Review
. 2013 Jul; 11:159.
doi: 10.1186/1741-7015-11-159.

Is network meta-analysis as valid as standard pairwise meta-analysis? It all depends on the distribution of effect modifiers

Jeroen P Jansen 1 Huseyin Naci  
Affiliations
  • PMID: 23826681
  •     23 References
  •     144 citations

Abstract

Background: In the last decade, network meta-analysis of randomized controlled trials has been introduced as an extension of pairwise meta-analysis. The advantage of network meta-analysis over standard pairwise meta-analysis is that it facilitates indirect comparisons of multiple interventions that have not been studied in a head-to-head fashion. Although assumptions underlying pairwise meta-analyses are well understood, those concerning network meta-analyses are perceived to be more complex and prone to misinterpretation.

Discussion: In this paper, we aim to provide a basic explanation when network meta-analysis is as valid as pairwise meta-analysis. We focus on the primary role of effect modifiers, which are study and patient characteristics associated with treatment effects. Because network meta-analysis includes different trials comparing different interventions, the distribution of effect modifiers cannot only vary across studies for a particular comparison (as with standard pairwise meta-analysis, causing heterogeneity), but also between comparisons (causing inconsistency). If there is an imbalance in the distribution of effect modifiers between different types of direct comparisons, the related indirect comparisons will be biased. If it can be assumed that this is not the case, network meta-analysis is as valid as pairwise meta-analysis.

Summary: The validity of network meta-analysis is based on the underlying assumption that there is no imbalance in the distribution of effect modifiers across the different types of direct treatment comparisons, regardless of the structure of the evidence network.

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Jinghong Liang, Jiayu Li, +5 authors, Yong Xu.
Clin Interv Aging, 2018 Nov 15; 13. PMID: 30425461    Free PMC article.
Systematic Review.
Cost-consequence model comparing eltrombopag versus romiplostim for adult patients with chronic immune thrombocytopenia.
Gabriel Tremblay, Mike Dolph, +3 authors, Andrew Briggs.
Clinicoecon Outcomes Res, 2018 Nov 23; 10. PMID: 30464563    Free PMC article.
Overcoming the Straw Man Effect in Oncology: Visualization and Ranking of Chemotherapy Regimens Using an Information Theoretic Approach.
Jeremy L Warner, Peter C Yang, Gil Alterovitz.
JCO Clin Cancer Inform, 2017 Nov 01; 1. PMID: 30657401    Free PMC article.
Are Nonpharmacologic Interventions for Chronic Low Back Pain More Cost Effective Than Usual Care? Proof of Concept Results From a Markov Model.
Patricia M Herman, Tara A Lavelle, +2 authors, Ian D Coulter.
Spine (Phila Pa 1976), 2019 May 17; 44(20). PMID: 31095119    Free PMC article.
Acute interventions for aggression and agitation in psychosis: study protocol for a systematic review and network meta-analysis.
Edoardo G Ostinelli, Armando D'Agostino, +2 authors, Toshi A Furukawa.
BMJ Open, 2019 Oct 12; 9(10). PMID: 31601607    Free PMC article.
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.
Antonios Athanasiou, Areti Angeliki Veroniki, +9 authors, Maria Kyrgiou.
BMJ Open, 2019 Oct 23; 9(10). PMID: 31636110    Free PMC article.
BUGSnet: an R package to facilitate the conduct and reporting of Bayesian network Meta-analyses.
Audrey Béliveau, Devon J Boyne, +2 authors, Paul Arora.
BMC Med Res Methodol, 2019 Oct 24; 19(1). PMID: 31640567    Free PMC article.
Vaccines for preventing herpes zoster in older adults.
Anna Mz Gagliardi, Brenda Ng Andriolo, +4 authors, Eduardo Canteiro Cruz.
Cochrane Database Syst Rev, 2019 Nov 08; 2019(11). PMID: 31696946    Free PMC article.
Systematic Review.
Exercise and adiposity in overweight and obese children and adolescents: a systematic review with network meta-analysis of randomised trials.
George A Kelley, Kristi S Kelley, Russell R Pate.
BMJ Open, 2019 Nov 14; 9(11). PMID: 31719081    Free PMC article.
Systematic Review.
Joint Estimation of Remission and Response for Methotrexate-Based DMARD Options in Rheumatoid Arthritis: A Bivariate Network Meta-Analysis.
