Considerations and methods for placebo controls in surgical trials (ASPIRE guidelines)

Placebo comparisons are increasingly being considered for randomised trials assessing the efficacy of surgical interventions. The aim of this Review is to provide a summary of knowledge on placebo controls in surgical trials. A placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. This Review outlines what a placebo control entails and present understanding of this tool in the context of surgery. We consider when placebo controls in surgery are acceptable (and when they are desirable) in terms of ethical 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 done and interpreted. Use of placebo controls is justified in randomised controlled trials of surgical interventions provided there is a strong scientific and ethical 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 high risk of bias, particularly because of the placebo effect. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. This Review forms an outline for best practice and provides guidance, in the form of the Applying Surgical Placebo in Randomised Evaluations (known as ASPIRE) checklist, for those considering the use of a placebo control in a surgical randomised controlled trial

Reducing bias in trials due to reactions to measurement: experts produced recommendations informed by evidence

Objective: This study (MEasurement Reactions In Trials) aimed to produce recommendations on how best to minimize bias from measurement reactivity (MR) in randomized controlled trials of interventions to improve health. Study design and setting: The MERIT study consisted of: (1) an updated systematic review that examined whether measuring participants had effects on participants’ health-related behaviors, relative to no-measurement controls, and three rapid reviews to identify: (i) existing guidance on MR; (ii) existing systematic reviews of studies that have quantified the effects of measurement on behavioral or affective outcomes; and (iii) studies that have investigated the effects of objective measurements of behavior on health-related behavior; (2) a Delphi study to identify the scope of the recommendations; and (3) an expert workshop in October 2018 to discuss potential recommendations in groups. Results: Fourteen recommendations were produced by the expert group to: (1) identify whether bias is likely to be a problem for a trial; (2) decide whether to collect data about whether bias is likely to be a problem; (3) design trials to minimize the likelihood of this bias. Conclusion: These recommendations raise awareness of how and where taking measurements can produce bias in trials, and are thus helpful for trial design

Placebo comparator group selection and use in surgical trials: the ASPIRE project including expert workshop.

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