Joining the Dots: Linking Disconnected Networks of Evidence Using Dose-Response Model-Based Network Meta-Analysis

Hugo Pedder*, Sofia Dias, Meg Bennetts, Martin Boucher, Nicky J Welton

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Introduction: Network meta-analysis (NMA) synthesises direct and indirect evidence on multiple treatments to estimate their relative effectiveness. However, comparisons between disconnected treatments are not possible without making strong assumptions. When studies including multiple doses of the same drug are available, model-based NMA (MBNMA) presents a novel solution to this problem by modelling a parametric dose-response relationship within a NMA framework. In this paper, we illustrate several scenarios in which dose-response MBNMA can connect and strengthen evidence networks.

Methods: We created illustrative datasets by removing studies or treatments from a NMA of triptans for migraine relief. We fitted MBNMA models with different dose-response relationships. For connected networks, we compared MBNMA estimates with NMA estimates. For ¬¬disconnected networks, we compared MBNMA estimates with NMA estimates from an “augmented” network connected by adding studies or treatments back into the dataset.

Results: In connected networks relative effect estimates from MBNMA were more precise than those from NMA models (ratio of posterior SDs NMAvsMBNMA: median=1.13; range=1.04-1.68). In disconnected networks MBNMA provided estimates for all treatments where NMA could not and were consistent with NMA estimates from augmented networks for 15/18 datasets. In the remaining 3/18 datasets a more complex dose-response relationship was required than could be fitted with the available evidence.

Conclusions: Where information on multiple doses is available, MBNMA can connect disconnected networks and increase precision, whilst making less strong assumptions than alternative approaches. MBNMA relies on correct specification of the dose-response relationship which requires sufficient data at different doses to allow reliable estimation. We recommend that systematic reviews for NMA search for and include evidence (including phase-II trials) on multiple doses of agents where available.
Original languageEnglish
Pages (from-to)194-208
Number of pages15
JournalMedical Decision Making
Issue number2
Publication statusPublished - 15 Jan 2021

Structured keywords

  • HEB


  • meta-analysis
  • synthesis
  • dose
  • linking
  • network
  • NMA


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