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).

‘It's not my greengrocer, it's someone from the medical profession’: A qualitative study regarding acceptability of deceptive and open‐label placebo prescribing in France

“…Although OLPs were initially thought and tested as ethically more acceptable interventions compared with deceptive placebos, our results seem to hint participants were not in agreement with respect to the ethical acceptability of OLPs. The question of comparing DP to OLP regarding efficacy is even more relevant with this in mind and is currently under investigation in published and undergoing trials (Druart et al, 2020; Locher et al, 2017).…”

“…The qualitative study was nested in a non‐inferiority randomized trial aimed at comparing the efficacy of DP and OLP on experimental pain with healthy participants (Druart et al, 2020). The study took place at the University of Grenoble and was approved by the national ethics committee (2017‐A01643‐50).…”

“…Both groups also underwent a no-treatment (NT) condition in which the pain stimulus was delivered with no treatment. The method used in the clinical trial as well as its registration information are detailed in a separate paper (Druart et al, 2020).…”

Placebo: a brief updated review

“…A trial in surgery patients showed that placebo improved somatic symptoms such as pain, discomfort or insomnia but did not intervene in the time or healing process of the surgical wound (Mathur et al 2018 ). Despite the increasing number of non-deceptive placebo trials, methodological issues, as ethical concerns, the role of placebo with deception vs. open-label placebo, etc., remains to be defined and are the subject of ongoing studies (Druart et al 2020 ).…”

Manual Therapy Effect in Placebo-Controlled Trials: A Systematic Review and Meta-Analysis

“…They must be non-active and harmless actions that by themselves should not produce any physical improvement/deterioration of the patient’s condition, residing here the importance of including a proper sham for each and every one of the evaluated manual therapies. Moreover, the blinding of the patients must be ensured to render a proper and adequate placebo intervention and reliable results [ 22 , 23 ].…”