Clozapine-IPD

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.