Why meta-analysis can mislead: when the highest level of evidence fails in evidence-based medicine
DOI:
https://doi.org/10.17267/2675-021Xevidence.2026.e6898Keywords:
Evidence-Based Medicine, Meta-Analysis, Bias, Reproducibility of Results, Clinical Decision-MakingAbstract
CONTEXT: Meta-analysis is widely positioned at the apex of the evidence hierarchy in evidence-based medicine (EBM), often serving as the foundation for clinical guidelines, policy decisions, and therapeutic recommendations. Their quantitative nature conveys an appearance of precision and objectivity that reinforces their authority in clinical reasoning. However, this perceived robustness may obscure important methodological and epistemological limitations. CONCEPTUALIZATION: This article critically examines the conditions under which meta-analysis may produce misleading inferences. We argue that the aggregation of evidence does not inherently generate validity, particularly in the presence of heterogeneity, publication bias, and variable study quality. By exploring structural limitations, including analytical flexibility, amplification of bias, and the misinterpretation of statistical significance, we demonstrate how meta-analysis can create an illusion of certainty. Rather than resolving uncertainty, they may repack it into quantitatively precise but conceptually fragile estimates. We propose that meta-analysis should be interpreted as conditional and context-dependent constructs, whose validity depends on rigorous methodological scrutiny and epistemological awareness. Reframing their role within EBM is essential to prevent overreliance and to promote more critical, responsible clinical decision-making.
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1. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn’t. BMJ. 1996;312(7023):71–2. https://doi.org/10.1136/bmj.312.7023.71
2. Guyatt G, Rennie D, Meade MO, Cook DJ. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. 3rd ed. New York: McGraw-Hill Professional Publishing; 2015.
3. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane Handbook for Systematic Reviews of Interventions. 2nd ed. Chichester: John Wiley & Sons; 2019.
4. Greenland S, Senn SJ, Rothman KJ, et al. Statistical tests, P values, confidence intervals, and power. Eur J Epidemiol. 2016;31(4):337–50. https://doi.org/10.1007/s10654-016-0149-3
5. Ioannidis JPA. Why most published research findings are false. PLoS Med. 2005;2(8):e124. https://doi.org/10.1371/journal.pmed.0020124
6. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to Meta-Analysis. Chichester: John Wiley & Sons; 2009.
7. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34. https://doi.org/10.1136/bmj.315.7109.629
8. Sterne J A C, Sutton A J, Ioannidis J P A, Terrin N, Jones D R, Lau J, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011;343:d4002. https://doi.org/10.1136/bmj.d4002
9. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and Its Influence on Apparent Efficacy. N Engl J Med. 2008;358(3):252–60. https://doi.org/10.1056/NEJMsa065779
10. Turner RM, Bird SM, Higgins JPT. The impact of study size on Meta-analyses: Examination of Underpowered Studies in Cochrane Reviews. Plos One. 2013;8(3):e59202. https://doi.org/10.1371/journal.pone.0059202
11. Nissen SE, Wolski K. Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes. N Engl J Med. 2007;356(24):2457–71. https://doi.org/10.1056/NEJMoa072761
12. Diamond GA, Bax L, Kaul S. Uncertain effects of rosiglitazone on the risk for myocardial infarction and cardiovascular death. Ann Intern Med. 2007;147(8):578–81. https://doi.org/10.7326/0003-4819-147-8-200710160-00182
13. Simmons JP, Nelson LD, Simonsohn U. False-Positive Psychology: Undisclosed Flexibility in Data Collection and Analysis Allows Presenting Anything as Significant. Psychol Sci. 2011;22(11):1359–66. https://doi.org/10.1177/0956797611417632
14. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. https://doi.org/10.1136/bmj.n71
15. Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358:j4008. https://doi.org/10.1136/bmj.j4008
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Copyright (c) 2026 Guilherme Rodrigues Oliveira, Isabela Martins Vecchi

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