Visualizing the flow of evidence in network meta‐analysis and characterizing mixed treatment comparisons
Abstract
Network meta‐analysis techniques allow for pooling evidence from different studies with only partially overlapping designs for getting a broader basis for decision support. The results are network‐based effect estimates that take indirect evidence into account for all pairs of treatments. The results critically depend on homogeneity and consistency assumptions, which are sometimes difficult to investigate. To support such evaluation, we propose a display of the flow of evidence and introduce new measures that characterize the structure of a mixed treatment comparison. Specifically, a linear fixed effects model for network meta‐analysis is considered, where the network estimates for two treatments are linear combinations of direct effect estimates comparing these or other treatments. The linear coefficients can be seen as the generalization of weights known from classical meta‐analysis. We summarize properties of these coefficients and display them as a weighted directed acyclic graph, representing the flow of evidence. Furthermore, measures are introduced that quantify the direct evidence proportion, the mean path length, and the minimal parallelism of mixed treatment comparisons. The graphical display and the measures are illustrated for two published network meta‐analyses. In these applications, the proposed methods are seen to render transparent the process of data pooling in mixed treatment comparisons. They can be expected to be more generally useful for guiding and facilitating the validity assessment in network meta‐analysis. Copyright © 2013 John Wiley & Sons, Ltd.
Citing Literature
Number of times cited according to CrossRef: 56
- Toby Pillinger, Robert A McCutcheon, Luke Vano, Yuya Mizuno, Atheeshaan Arumuham, Guy Hindley, Katherine Beck, Sridhar Natesan, Orestis Efthimiou, Andrea Cipriani, Oliver D Howes, Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis, The Lancet Psychiatry, 10.1016/S2215-0366(19)30416-X, 7, 1, (64-77), (2020).
- Michael Kossmeier, Ulrich S. Tran, Martin Voracek, Charting the landscape of graphical displays for meta-analysis and systematic reviews: a comprehensive review, taxonomy, and feature analysis, BMC Medical Research Methodology, 10.1186/s12874-020-0911-9, 20, 1, (2020).
- Hongda Ding, Yingshi Zhang, Liang Zhao, Si Wu, Junpeng Liu, Caibin Wang, Tong Pei, Yang Su, What Intervention Regimen is Most Effective Prevention for Portal Venous System Thrombosis After Splenectomy in Cirrhotics Patients with Portal Hypertension? Systematic Review and Network Meta-analysis, Pharmacological Research, 10.1016/j.phrs.2020.104825, (104825), (2020).
- Dagmar E. Slot, Cees Valkenburg, G.A. (Fridus) Van der Weijden, Mechanical plaque removal of periodontal maintenance patients: A systematic review and network meta‐analysis, Journal of Clinical Periodontology, 10.1111/jcpe.13275, 47, S22, (107-124), (2020).
- Aiwen Xing, Haitao Chu, Lifeng Lin, Fragility index of network meta-analysis with application to smoking cessation data, Journal of Clinical Epidemiology, 10.1016/j.jclinepi.2020.07.003, 127, (29-39), (2020).
- Gerta Rücker, Adriani Nikolakopoulou, Theodoros Papakonstantinou, Georgia Salanti, Richard D. Riley, Guido Schwarzer, The statistical importance of a study for a network meta-analysis estimate, BMC Medical Research Methodology, 10.1186/s12874-020-01075-y, 20, 1, (2020).
- Kendrick Qijun Li, Kenneth Rice, Improved inference for fixed‐effects meta‐analysis of 2 × 2 tables, Research Synthesis Methods, 10.1002/jrsm.1401, 11, 3, (387-396), (2020).
- Theodoros Papakonstantinou, Adriani Nikolakopoulou, Matthias Egger, Georgia Salanti, In network meta-analysis, most of the information comes from indirect evidence: empirical study, Journal of Clinical Epidemiology, 10.1016/j.jclinepi.2020.04.009, 124, (42-49), (2020).
