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The appropriateness of asymmetry tests for publication bias in meta-analyses: a large survey
Open accessAbstract
BACKGROUND: Statistical tests for funnel-plot asymmetry are common in meta-analyses. Inappropriate application can generate misleading inferences about publication bias. We aimed to measure, in a survey of meta-analyses, how frequently the application of these tests would be not meaningful or inappropriate. METHODS: We evaluated all meta-analyses of binary outcomes with é 3 studies in the Cochrane Database of Systematic Reviews (2003, issue 2). A separate, restricted analysis was confined to the largest meta-analysis in each of the review articles. In each meta-analysis, we assessed whether criteria to apply asymmetry tests were met: no significant heterogeneity, I2 < 50%, é 10 studies (with statistically significant results in at least 1) and ratio of the maximal to minimal variance across studies > 4. We performed a correlation and 2 regression asymmetry tests and evaluated their concordance. Finally, we sampled 60 meta-analyses from print journals in 2005 that cited use of the standard regression test. RESULTS: A total of 366 of 6873 (5%) and 98 of 846 meta-analyses (12%) in the wider and restricted Cochrane data set, respectively, would have qualified for use of asymmetry tests. Asymmetry test results were significant in 7%-18% of the meta-analyses. Concordance between the 3 tests was modest (estimated k 0.33-0.66). Of the 60 journal meta-analyses, 7 (12%) would qualify for asymmetry tests; all 11 claims for identification of publication bias were made in the face of large and significant heterogeneity. INTERPRETATION: Statistical conditions for employing asymmetry tests for publication bias are absent from most meta-analyses; yet, in medical journals these tests are performed often and interpreted erroneously.
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“However, publication bias tests might be problematic for IN-OT studies due to small sample sizes resulting in insufficient statistical power and sample size variability for the tests to yield reliable and significant results (26).”
From Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies (2016) · cites this paper as [26]
Experimental — accuracy not yet measuredIn the citing paper
“The small number of studies and presence of significant heterogeneity precluded formal testing for publication bias[35].”
From Daily Sitting Time and All-Cause Mortality: A Meta-Analysis (2013) · cites this paper as [35]
In the citing paper
“Of 60 meta-analyses in 24 articles published in 2005 in which formal assessments were reported, most were based on fewer than ten studies; most displayed statistically significant heterogeneity; and many reviewers misinterpreted the results of the tests employed [123].”
From The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration (2009) · cites this paper as [123]
In the citing paper
“Although evidence that smaller studies had larger estimated effects than large ones may suggest the possibility that the available evidence is biased, misinterpretation of such data is common [123].”
From The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration (2009) · cites this paper as [123]
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“Assessment of small-study effects or publication bias (e.g., funnel plot asymmetry) was not performed because the number of studies per meta-analysis was below the recommended threshold (k 10) [36].”
Sun, M., Yu, C., Zeng, Z., Song, Y., Ji, F., Liu, Y., Peng, S., Liu, B., Wang, R., & Wu, S. (2026) · Frontiers in Reproductive Health · doi:10.3389/frph.2026.1735652 · Cited by 1
“Because of the small number of studies included in each analysis ( 5), funnel plots and Egger’s test were considered unreliable for assessing publication bias (15).”
Hu, Y., Liu, Y., Li, W., & Wang, Y. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1807826 · Cited by 1
“Therefore, selective non-publication and small study effects cannot be excluded and should be regarded as additional sources of uncertainty when interpreting the pooled estimates (40).”
Golpasand, S., Hossein‐Zadeh, N. G., & Ghovvati, S. (2026) · PLoS ONE · doi:10.1371/journal.pone.0344752 · Cited by 2
Kyrkili, A., Saltaouras, G., Bountziouka, V., Bathrellou, E., Georgoulis, M., Yannakoulia, M., Charmandari, E., Dimitrakopoulos, G., & Kontogianni, M. D. (2026) · Nutrition Reviews · doi:10.1093/nutrit/nuag079 · Cited by 1
Determinants and associated factors for hallux valgus: a systematic review and meta-analysis
Zhang, G., Ma, Y., & Zhang, S. (2026) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-026-10054-1 · Cited by 1
“Following the recommendations of the Cochrane Handbook [29], assessment of publication bias was only performed for analyses or subgroups that included at least 10 studies to ensure adequate statistical power [30].”
