PainSci summary of Hróbjartsson 2010?This page is one of thousands in the PainScience.com bibliography. It is not a general article: it is focused on a single scientific paper, and it may provide only just enough context for the summary to make sense. Links to other papers and more general information are provided at the bottom of the page, as often as possible. ★★★★★5-star ratings are for sentinel studies, excellent experiments with meaningful results. Ratings are a highly subjective opinion, and subject to revision at any time. If you think this paper has been incorrectly rated, please let me know.
The nugget of this large review of placebo effects: “We did not find that placebo interventions have important clinical effects in general.” And, particularly pertinent to this website, “The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important.” This is consistent with my position that placebo is far from “powerful,” but may have a strong impact on pain in ideal circumstances. As Dr. Steven Novella summarized it, “In other words, the best research we have strongly suggests that placebo effects are illusions, not real physiological effects.”
original abstract†Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.
BACKGROUND: Placebo interventions are often claimed to substantially improve patient-reported and observer-reported outcomes in many clinical conditions, but most reports on effects of placebos are based on studies that have not randomised patients to placebo or no treatment. Two previous versions of this review from 2001 and 2004 found that placebo interventions in general did not have clinically important effects, but that there were possible beneficial effects on patient-reported outcomes, especially pain. Since then several relevant trials have been published.
OBJECTIVES: Our primary aims were to assess the effect of placebo interventions in general across all clinical conditions, and to investigate the effects of placebo interventions on specific clinical conditions. Our secondary aims were to assess whether the effect of placebo treatments differed for patient-reported and observer-reported outcomes, and to explore other reasons for variations in effect.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 4, 2007), MEDLINE (1966 to March 2008), EMBASE (1980 to March 2008), PsycINFO (1887 to March 2008) and Biological Abstracts (1986 to March 2008). We contacted experts on placebo research, and read references in the included trials.
SELECTION CRITERIA: We included randomised placebo trials with a no-treatment control group investigating any health problem.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. Trials with binary data were summarised using relative risk (a value of less than 1 indicates a beneficial effect of placebo), and trials with continuous outcomes were summarised using standardised mean difference (a negative value indicates a beneficial effect of placebo).
MAIN RESULTS: Outcome data were available in 202 out of 234 included trials, investigating 60 clinical conditions. We regarded the risk of bias as low in only 16 trials (8%), five of which had binary outcomes.In 44 studies with binary outcomes (6041 patients), there was moderate heterogeneity (P < 0.001; I(2) 45%) but no clear difference in effects between small and large trials (symmetrical funnel plot). The overall pooled effect of placebo was a relative risk of 0.93 (95% confidence interval (CI) 0.88 to 0.99). The pooled relative risk for patient-reported outcomes was 0.93 (95% CI 0.86 to 1.00) and for observer-reported outcomes 0.93 (95% CI 0.85 to 1.02). We found no statistically significant effect of placebo interventions in four clinical conditions that had been investigated in three trials or more: pain, nausea, smoking, and depression, but confidence intervals were wide. The effect on pain varied considerably, even among trials with low risk of bias.In 158 trials with continuous outcomes (10,525 patients), there was moderate heterogeneity (P < 0.001; I(2) 42%), and considerable variation in effects between small and large trials (asymmetrical funnel plot). It is therefore a questionable procedure to pool all the trials, and we did so mainly as a basis for exploring causes for heterogeneity. We found an overall effect of placebo treatments, standardised mean difference (SMD) -0.23 (95% CI -0.28 to -0.17). The SMD for patient-reported outcomes was -0.26 (95% CI -0.32 to -0.19), and for observer-reported outcomes, SMD -0.13 (95% CI -0.24 to -0.02). We found an effect on pain, SMD -0.28 (95% CI -0.36 to -0.19)); nausea, SMD -0.25 (-0.46 to -0.04)), asthma (-0.35 (-0.70 to -0.01)), and phobia (SMD -0.63 (95% CI -1.17 to -0.08)). The effect on pain was very variable, also among trials with low risk of bias. Four similarly-designed acupuncture trials conducted by an overlapping group of authors reported large effects (SMD -0.68 (-0.85 to -0.50)) whereas three other pain trials reported low or no effect (SMD -0.13 (-0.28 to 0.03)). The pooled effect on nausea was small, but consistent. The effects on phobia and asthma were very uncertain due to high risk of bias. There was no statistically significant effect of placebo interventions in the seven other clinical conditions investigated in three trials or more: smoking, dementia, depression, obesity, hypertension, insomnia and anxiety, but confidence intervals were wide. Meta-regression analyses showed that larger effects of placebo interventions were associated with physical placebo interventions (e.g. sham acupuncture), patient-involved outcomes (patient-reported outcomes and observer-reported outcomes involving patient cooperation), small trials, and trials with the explicit purpose of studying placebo. Larger effects of placebo were also found in trials that did not inform patients about the possible placebo intervention.
AUTHORS' CONCLUSIONS: We did not find that placebo interventions have important clinical effects in general. However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting. The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important. Variations in the effect of placebo were partly explained by variations in how trials were conducted and how patients were informed.
- “Placebo effect studies are susceptible to response bias and to other types of biases,” Asbjørn Hróbjartsson, Ted J Kaptchuk, and Franklin G Miller, J Clin Epidemiol, 2011.
Specifically regarding Hróbjartsson 2010:
One article on PainScience.com cites Hróbjartsson 2010 as a source:
- PS Placebo Power Hype — The placebo effect is fascinating, but its “power” isn’t all it’s cracked up to be
This page is part of the PainScience BIBLIOGRAPHY, which contains plain language summaries of thousands of scientific papers & others sources. It’s like a highly specialized blog. A few highlights:
- Effectiveness of customised foot orthoses for Achilles tendinopathy: a randomised controlled trial. Munteanu 2015 Br J Sports Med.
- A Bayesian model-averaged meta-analysis of the power pose effect with informed and default priors: the case of felt power. Gronau 2017 Comprehensive Results in Social Psychology.
- The neck and headaches. Bogduk 2014 Neurol Clin.
- Agreement of self-reported items and clinically assessed nerve root involvement (or sciatica) in a primary care setting. Konstantinou 2012 Eur Spine J.
- Effect of NSAIDs on Recovery From Acute Skeletal Muscle Injury: A Systematic Review and Meta-analysis. Morelli 2017 Am J Sports Med.