State-of-the-art workshop: Methods for placebo comparator group selection and use in surgical trials

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.

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).