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Empirical evaluation of fundamental principles of evidence-based medicine: a meta-epidemiological study
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  • Benjamin Djulbegovic,
  • Muhammad Muneeb Ahmed,
  • Iztok Hozo,
  • Despina Koletsi,
  • Lars Hemkens,
  • Amy Price,
  • Rachel Riera,
  • Paulo Nadanovsky,
  • Ana Paula Pires dos Santos,
  • Daniela Melo,
  • Ranjan Pathak,
  • Rafael Pacheco,
  • Luis Fontes,
  • David Nunan
Benjamin Djulbegovic
City of Hope National Medical Center

Corresponding Author:[email protected]

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Muhammad Muneeb Ahmed
McMaster University Michael G DeGroote School of Medicine
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Iztok Hozo
Indiana University Northwest
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Despina Koletsi
Department of Orthodontics, School of Dentistry, University of Athens
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Lars Hemkens
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Rachel Riera
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Paulo Nadanovsky
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Ana Paula Pires dos Santos
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Daniela Melo
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Ranjan Pathak
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Rafael Pacheco
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Luis Fontes
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David Nunan
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Rationale, aims and objectives 39 Evidence-based medicine (EBM) holds that estimates of effects of health interventions based on 40 high-certainty evidence (CoE) are expected to change less frequently than the effects generated 41 in low CoE studies. However, this foundational principle of EBM has never been empirically 42 tested. 43 Methods 44 We reviewed all systematic reviews and meta-analyses in Cochrane Database of Systematic 45 Reviews from January 2016 through May 2021 (n=3,323). We identified 414(207x2) and 384 46 (192x2) pairs of original and updated Cochrane reviews that assessed CoE and pooled 47 treatment effect estimates. We appraised CoE using the Grading of Recommendations 48 Assessment, Development and Evaluation (GRADE) method. We assessed the difference in 49 effect sizes between the original versus updated reviews as a function of change in CoE, which 50 we report as a ratio of odds ratio (ROR). We compared ROR generated in the studies that 51 changed CoE from very low/low (VL/L) to moderate/high (M/H) vs. MH/H VL/L. We also 52 assessed the heterogeneity and inconsistency (using the tau and I2 statistic), the change in 53 precision of effect estimates (by calculating the ratio of standard errors) (seR), and the absolute 54 deviation in estimates of treatment effects (aROR). 55 Results 56 57 We found that CoE originally appraised as VL/L had 2.1 (95%CI: 1.19 to 4.12; p=0.0091) times 58 higher odds to be changed in the future studies than M/H CoE. However, the effect size was not 59 different when CoE changed from VL/L M/H vs. M/H VL/L [ROR=1.02 (95%CI: 0.74 to 1.39) 60 vs. 1.02 (95%CI: 0.44 to 2.37); p=1 for the between subgroup differences]. aROR was similar 61 between the subgroups [median (IQR):1.12 (1.07 to 1.57) vs 1.21 (1.12 to 2.43)]. We observed 62 large inconsistency (I 2=99%) and imprecision in treatment effects (seR=1.09). 63 Conclusions 64 We provide the first empirical support for a foundational principle of EBM showing that low65 quality evidence changes more often than high CoE. However, the effect size was not different 66 between studies with low vs high CoE. The finding that the effect size did not differ between low 67 and high CoE indicate urgent need to refine current EBM critical appraisal methods
28 Nov 2021Submitted to Journal of Evaluation in Clinical Practice
30 Nov 2021Submission Checks Completed
30 Nov 2021Assigned to Editor
30 Nov 2021Reviewer(s) Assigned
16 Dec 2021Review(s) Completed, Editorial Evaluation Pending
16 Dec 2021Editorial Decision: Revise Minor
18 Dec 20211st Revision Received
23 Dec 2021Submission Checks Completed
23 Dec 2021Assigned to Editor
03 Jan 2022Review(s) Completed, Editorial Evaluation Pending
03 Jan 2022Editorial Decision: Accept