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BMC Medical Research Methodology
Published in: BMC Medical Research Methodology 1/2018

Open Access 01-12-2018 | Research article

The use of single armed observational data to closing the gap in otherwise disconnected evidence networks: a network meta-analysis in multiple myeloma

Authors: Susanne Schmitz, Áine Maguire, James Morris, Kai Ruggeri, Elisa Haller, Isla Kuhn, Joy Leahy, Natalia Homer, Ayesha Khan, Jack Bowden, Vanessa Buchanan, Michael O’Dwyer, Gordon Cook, Cathal Walsh

Published in: BMC Medical Research Methodology | Issue 1/2018

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Abstract

Background

Network meta-analysis (NMA) allows for the estimation of comparative effectiveness of treatments that have not been studied in head-to-head trials; however, relative treatment effects for all interventions can only be derived where available evidence forms a connected network. Head-to-head evidence is limited in many disease areas, regularly resulting in disconnected evidence structures where a large number of treatments are available. This is also the case in the evidence of treatments for relapsed or refractory multiple myeloma.

Methods

Randomised controlled trials (RCTs) identified in a systematic literature review form two disconnected evidence networks. Standard Bayesian NMA models are fitted to obtain estimates of relative effects within each network. Observational evidence was identified to fill the evidence gap. Single armed trials are matched to act as each other’s control group based on a distance metric derived from covariate information. Uncertainty resulting from including this evidence is incorporated by analysing the space of possible matches.

Results

Twenty five randomised controlled trials form two disconnected evidence networks; 12 single armed observational studies are considered for bridging between the networks. Five matches are selected to bridge between the networks. While significant variation in the ranking is observed, daratumumab in combination with dexamethasone and either lenalidomide or bortezomib, as well as triple therapy of carfilzomib, ixazomib and elozumatab, in combination with lenalidomide and dexamethasone, show the highest effects on progression free survival, on average.

Conclusions

The analysis shows how observational data can be used to fill gaps in the existing networks of RCT evidence; allowing for the indirect comparison of a large number of treatments, which could not be compared otherwise. Additional uncertainty is accounted for by scenario analyses reducing the risk of over confidence in interpretation of results.
Appendix
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Metadata
Title
The use of single armed observational data to closing the gap in otherwise disconnected evidence networks: a network meta-analysis in multiple myeloma
Authors
Susanne Schmitz
Áine Maguire
James Morris
Kai Ruggeri
Elisa Haller
Isla Kuhn
Joy Leahy
Natalia Homer
Ayesha Khan
Jack Bowden
Vanessa Buchanan
Michael O’Dwyer
Gordon Cook
Cathal Walsh
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Medical Research Methodology / Issue 1/2018
Electronic ISSN: 1471-2288
DOI
https://doi.org/10.1186/s12874-018-0509-7

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