Procedures, Operative",

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

note = "The work was co-commissioned and jointly funded by The Medical Research Council UK (MRC) & The National Institute for Health Research UK (NIHR) Methodology Research Programme in response to a commissioned call for a State-of-the-Art workshop on this topic. It was also funded by the NIHR Biomedical Research Centres at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol (BRC-1215-20011) and Oxford Health NHS Foundation Trust and the University of Oxford. Applicants for the commission were; Professor David Beard, Associate Professor Jonathan Cook, Professor Marion Campbell, Professor Jane Blazeby, Professor Andrew Carr, Associate Professor Thomas Pinkney, Professor Brian Cuthbertson, Professor Irene Tracey, Professor Rachelle Buchbinder, Professor Julian Savulescu, Mr Dair Farrar-Hockley and Dr Natalie Blencowe. As part of the process of developing the guidance, a two-day workshop was held in St Anne{\textquoteright}s College Oxford in December 2018. In addition to the applicants, the academic workshop participants were: Dr Jonathan Pugh, Dr Felicity Bishop, Dr Sian Cousins, Professor Charles Weijer, Prof Richard Huxtable, Professor Jon Nicholl, Dr Pascal Probst, Professor Peter Brocklehurst, Dr Andrew Cook, Dr Katie Gillies, Professor Freddie Hamdy, Professor Ian Harris, Dr Naomi Lee, Professor Stefan Lohmander, Professor Amar Rangan, Professor Barnaby Reeves, Dr Samual Rowley. Dr Carol Brennan and Mr Dair Farrar-Hockley kindly participated and contributed as patient representatives. Mr Dair Farrar-Hockley was also a co-applicant on the workshop grant application. Dr Sian Cousins and Dr Natalie Blencowe kindly took detailed cross referenced notes throughout and recorded the workshop discussions. Ms Katie Chegwin was responsible for administration and organisation. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the MRC or the Department of Health and Social Care. AC and JMB are NIHR Senior Investigators.",

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

Abstract

Bibliographical note

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Kate Gillies

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

Abstract

Bibliographical note

Keywords

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Kate Gillies

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