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Psych Congress  

The Impact of Study Design in Comparative Effectiveness Research in Schizophrenia

Bruce Wong, MD; Noam Kirson, PhD; Sander Yermakov, MS; Wayne Huang, MPP; Thomas Samuelson, BA; Steve Offord, PhD; Paul Greenberg, MS
Otsuka America Pharmaceutical, Inc.

BACKGROUND: Randomized controlled trials (RCTs) and observational studies have yielded inconsistent results when comparing oral vs. depot formulations of antipsychotics, highlighting the question of how research design affects estimates of comparative effectiveness (CE). We quantify the effect of study design on the CE of antipsychotic formulations. METHODS: A search of English literature since 2000 for studies with depot and oral antipsychotic treatment arms for schizophrenia with relapse, hospitalization or all-cause discontinuation endpoints. Baseline characteristics were used to adjust endpoints for age and gender. Adjusted endpoints were converted to risk ratios (RR) [depot/oral; RR<1 favors depot] and pooled by study design (RCT, prospective, and retrospective). Meta-analysis with random effects was used to estimate the pooled RR and 95% confidence interval (CI) of all endpoints combined within each study design. The ratios of resulting point estimates were used to calculate average conversion factors between study designs. RESULTS: 13 studies (5 RCTs and 8 observational studies) with 19 depot-oral comparisons were included. Meta-analysis of adjusted endpoints resulted in RR [CI] of 0.88 [0.64-1.20] for RCTs, 0.62 [0.48-0.81] for prospective and 0.56 [0.44-0.71] for retrospective studies. These imply conversion factors of 1.41 and 1.57 between RCTs and prospective and retrospective designs, respectively. CONCLUSIONS: Study design has a systematic effect on the comparison of Depot vs. Oral antipsychotic agents with implications for the application of study results to clinical practice. Depot antipsychotics display increasing effectiveness compared with oral formulations as study design shifts from RCTs towards real-world clinical settings.

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