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.

Article history

This issue of the Health Technology Assessment journal series contains a project commissioned by the MRC–NIHR Methodology Research Programme (MRP). MRP aims to improve efficiency, quality and impact across the entire spectrum of biomedical and health-related research. In addition to the MRC and NIHR funding partners, MRP takes into account the needs of other stakeholders including the devolved administrations, industry R&D, and regulatory/advisory agencies and other public bodies. MRP supports investigator-led methodology research from across the UK that maximises benefits for researchers, patients and the general population – improving the methods available to ensure health research, decisions and policy are built on the best possible evidence.

To improve availability and uptake of methodological innovation, MRC and NIHR jointly supported a series of workshops to develop guidance in specified areas of methodological controversy or uncertainty (Methodology State-of-the-Art Workshop Programme). Workshops were commissioned by open calls for applications led by UK-based researchers. Workshop outputs are incorporated into this report, and MRC and NIHR endorse the methodological recommendations as state-of-the-art guidance at time of publication.

The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.