P 17 | Optimising the Design of Placebo-Controlled RCTs of Invasive Procedures: An Analysis of Published Rcts: Abstracts from the SCT 39th Annual Meeting (2018)

Introduction

Randomized controlled trials (RCTs) are considered the gold standard for informing evidence based healthcare. High quality RCTs, however, have been difficult to conduct in trials of invasive procedures; one reason for this is linked to the challenges associated with minimising bias. Whilst invasive placebo procedures are desirable there are unique practical considerations, compared to pharmaceutical placebos, and there is debate regarding their ethical acceptability to patients and healthcare staff. Pilot work assessing the practical feasibility and acceptability of RCTs, including testing of procedures and estimation of recruitment/retention, is considered crucial in the development and evaluation of complex interventions, such as invasive procedures.

Aim

To study in detail and summarise reported development of placebo procedures to inform placebo-controlled RCTs of invasive procedures.

Methods

Randomised trials, including pilot RCTs, comparing invasive procedures with placebo were identified from systematic searches of Medline, Embase, CENTRAL and ClinicalTrials.gov databases (Wartolowska, BMJ Open, 2016). Trials were published between database inception and 14th November 2014. Additional trials and pilot RCTs were identified by hand searching references and expert knowledge. Trial protocols, summaries from trial registries and texts referenced in the report outlining methods or pilot work were also retrieved. Data on type of invasive procedure, how the placebo was developed and tested, and lessons learnt from the placebo design were extracted.

Results

Seventy-three placebo-controlled trials were included. Procedures was mostly endoscopic (n=34, 47%), with 28 (38%) standard surgical procedures with an incision and 11 (15%) via a percutaneous puncture. Ten pilot studies were retrieved, however the focus of 8 of them was assessment of the standard invasive procedure and not the design or delivery of the placebo procedure. Two pilot RCTs assessed feasibility of recruitment, however only one commented on the feasibility of delivering the placebo procedure specifically. This report also outlined in-depth development work, which included interviews with key stakeholders exploring placebo development and the acceptability of the placebo-controlled RCT. Authors in 15 (21%) of the studies reflected on the quality of the placebo procedure in their trial. This was limited to discussion of the differences/similarities between the placebo and invasive procedures and how this may have impacted the blinding of patients and investigators, with none commenting on the need for pilot work to optimise the development of the placebo procedures.

Conclusion

Given the practical challenges and ethical considerations in designing and delivering placebo invasive procedures, the scarcity of pilot work revealed by this review is surprising. Pilot work is an ideal opportunity to assess and improve the placebo, and test whether it can be detected as such. Increased investment in pre-trial development and pilot work is recommended to optimise the design and delivery of placebo invasive procedures and improve the quality of RCTs in this area.

Contributors

Alexander Gormley

Bristol Dental School

Natalie Blencowe

Bristol Centre for Surgical Research

Jane Blazeby

Bristol Centre for Surgical Research