Gyanendra Pokharel, Rob Deardon, +12 authors, Canadian Early Arthritis Cohort (CATCH) Investigators.
ACR Open Rheumatol, 2019 Nov 30; 1(8). PMID: 31777827    Free PMC article.
[Basic concepts for network meta-analysis].
Ferrán Catalá-López, Aurelio Tobías, Marta Roqué.
Aten Primaria, 2014 May 07; 46(10). PMID: 24796656    Free PMC article.
Suture choice to reduce occurrence of surgical site infection, hernia, wound dehiscence and sinus/fistula: a network meta-analysis.
B E Zucker, C Simillis, P Tekkis, C Kontovounisios.
Ann R Coll Surg Engl, 2018 Oct 06; 101(3). PMID: 30286645    Free PMC article.
Systematic Review.
Interventions for improving upper limb function after stroke.
Alex Pollock, Sybil E Farmer, +4 authors, Frederike van Wijck.
Cochrane Database Syst Rev, 2014 Nov 12; (11). PMID: 25387001    Free PMC article.
Highly Cited. Systematic Review.
Dressings and topical agents for treating pressure ulcers.
Maggie J Westby, Jo C Dumville, +2 authors, Gill Norman.
Cochrane Database Syst Rev, 2017 Jun 24; 6. PMID: 28639707    Free PMC article.
Systematic Review.
Dressings and topical agents for treating venous leg ulcers.
Gill Norman, Maggie J Westby, +3 authors, Jo C Dumville.
Cochrane Database Syst Rev, 2018 Jun 16; 6. PMID: 29906322    Free PMC article.
Systematic Review.
Borrowing of strength from indirect evidence in 40 network meta-analyses.
Lifeng Lin, Aiwen Xing, Michael J Kofler, Mohammad Hassan Murad.
J Clin Epidemiol, 2018 Oct 21; 106. PMID: 30342086    Free PMC article.
Comparative efficacy of interventions for reducing injection and sexual risk behaviours to prevent HIV in injection drug users: protocol for Bayesian network meta-analysis.
Junjie Lang, Lairun Jin, Yingshui Yao.
BMJ Open, 2019 Jan 31; 9(1). PMID: 30696672    Free PMC article.
Description of network meta-analysis geometry: A metrics design study.
Fernanda S Tonin, Helena H Borba, +3 authors, Roberto Pontarolo.
PLoS One, 2019 Feb 21; 14(2). PMID: 30785955    Free PMC article.
Indirect treatment comparisons including network meta-analysis: Lenvatinib plus everolimus for the second-line treatment of advanced/metastatic renal cell carcinoma.
Gabriel Tremblay, Heather J McElroy, +3 authors, Matthew Guo.
PLoS One, 2019 Mar 06; 14(3). PMID: 30835737    Free PMC article.
Systematic Review.
Assessment of Reported Comparative Effectiveness and Safety of Atypical Antipsychotics in the Treatment of Behavioral and Psychological Symptoms of Dementia: A Network Meta-analysis.
Ismaeel Yunusa, Adnan Alsumali, +2 authors, Tewodros Eguale.
JAMA Netw Open, 2019 Mar 23; 2(3). PMID: 30901041    Free PMC article.
Systematic Review.
The effects of aerobic, resistance, and meditative movement exercise on sleep in individuals with depression: protocol for a systematic review and network meta-analysis.
Gavin Brupbacher, Heike Gerger, +6 authors, Arno Schmidt-Trucksäss.
Syst Rev, 2019 Apr 28; 8(1). PMID: 31027509    Free PMC article.
Systematic Review.
Comparative efficacy of once-weekly semaglutide versus SGLT-2 inhibitors in patients inadequately controlled with one to two oral antidiabetic drugs: a systematic literature review and network meta-analysis.
Steve Kanters, Lars Wilkinson, +4 authors, Eric Druyts.
BMJ Open, 2019 Jul 26; 9(7). PMID: 31340953    Free PMC article.
Systematic Review.
Comparative efficacy and complication rates 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.
Antonios Athanasiou, Areti Angeliki Veroniki, +9 authors, Maria Kyrgiou.
BMJ Open, 2019 Aug 05; 9(8). PMID: 31377697    Free PMC article.
