Placebo treatment versus no treatment.
BACKGROUND
Placebo interventions are often believed to improve patient reported and observer reported outcomes, but this belief is not based on evidence from randomised trials that compare placebo with no treatment.


OBJECTIVE
To assess the effect of placebo interventions.


METHODS
We searched the Cochrane Controlled Trials Register (The Cochrane Library, issue 3, 1998), MEDLINE (Jan 1966 to Dec 1998), EMBASE (Jan 1980 to Dec 1998), Biological Abstracts (Jan 1986 to Dec 1998), PsycLIT (Jan 1887 to Dec 1998). Experts on placebo research were contacted and references in the included trials were read.


METHODS
Randomised placebo trials with a no-treatment control group investigating any health problem were included.


METHODS
Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information.


RESULTS
Outcome data were available in 114 out of 130 included trials, investigating 40 clinical conditions. Outcomes were binary in 32 trials (3795 patients) and continuous in 82 (4730 patients). We found no statistically significant pooled effect of placebo in studies with binary outcomes, relative risk 0.95 (95 per cent confidence interval 0.88 to 1.02). The pooled relative risk for subjective (patient reported) outcomes was 0.95 (0.86 to 1.05) and for objective (observer reported) outcomes 0.91 (0.80 to 1.04). There was statistically significant heterogeneity (P < 0.03), but no evidence of sample size bias (P = 0.56). We found an overall positive effect of placebo treatments in trials with continuous outcomes, standardised mean difference -0.28 (95 per cent confidence interval -0.38 to -0.19). The standardised mean difference for subjective outcomes was -0.36 (-0.47 to -0.25), whereas no statistically significant effect was found for objective outcomes, standardised mean difference -0.12 (-0.27 to 0.03). There was statistically significant heterogeneity (P < 0.001), and evidence of sample size bias (P = 0.05). There was no statistically significant effect of placebo interventions in eight out of nine clinical conditions investigated in three trials or more (nausea, relapse in prevention of smoking and depression, overweight, asthma, hypertension, insomnia and anxiety), but confidence intervals were wide. There was a modest apparent analgesic effect of placebo interventions, standardised mean difference -0.27 (-0.40 to -0.15), but also a substantial risk of bias.


CONCLUSIONS
There was no evidence that placebo interventions in general have clinically important effects. A possible moderate effect on subjective continuous outcomes, especially pain, could not be clearly distinguished from bias.
Hróbjartsson
A
A
The Nordic Cochrane Centre, Rigshospitalet, Department 7112, Blegdamsvej 9, Copenhagen Ø, Denmark, DK-2100. a.hrobjartsson@cochrane.dk
Gøtzsche
P C
PC
D006801:Humans; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic; D016079:Refusal to Treat; D016896:Treatment Outcome