Risk and Protective Factors for Suicide Mortality in Youths
Geoffroy, M., Baker‐Sullivan, E., Nitu, N. J., Civita, A., Boruff, J. T., Sinyor, M., Robinson, J., MacDonald, K., Anzarouth, L., Chartrand, E., et al. (2026) · JAMA Network Open · doi:10.1001/jamanetworkopen.2026.21622 · Cited by 1
Tseng, L.-Y., & Tseng, K. C. (2026) · International Journal for Quality in Health Care · doi:10.1093/intqhc/mzag151 · Cited by 1
Lee, M.-S., Flammer, A. J., & Lerman, A. (2013) · Korean Circulation Journal · doi:10.4070/kcj.2013.43.7.443 · Cited by 1
A short note on detection of and adjusting for publication bias in meta‐analysis
Flammer, E. (2008) · Contemporary Hypnosis · doi:10.1002/ch.354 · Cited by 1
Pacilli, A., Prudente, S., Copetti, M., Fontana, A., Mercuri, L., Bacci, S., Marucci, A., Alberico, F., Viti, R., Palena, A. P., et al. (2016) · Endocrine · doi:10.1007/s12020-016-0906-9 · Cited by 1
Kunwar, S., Devkota, A. R., Ghimire, D. K. C., & Adhikari, P. (2017) · Drugs & Therapy Perspectives · doi:10.1007/s40267-017-0401-2 · Cited by 1
Matrix devices for healing foot ulcers in people with diabetes
Lev‐Tov, H. A., Dahle, S. E., McNamara, S., Margolis, D. J., & Isseroff, R. R. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013146 · Cited by 1
Chan, H., Lam, P. Y., Cheung, C. Y., Chow, K. T., Lau, C. H., Lee, K. Y., Po, S. Y., Askin, N., Rabbani, R., Zarychanski, R., et al. (2022) · European Journal of Physiotherapy · doi:10.1080/21679169.2022.2161628 · Cited by 1
“Publication bias was conducted if at least seven trials were included for an outcome using funnel plot techniques [17].”
MethodIwamoto, Y., Imura, T., Takahashi, M. K., & Tanaka, R. (2023) · PubMed Central · doi:10.18999/nagjms.85.2.275 · Cited by 1
Nath, A., Mathew, S., Pant, A., & Thadi, Y. (2024) · Journal of Diabetes & Metabolic Disorders · doi:10.1007/s40200-024-01471-x · Cited by 2
“The assessment of publication bias was not performed since, as a general guideline, tests for funnel plot asymmetry should only be applied when at least ten eligible studies are available for inclusion in the meta-analysis [15, 16 ].”
Biocontrol insects have stronger effects than non-biocontrol insects on plants
STILING, P. D., & Lajeunesse, M. J. (2025) · BioControl · doi:10.1007/s10526-025-10310-8 · Cited by 1
“1c), the composition of the effect sizes violated one of the four assumptions of the test (i.e., significant between-study heterogeneity: Q H = 1461.75, df = 339, p < 0.001; see Ioannidis and Trikalinos 2007).”
InfluentialMethodological Framework for Evaluation and Prevention of Publication Bias in Surgical Studies
Yakoub, D., Panesar, S. S., & Athanasiou, T. (2010) · Springer eBooks · doi:10.1007/978-3-540-71915-1_34 · Cited by 1
Khayatzadeh, S., Awat, F., Saneei, P., & Ahmad, E. (2015) · Cited by 1
Systematic Reviews and Meta-Analyses in Surgery
Panesar, S., Siow, W., & Athanasiou, T. (2010) · Springer eBooks · doi:10.1007/978-3-540-71915-1_30
Créquit, P., Yavchitz, A., Trinquart, L., Ravaud, P., & Cadranel, J. L. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012901 · Cited by 1
Gao, S., Wang, H., Zhou, C., Guan, M., Li, X., Dai, J., Zou, Y., & Fang, H. (2018) · Journal of Genetics · doi:10.1007/s12041-018-0966-0 · Cited by 1
Metadata
- Authors
- Ioannidis, J. P. A., & Trikalinos, T. A.
- Affiliations
- Tufts University (US)
- Venue
- Canadian Medical Association Journal
- Publisher
- CMA Joule Inc.
- Published
- 2007-04-10
- Volume
- 176
- Issue
- 8
- Pages
- 1091-1096
- ISSN
- 0820-3946 (ISSN-L)
- 1488-2329
- PMC
- PMC1839799
- OpenAlex
- W2164093802
- Cited by
- 1,052
- References
- 40
- Citations by year
- 2026: 49 · 2025: 48 · 2024: 64 · 2023: 49 · 2022: 81 · 2021: 73 · 2020: 83 · 2019: 81 · 2018: 73 · 2017: 55 · 2016: 62 · 2015: 64 · 2014: 68 · 2013: 38 · 2012: 39
- FWCI
- 31.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Canadian Medical Association Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Social Sciences › Library and Information Sciences › scientometrics and bibliometrics research
- Keywords
- publication bias, funnel plot asymmetry, meta-analysis, heterogeneity, Cochrane Database of Systematic Reviews, binary outcomes, test concordance
- MeSH terms
- Data Interpretation, Statistical, Humans, Periodicals as Topic, Meta-Analysis as Topic, Databases, Bibliographic, Publication Bias
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