AbstractRandomized controlled trials (RCTs) have been considered as gold standard for establishing the efficacy and safety of investigational new drugs; nonetheless, the generalizability of their findings has been questioned. To address this issue, an increasing number of naturalistic studies and real-world database analyses have been conducted. The question of how much information from these two approaches is congruent or discrepant with each other is of great importance for the clinical practice. To answer this question, we focused on data from the antipsychotic (AP) treatment of schizophrenia. Our aim was two-fold: to conduct a meta-analysis of real-world studies (RWS), and to compare the results of RWS meta-analysis with previously published meta-analyses of RCTs. The principal measure of effectiveness was all-cause treatment discontinuation for both RWS and RCTs (when not available, then drop out for RCTs). We included publications for 8 selected APs (oral formulations of amisulpride, aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and long-acting injectable (LAI) risperidone). We identified 11 RWS and 7 RCT meta-analyses for inclusion. Our results indicated that the RWS yielded statistically conclusive and consistent findings across individual investigations. For the overwhelming majority of the comparisons where both RWS and RCT meta-analyses were available, there was good congruency between the RWS and the RCT results. Our results support that RCTs, despite their limitations, provide evidence which is generalizable to real-world settings. This is an important finding for both regulators and clinicians. RWS can provide guidance for situations where no evidence is available from double-blind clinical trials.
The trade-off between impartiality and freedom in the 21st Century Cures Act
