Evaluating and informing innovations in medications for opioid use disorder modalities amidst the evolving illicit drug supply - PROJECT SUMMARY / ABSTRACT This R01 application proposes the continuation of a 29-year-old, NIDA-funded cohort study to evaluate the impacts of the evolving unregulated drug supply, innovative medications for opioid use disorder (MOUD) modalities, and complementary overdose prevention interventions on MOUD access, retention and outcomes in Vancouver, Canada. To enable a rigorous evaluation of these innovations, we propose maintaining the VIDUS- Opioid (VIDUS-O) cohort, a subset of the Vancouver Injection Drug Users Study (VIDUS) - one of the longest- running (since 1996), prospective cohort studies of community-recruited people who use drugs globally. The US and Canada have been grappling with a severe overdose crisis driven by potent synthetic opioids (e.g., fentanyl) in the unregulated drug supply, further exacerbated by emerging novel adulterants (e.g., new psychoactive substance [NPS] benzodiazepines). While MOUD remains the primary clinical tool to address the crisis, there is a need for greater innovation because existing MOUD modalities and guidelines, largely developed prior to the emergence of fentanyl, may not adequately address the needs of individuals with high opioid tolerance due to fentanyl exposure. Providing a greater number of MOUD options is needed to fully address patient needs and improve MOUD access and retention. A significant research gap also exists in accounting for the dynamic and often unpredictable changes in the unregulated drug supply (e.g., extreme fluctuations of fentanyl concentration, the emergence of NPS benzodiazepines), and the associated impact on MOUD access, retention and outcomes. Further, recognizing that continued opioid use is common among MOUD patients, it is also crucial to investigate the potential synergistic effects of other overdose prevention services (e.g., drug checking services and overdose prevention centers [OPCs]) in supporting MOUD engagement and preventing overdoses. The VIDUS-O cohort of community-recruited 700 people who use opioids provides an ideal infrastructure for addressing these critical research gaps. In recent years, Vancouver has implemented many innovative MOUD modalities that have not yet been trialed in the US, including slow-release oral morphine (SROM), fentanyl-based MOUD and flexible swithcing of MOUD modalities. Also, drug checking and OPCs have been widely implemented since 2017. Further, wide-scale implementation of drug checking enables us to capture rare data on dynamic changes in the unregulated drug supply. Specific aims of this study include evaluating: (1) access to, retention in and outcomes (e.g., overdose risks) of novel and flexible MOUD (e.g., SROM, fentanyl-based MOUD and switching MOUD modalities); (2) the impacts of drug supply changes on MOUD access, retention and outcomes; (3) the impacts of drug checking/OPC use on MOUD access and retention; and (4) the potential joint effect of MOUD and drug checking/OPC use on overdose risks. This study will advance the optimization of MOUD and complementary interventions and serve to inform responses to the ongoing overdose crisis in the US and throughout North America.
