Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study.
OBJECTIVE
To examine the presence and extent of small study effects in clinical osteoarthritis research.


METHODS
Meta-epidemiological study.


METHODS
13 meta-analyses including 153 randomised trials (41 605 patients) that compared therapeutic interventions with placebo or non-intervention control in patients with osteoarthritis of the hip or knee and used patients' reported pain as an outcome.


METHODS
We compared estimated benefits of treatment between large trials (at least 100 patients per arm) and small trials, explored funnel plots supplemented with lines of predicted effects and contours of significance, and used three approaches to estimate treatment effects: meta-analyses including all trials irrespective of sample size, meta-analyses restricted to large trials, and treatment effects predicted for large trials.


RESULTS
On average, treatment effects were more beneficial in small than in large trials (difference in effect sizes -0.21, 95% confidence interval -0.34 to -0.08, P=0.001). Depending on criteria used, six to eight funnel plots indicated small study effects. In six of 13 meta-analyses, the overall pooled estimate suggested a clinically relevant, significant benefit of treatment, whereas analyses restricted to large trials and predicted effects in large trials yielded smaller non-significant estimates.


CONCLUSIONS
Small study effects can often distort results of meta-analyses. The influence of small trials on estimated treatment effects should be routinely assessed.
Nüesch
Eveline
E
Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland.
Trelle
Sven
S
Reichenbach
Stephan
S
Rutjes
Anne W S
AW
Tschannen
Beatrice
B
Altman
Douglas G
DG
Egger
Matthias
M
Jüni
Peter
P
D006801:Humans; D015207:Osteoarthritis, Hip / Q000628:therapy*; D020370:Osteoarthritis, Knee / Q000628:therapy*; D010146:Pain / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D018401:Sample Size; D016896:Treatment Outcome