Can an Open-Label Placebo Be as Effective as a Deceptive Placebo? Methodological Considerations of a Study Protocol

Abstract

Background: Placebo has been studied for many years and is ever-present in healthcare. In clinical practice, its use is limited by ethical issues raised by the deception entailed by its administration. Objective: To investigate whether, when given detailed information about pain and underlying placebo mechanisms, subjects will have a response similar to that of those subjected to a procedure in which they receive a conventional placebo treatment. Methods: The study is designed as a non-inferiority randomized, parallel with a nested crossover trial. In addition, 126 subjects without any known pathology will be included. They will be randomized into two groups. Each subject will undergo three Cold Pressor Tests (CPT): calibration, condition of interest (deceptive placebo or educated placebo), and control. Our main judgment criterion will be the comparison in pain intensity experienced on the visual analog scale between the two CPTs with placebo conditions. Results: This study will allow us to rule on the non-inferiority of an "educated" placebo compared to a deceptive placebo in the context of an acute painful stimulation. It is another step towards the understanding of open-label placebo and its use in clinical practice. Conclusions: This study has been approved by the ethics committee in France (2017-A01643-50) and registered on ClinicalTrials.gov (NCT03934138).

Keywords: clinical trial; cold pressor test; ethics; open label placebo; pain; placebo.

Figure 1

CPT order diagram.

Figure 2

Detailed study flow for a subject. From top to bottom for an animated version of this figure, see: http://bit.ly/Placethic-Figure.

Figure 3

Clinical trial set-up during a CPT test.