Vibration of effects from diverse inclusion/exclusion criteria and analytical choices: 9216 different ways to perform an indirect comparison meta-analysis.
Clément Palpacuer, Karima Hammas, +3 authors, Florian Naudet.
BMC Med, 2019 Sep 19; 17(1). PMID: 31526369    Free PMC article.
Comparison of ventilatory modes to facilitate liberation from mechanical ventilation: protocol for a systematic review and network meta-analysis.
Kimberley A Lewis, Dipayan Chaudhuri, +9 authors, Bram Rochwerg.
BMJ Open, 2019 Sep 08; 9(9). PMID: 31492786    Free PMC article.
Effects of Nutritional Strategies on Glucose Homeostasis in Gestational Diabetes Mellitus: A Systematic Review and Network Meta-Analysis.
Shixiao Jin, Liyan Sha, +4 authors, Bing Hu.
J Diabetes Res, 2020 Mar 19; 2020. PMID: 32185236    Free PMC article.
Systematic Review.
Treatment of newly diagnosed glioblastoma in the elderly: a network meta-analysis.
Catherine Hanna, Theresa A Lawrie, +6 authors, Robin Grant.
Cochrane Database Syst Rev, 2020 Mar 24; 3. PMID: 32202316    Free PMC article.
Systematic Review.
Interventions for the management of malignant pleural effusions: a network meta-analysis.
Alexandra Dipper, Hayley E Jones, +3 authors, Amelia O Clive.
Cochrane Database Syst Rev, 2020 Apr 22; 4. PMID: 32315458    Free PMC article.
Systematic Review.
Is psychotherapy effective? A re-analysis of treatments for depression.
T Munder, C Flückiger, +6 authors, B E Wampold.
Epidemiol Psychiatr Sci, 2018 Jul 31; 28(3). PMID: 30058524    Free PMC article.
Rapid network meta-analysis using data from Food and Drug Administration approval packages is feasible but with limitations.
Lin Wang, Benjamin Rouse, +7 authors, Tianjing Li.
J Clin Epidemiol, 2019 Jun 22; 114. PMID: 31226413    Free PMC article.
Comparative Efficacy and Acceptability of Pharmacological, Psychotherapeutic, and Combination Treatments in Adults With Posttraumatic Stress Disorder: A Network Meta-analysis.
Jasmin Merz, Guido Schwarzer, Heike Gerger.
JAMA Psychiatry, 2019 Jun 13; 76(9). PMID: 31188399    Free PMC article.
Comparative Effects Between Direct Oral Anticoagulants for Acute Venous Thromboembolism: Indirect Comparison From Randomized Controlled Trials.
Guowei Li, Jie Zeng, Junguo Zhang, Lehana Thabane.
Front Med (Lausanne), 2020 Jul 09; 7. PMID: 32637418    Free PMC article.
Systematic Review.
Treatment strategies for asymptomatic carotid artery stenosis in the era of lipid-lowering drugs: protocol for a systematic review and network meta-analysis.
Xuesong Bai, Yao Feng, +7 authors, Liqun Jiao.
BMJ Open, 2020 Jul 07; 10(7). PMID: 32624471    Free PMC article.
The number needed to treat and relevant between-trial comparisons of competing interventions.
Jeroen P Jansen, Javaria Mona Khalid, Michael D Smyth, Haridarshan Patel.
Clinicoecon Outcomes Res, 2018 Dec 28; 10. PMID: 30588048    Free PMC article.
Review.
Comparative Efficacy and Tolerability of Neoadjuvant Immunotherapy Regimens for Patients with HER2-Positive Breast Cancer: A Network Meta-Analysis.
Di Wu, Tiejun Chen, +5 authors, Fenfang Wu.
J Oncol, 2019 Apr 25; 2019. PMID: 31015833    Free PMC article.
Systematic review and network meta-analysis of approved medicines for the treatment of idiopathic pulmonary fibrosis.
Aristeidis Skandamis, Chara Kani, Sophia L Markantonis, Kyriakos Souliotis.
J Drug Assess, 2019 May 03; 8(1). PMID: 31044096    Free PMC article.
Efficacy of Enamel Derivatives to Improve Keratinized Tissue as Adjunct to Coverage of Gingival Recessions: A Systematic Review and Meta-Analysis.
Nicola Discepoli, Raffaele Mirra, Marco Ferrari.
