Design and Rationale of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) Study

Abstract

Background: Public health considerations require that clinical trials address the complex "real-world" needs of patients with chronic illnesses. This is particularly true for persons with schizophrenia, whose management is frequently complicated by factors such as comorbid substance abuse, homelessness, and contact with the criminal justice system. In addition, barriers to obtaining health care in the United States often prevent successful community reentry and optimal patient management. Further, nonadherence to treatment is common, and this reinforces cycles of relapse and recidivism.Long-acting injectable antipsychotic therapy may facilitate continuity of treatment and support better outcomes, particularly in patients who face these challenges. Clinical trials with classical explanatory designs may not be the best approaches for evaluating these considerations. We describe the design and rationale of a novel trial that combines both explanatory and pragmatic design features and studies persons with schizophrenia who face these challenges. Design and Rationale:The Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study is a prospective, open-label, randomized, 15-month study conducted between May 5, 2010, and December 9, 2013, comparing long-acting injectable paliperidone palmitate and oral antipsychotic medications in subjects with schizophrenia (according to DSM-IV criteria). Investigators and subjects had broad flexibility for treatment decision-making, thus making it a model that better reflects real-world practice. The primary end point was time to treatment failure, defined as arrest/incarceration psychiatric hospitalization; suicide; treatment discontinuation or supplementation due to inadequate efficacy, safety, or tolerability; or increased psychiatric services to prevent hospitalization. This end point was adjudicated by a blinded event monitoring board. Patients were followed to the 15-month end point, regardless of whether they were maintained on their initial randomized treatment. This article provides some of the reasoning behind the authors' choices when combining features from both explanatory and pragmatic approaches to this trial's design. Conclusions:The PRIDE study incorporates real-world design features in a novel, prospective, comparative study of long-acting injectable and oral antipsychotics in persons with schizophrenia who have had recent contact with the criminal justice system. Insights provided should help the reader to better understand the need for more real-world approaches for clinical studies and how a broader approach can better aid clinical treatment and public health decision-making.Trial Registration: ClinicalTrials.gov identifier: NCT01157351

Treatment effect with paliperidone palmitate compared with oral antipsychotics in patients with recent‐onset versus more chronic schizophrenia and a history of criminal justice system involvement

“…Similarly, expansion of the primary end‐point to include events such as time to arrest (i.e. the most common treatment failure outcome for this study) extended observations to include events that are of broad public health interest and that can be highly informative 21. However, to our knowledge, this outcome has not been previously assessed in this type of trial.…”

“…PRIDE is a prospective, randomized, open‐label, event monitoring board (EMB)–blinded, parallel‐group, multicentre US study conducted between 5 May 2010 and 9 December 2013 (ClinicalTrials.gov identifier, NCT01157351) 21, 22. The study included a screening phase of up to 2 weeks, followed by a 15‐month randomized treatment phase.…”

“…The Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study (ClinicalTrials.gov identifier, NCT01157351) is a prospective, randomized study that compared the effects of once‐monthly paliperidone palmitate (PP) with the effects of daily oral APs on time to treatment failure 21, 22. The study was designed to evaluate response under conditions that reflect real‐world treatment 21.…”

“…The study was designed to evaluate response under conditions that reflect real‐world treatment 21. It is unique among schizophrenia treatment trials in that it enrolled patients who are customarily excluded from clinical trials, such as those with a history of incarceration and comorbid substance abuse.…”

“…The trial compared PP treatment response with that of oral AP medications and allowed clinicians extensive flexibility in making treatment and management decisions during the course of the study. End‐points included a range of important real‐world consequences of poor treatment response, such as arrest or incarceration, hospitalization and treatment discontinuation 21. Overall study results showed that median time to treatment failure was significantly delayed by 190 days with PP compared with daily oral APs 22…”