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. 2023 Aug;12(8):e220132.
doi: 10.57264/cer-2022-0132. Epub 2023 Jul 29.

Handling related publications reporting real-world evidence in network meta-analysis: a case study in multiple sclerosis

Marissa Betts  1 , Kyle Fahrbach  1 , Binod Neupane  2 , Mahmoud Slim  2 , Maria Pia Sormani  3 , Gary Cutter  4 , Thomas Pa Debray  5   6 , Marvin Rock  7
Affiliations

Handling related publications reporting real-world evidence in network meta-analysis: a case study in multiple sclerosis

Marissa Betts et al. J Comp Eff Res. 2023 Aug.

Abstract

Aim: The presence of two or more publications that report on overlapping patient cohorts poses a challenge for quantitatively synthesizing real-world evidence (RWE) studies. Thus, we evaluated eight approaches for handling such related publications in network meta-analyses (NMA) of RWE studies. Methods: Bayesian NMAs were conducted to estimate the annualized relapse rate (ARR) of disease-modifying therapies in multiple sclerosis. The NMA explored the impact of hierarchically selecting one pivotal study from related publications versus including all of them while adjusting for correlations. Results: When selecting one pivotal study from related publications, the ARR ratios were mostly similar regardless of the pivotal study selected. When including all related publications, there were shifts in the point estimates and the statistical significance. Conclusion: An a priori hierarchy should guide the selection among related publications in NMAs of RWE. Sensitivity analyses modifying the hierarchy should be considered for networks with few or small studies.

Keywords: dimethyl fumarate; disease-modifying therapies; multiple sclerosis; network meta-analysis; real-world evidence.

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Conflict of interest statement

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.. Mixed prior treatment evidence network.
Related publications are displayed in grey color. *IFN/GA corresponds to patients who received any IFN or GA; this does not include the other IFN or GA treatment arms which were reported and analyzed separately. ALEM: Alemtuzumab; AMSTR: Austrian MS Treatment Registry; DMF: Dimethyl fumarate; FTY: Fingolimod; GA: Glatiramer acetate; IFN: Interferon betas; NTD: NeuroTransData; NTZ: Natalizumab; SFCTHIR: Swiss Federation for Common Tasks of Health Insurances Registry; TERI: Teriflunomide.
Figure 2.
Figure 2.. Previously treated evidence network.
Related publications are displayed in grey color. DMF: Dimethyl fumarate; FTY: Fingolimod; GA: Glatiramer acetate; IFN: Interferon beta; NTZ: Natalizumab; SFCTHIR: Swiss Federation for Common Tasks of Health Insurances Registry; TERI: Teriflunomide; TOP: TYSABRI Observational Program.
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