Objective: To investigate discrepancies between direct comparison and adjusted indirect comparison in meta-analyses of new versus conventional pharmaceutical interventions.
Study design and setting: Results of direct comparison were compared with results of adjusted indirect comparison in three meta-analyses of new versus conventional drugs. The three case studies are (1) bupropion versus nicotine replacement therapy for smoking cessation, (2) risperidone versus haloperidol for schizophrenia, and (3) fluoxetine versus imipramine for depressive disorders.
Results: In all the three cases, effects of new drugs estimated by head-to-head trials tend to be greater than that by adjusted indirect comparisons. The observed discrepancies could not be satisfactorily explained by the play of chance or by bias and heterogeneity in adjusted indirect comparison. This observation, along with analysis of possible systematic bias in the direct comparisons, suggested that the indirect method might have produced less biased results. Simulations found that adjusted indirect comparison may counterbalance bias under certain circumstances.
Conclusion: Adjusted indirect comparison could be used to cross-examine the validity and applicability of results from head-to-head randomized trials. The hypothesis that adjusted indirect comparison may provide less biased results than head-to-head randomized trials needs to be investigated by further research.