Abstract

Network meta‐analysis (NMA) is gaining popularity for comparing multiple treatments in a single analysis. Generalized linear mixed models provide a unifying framework for NMA, allow us to analyze datasets with dichotomous, continuous or count endpoints, and take into account multiarm trials, potential heterogeneity between trials and network inconsistency. To perform inference within such NMA models, the use of Bayesian methods is often advocated. The standard inference tool is Markov chain Monte Carlo (MCMC), which is computationally expensive and requires convergence diagnostics. A deterministic approach to do fully Bayesian inference for latent Gaussian models can be achieved by integrated nested Laplace approximations (INLA), which is a fast and accurate alternative to MCMC. We show how NMA models fit in the class of latent Gaussian models and how NMA models are implemented using INLA and demonstrate that the estimates obtained by INLA are in close agreement with the ones obtained by MCMC. Specifically, we emphasize the design‐by‐treatment interaction model with random inconsistency parameters (also known as the Jackson model). Also, we have proposed a network meta‐regression model, which is constructed by incorporating trial‐level covariates to the Jackson model to explain possible sources of heterogeneity and/or inconsistency in the network. A publicly available R package, nmaINLA, is developed to automate the INLA implementation of NMA models, which are considered in this paper. Three applications illustrate the use of INLA for a NMA.

Highlights

  • Network meta-analysis (NMA)[1] or mixed treatment comparison,[2] which is a generalization of the pairwise (2 treatments) meta-analysis,[3] allows us to compare multiple treatments, they have not been evaluated directly in a single trial

  • We show how NMA models fit in the class of latent Gaussian models and how NMA models are implemented using integrated nested Laplace approximations (INLA) and demonstrate that the estimates obtained by INLA are in close agreement with the ones obtained by Markov chain Monte Carlo (MCMC)

  • Sauter and Held[25] showed that many NMA models that are in the class of latent Gaussian models (LGMs) and INLA can be used as an inference technique alternative to MCMC for NMA models

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Summary

INTRODUCTION

Network meta-analysis (NMA)[1] or mixed treatment comparison,[2] which is a generalization of the pairwise (2 treatments) meta-analysis,[3] allows us to compare multiple treatments, they have not been evaluated directly in a single trial. What is already known: Bayesian inference using Markov chain Monte Carlo (MCMC) is one of the most popular approaches for fitting network meta-analysis (NMA) models to take into account possible heterogeneity and inconsistency in the network. Sauter and Held[25] showed that many NMA models that are in the class of LGMs and INLA can be used as an inference technique alternative to MCMC for NMA models They demonstrated how INLA can be applied to a NMA model with difference-based likelihood,[1] with arm-based likelihood[2] and the node-splitting approach.[10]. We use a common regression framework, which allows us to analyze datasets with different type of outcomes including continuous, dichotomous, and count using INLA Another contribution to the existing literature is the introduction of an R package, nmaINLA (https://CRAN.R-project.org/package=nmaINLA), which is developed to automate INLA implementation of NMA models described in the paper and publicly available from CRAN. We close with some conclusions and provide a brief discussion

STATISTICAL MODELS FOR NMA
Fixed effect model
Consistency model
Network meta-regression
BAYESIAN INFERENCE FOR FITTING NETWORK META-ANALYSIS MODELS USING INLA
APPLICATIONS
Diabetes
Smoking cessation
Stroke prevention: network meta-regression with dichotomous endpoints
Findings
DISCUSSION

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