Effects of Buprenorphine Dose and Therapeutic Engagement on Illicit Opiate Use in Opioid Use Disorder Treatment Trials

The impact of agonist dose and of physician, staff and patient engagement on treatment have not been evaluated together in an analysis of treatment for opioid use disorder. Our hypotheses were that greater agonist dose and therapeutic engagement would be associated with reduced illicit opiate use in a time-dependent manner. Publicly-available treatment data from six buprenorphine efficacy and safety trials from the Federally-supported Clinical Trials Network were used to derive treatment variables. Three novel predictors were constructed to capture the time weighted effects of buprenorphine dosage (mg buprenorphine per day), dosing protocol (whether physician could adjust dose), and clinic visits (whether patient attended clinic). We used time-in-trial as a predictor to account for the therapeutic benefits of treatment persistence. The outcome was illicit opiate use defined by self-report or urinalysis. Trial participants (N = 3022 patients with opioid dependence, mean age 36 years, 33% female, 14% Black, 16% Hispanic) were analyzed using a generalized linear mixed model. Treatment variables dose, Odds Ratio (OR) = 0.63 (95% Confidence Interval (95%CI) 0.59-0.67), dosing protocol, OR = 0.70 (95%CI 0.65-0.76), time-in-trial, OR = 0.75 (95%CI 0.71-0.80) and clinic visits, OR = 0.81 (95%CI 0.76-0.87) were significant (p-values < 0.001) protective factors. Treatment implications support higher doses of buprenorphine and greater engagement of patients with providers and clinic staff.