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.

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).

Publications

10 25 50
 
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 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