Materials (Basel), 2019 Sep 05; 12(17). PMID: 31480232    Free PMC article.
Review.
Effectiveness and adverse events of topical and allergen immunotherapy for atopic dermatitis: a systematic review and network meta-analysis protocol.
Luis Guillermo Gómez-Escobar, Hansel Mora-Ochoa, +6 authors, Juan José Yepes-Nuñez.
Syst Rev, 2020 Sep 30; 9(1). PMID: 32988419    Free PMC article.
Minimally invasive techniques for transthoracic oesophagectomy for oesophageal cancer: systematic review and network meta-analysis.
K Siaw-Acheampong, S K Kamarajah, +3 authors, E A Griffiths.
BJS Open, 2020 Sep 08; 4(5). PMID: 32894001    Free PMC article.
Review.
Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis.
Howard Thom, Jeroen Jansen, +5 authors, Nirmish Shah.
BMJ Open, 2020 Sep 20; 10(9). PMID: 32948541    Free PMC article.
Systematic Review.
Psychological interventions for chronic non-specific low back pain: protocol of a systematic review with network meta-analysis.
Emma Ho, Manuela Ferreira, +5 authors, Paulo Ferreira.
BMJ Open, 2020 Sep 20; 10(9). PMID: 32948543    Free PMC article.
Analgesic medicines for adults with low back pain: protocol for a systematic review and network meta-analysis.
Michael A Wewege, Matthew K Bagg, +2 authors, ANiMALIA investigators.
Syst Rev, 2020 Nov 06; 9(1). PMID: 33148322    Free PMC article.
Treatment with disease-modifying drugs for people with a first clinical attack suggestive of multiple sclerosis.
Graziella Filippini, Cinzia Del Giovane, +7 authors, Georgia Salanti.
Cochrane Database Syst Rev, 2017 Apr 26; 4. PMID: 28440858    Free PMC article.
Systematic Review.
An efficacy comparison of anti-vascular growth factor agents and laser photocoagulation in diabetic macular edema: a network meta-analysis incorporating individual patient-level data.
Dominic Muston, Jean-Francois Korobelnik, +4 authors, Peter K Kaiser.
BMC Ophthalmol, 2018 Dec 29; 18(1). PMID: 30591022    Free PMC article.
Impact of different dietary approaches on blood lipid control in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis.
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Eur J Epidemiol, 2019 Jun 16; 34(9). PMID: 31201670
Systematic Review.
Comparative efficacy and tolerability of front-line treatments for newly diagnosed chronic-phase chronic myeloid leukemia: an update network meta-analysis.
Lu Tang, Huan Zhang, +5 authors, Yu Hu.
BMC Cancer, 2019 Aug 30; 19(1). PMID: 31462241    Free PMC article.
Comparative efficacy and safety of adjuvant nivolumab versus other treatments in adults with resected melanoma: a systematic literature review and network meta-analysis.
Kabirraaj Toor, Mark R Middleton, +3 authors, Srividya Kotapati.
BMC Cancer, 2021 Jan 07; 21(1). PMID: 33402121    Free PMC article.
Systematic Review.
Network meta-analysis on the comparative efficacy of family interventions for psychotic disorders: a protocol.
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BMJ Open, 2021 Jan 22; 11(1). PMID: 33472774    Free PMC article.
What exercise prescription is optimal to improve body composition and cardiorespiratory fitness in adults living with obesity? A network meta-analysis.
Grainne O'Donoghue, Catherine Blake, +2 authors, Carla Perrotta.
Obes Rev, 2020 Sep 09; 22(2). PMID: 32896055    Free PMC article.
Review.
Efficacy and safety of oral phosphodiesterase 5 inhibitors for erectile dysfunction: a network meta-analysis and multicriteria decision analysis.
Camilla R Madeira, Fernanda S Tonin, +9 authors, Roberto Pontarolo.
World J Urol, 2020 May 11; 39(3). PMID: 32388784
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Comparative Efficacy and Safety of Ultra-Long-Acting, Long-Acting, Intermediate-Acting, and Biosimilar Insulins for Type 1 Diabetes Mellitus: a Systematic Review and Network Meta-Analysis.
Andrea C Tricco, Huda M Ashoor, +13 authors, Sharon E Straus.
J Gen Intern Med, 2021 Mar 21; 36(8). PMID: 33742305    Free PMC article.
Review.
