Methodological considerations for designing and conducting open-label placebo trials

Pain, vol. 167, pp. 2248–2262

Abstract

ABSTRACT: In pain and other research fields, placebos have traditionally been associated with deception, although harnessing placebo effects does not necessarily require deception. Open-label placebos (OLPs) represent a novel approach in which inert treatments are administered openly and transparently, allowing patients to knowingly receive an inert treatment while still experiencing therapeutic benefits (eg, pain relief). As OLP research grows, concerns have been raised regarding methodological rigor and the unique challenges posed by unblinded designs in both experimental and clinical contexts. Given the inherent transparency regarding treatment group allocation in OLP trials, particular attention is needed when defining appropriate control groups, implementing feasible blinding strategies, and providing a treatment rationale to adequately explain OLPs. Addressing these challenges is crucial to advancing both the scientific understanding of the psychoneurobiological mechanisms underlying OLP effects and their clinical relevance in pain. In this review, we outline key methodological considerations for designing and conducting OLP studies in pain research and beyond, providing guidance on control group selection, blinding strategies, and reporting standards. In addition, we integrate insights from the patient advisory board of the transregional Collaborative Research Center (CRC/TRR) 289 "Treatment Expectation" to incorporate patient perspectives on the feasibility and acceptability of OLPs. Aligning study designs with patient needs and expectations may foster a more meaningful, patient-centered approach to OLP research. By combining methodological guidance and emphasizing patient-centered insights, this review aims to enhance the quality, relevance, and clinical translation of OLP research in pain.

Authors 13

1. Helena Hartmann

   Essen University Hospital · University of Duisburg-Essen

   Affiliation as printed

   Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

2. Diana Müßgens

   Essen University Hospital · University of Duisburg-Essen

   Affiliation as printed

   Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

3. Livia Asan

   Essen University Hospital · University of Duisburg-Essen

   Affiliation as printed

   Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

4. Aleksandrina Skvortsova Aachen Health Faculty of Social and Behavioural Sciences

   Leiden University

   Affiliation as printed

   Health, Medical and Neuropsychology, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands

5. Julian Kleine‐Borgmann

   Essen University Hospital · University of Duisburg-Essen

   Affiliation as printed

   Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

6. Katharina Schmidt

   Essen University Hospital · University of Duisburg-Essen

   Affiliation as printed

   Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

7. Aurore Fernandez

   Centre Hospitalier Universitaire Vaudois · University of Lausanne

   Affiliation as printed

   Center for Integrative and Complementary Medicine, Department of Anesthesiology, Lausanne University Hospital (CHUV), Lausanne, Switzerland

   Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland

   Pain Center, Department of Anesthesiology, Lausanne University Hospital (CHUV), Lausanne, Switzerland

8. Jules Phalip

   Inserm · Université Clermont Auvergne · Physiopathologie et pharmacologie de la douleur et de la migraine · Centre Hospitalier Universitaire de Clermont-Ferrand

   Affiliation as printed

   Centre Hospitalier Universitaire de Clermont-Ferrand, Service de pharmacologie médicale, Clermont-Ferrand, France

   Fondation ANALGESIA, UFR Médecine et professions paramédicales, Université Clermont Auvergne, Clermont-Ferrand, France

   Université Clermont Auvergne, Inserm 1107 Neuro-Dol, Clermont-Ferrand, France

9. Marco Valerio

   UNSW Sydney

   Affiliation as printed

   School of Psychology, Faculty of Science, University of New South Wales, Sydney, Australia

10. Meike C. Shedden Mora

    Universität Hamburg · MSH Medical School Hamburg – University of Applied Sciences and Medical University · University Medical Center Hamburg-Eppendorf

    Affiliation as printed

    Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Institute for Clinical Psychology and Psychotherapy & Department of Psychology, Medical School Hamburg, Hamburg, Germany

11. Ulrike Bingel

    Essen University Hospital · University of Duisburg-Essen

    Affiliation as printed

    Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

12. Patient Advisory Board of the CRC/TRR 289 Treatment Expectation
13. Jana Aulenkamp

    Essen University Hospital · University of Duisburg-Essen

    Affiliation as printed

    Department of Anesthesiology and Intensive Care Medicine, University Duisburg-Essen, University Hospital Essen, Essen, Germany

    Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany