Adjusted indirect comparison may be less biased than direct comparison for evaluating new pharmaceutical interventions.
OBJECTIVE
To investigate discrepancies between direct comparison and adjusted indirect comparison in meta-analyses of new versus conventional pharmaceutical interventions.


METHODS
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.


CONCLUSIONS
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.
Song
F
F
School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, Norfolk NR4 7TJ, UK. fujian.song@uea.ac.uk
Harvey
I
I
Lilford
R
R
D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D015982:Bias; D016642:Bupropion / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D004358:Drug Therapy; D005473:Fluoxetine / Q000627:therapeutic use; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D007099:Imipramine / Q000627:therapeutic use; D015201:Meta-Analysis as Topic; D009538:Nicotine / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy; D016540:Smoking Cessation / Q000379:methods; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D005473:Fluoxetine; D016642:Bupropion; D009538:Nicotine; D006220:Haloperidol; D018967:Risperidone; D007099:Imipramine