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World J Methodol. May 20, 2022; 12(3): 92-98
Published online May 20, 2022. doi: 10.5662/wjm.v12.i3.92
Network meta-analyses: Methodological prerequisites and clinical usefulness
Savvas Ilias Christofilos, Konstantinos Tsikopoulos, Alexios Tsikopoulos, Dimitrios Kitridis, Konstantinos Sidiropoulos, Panagiotis Nikolaos Stoikos, Venu Kavarthapu
Savvas Ilias Christofilos, Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, United Kingdom
Konstantinos Tsikopoulos, Department of Pharmacology, School of Medicine, Faculty of Health Sciences Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
Alexios Tsikopoulos, Department of Otolaryngology-Head and Neck Surgery, AHEPA University General Hospital, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
Dimitrios Kitridis, Department of Orthopaedics, Aristotle University of Thessaloniki, School of Medicine, George Papanikolaou Hospital Thessaloniki, Thessaloniki 57010, Greece
Konstantinos Sidiropoulos, Department of Orthopedics, General Hospital of Serres, Serres 62100, Greece
Panagiotis Nikolaos Stoikos, Department of Medicine, University of Thessaly, Larissa 41500, Greece
Venu Kavarthapu, Department of Trauma and Orthopaedics, King’s College Hospital NHS Foundation Trust, London SE5 9RS, United Kingdom
Author contributions: Karthavapu V and Tsikopoulos K were involved in the conceptualization of the study; Tsikopoulos A and Sidiropoulos K conducted the literature research and extracted relevant information; Tsikopoulos K and Kitridis D assessed the quality of the included studies; Christofilos SI and Stoikos PN were involved in the generation of tables and the writing of the paper; Karthavapu V supervised and revised the paper accordingly; Throughout the study, Christofilos SI was an intern of Professor Maniatis's group at University College London; all authors have read and approved the final manuscript.
Conflict-of-interest statement: All authors declare there is no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Savvas Ilias Christofilos, MD, Doctor, Department of Genetics, Evolution, and Environment, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Received: October 19, 2021
Peer-review started: October 19, 2021
First decision: January 18, 2022
Revised: February 5, 2022
Accepted: March 26, 2022
Article in press: March 26, 2022
Published online: May 20, 2022

It is an undeniable fact that systematic reviews play a crucial role in informing clinical practice; however, conventional head-to-head meta-analyses do have limitations. In particular, studies can only be compared in a pair-wise fashion, and conclusions can only be drawn in the light of direct evidence. In contrast, network meta-analyses can not only compare multiple interventions but also utilize indirect evidence which increases their precision. On top of that, they can also rank competing interventions. In this mini-review, we have aimed to elaborate on the principles and techniques governing network meta-analyses to achieve a methodologically sound synthesis, thus enabling safe conclusions to be drawn in clinical practice. We have emphasized the prerequisites of a well-conducted Network Meta-Analysis (NMA), the value of selecting appropriate outcomes according to guidelines for transparent reporting, and the clarity achieved via sophisticated graphical tools. What is more, we have addressed the importance of incorporating the level of evidence into the results and interpreting the findings according to validated appraisal systems (i.e., the Grade of Recommendations, Assessment, Development, and Evaluation system - GRADE). Lastly, we have addressed the possibility of planning future research via NMAs. Thus, we can conclude that NMAs could be of great value to clinical practice.

Keywords: Network meta-analysis, Quality of evidence, Evidence-based medicine, Systematic reviews

Core Tip: Systematic reviews with or without meta-analyses provide the highest quality of evidence, thus lying on the top of evidence-based medicine hierarchy. However, pair-wise meta-analyses present the inherent limitation of exclusively comparing direct evidence. By contrast, Network Meta-Analyses (NMAs) also consider indirect evidence, thereby offering additional useful information. Conducting an NMA, however, has certain requirements such as assuming that transitivity across the included studies exists. What is more, maintaining sufficient statistical power in the analyses is crucial. In addition, performing head-to-head statistical comparisons before setting up networks of interventions is a prerequisite for a methodologically sound NMA, and selecting not only positive but also negative outcomes is required. Lastly, implementing quality appraisal systems to grade the level of evidence is highly recommended. Should all the above criteria be fulfilled, then accurate clinical conclusions can be drawn from an NMA.