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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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Tang, S., Ruan, Z., Ma, A., Wang, D., & Kou, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1063349 · Cited by 22
Characteristics of shunt failure in 38,095 adult shunt insertion surgeries: a systematic review and meta-analysis
Isaacs, A. M., Yang, R., Cadieux, M., Ben‐Israel, D., Sader, N., Opoku-Darko, M., Frizon, L. A., Yong, H. Y. F., Premji, Z., Nagel, S. J., et al. (2023) · Neurosurgical FOCUS · doi:10.3171/2023.1.focus22637 · Cited by 22
Single-balloon catheter with concomitant vaginal misoprostol is the most effective strategy for labor induction: a meta-review with network meta-analysis
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Single-Shot Regional Anesthesia for Bariatric Surgery: a Systematic Review and Network Meta-Analysis
CASSAI, A. D., Paganini, G., Pettenuzzo, T., Zarantonello, F., Boscolo, A., Tulgar, S., Carron, M., Munari, M., & Navalesi, P. (2023) · Obesity Surgery · doi:10.1007/s11695-023-06737-6 · Cited by 22
“We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach to assess the certainty of evidence related to each of the outcomes [10].”
Method
Comparison of the efficacy and safety of ciprofol and propofol in sedating patients in the operating room and outside the operating room: a meta-analysis and systematic review
Yang, Y., Lang, Z., Wang, X., Yang, P., Meng, N., Yang, X. H., & Liu, Y. (2024) · BMC Anesthesiology · doi:10.1186/s12871-024-02609-3 · Cited by 22
“Nevertheless, this level of evidence may be reduced based on limitations observed in five key aspects: risk of bias, consistency, indirectness, imprecision, and publication bias [10].”
Background
READY: relative efficacy of loop diuretics in patients with chronic systolic heart failure—a systematic review and network meta-analysis of randomised trials
Täger, T., Fröhlich, H., Seiz, M., Katus, H. A., & Frankenstein, L. (2019) · Heart Failure Reviews · doi:10.1007/s10741-019-09771-8 · Cited by 22
Efficacy of Treatments for Polycystic Ovarian Syndrome Management in Adolescents
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“Additionally, for network meta-analysis (NMA) the evidence can be rated down for intransitivity, and incoherence [27, 28].”
Background
Convolutional neural networks in the computer-aided diagnosis of Helicobacter pylori infection and non-causal comparison to physician endoscopists: a systematic review with meta-analysis
Mohan, B. P. (2020) · Annals of Gastroenterology · doi:10.20524/aog.2020.0542 · Cited by 22
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Wu, J., Wu, J., Tang, B., Zhang, Z., Wei, F., Yu, D., Li, L., Zhao, Y., Wang, B., Wu, W., et al. (2024) · Frontiers in Public Health · doi:10.3389/fpubh.2024.1373691 · Cited by 28
PROTOCOL: Deworming and adjuvant interventions for improving the developmental health and well-being of children in low-and middle-income countries: a systematic review and network meta-analysis
Welch, V. A., Awasthi, S., Cumberbatch, C., Fletcher, R. H., McGowan, J., Merritt, K., Krishnaratne, S., Sohani, S., Tugwell, P., & Wells, G. (2013) · Campbell Systematic Reviews · doi:10.1002/cl2.115 · Cited by 21
A systematic review and network meta-analysis of the comparative efficacy of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in hypertension
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“NMA was carried out with R version 3.3.3., using package “netmeta.””
BackgroundInfluential
Comparative effectiveness of conservative and pharmacological interventions for chronic non-specific neck pain
Pillastrini, P., Castellini, G., Chiarotto, A., Fasciani, F., Marzioni, F., Vanti, C., Bertozzi, L., & Gianola, S. (2019) · Medicine · doi:10.1097/md.0000000000016762 · Cited by 22
“We will use the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach to evaluate the quality of the body of evidence contributed to the network.([32,33]) We will appraise the GRADE domains (study limitations, indirectness, inconsistency, imprecision and publication bias).”
