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A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis

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Puhan, M. A., Schunemann, H. J., Murad, M. H., Li, T., Brignardello-Petersen, R., Singh, J. A., Kessels, A. G., Guyatt, G. H., for the GRADE Working Group·2014·BMJ

DOI 10.1136/bmj.g5630

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Abstract

Network meta-analysis (NMA), combining direct and indirect comparisons, is increasingly being used to examine the comparative effectiveness of medical interventions. Minimal guidance exists on how to rate the quality of evidence supporting treatment effect estimates obtained from NMA. We present a four-step approach to rate the quality of evidence in each of the direct, indirect, and NMA estimates based on methods developed by the GRADE working group. Using an example of a published NMA, we show that the quality of evidence supporting NMA estimates varies from high to very low across comparisons, and that quality ratings given to a whole network are uninformative and likely to mislead.

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GRADE guidelines: 3. Rating the quality of evidence
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“The quality of each included study was evaluated in duplicate using the Cochrane Risk of Bias tool, and the Cochrane Confidence in Network Meta-Analysis (CINeMA) tool was used for the risk of bias assessment specific to NMAs [18, 46].”
Method
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Miroshnychenko, A., Ibrahim, S., Azab, M., Roldán, Y., Martinez, J. P. D., Tamilselvan, D., He, L., Little, J. W., Urquhart, O., Tampi, M. P., et al. (2023) · Journal of Dental Research · doi:10.1177/00220345221139230 · Cited by 57
“Appendix Figures 1 to 21.6 and Appendix Tables 12 to 28 include network plots and forest plots of pairwise meta-analyses for all outcomes, as well as detailed relative and absolute effect estimates from the NMAs and the certainty of evidence for all comparisons and outcomes.”
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MethodInfluential
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Method
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“Cochrane Database of Systematic Reviews guidelines (Brignardello-Petersen 2018; Brignardello-Petersen 2019a; Brignardello-Petersen 2019b; Puhan 2014).”
Method
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“the quality of evidence in each of the direct, indirect and NMA estimates.(22) The rating of indirect estimates starts”
BackgroundSelf-citation
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“In contrast, the GRADE system somewhat simplistically focuses on the most influential path of length 2, along with the direct evidence (28,29).”
Background
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“Direct comparisons (number of studies) CCTA vs Exercise ECG (1) CCTA vs SPECT-MPI (2) CCTA vs Standard care (7) CMR vs Standard care (2) Exercise ECG vs Standard care (1) Exercise ECG vs Stress Echo (4) SPECT-MPI vs Standard care (2) Standard care vs Stress Echo (1)”
BackgroundMethodInfluential
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Self-citation
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“Recently, two methods to extend the GRADE framework to NMA have been proposed (Puhan et al. , 2014; Salanti et al. , 2014).”
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“In addition, we used the GRADE guideline to assess the certainty of the evidence for each outcome as high, moderate, low, or very low [22,23].”
Method
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Self-citation
Efficacy and Safety of Oral Premedication on Pain after Nonsurgical Root Canal Treatment: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials
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Comparative effectiveness of hyaluronic acid, platelet-rich plasma, and platelet-rich fibrin in treating temporomandibular disorders: a systematic review and network meta-analysis
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“Finally, to evaluate the evidence quality, the GRADE system was adopted according to the results of the above network meta-analysis [29].”
Method
Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension
Jain, S., Khera, R., Girotra, S. R., Badesch, D. B., Wang, Z., Murad, M. H., Blevins, A., Schmidt, G. A., Singh, S., & Gerke, A. K. (2016) · CHEST Journal · doi:10.1016/j.chest.2016.08.1461 · Cited by 47
“Galie(33)/2008 (ARIES 2) 50 (16) 51 (14) 81 68 65 35 65 36 355 (84) 343 (86) 2 44 52 2 3 37 57 3 None NA NA”
Self-citation
Efficacy and Safety of Antibiotic Therapy in Early Cutaneous Lyme Borreliosis
Torbahn, G., Hofmann, H., Rücker, G., Bischoff, K., Freitag, M., Dersch, R. S., Fingerle, V., Motschall, E., Meerpohl, J. J., & Schmucker, C. M. (2018) · JAMA Dermatology · doi:10.1001/jamadermatol.2018.3186 · Cited by 46
Efficacy of complementary and integrative medicine on health-related quality of life in cancer patients: a systematic review and meta-analysis
Lin, W., Zhong, M., Zhou, Q.-H., Zhang, Y.-R., Wang, H., Zhao, Z., Cheng, B., & Ling, C. (2019) · Cancer Management and Research · doi:10.2147/cmar.s195935 · Cited by 46
“Quality of evidence We assessed the quality of evidence of estimates derived from network meta-analysis using the GRADE methodology.(12,19) For direct comparisons in this system, RCTs start at high quality and may be downgraded to levels of moderate, low, and very low quality owing to heterogeneity, risk of bias, indi…”
Method

Authors: Puhan, M. A., Schunemann, H. J., Murad, M. H., Li, T., Brignardello-Petersen, R., Singh, J. A., Kessels, A. G., Guyatt, G. H., & for the GRADE Working Group
Affiliations: University of Zurich (CH)
Mayo Clinic (US)
Johns Hopkins University (US)
University of Alabama (US)
Maastricht University (NL)
McMaster University (CA)
Corresponding author: Puhan, M. A.
ORCID: Puhan, M. A.
Murad, M. H.
Li, T.
Singh, J. A.
Guyatt, G. H.
Venue: BMJ
Publisher: BMJ
Published: 2014-09-24
Volume: 349
Issue: sep24 5
Pages: g5630-g5630
ISSN: 1756-1833 (ISSN-L)
DOI: 10.1136/bmj.g5630
OpenAlex: W2155798268
Cited by: 1,812
References: 39
Citations by year: 2026: 160 · 2025: 177 · 2024: 216 · 2023: 175 · 2022: 205 · 2021: 276 · 2020: 201 · 2019: 128 · 2018: 96 · 2017: 72 · 2016: 63 · 2015: 36 · 2014: 4
FWCI: 57.15
Type: journal article
Language: en
Update notices: correction (2015-06-17)
Open access: bronze
doi.org
Locations: BMJ (publishedVersion)
PubMed (publishedVersion)
Research Publications (Maastricht University) (publishedVersion, other-oa)
Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
HighWire Press Open Archive (submittedVersion)
Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
Research Publications (Maastricht University) (submittedVersion, other-oa)
Zurich Open Repository and Archive (University of Zurich)
Topics: Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
Social Sciences › Sociology and Political Science › Delphi Technique in Research
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Clinical practice guidelines implementation
Keywords: network meta-analysis, quality of evidence, GRADE, treatment effect estimates, comparative effectiveness
MeSH terms: Humans, Quality Assurance, Health Care, Meta-Analysis as Topic, Practice Guidelines as Topic, Evidence-Based Medicine, Guideline Adherence

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A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis

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