- Hugo Pedder, Martin Boucher, Sofia Dias, Margherita Bennetts, Nicky J. Welton, Performance of model‐based network meta‐analysis (MBNMA) of time‐course relationships: A simulation study, Research Synthesis Methods, 10.1002/jrsm.1432, 11, 5, (678-697), (2020).
- Konstantinos Tsikopoulos, Konstantinos Sidiropoulos, Dimitrios Kitridis, Spencer M. Cain, Dimitrios Metaxiotis, Ashique Ali, Do External Supports Improve Dynamic Balance in Patients with Chronic Ankle Instability? A Network Meta-analysis, Clinical Orthopaedics and Related Research, 10.1097/CORR.0000000000000946, 478, 2, (359-377), (2020).
- Howard Thom, Gill Norman, Nicky J. Welton, Emma J. Crosbie, Jane Blazeby, Jo C. Dumville, Intra-Cavity Lavage and Wound Irrigation for Prevention of Surgical Site Infection: Systematic Review and Network Meta-Analysis, Surgical Infections, 10.1089/sur.2019.318, (2020).
- Chiara Baglioni, Zarina Bostanova, Valeria Bacaro, Fee Benz, Elisabeth Hertenstein, Kai Spiegelhalder, Gerta Rücker, Lukas Frase, Dieter Riemann, Bernd Feige, A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials Evaluating the Evidence Base of Melatonin, Light Exposure, Exercise, and Complementary and Alternative Medicine for Patients with Insomnia Disorder, Journal of Clinical Medicine, 10.3390/jcm9061949, 9, 6, (1949), (2020).
- Marco Fiore, Aniello Alfieri, Sveva Di Franco, Maria Caterina Pace, Vittorio Simeon, Giulia Ingoglia, Andrea Cortegiani, Ceftazidime-Avibactam Combination Therapy Compared to Ceftazidime-Avibactam Monotherapy for the Treatment of Severe Infections Due to Carbapenem-Resistant Pathogens: A Systematic Review and Network Meta-Analysis, Antibiotics, 10.3390/antibiotics9070388, 9, 7, (388), (2020).
- Angela M Kunzler, Isabella Helmreich, Jochem König, Andrea Chmitorz, Michèle Wessa, Harald Binder, Klaus Lieb, Psychological interventions to foster resilience in healthcare students, Cochrane Database of Systematic Reviews, 10.1002/14651858.CD013684, (2020).
- Angela M Kunzler, Isabella Helmreich, Andrea Chmitorz, Jochem König, Harald Binder, Michèle Wessa, Klaus Lieb, Psychological interventions to foster resilience in healthcare professionals, Cochrane Database of Systematic Reviews, 10.1002/14651858.CD012527.pub2, (2020).
- David J. Miklowitz, Orestis Efthimiou, Toshi A. Furukawa, Jan Scott, Ross McLaren, John R. Geddes, Andrea Cipriani, Adjunctive Psychotherapy for Bipolar Disorder, JAMA Psychiatry, 10.1001/jamapsychiatry.2020.2993, (2020).
- Adam Christopher Gaunt, Pádraig Thomas Kitterick, Determining the Sample Size for Future Trials of Hearing Instruments for Unilaterally Deaf Adults, Otology & Neurotology, 10.1097/MAO.0000000000002186, 40, 4, (e342-e348), (2019).
- Antonios Athanasiou, Areti Angeliki Veroniki, Orestis Efthimiou, Ilkka Kalliala, Huseyin Naci, Sarah Bowden, Maria Paraskevaidi, Pierre Martin-Hirsch, Philip Bennett, Evangelos Paraskevaidis, Georgia Salanti, Maria Kyrgiou, Comparative fertility and pregnancy outcomes after local treatment for cervical intraepithelial neoplasia and stage 1a1 cervical cancer: protocol for a systematic review and network meta-analysis from the CIRCLE group, BMJ Open, 10.1136/bmjopen-2018-028009, 9, 10, (e028009), (2019).