Method
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Fang, M., Liu, G., Luo, G., & Wu, T. (2019) · International Wound Journal · doi:10.1111/iwj.13224 · Cited by 21
“controlled trial (RCT) (74 cases),(40) and 4 non-randomised controlled trials (NRCTs) (574 cases),(41-44) describing a total of 20 868 patients (mean age, 36–56 years), derived from China (7), United States (6), Italy (5), Germany (5), Korea (2), Japan (2), Spain (1), Poland (1), France (1), United Arab Emirates (1),…”
Background
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Cho, Y., Choi, G. J., Ahn, E. J., & Kang, H. (2021) · PLoS ONE · doi:10.1371/journal.pone.0243865 · Cited by 22
Effect of rituximab dose on induction therapy in ABO-incompatible living kidney transplantation
Lee, H. R., Kim, K., Lee, S. W., Song, J. H., Lee, J. H., & Hwang, S. D. (2021) · Medicine · doi:10.1097/md.0000000000024853 · Cited by 21
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Du, Y., Biao, D., Diao, Y. P., Yin, Z., Li, J., Shu, Y., Zhang, Z., & Chen, L. (2021) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2021.102664 · Cited by 21
Comparative effectiveness of pharmacological interventions to prevent postoperative delirium: a network meta-analysis
Park, S.-K., Lim, T., Cho, H.-Y., Yoon, H., Lee, H., Lee, J., Yoo, S., Kim, J., & Kim, W. H. (2021) · Scientific Reports · doi:10.1038/s41598-021-91314-z · Cited by 23
Prognostic role of selection criteria for liver transplantation in patients with hepatocellular carcinoma: a network meta-analysis
Lozanovski, V. J., Ramouz, A., Aminizadeh, E., Ali‐Hasan‐Al‐Saegh, S., Khajeh, E., Probst, H., Picardi, S., Rupp, C., Chang, D., Probst, P., et al. (2021) · BJS Open · doi:10.1093/bjsopen/zrab130 · Cited by 20
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Wang, Y., Liu, W., Chen, J., Bai, J., Yu, H., Ma, H., Jiang, R., & Xu, G. (2023) · Therapeutic Advances in Chronic Disease · doi:10.1177/20406223231168754 · Cited by 22
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Kim, H., Choi, C. U., Rhew, K., Park, J., Lim, Y., Kim, M. G., & Kim, K. (2024) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2024.117490 · Cited by 21
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Moura, M. C., Novaes, M. R. C. G., Zago, Y. S. S. P., Eduardo, E. J., & Casulari, L. A. (2016) · Journal of Clinical Medicine Research · doi:10.14740/jocmr2495w · Cited by 21
“The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) model [12] was used to access the quality of the studies.”
Method
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Flórez, I. D., Khalifah, R. A. A., Sierra, J. M., Granados, C., Yepes-Núñez, J. J., Cuello‐García, C. A., Pérez‐Gaxiola, G., Zea, A. M., Hernández, G., Veroniki, A. A., et al. (2016) · Systematic Reviews · doi:10.1186/s13643-016-0186-8 · Cited by 23
“For this purpose, the GRADE approach recommends to assess the incoherence (or inconsistency as described in the “The network metaanalysis: the direct and the indirect evidence” section) criteria, which is defined as the differences between direct and indirect estimates of effect [54].”
InfluentialSelf-citation
Applying GRADE to a network meta-analysis of antidepressants led to more conservative conclusions
Bonner, A., Alexander, P. E., Brignardello‐Petersen, R., Furukawa, T. A., Siemieniuk, R. A. C., Zhang, Y., Wiercioch, W., Flórez, I. D., Fei, Y., Agarwal, A., et al. (2018) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2018.05.009 · Cited by 20
Self-citation
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Kim, D. K., Lee, J. Y., Jung, J. H., Hah, Y. S., Koo, K. C., Lee, K. S., Chung, B. H., & Cho, K. S. (2019) · Scientific Reports · doi:10.1038/s41598-019-41412-w · Cited by 21
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Systematic review with meta‐analysis: the gastrointestinal benefits of COX ‐2 selective inhibitors with concomitant use of low‐dose aspirin
Yuan, J.-Q., Yang, M. G., Threapleton, D. E., Qi, X., Ye, D., Mao, C., Tang, J.-L., & Higgins, J. P. T. (2016) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13776 · Cited by 21
“The strength of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system (GRADE).(26) The quality of evidence was graded as ‘High’, ‘Moderate’, ‘Low’ and ‘Very low’ based on the fundamental study design and additional methodological factors.”
