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Small studies are more heterogeneous than large ones: a meta-meta-analysis
Open accessAbstract
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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“but this is also influenced by unique patient characteristics, treatment techniques, and variability in measured outcomes.58”
From The Effect of Upper Cervical Mobilization/Manipulation on Temporomandibular Joint Pain, Maximal Mouth Opening, and Pressure Pain Thresholds: A Systematic Review and Meta-Analysis (2023) · cites this paper as [58]
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“This is due to the wide variety of study designs, the wide confidence intervals of individual studies, and the inclusion of low-weight studies, which can have a disproportionate effect on heterogeneity, especially in random-effects models [58].”
From Safety outcomes of statin vs non-statin lipid-lowering interventions in patients with prior statin-associated muscle symptoms: A systematic review and meta-analysis (2025) · cites this paper as [58]
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“[11] argued that underpowered studies are prone to several analytical and reporting biases.”
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Metadata
- 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
- Venue
- Journal of Clinical Epidemiology
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 68
- Issue
- 8
- Pages
- 860-869
- ISSN
- 0895-4356 (ISSN-L)
- 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
- 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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