- Anna Chaimani, Deborah M Caldwell, Tianjing Li, Julian PT Higgins, Georgia Salanti, Undertaking network meta‐analyses, Cochrane Handbook for Systematic Reviews of Interventions, 10.1002/9781119536604, (285-320), (2019).
- Kiyomi Shinohara, Orestis Efthimiou, Edoardo G Ostinelli, Anneka Tomlinson, John R Geddes, Andrew A Nierenberg, Henricus G Ruhe, Toshi A Furukawa, Andrea Cipriani, Comparative efficacy and acceptability of antidepressants in the long-term treatment of major depression: protocol for a systematic review and networkmeta-analysis, BMJ Open, 10.1136/bmjopen-2018-027574, 9, 5, (e027574), (2019).
- Caitlin H Daly, Binod Neupane, Joseph Beyene, Lehana Thabane, Sharon E Straus, Jemila S Hamid, Empirical evaluation of SUCRA-based treatment ranks in network meta-analysis: quantifying robustness using Cohen’s kappa, BMJ Open, 10.1136/bmjopen-2018-024625, 9, 9, (e024625), (2019).
- Cees Valkenburg, Yasmin Kashmour, Angelique Dao, G. A. (Fridus) Van der Weijden, Dagmar Else Slot, The efficacy of baking soda dentifrice in controlling plaque and gingivitis: A systematic review, International Journal of Dental Hygiene, 10.1111/idh.12390, 17, 2, (99-116), (2019).
- Fernanda S. Tonin, Helena H. Borba, Antonio M. Mendes, Astrid Wiens, Fernando Fernandez-Llimos, Roberto Pontarolo, Description of network meta-analysis geometry: A metrics design study, PLOS ONE, 10.1371/journal.pone.0212650, 14, 2, (e0212650), (2019).
- Jiaru Yang, Subhash Dhital, Thomas Naderer, Efficacy and Safety of Injectable and Oral Antibiotics in Treating Gonorrhea: A Systematic Review and Network Meta-Analysis, Journal of Clinical Medicine, 10.3390/jcm8122182, 8, 12, (2182), (2019).
- Alessandro Belletti, Umberto Benedetto, Alessandro Putzu, Enrico A. Martino, Giuseppe Biondi-Zoccai, Gianni D. Angelini, Alberto Zangrillo, Giovanni Landoni, Vasopressors During Cardiopulmonary Resuscitation. A Network Meta-Analysis of Randomized Trials, Critical Care Medicine, 10.1097/CCM.0000000000003049, 46, 5, (e443-e451), (2018).
- Theodoros Papakonstantinou, Adriani Nikolakopoulou, Gerta Rücker, Anna Chaimani, Guido Schwarzer, Matthias Egger, Georgia Salanti, Estimating the contribution of studies in network meta-analysis: paths, flows and streams, F1000Research, 10.12688/f1000research.14770.2, 7, (610), (2018).
- Theodoros Papakonstantinou, Adriani Nikolakopoulou, Gerta Rücker, Anna Chaimani, Guido Schwarzer, Matthias Egger, Georgia Salanti, Estimating the contribution of studies in network meta-analysis: paths, flows and streams, F1000Research, 10.12688/f1000research.14770.3, 7, (610), (2018).
- Theodoros Papakonstantinou, Adriani Nikolakopoulou, Gerta Rücker, Anna Chaimani, Guido Schwarzer, Matthias Egger, Georgia Salanti, Estimating the contribution of studies in network meta-analysis: paths, flows and streams, F1000Research, 10.12688/f1000research.14770.1, 7, (610), (2018).
- Sofia Dias, A. E. Ades, Nicky J. Welton, Jeroen P. Jansen, Alexander J. Sutton, References, Network Meta‐Analysis for Decision Making, 10.1002/9781118951651, (409-445), (2018).
