Standardized mean differences cause funnel plot distortion in publication bias assessments

Author:

Zwetsloot Peter-Paul12,Van Der Naald Mira12,Sena Emily S3ORCID,Howells David W4,IntHout Joanna5,De Groot Joris AH6,Chamuleau Steven AJ127,MacLeod Malcolm R3ORCID,Wever Kimberley E8ORCID

Affiliation:

1. Cardiology, Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, Netherlands

2. Netherlands Heart Institute, Utrecht, Netherlands

3. Center for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom

4. School of Medicine, University of Tasmania, Hobart, Australia

5. Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands

6. Julius Center for Health Sciences and Primary care, University Medical Center Utrecht, Utrecht, Netherlands

7. Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, Netherlands

8. Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE), Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands

Abstract

Meta-analyses are increasingly used for synthesis of evidence from biomedical research, and often include an assessment of publication bias based on visual or analytical detection of asymmetry in funnel plots. We studied the influence of different normalisation approaches, sample size and intervention effects on funnel plot asymmetry, using empirical datasets and illustrative simulations. We found that funnel plots of the Standardized Mean Difference (SMD) plotted against the standard error (SE) are susceptible to distortion, leading to overestimation of the existence and extent of publication bias. Distortion was more severe when the primary studies had a small sample size and when an intervention effect was present. We show that using the Normalised Mean Difference measure as effect size (when possible), or plotting the SMD against a sample size-based precision estimate, are more reliable alternatives. We conclude that funnel plots using the SMD in combination with the SE are unsuitable for publication bias assessments and can lead to false-positive results.

Funder

National Institute of Environmental Health Sciences

Netherlands Cardiovascular Research Initiative

National Centre for the Replacement, Refinement and Reduction of Animals in Research

Alexander Suerman Program

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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