Methodological guideline for REA of pharmaceuticals: Direct and indirect comparison

Direct comparison is generally thought to provide the best evidence of relative effectiveness and is in general recommended. However, the use of multiple treatment comparisons allows the consideration of a larger evidence base. When both direct and indirect evidence are available, it may be pragmatic to investigate both first separately and then pool the results. Although Bucher’s method of adjusted indirect comparison is the most computationally straightforward of the multiple treatment methods, Bayesian MTC can be used to analyse very complex networks and can incorporate meta-regression to include study-level covariates. The choice of methodology is ultimately context specific and should be appropriate to the data available.