Uncovered, underfunded, and undervalued: How policy contexts shape knowledge production in multi-site substance use trials

• Multisite qualitative study of people who use drugs in a pragmatic trial. • Structural stigma manifests in treatment policies and priorities. • Provincial approaches to treatment shape trial enrollment and study experiences. • Pragmatic drug trials are locally situated and embedded in policy contexts. Pragmatic trials evaluate the effectiveness or feasibility of a treatment in clinical practice. However, in substance use research, the “real world” is characterized by patterns of structural stigma embedded in everchanging drug policies and public perceptions that vary by jurisdiction. While such contextual influences typically go unmeasured in clinical research, these localized features may shape participants’ trial experiences and outcomes, with relevance for the conduct of multisite trials and their results. We conducted a nested qualitative study with people who use drugs (PWUD) enrolled in a multi-site, pragmatic randomized controlled trial testing models of care for opioid use disorder. We analyzed 115 semi-structured interviews from 75 participants across four Canadian provinces using a flexible coding approach and thematic analysis. We investigate how jurisdictional differences in treatment-related policies shaped pragmatic trial experiences. In Alberta, participants described abrupt loss of study medication coverage due to restrictive income assistance policies, which could lead to treatment interruption. In Ontario and Quebec, long wait times for medications motivated enrollment in the trial, which participants viewed as a faster pathway to care. In British Columbia, participants highlighted concerns with inadequate medication formulations and limited access to emerging treatments. These site-specific dynamics underscore how structural stigma and treatment policies can manifest in research to complicate trial conduct and the interpretation of findings. Jurisdictional policy contexts and embedded structural stigma shape participants’ experiences with substance use treatment and, consequently, treatment trials, necessitating the consideration of trial results across research settings.