Redesigning a Stopped Clinical Trial as an Emulated Trial Using Real-World Data to Explore the Effectiveness of Slow-Release Oral Morphine as a Treatment for Opioid Use Disorder.

Abstract

Canada is currently experiencing a problematic opioid crisis with increasing mortality rates. Traditional randomized controlled trials (RCTs) that examine the effectiveness of pharmacological treatment options for people with opioid use disorder (OUD) are challenging to conduct. An increasingly popular methodology is through the implementation of emulated clinical trials, a methodology in which key elements of a "target" RCT are replicated using previously collected healthcare-based data. They can possibly address some of the common challenges found in the conduct of RCTs, such as prolonged timelines, high cost, and poor participant recruitment. In effect, emulated trials accelerate knowledge generation by producing real-world evidence that can be akin to phase 3 effectiveness trials, without any need to recruit live participants or administer investigational products. During the COVID-19 pandemic, several trials were stopped due to increased pandemic-related research restrictions, leaving important questions about OUD treatment unanswered. In this commentary, we describe the transition of a traditional RCT to an emulated trial spurred by challenges posed by the COVID-19 pandemic. We describe our transition using a notable published framework with regards to the population sample, interventions, outcomes, and proposed analyses. This commentary aims to help other researchers and trialists apply emulated trials in substance use research and beyond, emphasizing the role of this methodology in clinical research and advancing scientific knowledge that could be otherwise lost or unattainable.