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Hypothesis and Theory ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00822

The use of (network) meta-analysis in clinical oncology

 Emil Ter Veer1*, Martijn G. van Oijen1 and Hanneke W. van Laarhoven2
  • 1Department of Medical Oncology, Medical Center, VU University Amsterdam, Netherlands
  • 2Amsterdam UMC, University of Amsterdam, Department of Medical Oncology, Cancer Centre Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands, Netherlands

Meta-analysis is important in oncological research to provide a more reliable answer to a clinical research question that was assessed in multiple studies but with inconsistent results. Pair-wise meta-analysis can be applied when comparing two treatments at once, whereas it is possible to compare multiple treatments at once with network meta-analysis (NMA).
After careful systematic review of the literature and quality assessment of the identified studies, the added value of meta-analysis should be evaluated first by examining the comparability of study populations. Second, the appropriate comparator in meta-analysis should be chosen according to the types of comparisons made in individual studies: 1. Experimental and comparator arms are different treatments (A vs B); 2. Substitution of a conventional treatment by an experimental treatment (A+B vs A+C); or 3. Addition of an experimental treatment (A+B vs B). Ideally there is one common comparator treatment, but when there are multiple common comparators, the most efficacious comparator is preferable. Third, treatments can only be adequately pooled in meta-analysis or merged into one treatment node in NMA when considering likewise mechanism of action and similar setting for which treatment is indicated.
To evaluate heterogeneity in both pair-wise meta-analysis and NMA, sub-analysis and sensitivity analysis can be applied to objectify a possible confounding factor. Network inconsistency in NMA can best be evaluated by node-split modelling.
NMA has advantages over pair-wise meta-analysis, such as clarification of inconsistent outcomes from multiple studies including multiple common comparators and indirect effect calculation of missing direct comparisons between important treatments. Also, NMA can provide increased statistical power and cross-validation of the observed treatment effect of weak connections with reasonable network connectivity and sufficient sample-sizes. However, inappropriate use of NMA can cause misleading results and may emerge when there is low network connectivity, and therefore low statistical power. Furthermore, indirect evidence is still observational and should be interpreted with caution.
Finally, the use of meta-analysis can be extended to other areas, for example the identification of prognostic and predictive factors. Also, the integration of evidence from both meta-analysis and expert opinion can improve the construction of prognostic models in real-world databases.

Keywords: Meta-analysis, Network meta analysis, Systematic review, Oncology (ONC), gastric cancer, Esophaeal cancer, Pancreatic Cancer

Received: 09 Apr 2019; Accepted: 12 Aug 2019.

Edited by:

Yawei Zhang, Yale University, United States

Reviewed by:

Sudabeh Alatab, Tehran University of Medical Sciences, Iran
Abdelbaset M. Elasbali, Al Jouf University, Saudi Arabia
Jianhua Yin, Second Military Medical University, China  

Copyright: © 2019 Ter Veer, van Oijen and van Laarhoven. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Emil Ter Veer, Department of Medical Oncology, Medical Center, VU University Amsterdam, Amsterdam, Netherlands,