Using the contribution matrix to evaluate complex study limitations in a network meta-analysis: a case study of bipolar maintenance pharmacotherapy review

Limitations in the primary studies constitute one important factor to be considered in the grading of recommendations assessment, development, and evaluation (GRADE) system of rating quality of evidence. However, in the network meta-analysis (NMA), such evaluation poses a special challenge because each network estimate receives different amounts of contributions from various studies via direct as well as indirect routes and because some biases have directions whose repercussion in the network can be complicated.