State-of-the-art workshop: Methods for placebo comparator group selection and use in surgical trials
Lead Research Organisation:
University of Oxford
Abstract
A workshop will develop guidance to inform the future design of surgical trials, specifically the optimal use of placebos.
Using a placebo control or comparator is often thought as the “best” trial design to investigate healthcare interventions. A placebo reduces several biases which otherwise undermine a comparative study’s validity. Placebo controlled trials in surgery are highly controversial for ethical and design reasons. The construction of a placebo surgical intervention, the achievement of satisfactory participation/acceptance by surgeons and other key personnel (e.g. anaesthetists) and interpretation of the trial can all be challenging.
It is crucial that trialists, patients and surgeons understand the circumstances in which a surgical placebo control a) could or should be used and b) if so, what type of placebo control would be appropriate. There is a need for clear guidance to aid trialists, funders, patients, journal editors and regulators. We will address this knowledge gap.
We propose to bring together leading national and international experts to produce state of the art thinking and knowledge on placebo control in surgical evaluation.
Using a placebo control or comparator is often thought as the “best” trial design to investigate healthcare interventions. A placebo reduces several biases which otherwise undermine a comparative study’s validity. Placebo controlled trials in surgery are highly controversial for ethical and design reasons. The construction of a placebo surgical intervention, the achievement of satisfactory participation/acceptance by surgeons and other key personnel (e.g. anaesthetists) and interpretation of the trial can all be challenging.
It is crucial that trialists, patients and surgeons understand the circumstances in which a surgical placebo control a) could or should be used and b) if so, what type of placebo control would be appropriate. There is a need for clear guidance to aid trialists, funders, patients, journal editors and regulators. We will address this knowledge gap.
We propose to bring together leading national and international experts to produce state of the art thinking and knowledge on placebo control in surgical evaluation.
Technical Summary
Leading national and international experts will produce state of the art thinking and knowledge on placebo control in surgical evaluation.
It could be argued that placebo designs are especially important for surgery for two main reasons. Firstly, surgical interventions have undergone far less rigorous evaluation, often being the treatment of last resort. Secondly, bias is particularly high for surgery with surgical interventions anticipated to have a larger placebo effect than other treatments, given the orchestration and personalisation around the intervention delivery. Indeed, recent work we and another group have undertaken has shown the substantial magnitude and duration of surgical placebo effects.
Previous reviews of placebo-controlled surgical trials have examined the characteristics of such studies, and some of the issues related to recruitment and feasibility, impact on outcome and serious adverse events. These reviews however, have not considered in detail trial design issues such as when it is appropriate to use a placebo control in a surgical trial, what factors should guide the choice of a placebo design and how that choice influences intervention standardisation (and fidelity assessment), selection and use of co-interventions. Further practical consideration of ethics is needed. Additionally, how placebo comparators are developed and piloted before use in a main trial has not been considered. Furthermore, beyond placebo analgesia studies using neuroimaging, there is little information on the neurophysiology of placebo in other contexts and little support to help recruitment to placebo surgical trials. Guidance around these core methodological considerations is urgently required to ensure that trialists can design (and funders can appropriately assess and fund) the optimal placebo controlled surgical trials of the future.
Workpackage 1: Summary of current position for placebo control relating to surgery.
Aim: To generate an overview of the state-of-the-art thinking on the placebo phenomenon as it applies to surgical research (incorporating ethical perspectives, neurophysiology, clinical frameworks and the regulatory/governance contexts).
Workpackage 2: Systematic review of the use of a surgical placebo in trials.
Aim: To identify new studies and key literature on surgical placebo control and review with specific attention on the rationale for placebo use, the type of placebo control used and any methodological/trial conduct implications these raise.
Workpackage 3: Modified Delphi process to achieve consensus on the structure and content of the Workshop.
Aim: To determine the scope of the workshop, optimise the programme, and ensure the output/guidance reflects stakeholders needs (focusing on subjects for which consensus is least well developed and for which open debate is needed).
It could be argued that placebo designs are especially important for surgery for two main reasons. Firstly, surgical interventions have undergone far less rigorous evaluation, often being the treatment of last resort. Secondly, bias is particularly high for surgery with surgical interventions anticipated to have a larger placebo effect than other treatments, given the orchestration and personalisation around the intervention delivery. Indeed, recent work we and another group have undertaken has shown the substantial magnitude and duration of surgical placebo effects.
