Sigurlaug H Hafliðadóttir1,2, Carsten B Juhl2,3, Sabrina M Nielsen1,4, Marius Henriksen5, Ian A Harris6,7,8, Henning Bliddal5, Robin Christensen9,10. 1. Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Nordre Fasanvej 57, DK-2000, Copenhagen F, Denmark. 2. SEARCH Research Group, Research Unit of Musculoskeletal Function and Physiotherapy, Institute of Sports Science and Clinical Biomechanics, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. 3. Department of Physiotherapy and Occupational Therapy, University Hospital of Copenhagen, Herlev, Gentofte, Denmark. 4. Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark. 5. The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark. 6. Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, Sydney, New South Wales, Australia. 7. Faculty of Medicine, South Western Sydney Clinical School, The University of New South Wales, Sydney, New South Wales, Australia. 8. Institute of Musculoskeletal Health, School of Public Health, The University of Sydney, Sydney, New South Wales, Australia. 9. Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Nordre Fasanvej 57, DK-2000, Copenhagen F, Denmark. Robin.Christensen@regionh.dk. 10. Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark. Robin.Christensen@regionh.dk.
Abstract
BACKGROUND: Contextual effects (i.e., placebo response) refer to all health changes resulting from administering an apparently inactive treatment. In a randomized clinical trial (RCT), the overall treatment effect (i.e., the post-treatment effect in the intervention group) can be regarded as the true effect of the intervention plus the impact of contextual effects. This meta-research was conducted to examine the average proportion of the overall treatment effect attributable to contextual effects in RCTs across clinical conditions and treatments and explore whether it varies with trial contextual factors. METHODS: Data was extracted from trials included in the main meta-analysis from the latest update of the Cochrane review on "Placebo interventions for all clinical conditions" (searched from 1966 to March 2008). Only RCTs reported in English having an experimental intervention group, a placebo comparator group, and a no-treatment control group were eligible. RESULTS: In total, 186 trials (16,655 patients) were included. On average, 54% (0.54, 95%CI 0.46 to 0.64) of the overall treatment effect was attributable to contextual effects. The contextual effects were higher for trials with blinded outcome assessor and concealed allocation. The contextual effects appeared to increase proportional to the placebo effect, lower mean age, and proportion of females. CONCLUSION: Approximately half of the overall treatment effect in RCTs seems attributable to contextual effects rather than to the specific effect of treatments. As the study did not include all important contextual factors (e.g., patient-provider interaction), the true proportion of contextual effects could differ from the study's results. However, contextual effects should be considered when assessing treatment effects in clinical practice. TRIAL REGISTRATION: PROSPERO CRD42019130257 . Registered on April 19, 2019.
BACKGROUND: Contextual effects (i.e., placebo response) refer to all health changes resulting from administering an apparently inactive treatment. In a randomized clinical trial (RCT), the overall treatment effect (i.e., the post-treatment effect in the intervention group) can be regarded as the true effect of the intervention plus the impact of contextual effects. This meta-research was conducted to examine the average proportion of the overall treatment effect attributable to contextual effects in RCTs across clinical conditions and treatments and explore whether it varies with trial contextual factors. METHODS: Data was extracted from trials included in the main meta-analysis from the latest update of the Cochrane review on "Placebo interventions for all clinical conditions" (searched from 1966 to March 2008). Only RCTs reported in English having an experimental intervention group, a placebo comparator group, and a no-treatment control group were eligible. RESULTS: In total, 186 trials (16,655 patients) were included. On average, 54% (0.54, 95%CI 0.46 to 0.64) of the overall treatment effect was attributable to contextual effects. The contextual effects were higher for trials with blinded outcome assessor and concealed allocation. The contextual effects appeared to increase proportional to the placebo effect, lower mean age, and proportion of females. CONCLUSION: Approximately half of the overall treatment effect in RCTs seems attributable to contextual effects rather than to the specific effect of treatments. As the study did not include all important contextual factors (e.g., patient-provider interaction), the true proportion of contextual effects could differ from the study's results. However, contextual effects should be considered when assessing treatment effects in clinical practice. TRIAL REGISTRATION: PROSPERO CRD42019130257 . Registered on April 19, 2019.
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