David J Beard1, Marion K Campbell2, Jane M Blazeby3, Andrew J Carr1, Charles Weijer4, Brian H Cuthbertson5, Rachelle Buchbinder6, Thomas Pinkney7, Felicity L Bishop8, Jonathan Pugh9, Sian Cousins3, Ian Harris10, L Stefan Lohmander11, Natalie Blencowe3, Katie Gillies2, Pascal Probst12, Carol Brennan13, Andrew Cook14, Dair Farrar-Hockley13, Julian Savulescu9, Richard Huxtable3, Amar Rangan1,15, Irene Tracey16, Peter Brocklehurst17, Manuela L Ferreira18, Jon Nicholl19, Barnaby C Reeves20, Freddie Hamdy21, Samuel Cs Rowley22, Naomi Lee23, Jonathan A Cook1. 1. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. 2. Health Services Research Unit, University of Aberdeen, Aberdeen, UK. 3. Centre for Surgical Research, NIHR Bristol and Weston Biomedical Research Centre, Population Health Sciences, University of Bristol, Bristol, UK. 4. Departments of Medicine, Epidemiology and Biostatistics, and Philosophy, Western University, London, ON, Canada. 5. Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada. 6. Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. 7. Academic Department of Surgery, University of Birmingham, Queen Elizabeth Hospital Birmingham, Birmingham, UK. 8. Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK. 9. The Oxford Uehiro Centre for Practical Ethics, University of Oxford, Oxford, UK. 10. Faculty of Medicine, South Western Sydney Clinical School, University of New South Wales, Sydney, NSW, Australia. 11. Department of Clinical Sciences Lund, Orthopedics, Clinical Epidemiology Unit, Lund University, Lund, Sweden. 12. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. 13. Patient representative, Oxford, UK. 14. Wessex Institute, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southampton, UK. 15. Department of Health Sciences, University of York, York, UK. 16. Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK. 17. Birmingham Clinical Trials Unit, Institute of Applied Health Research, University of Birmingham, Birmingham, UK. 18. Faculty of Medicine and Health, Institute of Bone and Joint Research, Northern Clinical School, The University of Sydney, Sydney, NSW, Australia. 19. School of Health and Related Research, University of Sheffield, Sheffield, UK. 20. Clinical Trials Evaluation Unit Bristol Medical School, University of Bristol, Bristol Royal Infirmary, Bristol, UK. 21. Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK. 22. Medical Research Council, London, UK. 23. Editorial Department, The Lancet, London, UK.
Abstract
BACKGROUND: The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. OBJECTIVES: To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials. DESIGN: To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout. SETTING: A workshop to discuss and summarise the existing knowledge and to develop the new guidelines. RESULTS: To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics 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 carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics 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 a high risk of bias, particularly because of the placebo effect. CONCLUSIONS: The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial. LIMITATIONS: Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS. FUTURE WORK: Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space. FUNDING: Funded by the Medical Research Council UK and the National Institute for Health Research as part of the Medical Research Council-National Institute for Health Research Methodology Research programme.
BACKGROUND: The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. OBJECTIVES: To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials. DESIGN: To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout. SETTING: A workshop to discuss and summarise the existing knowledge and to develop the new guidelines. RESULTS: To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics 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 carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics 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 a high risk of bias, particularly because of the placebo effect. CONCLUSIONS: The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial. LIMITATIONS: Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS. FUTURE WORK: Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space. FUNDING: Funded by the Medical Research Council UK and the National Institute for Health Research as part of the Medical Research Council-National Institute for Health Research Methodology Research programme.
Entities:
Keywords:
ETHICS; INVASIVE; PLACEBO CONTROL; PROCEDURE; RCT; SURGERY
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