Modulating Placebo Effects in Clinical Trials: Study Team Briefing to Optimize Drug–Placebo Differences

Clinical and Translational Science, vol. 18, pp. e70399

Abstract

Clinical trials often face challenges with placebo effects that can mask actual drug effects. We evaluated whether briefing the study team members on placebo mechanisms influenced analgesia. In this study, we compared the analgesic effects of oxycodone and placebo in three groups of 32 subjects. The groups were treated by an untrained study team (Arm A), a team trained to maximize (Arm B) and a team trained to minimize placebo effects (Arm C). The primary outcome was the reduction of pain during the cold pressor test, assessed by the area under the pain curve of the visual analog scale before and after blinded administration of oxycodone or placebo. Oxycodone and placebo demonstrated the expected differences in pain reduction across all study arms. Briefing the study team did not significantly affect pain reduction or treatment expectation, regardless of treatment. However, treatment expectations were more pronounced with oxycodone compared to placebo, showing a positive correlation of expectation and treatment effect only in the oxycodone group, possibly reflecting the influence of unblinding due to adverse effects. These findings suggest that a brief training of the study team may not be sufficient to alter treatment expectations and placebo analgesia. This insight will inform future efforts to apply placebo research to optimize blinded trial design and drug treatments in clinical settings. Trial Registration: DRKS 00013586 (German Clinical Trials Register), registered on December, 22nd 2017; URL: https://www.drks.de/drks_web/setLocale_EN.do.

Authors 9

1. Martin Coenen corresponding

   University Hospital Bonn

   Affiliation as printed

   Clinical Study Core Unit, Study Center Bonn (SZB) University Hospital Bonn Bonn Germany

   Institute of Clinical Chemistry and Clinical Pharmacology University Hospital Bonn Bonn Germany

   Clinical Study Core Unit, Study Center Bonn (SZB), University Hospital Bonn, Bonn, Germany

2. Ulrike Bingel

   Essen University Hospital

   Affiliation as printed

   Department of Neurology, Center for Translational Neuro‐ and Behavioural Sciences University Hospital Essen Essen Germany

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

3. Maria Soledad Berdaguer

   University Hospital Bonn

   Affiliation as printed

   Clinical Study Core Unit, Study Center Bonn (SZB) University Hospital Bonn Bonn Germany

   Institute of Clinical Chemistry and Clinical Pharmacology University Hospital Bonn Bonn Germany

   Clinical Study Core Unit, Study Center Bonn (SZB), University Hospital Bonn, Bonn, Germany

4. Christine Fuhrmann

   University Hospital Bonn

   Affiliation as printed

   Clinical Study Core Unit, Study Center Bonn (SZB) University Hospital Bonn Bonn Germany

   Institute of Clinical Chemistry and Clinical Pharmacology University Hospital Bonn Bonn Germany

   Clinical Study Core Unit, Study Center Bonn (SZB), University Hospital Bonn, Bonn, Germany

5. Robert Németh

   University Hospital Bonn · Institut für Medizinische Biometrie, Informatik und Epidemiologie

   Affiliation as printed

   Clinical Study Core Unit, Study Center Bonn (SZB) University Hospital Bonn Bonn Germany

   Institute of Medical Biometrics, Informatics and Epidemiology University Hospital Bonn Bonn Germany

   Clinical Study Core Unit, Study Center Bonn (SZB), University Hospital Bonn, Bonn, Germany

6. Jens Rengelshausen Aachen Institute for Occupational, Social and Environmental Medicine

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Occupational, Social and Environmental Medicine Uniklinik RWTH Aachen Aachen Germany

   Institute for Occupational, Social and Environmental Medicine, Uniklinik RWTH Aachen, Aachen, Germany

7. Gunther Hartmann

   University of Bonn · University Hospital Bonn

   Affiliation as printed

   Institute of Clinical Chemistry and Clinical Pharmacology University Hospital Bonn Bonn Germany

   Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany

8. Christoph Coch

   University Hospital Bonn

   Affiliation as printed

   Clinic and Policlinic for Neurosurgery Leipzig Germany

   Clinical Study Core Unit, Study Center Bonn (SZB) University Hospital Bonn Bonn Germany

   Institute of Clinical Chemistry and Clinical Pharmacology University Hospital Bonn Bonn Germany

   Clinic and Policlinic for Neurosurgery, Leipzig, Germany

   Clinical Study Core Unit, Study Center Bonn (SZB), University Hospital Bonn, Bonn, Germany

9. Manfred Schedlowski

   Karolinska Institutet · Essen University Hospital

   Affiliation as printed

   Department of Clinical Neuroscience, Osher Center for Integrative Medicine Karolinska Institutet Stockholm Sweden

   Institute of Medical Psychology and Behavioral Immunobiology, Center for Translational Neuro‐ and Behavioural Sciences University Hospital Essen Essen Germany

   Department of Clinical Neuroscience, Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden

   Institute of Medical Psychology and Behavioral Immunobiology, Center for Translational Neuro- and Behavioural Sciences, University Hospital Essen, Essen, Germany