Long-acting injectable versus daily oral antipsychotic treatment trials in schizophrenia: pragmatic versus explanatory study designs

• Published in: International clinical psychopharmacology Vol. 30; no. 5; p. 272
• Main Authors: Bossie, Cynthia A, Alphs, Larry D, Correll, Christoph U
• Format: Journal Article
• Language: English
• Published: England 01.09.2015
• Subjects: Administration, Oral; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - therapeutic use; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - therapeutic use; Humans; Injections, Intramuscular; Pragmatic Clinical Trials as Topic; Research Design; Schizophrenia - drug therapy
• DOI: 10.1097/YIC.0000000000000082

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.