Incorporating Multiple Interventions in Meta-Analysis: An Evaluation of the Mixed Treatment Comparison with the Adjusted Indirect Comparison

Background:Comparing the effectiveness of interventions is now a requirement for regulatoryapproval in several countries. It also aids in clinical and public health decision-making. However, inthe absence of head-to-head randomized trials (RCTs), determining the relative effectiveness ofinterventions is challenging. Several methodological options are now available. We aimed todetermine the comparative validity of the adjusted indirect comparisons of RCTs with the mixedtreatment comparison approach.Methods:Using systematic searching, we identified all meta-analyses evaluating more than 3interventions for a similar disease state with binary outcomes. We abstracted data on each clinicaltrial including population n and outcomes. We conducted fixed effects meta-analysis of eachintervention versus mutual comparator and then applied the adjusted indirect comparison. Weconducted a mixed treatment meta-analysis on all trials and compared the point estimates and 95%confidence/credible intervals (CIs/CrIs) to determine important differences.Results:We included data from 7 reviews that met our inclusion criteria, allowing a total of 51comparisons. According to the a priori consistency rule, we found 2 examples where the analyticcomparisons were statistically significant using the mixed treatment comparison over the adjustedindirect comparisons and 1 example where this was vice versa. We found 6 examples where thedirection of effect differed according to the indirect comparison method chosen and we found 9examples where the confidence intervals were importantly different between approaches.Conclusion:In most analyses, the adjusted indirect comparison yields estimates of relativeeffectiveness equal to the mixed treatment comparison. In less complex indirect comparisons,where all studies share a mutual comparator, both approaches yield similar benefits. Ascomparisons become more complex, the mixed treatment comparison may be favoured.