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Abstract
Background: Active placebo controls are designed to mimic the nontherapeutic adverse effects of drugs in randomised trials. Active placebos are rarely used but could reduce the risk of bias due to unblinding.
Objectives: We aimed to estimate the difference in drug effects when an experimental drug is compared with an active placebo versus a standard placebo control intervention, and to explore causes for heterogeneity. In the context of a randomised trial, this difference in drug effects can be estimated by directly comparing the effect difference between active placebo and standard placebo intervention. Design: A systematic review
Methods: We searched PubMed, CENTRAL, Embase, and other sources up to October 2020 and included randomised trials directly comparing active placebo versus standard placebo. Our primary inverse-variance, random-effects meta-analysis used standardised mean differences (SMDs) of participant-reported outcomes at earliest post-treatment assessment. An SMD
Results: We included 21 trials (1,462 participants). The pooled SMD in our primary analysis was -0.08 (95% CI -0.20 to 0.04; Figure 1). The difference was more pronounced and statistically significant in the sensitivity analyses restricting to trials with overall low risk of bias (pooled SMD -0.24; 95% CI -0.34 to -0.13) and using a fixed-effect model (pooled SMD - 0.15; 95% CI -0.23 to -0.07). The pooled SMD of observer-reported outcomes was similar to the primary analysis. The pooled odds ratio for harms was 3.08 (95% CI 1.56 to 6.07), and for attrition, 1.22 (95% CI 0.74 to 2.03). Cointervention data were limited. Meta-regression found no statistically significant association with adequacy of the active placebo or risk of unintended therapeutic effect.
Conclusions: We did not find a statistically significant difference between active and standard placebo interventions in our primary analysis, but the result was imprecise and compatible with a difference ranging from important to irrelevant. Furthermore, the result was not robust, for example, when restricting to trials with overall low risk of bias.
Patient, public and/or healthcare consumer involvement: None.
Objectives: We aimed to estimate the difference in drug effects when an experimental drug is compared with an active placebo versus a standard placebo control intervention, and to explore causes for heterogeneity. In the context of a randomised trial, this difference in drug effects can be estimated by directly comparing the effect difference between active placebo and standard placebo intervention. Design: A systematic review
Methods: We searched PubMed, CENTRAL, Embase, and other sources up to October 2020 and included randomised trials directly comparing active placebo versus standard placebo. Our primary inverse-variance, random-effects meta-analysis used standardised mean differences (SMDs) of participant-reported outcomes at earliest post-treatment assessment. An SMD
Results: We included 21 trials (1,462 participants). The pooled SMD in our primary analysis was -0.08 (95% CI -0.20 to 0.04; Figure 1). The difference was more pronounced and statistically significant in the sensitivity analyses restricting to trials with overall low risk of bias (pooled SMD -0.24; 95% CI -0.34 to -0.13) and using a fixed-effect model (pooled SMD - 0.15; 95% CI -0.23 to -0.07). The pooled SMD of observer-reported outcomes was similar to the primary analysis. The pooled odds ratio for harms was 3.08 (95% CI 1.56 to 6.07), and for attrition, 1.22 (95% CI 0.74 to 2.03). Cointervention data were limited. Meta-regression found no statistically significant association with adequacy of the active placebo or risk of unintended therapeutic effect.
Conclusions: We did not find a statistically significant difference between active and standard placebo interventions in our primary analysis, but the result was imprecise and compatible with a difference ranging from important to irrelevant. Furthermore, the result was not robust, for example, when restricting to trials with overall low risk of bias.
Patient, public and/or healthcare consumer involvement: None.
| Original language | English |
|---|---|
| Title of host publication | Cochrane Database of Systematic Reviews : Abstracts accepted for the 27th Cochrane Colloquium, London, UK |
| Volume | 2023 |
| Publication date | 2023 |
| Edition | 1 Suppl 1 |
| Article number | 36430 |
| DOIs | |
| Publication status | Published - 2023 |
| Event | Cochrane Colloquium 2023 - London, United Kingdom Duration: 3. Sept 2023 → 6. Sept 2023 Conference number: 27 https://events.cochrane.org/colloquium-2023 |
Conference
| Conference | Cochrane Colloquium 2023 |
|---|---|
| Number | 27 |
| Country/Territory | United Kingdom |
| City | London |
| Period | 03/09/2023 → 06/09/2023 |
| Internet address |
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Dive into the research topics of 'Impact of active placebo controls on estimated drug effects in randomised trials'. Together they form a unique fingerprint.Related research output
- 1 Journal article
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Impact of active placebo controls on estimated drug effects in randomised trials: a systematic review of trials with both active placebo and standard placebo
Laursen, D. R., Nejstgaard, C. H., Bjørkedal, E., Frost, A. D., Hansen, M. R., Paludan-Müller, A. S., Prosenz, J., Werner, C. P. & Hróbjartsson, A., 6. Mar 2023, In: Cochrane Database of Systematic Reviews. 2023, 3, MR000055.Research output: Contribution to journal › Journal article › Research › peer-review
Open AccessFile69 Downloads (Pure)
Related projects
- 1 Finished
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Active placebo versus standard placebo control interventions in pharmacological randomised trials: a systematic review
Laursen, D. R. T. (Head coordinator)
01/10/2018 → 06/03/2023
Project: Research