BackgroundMethodInfluential
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Noori, A., Sadeghirad, B., Wang, L., Siemieniuk, R. A. C., Shokoohi, M., Kum, E., Jeddi, M., Montoya, L., Hong, P. J., Zhou, E., et al. (2022) · British Journal of Anaesthesia · doi:10.1016/j.bja.2022.05.031 · Cited by 19
Self-citation
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Sabeti, M. A., Ihsan, M. S., & Aminoshariae, A. (2023) · Journal of Endodontics · doi:10.1016/j.joen.2023.11.007 · Cited by 20
State-of-the-Art Reporting
Ōnishi, A., & Furukawa, T. A. (2016) · Springer eBooks · doi:10.1007/978-3-319-25655-9_13 · Cited by 20
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Cohen, A. T., Berger, S. E., Milenković, D., Hill, N. R., & Lister, S. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.03.017 · Cited by 21
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Darling, K. E., Benore, E. R., & Webster, E. E. (2019) · Translational Behavioral Medicine · doi:10.1093/tbm/ibz124 · Cited by 22
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Miao, Z., Lü, J., Yan, J., Lu, L., Ye, B., & Gu, M. (2020) · Clinical Therapeutics · doi:10.1016/j.clinthera.2020.04.014 · Cited by 21
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Subramani, Y., Nagappa, M., Kumar, K., Fochesato, L.-A., Chohan, M. B. Y., Zhu, Y. F., Armstrong, K., & Singh, S. (2020) · BMC Anesthesiology · doi:10.1186/s12871-020-01116-5 · Cited by 22
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Jin, L., Guo, S., Zhang, X., Mo, Y., Ke, S., & Duan, C. (2020) · Neurosurgical Review · doi:10.1007/s10143-020-01403-2 · Cited by 20
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“Until now, it has not been clarified whether there are any differences in pharmacologic effects between individual drugs or their combinations within the same drug class other than LAMA/ LABA in the treatment of COPD patients [43].”
BackgroundResultInfluential
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“8,9 CLINICAL PERSPECTIVE What Is New?”
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Shiue, Y., Tseng, P., Zeng, B., Chen, Y., Yang, C., Su, K., Chen, T., Wu, Y., Tu, Y., Lin, P., et al. (2022) · Current Neuropharmacology · doi:10.2174/1570159x20666220420122322 · Cited by 21
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“The level of evidence supporting the efficacy of these CPAs using GRADE methodology adapted for NMA was high for celecoxib, moderate for low-dose aspirin and low for calcium.(65) COX-2 inhibitors (celecoxib 400–800 mg/day) had a greater protective effect than low-dose aspirin and calcium in reducing the incidence of a…”
Method
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“ity of evidence for each outcome using the GRADE methodology for NMA (Puhan et al., 2014; Yepes-Nuñez et al., 2019).”
MethodInfluential
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Burlá, M. M., Gomes, C. P., Calvi, I. P., Oliveira, E. S. C., da Hora, D. A. B., Mao, R.-M. D., de Figueiredo, S. M. P., & Lu, R. (2023) · Hernia · doi:10.1007/s10029-023-02808-w · Cited by 19
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Calabrese, L., Cartocci, A., Rubegni, P., French, L. E., & Kendziora, B. (2025) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.20617 · Cited by 19
GRADE-Leitlinien: 18. Wie ROBINS-I und andere Instrumente zur Einschätzung des Risikos für Bias von nicht-randomisierten Studien verwendet werden sollten, um die Vertrauenswürdigkeit eines Evidenzkörpers zu bewerten
Morche, J., Freitag, S., Hoffmann, F., Rissling, O., Langer, G., Nußbaumer-Streit, B., Toews, I., Gartlehner, G., & Meerpohl, J. J. (2020) · Zeitschrift für Evidenz Fortbildung und Qualität im Gesundheitswesen · doi:10.1016/j.zefq.2019.11.003 · Cited by 20

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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