title: Long-acting injectable versus daily oral antipsychotic treatment trials in schizophrenia: pragmatic versus explanatory study designs.
abstract: Trial design characteristics related to the explanatory : pragmatic spectrum may contribute toward the inconsistent results reported in studies comparing long-acting injectable (LAI) versus daily oral antipsychotic (AP) treatments in schizophrenia. A novel approach examined the hypothesis that a more pragmatic design is important to show the advantages of LAI versus oral APs. A literature search identified comparative studies assessing the clinical efficacy/effectiveness of LAI versus oral APs in more than 100 schizophrenia patients, with 6-month or more duration/follow-up, and published between January 1993 and December 2013 (n=11). Each study's design was rated using the six-domain ASPECT-R (A Study Pragmatic : Explanatory Characterization Tool-Rating). Nonparametric Wilcoxon rank-sum tests compared ratings of studies supporting (n=7) and not supporting (n=4) a LAI advantage. ASPECT-R total and domain scores were significantly higher (more pragmatic) in studies finding a LAI versus oral AP treatment advantage than those that did not. The rank order of this significance among domains was as follows: 'participant compliance assessment' (P=0.005), 'medical practice setting/practitioner expertise' (P=0.006), 'intervention flexibility' (P=0.007), 'follow-up intensity/duration' (P=0.009), 'primary trial outcomes' (P=0.012), and 'participant eligibility' (P=0.015). Findings support that more pragmatic, less explanatory design features are important to show advantages for LAI treatment. Explanatory studies may introduce features that obscure advantages related to adherence.
authors.affiliation: aJanssen Scientific Affairs, LLC, Titusville, New Jersey bDepartment of Psychiatry, The Zucker Hillside Hospital, Glen Oaks cHofstra-North Shore LIJ School of Medicine, Hempstead, New York, USA.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Bossie
authors.forename: Larry D
authors.initials: LD
authors.lastname: Alphs
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D000284:Administration, Oral; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007273:Injections, Intramuscular; D064792:Pragmatic Clinical Trials as Topic; D012107:Research Design; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations