title: Geographic variation in efficacy of atypical antipsychotics for the acute treatment of schizophrenia - an individual patient data meta-analysis.
abstract: Generalizability of efficacy results from medication trials across geographic regions is disputed. Geographic differences in factors such as patient characteristics, treatment practices and disease definitions might lead to differences in effect sizes across regions. This study examined geographic variation in efficacy results of schizophrenia trials with atypical antipsychotics using individual-patient data meta-analysis. Twenty-two studies including in total 5233 patients from three regions (North America, Europe, and the rest of the world) were included in the random effects meta-analysis. The effect size in North American patients was smaller in terms of mean change from baseline and in terms of responders (Hedge׳s G=0.37, 95% CI 0.28-0.46; OR 1.71, 95% CI 1.35-2.17) as compared to patients in Europe (Hedge׳s G=0.56, 95% CI 0.34-0.79; OR 2.25, 95% CI 1.62-3.12) and the rest of the world (Hedge׳s G=0.53, 95% CI 0.12-0.75; OR 2.61, 95% CI 1.66-4.17). The differences were not statistically significant. The observed differences remained when the confounding effect of unequal distribution of compounds was controlled for by analyzing separately the compounds that were studied across all three regions. Based on these results it cannot be excluded that there are differences in efficacy results of atypical antipsychotics trials across geographic regions. The observed trend towards differential efficacy across geographic regions warrants further examination of the determinants of these differences.
authors.affiliation: Medicines Evaluation Board, Utrecht, The Netherlands. Electronic address: tk.mattila@cbg-meb.nl.
authors.forename: Taina
authors.initials: T
authors.lastname: Mattila
authors.affiliation: Medicines Evaluation Board, Utrecht, The Netherlands; Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tamar
authors.initials: T
authors.lastname: Wohlfarth
authors.affiliation: Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Koeter
authors.affiliation: Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jitschak
authors.initials: J
authors.lastname: Storosum
authors.affiliation: Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
authors.affiliation: Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lieuwe
authors.initials: L
authors.lastname: de Haan
authors.affiliation: Medicines Evaluation Board, Utrecht, The Netherlands.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Leufkens
authors.affiliation: Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Damiaan
authors.initials: D
authors.lastname: Denys
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D005060:Europe; D006801:Humans; D009656:North America; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents
keywords: Antipsychotics; Meta-analysis; Region; Schizophrenia