Multivariate network meta-analysis to mitigate the effects of outcome reporting bias

Outcome reporting bias (ORB) is recognized as a threat to the validity of both pairwise and network meta-analysis (NMA). In recent years, multivariate meta-analytic methods have been proposed to reduce the impact of ORB in the pairwise setting. These methods have shown that multivariate meta-analysis can reduce bias and increase efficiency of pooled effect sizes. However, it is unknown whether multivariate NMA (MNMA) can similarly reduce the impact of ORB. Additionally, it is quite challenging to implement MNMA due to the fact that correlation between treatments and outcomes must be modeled; thus, the dimension of the covariance matrix and number of components to estimate grows quickly with the number of treatments and number of outcomes. To determine whether MNMA can reduce the effects of ORB on pooled treatment effect sizes, we present an extensive simulation study of Bayesian MNMA. Via simulation studies, we show that MNMA reduces the bias of pooled effect sizes under a variety of outcome missingness scenarios, including missing at random and missing not at random. Further, MNMA improves the precision of estimates, producing narrower credible intervals. We demonstrate the applicability of the approach via application of MNMA to a multi-treatment systematic review of randomized controlled trials of anti-depressants for the treatment of depression in older adults.