Comparison of the prognosis of four different treatment strategies for acute left malignant colonic obstruction: a systematic review and network meta-analysis.
Ling Tan, Zi-Lin Liu, +6 authors, Jiang-Wei Xiao.
World J Emerg Surg, 2021 Mar 20; 16(1). PMID: 33736680    Free PMC article.
Adjusted Indirect and Mixed Comparisons of Interventions for the Patient-Reported Outcomes Measures (PROMs) of Disabled Adults: A Systematic Review and Network Meta-Analysis.
Yining Xu, Xin Li, +3 authors, Yaodong Gu.
Int J Environ Res Public Health, 2021 Apr 04; 18(5). PMID: 33804553    Free PMC article.
Systematic Review.
Effectiveness comparisons of various psychosocial therapies for children and adolescents with depression: a Bayesian network meta-analysis.
Jing-Hong Liang, Jing Li, +6 authors, Yong Xu.
Eur Child Adolesc Psychiatry, 2020 Feb 23; 30(5). PMID: 32076871
Review.
Comparative Efficacy and Acceptability of Psychotherapies for Self-harm and Suicidal Behavior Among Children and Adolescents: A Systematic Review and Network Meta-analysis.
Anees Bahji, Matthew Pierce, +3 authors, Scott Patten.
JAMA Netw Open, 2021 Apr 17; 4(4). PMID: 33861328    Free PMC article.
Systematic Review.
Effects of different aerobic exercise training on glycemia in patients with type 2 diabetes: A protocol for systematic review and meta analysis.
Ying Li, Runmin Li, +3 authors, Dongying Li.
Medicine (Baltimore), 2021 May 06; 100(18). PMID: 33950940    Free PMC article.
Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis.
Elizabeth M Salvo, Abril Oliva Ramirez, +4 authors, Imtiaz A Samjoo.
Breast, 2021 Mar 08; 57. PMID: 33677313    Free PMC article.
Evidence inconsistency degrees of freedom in Bayesian network meta-analysis.
Lifeng Lin.
J Biopharm Stat, 2020 Dec 10; 31(3). PMID: 33296239    Free PMC article.
A method for assessing robustness of the results of a star-shaped network meta-analysis under the unidentifiable consistency assumption.
Jeong-Hwa Yoon, Sofia Dias, Seokyung Hahn.
BMC Med Res Methodol, 2021 Jun 03; 21(1). PMID: 34074239    Free PMC article.
Comparative effectiveness of pharmacological interventions to prevent postoperative delirium: a network meta-analysis.
Sun-Kyung Park, Taeyoon Lim, +6 authors, Won Ho Kim.
Sci Rep, 2021 Jun 09; 11(1). PMID: 34099790    Free PMC article.
Aerobic, resistance, and mind-body exercise are equivalent to mitigate symptoms of depression in older adults: A systematic review and network meta-analysis of randomised controlled trials.
Kyle J Miller, Pinyadapat Areerob, +3 authors, Fergal Grace.
F1000Res, 2021 Aug 07; 9. PMID: 34158928    Free PMC article.
Systematic Review.
Repetitive transcranial magnetic stimulation for lower extremity motor function in patients with stroke: a systematic review and network meta-analysis.
Yun-Juan Xie, Yi Chen, +3 authors, Qiang Gao.
Neural Regen Res, 2020 Dec 04; 16(6). PMID: 33269766    Free PMC article.
Review.
Methodological review to develop a list of bias items used to assess reviews incorporating network meta-analysis: protocol and rationale.
Carole Lunny, Andrea C Tricco, +6 authors, Penny Whiting.
BMJ Open, 2021 Jun 26; 11(6). PMID: 34168027    Free PMC article.
Review.
Physical relaxation for occupational stress in healthcare workers: A systematic review and network meta-analysis of randomized controlled trials.
Michael Zhang, Brittany Murphy, Abegail Cabanilla, Christina Yidi.
J Occup Health, 2021 Jul 09; 63(1). PMID: 34235817    Free PMC article.
Systematic Review.
Management of social isolation and loneliness in community-dwelling older adults: protocol for a network meta-analysis of randomised controlled trials.
Ahreum Lee, Caitlin McArthur, +6 authors, Alexandra Papaioannou.
BMJ Open, 2021 Jul 07; 11(7). PMID: 34226209    Free PMC article.