Discussion
SUDs, OUD
DISORDER, DISORDERS
Our study suggests that stimulant use is a barrier to buprenorphine or XR-NTX initiation. Whether associations were estimated in randomized trials or generalized to people needing SUD treatment, people entering SUD treatment, or people from rural communities with high rates of IDU, concurrent stimulant use was associated with a 25–40% reduction in the likelihood of initiating MOUD. Although many of our generalized results failed to reach statistical significance, previous research has generally shown a negative association between stimulant use, especially MA, and MOUD initiation, with effect sizes similar to those observed in our study [Understanding differences between source (i.e., clinical trial participants) and target populations (people identifying the need for treatment, people entering treatment, and rural people with high rates of IDU) is critical to interpreting and applying results. RCTs frequently do not represent real-world populations of clinical relevance, and the degree to which exposure effects estimated from clinical trials are generalizable depends on differences in variables that modify the treatment effect [Stimulant use may inhibit MOUD initiation through several causal pathways, both structural and personal. Historically, clinical guidelines discouraged buprenorphine treatment for people who use other substances along with opioids; these were updated in 2020 with the caveat that this population may require additional support and more intensive care [NSDUH respondents were more likely to be white, highly educated, employed, and female than trial participants. The NSDUH is also a household survey, failing to reach the substantial number of people with SUDs who experience homelessness (nearly 30% of clinical trial participants had been recently homeless). Also, rates of IDU, a marker of the severity of substance use disorder, were about half as high in the NSDUH compared to the clinical trials. Results suggest that the impact of stimulant use may have been reduced in this population compared to that observed in the clinical trials, although results failed to reach statistical significance. Differences may be attributable to more support structures, resources, and/or other advantages available to racial/ethnic majority, educated, employed, and housed people with less severe substance use disorders responding to the NSDUH.The CTN trials seem to be a better approximation of the population entering SUD treatment, as characterized by TEDS. This is supported by a previous analysis of TEDS data showing that people admitted for OUD treatment who also used MA were 35% less likely to have MOUD as part of the treatment plan, an effect size similar to that observed in the trials [On the other hand, the negative impact of stimulant use on treatment initiation was nearly doubled in the population from rural areas, which were generally non-treatment seeking, had lower levels of education, and much higher rates of homelessness and IDU than the clinical trial participants. Stimulant use may be associated with as much as a 40% reduction in the likelihood of MOUD initiation in this population, which already suffers from limited access to SUD treatment [Our findings highlight the need for evidence-based interventions to reduce stimulant use among people from rural communities with OUD, who are rarely included in clinical trials [Generalizability and transportability analyses offer several advantages when answering questions about “real-world” impacts of treatment compared to using a single dataset, even if that dataset is large and representative of the target population [Our study is subject to several limitations. Most notably, generalizability analysis relies on untestable assumptions about the causal mechanisms giving rise to differential treatment effects across populations. All observational studies rely on similar untestable assumptions; we utilized a combination of subject-matter expertise, protocols, previous literature, and data to select a covariate set for IPSW estimation, and we publish our assumptions in the form of a “selection diagram” (Additional
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