Date of Award

2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy in Pharmaceutical Sciences

Department

Biomedical and Pharmaceutical Sciences

First Advisor

Ashely L. Buchanan

Abstract

The United States is facing an unprecedented crisis of drug overdose and poisoning deaths. In this dissertation, we studied three different aspects of opioid use disorder and health-related outcomes using routinely collected data.

Manuscript 1: We designed a cross-sectional study to evaluate the association between early buprenorphine-naloxone initiation (within 90 days after the diagnosis of opioid use disorder) and health-related outcomes among insured adults with opioid use disorder in the United States from 2010 to 2018. Generalized linear models with multiple imputation to account for missing data were applied to estimate the association and adjust for self-reported socioeconomic status, comorbidities, and concomitant medications. We found that timely buprenorphine-naloxone initiation was associated with a reduced occurrence of opioid overdose and a statistically significant reduction in opioid overdose-related emergency department visits and costs.

Manuscript 2: We designed a retrospective study to evaluate the association between time-varying buprenorphine-naloxone prescribing and subsequent opioid overdose or death among insured adults with opioid use disorder in the United States from 2010 to 2017. We fit a marginal structural model using inverse probability weights to account for measured baseline and time-varying confounders, as well as selection bias due to possibly informative lost-to-follow-up. We found that continuously receiving buprenorphine-naloxone was associated with reduced risk of opioid overdose and all-cause mortality.

Manuscript 3: We designed a retrospective study to estimate the direct and disseminated effects of buprenorphine-naloxone prescribing on subsequent health-related outcomes (opioid overdose, death, emergency department visit, hospitalization) among insured adults with opioid use disorder in the United States between from 2010 to 2017. We used both an inverse probability weighted estimator and a stabilized estimator to estimate the causal effects of buprenorphine-naloxone with possible spillover or interference. We found that showed that being prescribed buprenorphine-naloxone was protective against opioid overdose, death, and hospitalization during a two-year follow-up period. Interestingly, among untreated patients, being in a cluster with 67% coverage of the medication (i.e., 67% of patients in the cluster were treated) was associated with a lower risk of opioid overdose and death than being in a cluster with lower coverage at 33% or 50%.

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