How study designs influence comparative effectiveness outcomes: the case of oral versus long-acting injectable antipsychotic treatments for schizophrenia.
This article reviews key methodological considerations for clinical trials that utilize explanatory and pragmatic trial designs and relates these contrasting approaches to the interpretation of results from comparisons of oral versus long-acting injectable (LAI) antipsychotics in schizophrenia. Explanatory randomized controlled trials (RCTs) generally measure the efficacy of a treatment in a homogeneous population with intensive, frequent, and often clinical trial-specific assessments. In contrast, pragmatic trials measure effectiveness in routine clinical practice and frequently aim to inform choices between treatments. Comparative effectiveness outcomes with pragmatic designs in naturalistic settings for schizophrenia treatments are of increasing interest to healthcare providers because outcomes of treatment (both efficacy and safety) may vary significantly when identified in an explanatory setting compared with a naturalistic pragmatic setting. Indeed, it has been suggested that the inconsistent outcomes observed in trials comparing oral and LAI antipsychotic medications may be a function of the use of explanatory or pragmatic trial designs. In practice, clinical trial designs are seldom purely explanatory or pragmatic. To identify the predominant orientation of a trial, one must consider multiple features. This paper reviews the relative impact of these features when comparing LAI and oral antipsychotic treatments and makes recommendations for improving these comparative designs.
Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, USA. Electronic address: lalphs@its.jnj.com.
Larry
L
Alphs
Department of Psychiatry & Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA. Electronic address: nina.schooler@gmail.com.
Nina
N
Schooler
Department of Psychiatry, University of Missouri, Columbia, MO, USA. Electronic address: laurielloj@health.missouri.edu.
John
J
Lauriello
D000284:Administration, Oral; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D057186:Comparative Effectiveness Research; D003692:Delayed-Action Preparations / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007267:Injections; D064792:Pragmatic Clinical Trials as Topic; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations
Effectiveness; Explanatory; Long-acting; Pragmatic