Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment
Four pages on PainSci cite Hróbjartsson 2004: 1. Placebo Power Hype 2. Can the mind create pain? (Member Post) 3. Placebo paradoxes pacified (Member Post) 4. A new placebo analgesia review
PainSci notes on Hróbjartsson 2004:
This paper was the first widely discussed challenge to the claim that placebo is “powerful” (starting with the first version in 2001, see Hróbjartsson, which followed a more obscure paper by Kienle in 1997). Hróbjartsson and Gøtzsche “found little evidence in general that placebos had powerful clinical effects” and concluded that there is “no justification for the use of placebos” outside clinical trials. The topic has been hotly debated ever since, but few experts still believe that placebo is “powerful.”
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: It is widely believed that placebo interventions induce powerful effects. We could not confirm this in a systematic review of 114 randomized trials that compared placebo-treated with untreated patients.
AIM: To study whether a new sample of trials would reproduce our earlier findings, and to update the review.
METHODS: Systematic review of trials that were published since our last search (or not previously identified), and of all available trials.
RESULTS: Data was available in 42 out of 52 new trials (3212 patients). The results were similar to our previous findings. The updated review summarizes data from 156 trials (11 737 patients). We found no statistically significant pooled effect in 38 trials with binary outcomes, relative risk 0.95 (95% confidence interval 0.89-1.01). The effect on continuous outcomes decreased with increasing sample size, and there was considerable variation in effect also between large trials; the effect estimates should therefore be interpreted cautiously. If this bias is disregarded, the pooled standardized mean difference in 118 trials with continuous outcomes was -0.24 (-0.31 to -0.17). For trials with patient-reported outcomes the effect was -0.30 (-0.38 to -0.21), but only -0.10 (-0.20 to 0.01) for trials with observer-reported outcomes. Of 10 clinical conditions investigated in three trials or more, placebo had a statistically significant pooled effect only on pain or phobia on continuous scales.
CONCLUSION: We found no evidence of a generally large effect of placebo interventions. A possible small effect on patient-reported continuous outcomes, especially pain, could not be clearly distinguished from bias.
related content
- “The powerful placebo,” Beecher, J Am Med Assoc, 1955.
- “The powerful placebo effect: fact or fiction?,” Kienle et al, J Clin Epidemiol, 1997.
- “Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment,” Hróbjartsson et al, New England Journal of Medicine, 2001.
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:
- Topical glyceryl trinitrate (GTN) and eccentric exercises in the treatment of mid-portion achilles tendinopathy (the NEAT trial): a randomised double-blind placebo-controlled trial. Kirwan 2024 Br J Sports Med.
- Placebo analgesia in physical and psychological interventions: Systematic review and meta-analysis of three-armed trials. Hohenschurz-Schmidt 2024 Eur J Pain.
- Recovery trajectories in common musculoskeletal complaints by diagnosis contra prognostic phenotypes. Aasdahl 2021 BMC Musculoskelet Disord.
- Cannabidiol (CBD) products for pain: ineffective, expensive, and with potential harms. Moore 2023 J Pain.
- Moderators of the effect of therapeutic exercise for knee and hip osteoarthritis: a systematic review and individual participant data meta-analysis. Holden 2023 The Lancet Rheumatology.