Previous reviews of placebo-controlled surgical trials have examined the characteristics of such studies, and some of the issues related to recruitment and feasibility, impact on outcome and serious adverse events. These reviews however, have not considered in detail trial design issues such as when it is appropriate to use a placebo control in a surgical trial, what factors should guide the choice of a placebo design and how that choice influences intervention standardisation (and fidelity assessment), selection and use of co-interventions. Further practical consideration of ethics is needed. Additionally, how placebo comparators are developed and piloted before use in a main trial has not been considered. Furthermore, beyond placebo analgesia studies using neuroimaging, there is little information on the neurophysiology of placebo in other contexts and little support to help recruitment to placebo surgical trials. Guidance around these core methodological considerations is urgently required to ensure that trialists can design (and funders can appropriately assess and fund) the optimal placebo controlled surgical trials of the future.
Workpackage 1: Summary of current position for placebo control relating to surgery.
Aim: To generate an overview of the state-of-the-art thinking on the placebo phenomenon as it applies to surgical research (incorporating ethical perspectives, neurophysiology, clinical frameworks and the regulatory/governance contexts).
Workpackage 2: Systematic review of the use of a surgical placebo in trials.
Aim: To identify new studies and key literature on surgical placebo control and review with specific attention on the rationale for placebo use, the type of placebo control used and any methodological/trial conduct implications these raise.
Workpackage 3: Modified Delphi process to achieve consensus on the structure and content of the Workshop.
Aim: To determine the scope of the workshop, optimise the programme, and ensure the output/guidance reflects stakeholders needs (focusing on subjects for which consensus is least well developed and for which open debate is needed).
Organisations
- University of Oxford, United Kingdom (Lead Research Organisation)
- University of Southampton, United Kingdom (Collaboration)
- Western University (Collaboration)
- Public Health England, Salisbury (Collaboration)
- University of Bristol, United Kingdom (Collaboration)
- Royal College of Surgeons of England, United Kingdom (Collaboration)
- University of Sydney, Australia (Collaboration)
- NHS England, United Kingdom (Collaboration)
- University of York, United Kingdom (Collaboration)
- University of Birmingham, United Kingdom (Collaboration)
- University of Toronto (Collaboration)
- University of Aberdeen, United Kingdom (Collaboration)
- University of Ottawa, Canada (Collaboration)
- Lund University (Collaboration)
- University of Melbourne, Australia (Collaboration)
- University of Heidelberg, Germany (Collaboration)
Publications

Beard D
(2020)
Considerations and methods for placebo controls in surgical trials (ASPIRE guidelines)
in The Lancet

Beard D
(2021)
Placebo comparator group selection and use in surgical trials: the ASPIRE project including expert workshop
in Health Technology Assessment

Cousins S
(2020)
Optimizing the design of invasive placebo interventions in randomized controlled trials.
in The British journal of surgery

Cousins S
(2020)
Reporting of key methodological issues in placebo-controlled trials of surgery needs improvement: a systematic review.
