Cited by 559Meta-analysis and systematic reviewsStatistical Methods in Clinical TrialsStatistical Methods in Epidemiology

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Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study

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Nuesch, E., Trelle, S., Reichenbach, S., Rutjes, A. W. S., Tschannen, B., Altman, D. G., Egger, M., Juni, P.·2010·BMJ

DOI 10.1136/bmj.c3515PMC PMC2905513

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Abstract

OBJECTIVE: To examine the presence and extent of small study effects in clinical osteoarthritis research. DESIGN: Meta-epidemiological study. DATA SOURCES: 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.

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Fig 1 Difference in effect sizes between 95 small trials with fewer than 100 patients per arm and 58 large trials. Negative differences indicate that small trials show more beneficial treatment effects. P values are for interaction between sample size and effect sizes. NSAIDs=non-steroidal anti-inflammatory drugsCC BY-NC · PubMed Central

Fig 2 Funnel plots of 13 included meta-analyses including prediction lines from univariable meta-regression models with SE as explanatory variable (dashed red) and 5% contour areas to display areas of significance (blue) and non-significance (pale blue). Lines for predicted effects should be interpreted independently of contours delineated by shaded areas. Extent of deviation of lines for predicted effects from vertical line should be considered, irrespective of relation of lines to contours. P values derived from regression tests for asymmetry. NSAIDs=non-steroidal anti-inflammatory drugsCC BY-NC · PubMed Central

Fig 3 Results of individual random effects meta-analyses of all trials (blue circle), results of random effects meta-analyses restricted to large trials with at least 100 patients per arm (open circle), and effect sizes for trials with SE of 0.1 predicted from random effects meta-regression models (green square). NSAIDs=non-steroidal anti-inflammatory drugsCC BY-NC · PubMed Central

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Authors: Nuesch, E., Trelle, S., Reichenbach, S., Rutjes, A. W. S., Tschannen, B., Altman, D. G., Egger, M., & Juni, P.
Affiliations: University of Bern (CH)
University of Oxford (GB)
ORCID: Trelle, S.
Reichenbach, S.
Rutjes, A. W. S.
Altman, D. G.
Egger, M.
Venue: BMJ
Publisher: BMJ
Published: 2010-07-16
Volume: 341
Issue: jul16 1
Pages: c3515-c3515
ISSN: 0007-1447 (ISSN-L)
0959-8138
1468-5833
DOI: 10.1136/bmj.c3515
PMC: PMC2905513
OpenAlex: W2063738853
Cited by: 559
References: 62
Citations by year: 2026: 13 · 2025: 28 · 2024: 28 · 2023: 15 · 2022: 25 · 2021: 27 · 2020: 22 · 2019: 41 · 2018: 43 · 2017: 63 · 2016: 59 · 2015: 48 · 2014: 47 · 2013: 44 · 2012: 28
FWCI: 32.52
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: BMJ (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by-nc)
BORIS (University Library Bern) (submittedVersion, cc-by-nc)
Open Access CRIS of the University of Bern
Funders: National Science Foundation
Cancer Research UK
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (115067, 104762, 66377, 066377, 66378)
Topics: Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
Keywords: small-study effects, osteoarthritis, hip osteoarthritis, knee osteoarthritis, meta-epidemiology, trial size, treatment effect estimation, pain outcomes, funnel plot, publication bias
MeSH terms: Humans, Pain, Osteoarthritis, Hip, Randomized Controlled Trials as Topic, Treatment Outcome, Sample Size, Osteoarthritis, Knee

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Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study

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