- Kuo‐Tung Tang, Chien‐Hua Tseng, Tsu‐Yi Hsieh, Der‐Yuan Chen, Induction therapy for membranous lupus nephritis: a systematic review and network meta‐analysis, International Journal of Rheumatic Diseases, 10.1111/1756-185X.13321, 21, 6, (1163-1172), (2018).
- David M. Phillippo, Sofia Dias, A. E. Ades, Vanessa Didelez, Nicky J. Welton, Sensitivity of treatment recommendations to bias in network meta‐analysis, Journal of the Royal Statistical Society: Series A (Statistics in Society), 10.1111/rssa.12341, 181, 3, (843-867), (2017).
- Hui Quan, Bingzhi Zhang, Christy Chuang-Stein, Byron Jones, Integrated Data Analysis for Assessing Treatment Effect through Combining Information from All Sources, Statistics in Biopharmaceutical Research, 10.1080/19466315.2016.1197150, 9, 1, (52-64), (2017).
- Abdullah Sulieman Terkawi, Dimitris Mavridis, Daniel I. Sessler, Megan S. Nunemaker, Khaled S. Doais, Rayan Sulieman Terkawi, Yazzed Sulieman Terkawi, Maria Petropoulou, Edward C. Nemergut, Pain Management Modalities after Total Knee Arthroplasty, Anesthesiology, 10.1097/ALN.0000000000001607, 126, 5, (923-937), (2017).
- Deborah M. Caldwell, A.E. Ades, Sofia Dias, Sarah Watkins, Tianjing Li, Nichole Taske, Bhash Naidoo, Nicky J. Welton, A threshold analysis assessed the credibility of conclusions from network meta-analysis, Journal of Clinical Epidemiology, 10.1016/j.jclinepi.2016.07.003, 80, (68-76), (2016).
- Young Ho Lee, Overview of Network Meta-analysis for a Rheumatologist, Journal of Rheumatic Diseases, 10.4078/jrd.2016.23.1.4, 23, 1, (4), (2016).
- Konstantinos Tsikopoulos, Haris S Vasiliadis, Dimitris Mavridis, Injection therapies for plantar fasciopathy (‘plantar fasciitis’): a systematic review and network meta-analysis of 22 randomised controlled trials, British Journal of Sports Medicine, 10.1136/bjsports-2015-095437, 50, 22, (1367-1375), (2016).
- Dimitris Mavridis, Orestis Efthimiou, Stefan Leucht, Georgia Salanti, Publication bias and small-study effects magnified effectiveness of antipsychotics but their relative ranking remained invariant, Journal of Clinical Epidemiology, 10.1016/j.jclinepi.2015.05.027, 69, (161-169), (2016).
- Hong Zhao, James S. Hodges, Haijun Ma, Qi Jiang, Bradley P. Carlin, Hierarchical Bayesian approaches for detecting inconsistency in network meta‐analysis, Statistics in Medicine, 10.1002/sim.6938, 35, 20, (3524-3536), (2016).
- Orestis Efthimiou, Thomas P. A. Debray, Gert Valkenhoef, Sven Trelle, Klea Panayidou, Karel G. M. Moons, Johannes B. Reitsma, Aijing Shang, Georgia Salanti, GetReal in network meta‐analysis: a review of the methodology, Research Synthesis Methods, 10.1002/jrsm.1195, 7, 3, (236-263), (2016).
- Stefanie Reken, Sibylle Sturtz, Corinna Kiefer, Yvonne-Beatrice Böhler, Beate Wieseler, Assumptions of Mixed Treatment Comparisons in Health Technology Assessments - Challenges and Possible Steps for Practical Application, PLOS ONE, 10.1371/journal.pone.0160712, 11, 8, (e0160712), (2016).
- Gunnar Gamper, Christof Havel, Jasmin Arrich, Heidrun Losert, Nathan L Pace, Marcus Müllner, Harald Herkner, Vasopressors for hypotensive shock, Cochrane Database of Systematic Reviews, 10.1002/14651858.CD003709.pub4, (2016).
