Patient Engagement With a Game-Based Digital Therapeutic for the Treatment of Opioid Use Disorder: Protocol for a Randomized Controlled Open-Label, Decentralized Trial
Authors: Luderer Hilary , Chiodo Lisa , Wilson Amanda , Brezing Christina , Martinez Suky , Xiong Xiaorui , Gerwien Robert , Imbert Bruce , Deeg Mark , Maricich Yuri , Campbell Aimee 
Published: November 2021

Background
Prescription digital therapeutics are software-based disease treatments that are regulated by the US Food and Drug Administration; the reSET-O prescription digital therapeutic was authorized in 2018 and delivers behavioral treatment for individuals receiving buprenorphine for opioid use disorder. Although reSET-O improves outcomes for individuals with opioid use disorder, most of the therapeutic content is delivered as narrative text. PEAR-008 is an investigational device based on reSET-O that uses an interactive, game-based platform to deliver similar therapeutic content designed to enhance patient engagement, which may further improve treatment outcomes.

Objective
We aim to investigate how participants interact with the prescription digital therapeutic’s new content delivery format. Secondary objectives include evaluating treatment success, symptoms of co-occurring mental health disorders, recovery capital, and skill development.

Methods
Due to the COVID-19 pandemic, this study was redesigned using a decentralized model because it was not possible to conduct medication initiation and study visits in person, as initially intended. A decentralized, randomized controlled trial design will be utilized to compare patient engagement with PEAR-008 and that with reSET-O using both subjective and objective assessments. The study population will consist of approximately 130 individuals with opioid use disorder (based on Diagnostic and Statistical Manual of Mental Disorders 5 criteria) who have recently started buprenorphine treatment for opioid use disorder. Participants will be virtually recruited and randomly assigned to receive either PEAR-008 or reSET-O. All study sessions will be virtual, and the duration of the study is 12 weeks. The primary outcome measure of engagement is operationalized as the number of active sessions per week with either PEAR-008 or reSET-O. (An active session is any session that contains some active participation in the app, such as navigating to a different screen, engaging with a learning module, or responding to a notification.) Subjective dimensions of engagement will be assessed with participant surveys. The hypothesis is that PEAR-008 will have significantly greater participant engagement than reSET-O.

Results
As of February 2021, participant enrollment is ongoing.

Conclusions
This randomized controlled trial will investigate if changing the delivery format and enhancing the content of a prescription digital therapeutic for opioid use disorder will affect how participants use and interact with the prescription digital therapeutic. The study design may serve as a useful model for conducting decentralized studies in this patient population.

Trial Registration
ClinicalTrials.gov NCT04542642; https://clinicaltrials.gov/ct2/show/NCT04542642

International Registered Report Identifier (IRRID)
DERR1-10.2196/32759