The opioid crisis in the United States poses a major threat to public health due to psychiatric and infectious disease comorbidities and death due to opioid use disorder (OUD). OUD is characterized by patterns of opioid misuse leading to persistent heavy use and overdose. The standard of care for treatment of OUD is medication-assisted treatment, in combination with behavioral therapy. Medications for opioid use disorder have been shown to improve OUD outcomes, including reduction and prevention of overdose. However, understanding the effectiveness of such medications has been limited due to non-adherence to assigned dose levels by study patients. To overcome this challenge, herein we develop a model that views dose history as a time-varying covariate. Proceeding in this fashion allows the model to estimate dose effect while accounting for lapses in adherence. The proposed model is used to conduct a secondary analysis of data collected from six efficacy and safety trials of buprenorphine maintenance treatment. This analysis provides further insight into the time-dependent treatment effects of buprenorphine and how different dose adherence patterns relate to risk of opioid use.
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