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 L Bishop; Jonathan Pugh; Sian Cousins; Ian A Harris; L Stefan Lohmander; Natalie Blencowe; Katie Gillies; Pascal Probst; Carol Brennan; Andrew Cook; Dair Farrar-Hockley; Julian Savulescu; Richard Huxtable; Amar Rangan; Irene Tracey; Peter Brocklehurst; Manuela L Ferreira; Jon Nicholl; Barnaby C Reeves; Freddie Hamdy; Samuel Cs Rowley; Jonathan A Cook

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

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

Lancet. 2020 Mar 7;395(10226):828-838. doi: 10.1016/S0140-6736(19)33137-X.

Authors

David J Beard¹, Marion K Campbell², Jane M Blazeby³, Andrew J Carr⁴, Charles Weijer⁵, Brian H Cuthbertson⁶, Rachelle Buchbinder⁷, Thomas Pinkney⁸, Felicity L Bishop⁹, Jonathan Pugh¹⁰, Sian Cousins³, Ian A Harris¹¹, L Stefan Lohmander¹², Natalie Blencowe³, Katie Gillies², Pascal Probst¹³, Carol Brennan¹⁴, Andrew Cook¹⁵, Dair Farrar-Hockley¹⁴, Julian Savulescu¹⁰, Richard Huxtable³, Amar Rangan¹⁶, Irene Tracey¹⁷, Peter Brocklehurst¹⁸, Manuela L Ferreira¹⁹, Jon Nicholl²⁰, Barnaby C Reeves²¹, Freddie Hamdy²², Samuel Cs Rowley²³, Jonathan A Cook⁴

Affiliations

¹ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK. Electronic address: david.beard@ndorms.ox.ac.uk.
² Health Services Research Unit, Health Sciences Building, University of Aberdeen, Aberdeen, UK.
³ Centre for Surgical Research Population Health Sciences, Beacon House, University of Bristol, Bristol.
⁴ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
⁵ Rotman Institute of Philosophy, Western Interdisciplinary Research Building, Western University, London, ON, Canada.
⁶ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
⁷ Cabrini-Monash Department of Clinical Epidemiology, Cabrini Institute and Monash University, Melbourne, VIC, Australia.
⁸ Academic Department of Surgery, Heritage Building, Queen Elizabeth Hospital Birmingham, University of Birmingham, Birmingham, UK.
⁹ Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.
¹⁰ The Oxford Uehiro Centre for Practical Ethics, University of Oxford, Oxford, UK.
¹¹ Ingham Institute for Applied Medical Research, South Western Sydney Clinical School, The University of New South Wales, Sydney, NSW, Australia.
¹² Department of Clinical Sciences Lund, Department of Orthopaedics Lund, Lund University, Lund, Sweden.
¹³ Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
¹⁴ Patient Representatives, Oxford, UK.
¹⁵ Wessex Institute, University of Southampton, Southampton, UK; University Hospital Southampton National Health Service Foundation Trust, Southampton, UK.
¹⁶ Department of Health Sciences, Seebohm Rowntree Building, University of York, York, UK.
¹⁷ Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.
¹⁸ Birmingham Clinical Trials Unit, Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
¹⁹ Faculty of Medicine and Health, Institute of Bone and Joint Research, Northern Clinical School, University of Sydney, Sydney, NSW, Australia.
²⁰ School of Health and Related Research, University of Sheffield, Sheffield, UK.
²¹ Bristol Trials Centre, University of Bristol, Bristol.
²² Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK; Old Road Campus Research Building, University of Oxford, Oxford, UK.
²³ Medical Research Council, London, UK.

PMID: 32145797
DOI: 10.1016/S0140-6736(19)33137-X

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.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

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

Substances

Placebos

Abstract

Publication types

MeSH terms

Substances

Grants and funding