Patterns of heroin use and extra-medical (EM) use of other opioid compounds have re-surfaced as important public health issues in the United States (US) and in many countries. Midway through a 21st century epidemic of death due to heroin overdose in the US, there are many gaps in epidemiological evidence. For example, experts have already have concluded that heroin often becomes an alternative or substitute for other prescription opioids because an unit dose of heroin has become less expensive and now is more readily available than diverted prescription opioids (Cicero et al., 2012; Jones 2013; Muhuri et al., 2013). Nonetheless, the evidence on this issue largely is based on case reports, and provides little basis for causal inference. This problem is compounded by the lack of published population-level estimates on heroin incidence rates, akin to estimates derived by Hunt & Chambers (1976), based upon treatment admissions during the US heroin epidemic of the 1960s and 1970s. The first aim of this dissertation addresses this incidence rate gap in epidemiological evidence for the US. It seeks to estimate heroin incidence for 1992-2012 using the Hunt-Chambers method based on opioid treatment admissions. The second dissertation aim is concentrated on a causal inference about the process of becoming a newly incident heroin user, and whether this process might be triggered by prior EM use of OxyContin®, a specific prescription opioid. Thus, the second specific aim is to conduct a case-crossover study to investigate a "triggering hypothesis" that links antecedent EM OxyContin® use with later heroin onset in the US. The third study of this dissertation aims to predict the probability of transitioning from EM prescription pain reliever use to heroin onset using survival analysis models, with attention to hypothesized subgroup variation (i.e., population density).Based on Hunt's model via re-calibration approaches using Treatment Episode Data Set - Admissions datasets (TEDS-A), heroin onset increased 160% from 2000 to its peak in 2010; the incidence rate in 2012 is similar to the first heroin epidemic in 1969. As for opioids other than heroin (e.g., prescription opioids), the incidence increased more than 250% from 2000 to 2010. The second study investigates whether EM OxyContin® use might have triggered heroin onset among 12-25 year olds in the period of 2004-2014. The excess risk of newly incident heroin use is seen in a four-month interval right after onset of EM OxyContin® use (case-crossover risk ratio = 1.9). Post-estimation exploratory analyses suggest no excess risk for EM users of other prescription pain relievers, and indicate no excess risk correlated with new formulations of OxyContin® per se. In the third study, the peak risk for transitioning from onset of extra-medical prescription pain reliever use (EMPPR) to heroin onset within 10 years emerged at the third year since first EMPPR use. Approximately 5% of participants initiated heroin use in 10 years since EMPPR onset. The estimates of these subgroups remain similar regardless of population density. EMPPR users who are male, White, and with early EMPPR onset have an increased risk of initiating heroin use. Heroin outbreaks and epidemics revisited the US in the 2010s after the first US heroin epidemic of the 1970s. If successful, this project's new evidence on heroin in the US population in recent epidemic years should improve our understanding of heroin epidemiology, and may be an aid to new public health responses for primary prevention, outreach, and treatment resources with respect to heroin in the current epidemic and during future epidemics.
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