Lead Investigator: Stefan Leucht, Technical University of Munich
Title of Proposal Research: Individual-patient-data (IPD) meta-analysis of the efficacy of clozapine versus second-generation antipsychotic drugs in patients with treatment-resistant schizophrenia
Vivli Data Request: 6881, 5484
Funding Source: Government Funding (German Ministry of Education and Research)
Potential Conflicts of Interest: In the last 3 years Stefan Leucht has received honoraria as a consultant or for lectures for LB Pharma, Otsuka, Lundbeck, Boehringer Ingelheim, LTS Lohmann, Janssen, Johnson&Johnson, TEVA, MSD, Sandoz, SanofiAventis, Angelini, Sunovion, Recordati and Geodon Richter.
None of these honoraria was related to the proposed research project. There is no other financial relationship (grant support, royalties, pending patents) with any of these or other companies. No conflict of interest results in this regard.
Stefan Leucht is the head of a section for evidence based medicine in psychiatry. His work group received research grants from the German Ministry of Education and Research to conduct the proposed project and other systematic reviews and meta-analyses in the field of psychiatry. No conflict of interest arises from this government-funding. The funding agency will not have any role in analysing or interpreting the data and it will not be involved in writing the report.
Stefan Leucht is the last author of a scientific publication on a network-meta-analysis in treatment resistant schizophrenia, which showed no significant difference in efficacy between clozapine and other second-generation antipsychotics, whereas another analysis found significant differences. With the proposed project, clozapine should be compared to other second-generation antipsychotics in more detail using IPD data. There is an academic interest to solve this important clinical question but no conflict of interest for the conduct of this project.
Summary of the Proposed Research:
Schizophrenia is a debilitating disorder affecting approximately 1% of the public (McGrath et al., 2008), and up to one third of the patients can be considered treatment-resistant (Lally et al, 2016). Clozapine is the only antipsychotic with approved superiority, yet it is reserved as last resort due to its poor tolerability (Hasan et al., 2012). Nevertheless, current syntheses of evidence based on meta-analyses of aggregated data (Samara et al., 2016; Asenjo Lobos et al., 2010; Siskind et al., 2017) show conflicting results and challenge the superiority of clozapine against the other so-called second-generation antipsychotics, which have a better safety profile.
Therefore, we will re-analyze randomized evidence of the comparison between clozapine and other second-generation antipsychotics in treatment-resistant schizophrenia using individual-participant-data (IPD) meta-analysis, which is the “gold standard” of systematic reviews. We will be able to produce more precise results and identify which patients might benefit from clozapine. Our methods will follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement for IPD (Stewart et al., 2015), and the highest Cochrane standards. Statistical analyses will be conducted in collaboration with Professor Georgia Salanti, one of the leading statisticians in meta-analysis. Our team includes experts in schizophrenia and IPD meta-analysis.
Results from this IPD analysis could be utilized in the production of clinical guidelines and in the design of future trials. Hence, they are very likely to have a real impact in the treatment of this critical population.
DOUBLE BLIND, DOUBLE DUMMY MULTICENTER, PARALLEL GROUP COMPARISON OF THE TOLERABILITY OF ZIPRASIDONE VS CLOZAPINE IN SCHIZOPHRENIC PATIENTS WHO ARE INTOLERANT TO ANTIPSYCHOTIC THERAPY
Study ID: NCT00649844
Sponsor ID: A1281039
(Note: Additional studies added as part of data request 6881)
Olanzapine Versus Clozapine in Refractory Schizophrenic Patients
Data Contributor: Lilly
Study ID: F1D-EW-HGCF