Modeling the evolution of the US opioid crisis for national policy development.

The opioid crisis is a major public health challenge in the United States, killing about 70,000 people in 2020 alone. Long delays and feedbacks between policy actions and their effects on drug-use behavior create dynamic complexity, complicating policy decision-making. In 2017, the National Academies of Sciences, Engineering, and Medicine called for a quantitative systems model to help understand and address this complexity and guide policy decisions. Here, we present SOURCE (Simulation of Opioid Use, Response, Consequences, and Effects), a dynamic simulation model developed in response to that charge. SOURCE tracks the US population aged ≥12 y through the stages of prescription and illicit opioid (e.g., heroin, illicit fentanyl) misuse and use disorder, addiction treatment, remission, and overdose death. Using data spanning from 1999 to 2020, we highlight how risks of drug use initiation and overdose have evolved in response to essential endogenous feedback mechanisms, including: 1) social influence on drug use initiation and escalation among people who use opioids; 2) risk perception and response based on overdose mortality, influencing potential new initiates; and 3) capacity limits on treatment engagement; as well as other drivers, such as 4) supply-side changes in prescription opioid and heroin availability; and 5) the competing influences of illicit fentanyl and overdose death prevention efforts. Our estimates yield a more nuanced understanding of the historical trajectory of the crisis, providing a basis for projecting future scenarios and informing policy planning.

Improving Estimates of the Prevalence of Opioid Use Disorder in the United States: Revising Keyes et al.

OBJECTIVES: The United States faces an ongoing drug overdose crisis, but accurate information on the prevalence of opioid use disorder (OUD) remains limited. A recent analysis by Keyes et al used a multiplier approach with drug poisoning mortality data to estimate OUD prevalence. Although insightful, this approach made stringent and partly inconsistent assumptions in interpreting mortality data, particularly synthetic opioid (SO)-involved and non-opioid-involved mortality. We revise that approach and resulting estimates to resolve inconsistencies and examine several alternative assumptions. METHODS: We examine 4 adjustments to Keyes and colleagues' estimation approach: (A) revising how the equations account for SO effects on mortality, (B) incorporating fentanyl prevalence data to inform estimates of SO lethality, (C) using opioid-involved drug poisoning data to estimate a plausible range for OUD prevalence, and (D) adjusting mortality data to account for underreporting of opioid involvement. RESULTS: Revising the estimation equation and SO lethality effect (adj. A and B) while using Keyes and colleagues' original assumption that people with OUD account for all fatal drug poisonings yields slightly higher estimates, with OUD population reaching 9.3 million in 2016 before declining to 7.6 million by 2019. Using only opioid-involved drug poisoning data (adj. C and D) provides a lower range, peaking at 6.4 million in 2014-2015 and declining to 3.8 million in 2019. CONCLUSIONS: The revised estimation equation presented is feasible and addresses limitations of the earlier method and hence should be used in future estimations. Alternative assumptions around drug poisoning data can also provide a plausible range of estimates for OUD population.

Temporal and spatial trends of fentanyl co-occurrence in the illicit drug supply in the United States: a serial cross-sectional analysis.

Background: Fentanyl and its analogs contribute substantially to drug overdose deaths in the United States. There is concern that people using drugs are being unknowingly exposed to fentanyl, increasing their risk of overdose death. This study examines temporal trends and spatial variations in the co-occurrence of fentanyl with other seized drugs. Methods: We identified fentanyl co-occurrence (the proportion of samples of non-fentanyl substances that also contain fentanyl) among 9 substances or substance classes of interest: methamphetamine, cannabis, cocaine, heroin, club drugs, hallucinogens, and prescription opioids, stimulants, and benzodiazepines. We used serial cross-sectional data on drug reports across 50 states and the District of Columbia from the National Forensic Laboratory Information System, the largest available database on the U.S. illicit drug supply, from January 2013 to December 2023. Findings: We analyzed data from 11,940,207 samples. Fentanyl co-occurrence with all examined substances increased monotonically over time (Mann-Kendall p < 0.0001). Nationally, fentanyl co-occurrence was highest among heroin samples (approx. 50%), but relatively low among methamphetamine (≤1%), cocaine (≤4%), and other drug samples. However, co-occurrence rates have grown to over 10% for cocaine and methamphetamine in several Northeast states in 2017-2023. Interpretation: Fentanyl co-occurs most commonly with heroin, but its presence in stimulant supplies is increasing in some areas, where it may pose a disproportionately high risk of overdose. Funding: This work was partly supported by FDA grant U01FD00745501. This article reflects the views of the authors and does not represent the views or policies of the FDA or US Department of Health and Human Services.

The association between longitudinal trends in receipt of buprenorphine for opioid use disorder and buprenorphine-waivered providers in the United States.

