A simulation study to compare different estimation approaches for network meta-analysis and corresponding methods to evaluate the consistency assumption

BACKGROUND: Network meta-analysis (NMA) is becoming increasingly popular in systematic reviews and health technology assessments. However, there is still ambiguity concerning the properties of the estimation approaches as well as for the methods to evaluate the consistency assumption. METHODS: We conducted a simulation study for networks with up to 5 interventions. We investigated the properties of different methods and give recommendations for practical application. We evaluated the performance of 3 different models for complex networks as well as corresponding global methods to evaluate the consistency assumption. The models are the frequentist graph-theoretical approach netmeta, the Bayesian mixed treatment comparisons (MTC) consistency model, and the MTC consistency model with stepwise removal of studies contributing to inconsistency identified in a leverage plot. RESULTS: We found that with a high degree of inconsistency none of the evaluated effect estimators produced reliable results, whereas with moderate or no inconsistency the estimator from the MTC consistency model and the netmeta estimator showed acceptable properties. We also saw a dependency on the amount of heterogeneity. Concerning the evaluated methods to evaluate the consistency assumption, none was shown to be suitable. CONCLUSIONS: Based on our results we recommend a pragmatic approach for practical application in NMA. The estimator from the netmeta approach or the estimator from the Bayesian MTC consistency model should be preferred. Since none of the methods to evaluate the consistency assumption showed satisfactory results, users should have a strong focus on the similarity as well as the homogeneity assumption.