Background: Indirect comparisons are becoming increasingly popular for evaluating medical treatments that have not been compared head-to-head in randomized clinical trials (RCTs). While indirect methods have grown in popularity and acceptance, little is known about the fragility of confidence interval estimations and hypothesis testing relying on this method.
Methods: We present the findings of a simulation study that examined the fragility of indirect confidence interval estimation and hypothesis testing relying on the adjusted indirect method.
Findings: Our results suggest that, for the settings considered in this study, indirect confidence interval estimation suffers from under-coverage while indirect hypothesis testing suffers from low power in the presence of moderate to large between-study heterogeneity. In addition, the risk of overestimation is large when the indirect comparison of interest relies on just one trial for one of the two direct comparisons.
Interpretation: Indirect comparisons typically suffer from low power. The risk of imprecision is increased when comparisons are unbalanced.