A meta-analysis of effectiveness of real-world studies of antipsychotics in schizophrenia: Are the results consistent with the findings of randomized controlled trials?

Abstract

Randomized 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.

Antipsychotic prescribing practices in real-life (APPREAL study): Findings from the French National Healthcare System Database (2007–2017)

“…Cyamemazine was also associated with a low adherence, but this might be due to the conditions of use of this drug, which can be more easily used as an as-needed treatment, since it targets anxiety or irritability. Regarding other oral antipsychotics, our results are in line with other studies, which found that clozapine was the antipsychotic drug with the highest level of adherence ( 19 ), and that olanzapine, quetiapine, and aripiprazole were associated with low rates of treatment discontinuation, when compared to other antipsychotics ( 20 ). However, our study is the first to confirm this in real-life French data.…”

Real‐world evidence for the long‐term effect of allergen immunotherapy: Current status on database‐derived European studies

“…One reason for this is the so‐called efficacy‐effectiveness gap, which means that the effectiveness in clinical practice is generally reduced compared to the efficacy shown in RCTs by transfer and implementation loss, for example, delivery of care, adherence to treatment, and time between treatment and assessment of the outcome 32,33 . Nevertheless, consistency between RWD and RCT data was already shown for indications like metastatic renal cell carcinoma when treated with the tyrosine kinase inhibitor sunitinib or the use of antipsychotics in schizophrenia 34,35 …”

Real-world evidence for the long-term effect of allergen immunotherapy: current status on database-derived studies

“…delivery of care, adherence to treatment, and time between treatment and assessment of the outcome (31,32). Nevertheless, consistency between RWD and RCT data were already shown for indications like metastatic renal cell carcinoma when treated with the tyrosine kinase inhibitor sunitinib or the use of antipsychotics in schizophrenia (33,34).…”