- Dan Jackson, Martin Law, Jessica K. Barrett, Rebecca Turner, Julian P. T. Higgins, Georgia Salanti, Ian R. White, Extending DerSimonian and Laird's methodology to perform network meta‐analyses with random inconsistency effects, Statistics in Medicine, 10.1002/sim.6752, 35, 6, (819-839), (2015).
- Adriani Nikolakopoulou, Dimitris Mavridis, Georgia Salanti, Planning future studies based on the precision of network meta‐analysis results, Statistics in Medicine, 10.1002/sim.6608, 35, 7, (978-1000), (2015).
- Gerta Rücker, Guido Schwarzer, Automated drawing of network plots in network meta‐analysis, Research Synthesis Methods, 10.1002/jrsm.1143, 7, 1, (94-107), (2015).
- Yu‐Kang Tu, Linear mixed model approach to network meta‐analysis for continuous outcomes in periodontal research, Journal of Clinical Periodontology, 10.1111/jcpe.12362, 42, 2, (204-212), (2015).
- Dimitris Mavridis, Myrsini Giannatsi, Andrea Cipriani, Georgia Salanti, A primer on network meta-analysis with emphasis on mental health, Evidence Based Mental Health, 10.1136/eb-2015-102088, 18, 2, (40-46), (2015).
- Deborah M. Caldwell, Sofia Dias, Nicky J. Welton, Extending Treatment Networks in Health Technology Assessment: How Far Should We Go?, Value in Health, 10.1016/j.jval.2015.03.1792, 18, 5, (673-681), (2015).
- Guido Schwarzer, James R. Carpenter, Gerta Rücker, Guido Schwarzer, James R. Carpenter, Gerta Rücker, Network Meta-Analysis, Meta-Analysis with R, 10.1007/978-3-319-21416-0_8, (187-216), (2015).
- Dan Jackson, Jessica K. Barrett, Stephen Rice, Ian R. White, Julian P.T. Higgins, A design‐by‐treatment interaction model for network meta‐analysis with random inconsistency effects, Statistics in Medicine, 10.1002/sim.6188, 33, 21, (3639-3654), (2014).
- Pascale Dequen, Alex J. Sutton, David A. Scott, Keith R. Abrams, Searching for Indirect Evidence and Extending the Network of Studies for Network Meta-Analysis: Case Study in Venous Thromboembolic Events Prevention Following Elective Total Knee Replacement Surgery, Value in Health, 10.1016/j.jval.2014.02.013, 17, 4, (416-423), (2014).
- Ulrike Krahn, Harald Binder, Jochem König, Visualizing inconsistency in network meta-analysis by independent path decomposition, BMC Medical Research Methodology, 10.1186/1471-2288-14-131, 14, 1, (2014).
- Deborah M Caldwell, An overview of conducting systematic reviews with network meta-analysis, Systematic Reviews, 10.1186/2046-4053-3-109, 3, 1, (2014).
- Dimitris Mavridis, Nicky J. Welton, Alex Sutton, Georgia Salanti, A selection model for accounting for publication bias in a full network meta‐analysis, Statistics in Medicine, 10.1002/sim.6321, 33, 30, (5399-5412), (2014).
- Gerta Rücker, Guido Schwarzer, Reduce dimension or reduce weights? Comparing two approaches to multi‐arm studies in network meta‐analysis, Statistics in Medicine, 10.1002/sim.6236, 33, 25, (4353-4369), (2014).
- Gerta Rücker, Network Meta‐Analysis, Wiley StatsRef: Statistics Reference Online, 10.1002/9781118445112, (1-8), (2014).
- Binod Neupane, Danielle Richer, Ashley Joel Bonner, Taddele Kibret, Joseph Beyene, Network Meta-Analysis Using R: A Review of Currently Available Automated Packages, PLoS ONE, 10.1371/journal.pone.0115065, 9, 12, (e115065), (2014).