in Journal of clinical epidemiology
Description | Surgical Placebo Methodology and Development |
Organisation | Heidelberg University |
Country | Germany |
Sector | Academic/University |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | Surgical Placebo Methodology and Development |
Organisation | Lund University |
Department | Faculty of Medicine |
Country | Sweden |
Sector | Academic/University |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | Surgical Placebo Methodology and Development |
Organisation | NHS England |
Department | NHS North of England Commissioning Support Unit |
Country | United Kingdom |
Sector | Hospitals |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | Surgical Placebo Methodology and Development |
Organisation | Public Health England |
Country | United Kingdom |
Sector | Public |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | Surgical Placebo Methodology and Development |
Organisation | Royal College of Surgeons of England |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | Surgical Placebo Methodology and Development |
Organisation | University of Aberdeen |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | Surgical Placebo Methodology and Development |
Organisation | University of Birmingham |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | Surgical Placebo Methodology and Development |
Organisation | University of Bristol |
Department | School of Social and Community Medicine |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | Surgical Placebo Methodology and Development |
Organisation | University of Melbourne |
Country | Australia |
Sector | Academic/University |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | Surgical Placebo Methodology and Development |
Organisation | University of Ottawa |
Department | Institute of Population Health |
Country | Canada |
Sector | Academic/University |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | Surgical Placebo Methodology and Development |
Organisation | University of Southampton |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | Surgical Placebo Methodology and Development |
Organisation | University of Sydney |
Department | Sydney Medical School |
Country | Australia |
Sector | Academic/University |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | Surgical Placebo Methodology and Development |
Organisation | University of Toronto |
Country | Canada |
Sector | Academic/University |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | Surgical Placebo Methodology and Development |
Organisation | University of York |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | Surgical Placebo Methodology and Development |
Organisation | Western University |
Country | Canada |
Sector | Academic/University |
PI Contribution | Added knowledge and publications |
Collaborator Contribution | added knowledge - co authors |
Impact | MRC NIHR Workshop Accepted Lancet publication NIHR report |
Start Year | 2017 |
Description | 'The Positives and Pitfalls of Placebo Comparison for Surgical Trials' |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Invited talk: 'The Positives and Pitfalls of Placebo Comparison for Surgical Trials'. Professor Beard presented and discussed the recent interest, need and growing expertise in evaluating surgical intervention. Abstract: The recent interest, need and growing expertise in evaluating surgical intervention has generated some fascinating conundrums for trials methodology. Selecting the correct comparison for both new and innovative treatments is key. The surgical specialities have attempted to mimic the medical (pharmacological) model by using placebo and/or sham controls for this testing. This allows fundamental assessment of efficacy and benefit by accounting for the strong placebo effects of undergoing a surgical procedure, but also introduces some incompatibilities and nuances. What constitutes placebo? Can a placebo effect be isolated from surgical interventions? Should a placebo always be used? Is there risk? Is it ethical? Do the surgical community support it? How can such a trial be operationalised and how can the tricky waters of equipoise and patient preference be navigated? These questions (some with solutions) will be raised and discussed in this talk (with plenty of time for discussion). |
Year(s) Of Engagement Activity | 2019 |
Description | Developing placebo-controlled studies: the need for developmental and early phase work |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Professor David Beard presented "Developing placebo-controlled studies: the need for developmental and early phase work" on Thursday 14th January 2021 (online discussion) as a potential Translational Research Collaboration (TRC) project. Aim of the meeting was to discuss a vision for a TRC n in invasive procedures and devices, and identify pan-BRC collaborative projects to improve early phase surgical research relevant to patients, clinicians and the NHS. |
Year(s) Of Engagement Activity | 2020,2021 |
Description | IDEAL 2021 conference presentation: Use of placebo controls in the evaluation of surgical procedures: the ASPIRE guidance |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Professor David Beard presented "Use of placebo controls in the evaluation of surgical procedures: the ASPIRE guidance" on Friday 16th April 2021 (online discussion) art the IDEAL 2021 virtual conference. IDEAL 2021 will bring together clinicians and researchers from all over the world. We will discuss the latest research methodology and developments for evaluating new surgical interventions and medical devices in a variety of clinical specialties. |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.ideal-collaboration.net/events/ideal-conference-2021/ |
Description | SCT 2021 Conference: Invited session - The ASPIRE guidance on surgical placebo controls in randomised trials |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Professor David Beard presented "The ASPIRE guidance on surgical placebo controls in randomised trials" [presented by David Beard, Marion Campbell, Sian Cousins & Dean Fergusson (as chair)] on Tuesday 18th May 2021 (online discussion) at the SCT 2021 virtual conference. This meeting brings together the clinical trials community from academia, the pharmaceutical and device industries, government agencies, medical groups and centres and clinical research entities. |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.sctweb.org/meeting/ |
Description | The role of placebos in the evaluation of surgical procedures |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Invited talk: The role of placebos in the evaluation of surgical procedures. Professor Beard presented and discussed the place of placebo controlled trials in the evaluation of surgical and other interventional procedures. He outlined the ethical controversies the involvement of a placebo-surgical procedure raises and discussed the design and conduct issues. |
Year(s) Of Engagement Activity | 2018 |