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Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis

IMPORTANCE: Persistent pain is a common and disabling health problem that is often difficult to treat. There is an increasing interest in medicinal cannabis for treatment of persistent pain; however, the limited superiority of cannabinoids over placebo in clinical trials suggests that positive expec...

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Autores principales: Gedin, Filip, Blomé, Sebastian, Pontén, Moa, Lalouni, Maria, Fust, Jens, Raquette, Andreé, Vadenmark Lundquist, Viktor, Thompson, William H., Jensen, Karin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9706362/
https://www.ncbi.nlm.nih.gov/pubmed/36441553
http://dx.doi.org/10.1001/jamanetworkopen.2022.43848
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author Gedin, Filip
Blomé, Sebastian
Pontén, Moa
Lalouni, Maria
Fust, Jens
Raquette, Andreé
Vadenmark Lundquist, Viktor
Thompson, William H.
Jensen, Karin
author_facet Gedin, Filip
Blomé, Sebastian
Pontén, Moa
Lalouni, Maria
Fust, Jens
Raquette, Andreé
Vadenmark Lundquist, Viktor
Thompson, William H.
Jensen, Karin
author_sort Gedin, Filip
collection PubMed
description IMPORTANCE: Persistent pain is a common and disabling health problem that is often difficult to treat. There is an increasing interest in medicinal cannabis for treatment of persistent pain; however, the limited superiority of cannabinoids over placebo in clinical trials suggests that positive expectations may contribute to the improvements. OBJECTIVE: To evaluate the size of placebo responses in randomized clinical trials in which cannabinoids were compared with placebo in the treatment of pain and to correlate these responses to objective estimates of media attention. DATA SOURCES: A systematic literature search was conducted within the MEDLINE and Embase databases. Studies published until September 2021 were considered. STUDY SELECTION: Cannabinoid studies with a double-blind, placebo-controlled design with participants 18 years or older with clinical pain of any duration were included. Studies were excluded if they treated individuals with HIV/AIDS or severe skin disorders. DATA EXTRACTION AND SYNTHESIS: The study followed the Preferred Reporting Items for Systematic Review and Meta-analyses reporting guideline. Data were extracted by independent reviewers. Quality assessment was performed using the Risk of Bias 2 tool. Attention and dissemination metrics for each trial were extracted from Altmetric and Crossref. Data were pooled and analyzed using a random-effects statistical model. MAIN OUTCOMES AND MEASURES: Change in pain intensity from before to after treatment, measured as bias-corrected standardized mean difference (Hedges g). RESULTS: Twenty studies, including 1459 individuals (mean [SD] age, 51 [7] years; age range, 33-62 years; 815 female [56%]), were included. Pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean [SE] Hedges g, 0.64 [0.13]; P < .001). Trials with low risk of bias had greater placebo responses (q(1) = 5.47; I(2) = 87.08; P = .02). The amount of media attention and dissemination linked to each trial was proportionally high, with a strong positive bias, but was not associated with the clinical outcomes. CONCLUSIONS AND RELEVANCE: Placebo contributes significantly to pain reduction seen in cannabinoid clinical trials. The positive media attention and wide dissemination may uphold high expectations and shape placebo responses in future trials, which has the potential to affect the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief.
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spelling pubmed-97063622022-12-14 Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis Gedin, Filip Blomé, Sebastian Pontén, Moa Lalouni, Maria Fust, Jens Raquette, Andreé Vadenmark Lundquist, Viktor Thompson, William H. Jensen, Karin JAMA Netw Open Original Investigation IMPORTANCE: Persistent pain is a common and disabling health problem that is often difficult to treat. There is an increasing interest in medicinal cannabis for treatment of persistent pain; however, the limited superiority of cannabinoids over placebo in clinical trials suggests that positive expectations may contribute to the improvements. OBJECTIVE: To evaluate the size of placebo responses in randomized clinical trials in which cannabinoids were compared with placebo in the treatment of pain and to correlate these responses to objective estimates of media attention. DATA SOURCES: A systematic literature search was conducted within the MEDLINE and Embase databases. Studies published until September 2021 were considered. STUDY SELECTION: Cannabinoid studies with a double-blind, placebo-controlled design with participants 18 years or older with clinical pain of any duration were included. Studies were excluded if they treated individuals with HIV/AIDS or severe skin disorders. DATA EXTRACTION AND SYNTHESIS: The study followed the Preferred Reporting Items for Systematic Review and Meta-analyses reporting guideline. Data were extracted by independent reviewers. Quality assessment was performed using the Risk of Bias 2 tool. Attention and dissemination metrics for each trial were extracted from Altmetric and Crossref. Data were pooled and analyzed using a random-effects statistical model. MAIN OUTCOMES AND MEASURES: Change in pain intensity from before to after treatment, measured as bias-corrected standardized mean difference (Hedges g). RESULTS: Twenty studies, including 1459 individuals (mean [SD] age, 51 [7] years; age range, 33-62 years; 815 female [56%]), were included. Pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean [SE] Hedges g, 0.64 [0.13]; P < .001). Trials with low risk of bias had greater placebo responses (q(1) = 5.47; I(2) = 87.08; P = .02). The amount of media attention and dissemination linked to each trial was proportionally high, with a strong positive bias, but was not associated with the clinical outcomes. CONCLUSIONS AND RELEVANCE: Placebo contributes significantly to pain reduction seen in cannabinoid clinical trials. The positive media attention and wide dissemination may uphold high expectations and shape placebo responses in future trials, which has the potential to affect the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief. American Medical Association 2022-11-28 /pmc/articles/PMC9706362/ /pubmed/36441553 http://dx.doi.org/10.1001/jamanetworkopen.2022.43848 Text en Copyright 2022 Gedin F et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Gedin, Filip
Blomé, Sebastian
Pontén, Moa
Lalouni, Maria
Fust, Jens
Raquette, Andreé
Vadenmark Lundquist, Viktor
Thompson, William H.
Jensen, Karin
Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis
title Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis
title_full Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis
title_fullStr Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis
title_full_unstemmed Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis
title_short Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis
title_sort placebo response and media attention in randomized clinical trials assessing cannabis-based therapies for pain: a systematic review and meta-analysis
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9706362/
https://www.ncbi.nlm.nih.gov/pubmed/36441553
http://dx.doi.org/10.1001/jamanetworkopen.2022.43848
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