Cited by 314Meta-analysis and systematic reviewsStatistical Methods in Clinical TrialsDelphi Technique in Research

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Small studies are more heterogeneous than large ones: a meta-meta-analysis

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IntHout, Joanna, Ioannidis, John P.A., Borm, George F., Goeman, Jelle J.·2015·Journal of Clinical Epidemiology

DOI 10.1016/j.jclinepi.2015.03.017

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Abstract

Objectives Between-study heterogeneity plays an important role in random-effects models for meta-analysis. Most clinical trials are small, and small trials are often associated with larger effect sizes. We empirically evaluated whether there is also a relationship between trial size and heterogeneity (τ). Study design and setting We selected the first meta-analysis per intervention review of the Cochrane Database of Systematic Reviews Issues 2009-2013 with a dichotomous (n = 2,009) or continuous (n = 1,254) outcome. The association between estimated τ and trial size was evaluated across meta-analyses using regression and within meta-analyses using a Bayesian approach. Small trials were predefined as those having standard errors (SEs) over 0.2 standardized effects. Results Most meta-analyses were based on few (median 4) trials. Within the same meta-analysis, the small study τS(2) was larger than the large-study τL(2) [average ratio 2.11; 95% credible interval (1.05, 3.87) for dichotomous and 3.11 (2.00, 4.78) for continuous meta-analyses]. The imprecision of τS was larger than of τL: median SE 0.39 vs. 0.20 for dichotomous and 0.22 vs. 0.13 for continuous small-study and large-study meta-analyses. Conclusion Heterogeneity between small studies is larger than between larger studies. The large imprecision with which τ is estimated in a typical small-studies' meta-analysis is another reason for concern, and sensitivity analyses are recommended.

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Additional file 2 of Diabetic dyslipidemia and its predictors among people with diabetes in Ethiopia: systematic review and meta-analysis
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Additional file 3 of Diabetic dyslipidemia and its predictors among people with diabetes in Ethiopia: systematic review and meta-analysis
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Additional file 1 of Classifying information-sharing methods
Nikolaidis, G. F., Woods, B., Palmer, S., & Soares, M. O. (2021) · Figshare · doi:10.6084/m9.figshare.14650907
Additional file 2 of Classifying information-sharing methods
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Additional file 2 of Influence of pilot and small trials in meta-analyses of behavioral interventions: a meta-epidemiological study
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Self-citation
Additional file 1 of Influence of pilot and small trials in meta-analyses of behavioral interventions: a meta-epidemiological study
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Additional file 1 of Diabetic dyslipidemia and its predictors among people with diabetes in Ethiopia: systematic review and meta-analysis
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Additional file 1 of The effect of zinc supplementation on anthropometric measurements in healthy children over two years: a systematic review and meta-analysis
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Additional file 5 of Quality of life of pediatric and adult individuals with osteogenesis imperfecta: a meta-analysis
Wehrli, S., Rohrbach, M., & Landolt, M. A. (2024) · Figshare · doi:10.6084/m9.figshare.26591546
Additional file 1 of Association between constipation and the development of asthma: a meta-analysis
Liu, L., Zhang, X., Jiang, Z., Wang, G., Wu, H., Chen, R., Zhang, Y., Li, M., & Yang, S. (2022) · Figshare · doi:10.6084/m9.figshare.20454593
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Modifiable methodological and reporting practices are associated with reproducibility of health sciences research: a systematic review and evidence and gap map
Kennett, J., Moss, S. J., Leigh, J. P., Bobrovitz, N., & Stelfox, H. T. (2026) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2026.112135 · Cited by 1

Authors: IntHout, J., Ioannidis, J. P. A., Borm, G. F., & Goeman, J. J.
Affiliations: Radboud University Medical Center (NL)
Stanford Medicine (US)
Corresponding author: IntHout, Joanna
ORCID: IntHout, Joanna
Ioannidis, John P.A.
Goeman, Jelle J.
Venue: Journal of Clinical Epidemiology
Publisher: Elsevier BV
Published: 2015-08
Volume: 68
Issue: 8
Pages: 860-869
ISSN: 0895-4356 (ISSN-L)
DOI: 10.1016/j.jclinepi.2015.03.017
OpenAlex: W1973158091
Cited by: 314
References: 42
Citations by year: 2026: 33 · 2025: 37 · 2024: 40 · 2023: 36 · 2022: 38 · 2021: 37 · 2020: 26 · 2019: 23 · 2018: 21 · 2017: 10 · 2016: 7 · 2015: 4
FWCI: 2.33
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 325 d)
Locations: Journal of Clinical Epidemiology (publishedVersion)
PubMed (publishedVersion)
Radboud Repository (Radboud University) (submittedVersion)
Radboud Repository (Radboud University) (submittedVersion, other-oa)
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
Social Sciences › Sociology and Political Science › Delphi Technique in Research
Keywords: study heterogeneity, small-study effects, trial size, random effects models, meta-analysis, sensitivity analysis, meta-meta-analysis
MeSH terms: Bayes Theorem, Clinical Trials as Topic, Epidemiologic Methods, Humans, Models, Theoretical, Research Design

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Small studies are more heterogeneous than large ones: a meta-meta-analysis

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