AIMS, DESIGN AND SETTING: We sought to describe longitudinal trends in buprenorphine receipt and buprenorphine-waivered providers in the United States from 2003 to 2021 and measure whether the relationship between the two differed after capacity-building strategies were enacted nationally in 2017. This was a retrospective study of two separate cohorts covering the years 2003-21, testing whether the association between two trends in these cohorts changed comparing 2003 to 2016 and from 2017 to 2021, among buprenorphine providers in the United States, regardless of treatment setting. Patients receiving dispensed buprenorphine at retail pharmacies. PARTICIPANTS: All providers who have obtained a waiver to prescribe buprenorphine in the United States, and an estimate of the annual number of patients who had buprenorphine for opioid use disorder (OUD) dispensed to them at a retail pharmacy. MEASUREMENTS: We synthesized and summarized data from multiple sources to assess the cumulative number of buprenorphine-waivered providers over time. We used national-level prescription data from IQVIA to estimate annual buprenorphine receipt for OUD. FINDINGS: From 2003 to 2021, the number of buprenorphine-waivered providers in the United States increased from fewer than 5000 in the first 2 years of Food and Drug Administration (FDA) approval to more than 114 000 in 2021, while patients receiving buprenorphine products for OUD increased from approximately 19 000 to more than 1.4 million. The strength of association between waivered providers and patients is significantly different before and after 2017 (P < 0.001). From 2003 to 2016, for each additional provider, there was an average increase of 32.1 [95% confidence interval (CI) = 28.7-35.6] patients, but an increase of only 4.6 (95% CI= 3.5-5.7) patients for each additional provider, beginning in 2017. CONCLUSIONS: In the United States, the relationship between the rates of growth in buprenorphine providers and patients became weaker after 2017. While efforts to increase buprenorphine-waivered providers were successful, there was less success in translating that into significant increases in buprenorphine receipt.

Enumerating contributions of fentanyls and other factors to the unprecedented 2020 rise in opioid overdose deaths: model-based analysis.

In 2020, the ongoing US opioid overdose crisis collided with the emerging COVID-19 pandemic. Opioid overdose deaths (OODs) rose an unprecedented 38%, due to a combination of COVID-19 disrupting services essential to people who use drugs, continued increases in fentanyls in the illicit drug supply, and other factors. How much did these factors contribute to increased OODs? We used a validated simulation model of the opioid overdose crisis, SOURCE, to estimate excess OODs in 2020 and the distribution of that excess attributable to various factors. Factors affecting OODs that could have been disrupted by COVID-19, and for which data were available, included opioid prescribing, naloxone distribution, and receipt of medications for opioid use disorder. We also accounted for fentanyls' presence in the heroin supply. We estimated a total of 18,276 potential excess OODs, including 1,792 lives saved due to increases in buprenorphine receipt and naloxone distribution and decreases in opioid prescribing. Critically, growth in fentanyls drove 43% (7,879) of the excess OODs. A further 8% is attributable to first-ever declines in methadone maintenance treatment and extended-released injectable naltrexone treatment, most likely due to COVID-19-related disruptions. In all, 49% of potential excess OODs remain unexplained, at least some of which are likely due to additional COVID-19-related disruptions. While the confluence of various COVID-19-related factors could have been responsible for more than half of excess OODs, fentanyls continued to play a singular role in excess OODs, highlighting the urgency of mitigating their effects on overdoses.

Long-Term Effects of Increasing Buprenorphine Treatment Seeking, Duration, and Capacity on Opioid Overdose Fatalities: A Model-based Analysis.

OBJECTIVES: Because buprenorphine treatment of opioid use disorder reduces opioid overdose deaths (OODs), expanding access to care is an important policy and clinical care goal. Policymakers must choose within capacity limitations whether to expand the number of people with opioid use disorder who are treated or extend duration for existing patients. This inherent tradeoff could be made less acute with expanded buprenorphine treatment capacity. METHODS: To inform such decisions, we used a validated simulation model to project the effects of increasing buprenorphine treatment-seeking, average episode duration, and capacity (patients per provider) on OODs in the United States from 2023 to 2033, varying the start time to assess the effects of implementation delays. RESULTS: Results show that increasing treatment duration alone could cost lives in the short term by reducing capacity for new admissions yet save more lives in the long term than accomplished by only increasing treatment seeking. Increasing provider capacity had negligible effects. The most effective 2-policy combination was increasing capacity and duration simultaneously, which would reduce OODs up to 18.6% over a decade. By 2033, the greatest reduction in OODs (≥20%) was achieved when capacity was doubled and average duration reached 2 years, but only if the policy changes started in 2023. Delaying even a year diminishes the benefits. Treatment-seeking increases were equally beneficial whether they began in 2023 or 2025 but of only marginal benefit beyond what capacity and duration achieved. CONCLUSIONS: If policymakers only target 2 policies to reduce OODs, they should be to increase capacity and duration, enacted quickly and aggressively.

Why Similar Policies Resulted In Different COVID-19 Outcomes: How Responsiveness And Culture Influenced Mortality Rates.

In the first two years of the COVID-19 pandemic, per capita mortality varied by more than a hundredfold across countries, despite most implementing similar nonpharmaceutical interventions. Factors such as policy stringency, gross domestic product, and age distribution explain only a small fraction of mortality variation. To address this puzzle, we built on a previously validated pandemic model in which perceived risk altered societal responses affecting SARS-CoV-2 transmission. Using data from more than 100 countries, we found that a key factor explaining heterogeneous death rates was not the policy responses themselves but rather variation in responsiveness. Responsiveness measures how sensitive communities are to evolving mortality risks and how readily they adopt nonpharmaceutical interventions in response, to curb transmission. We further found that responsiveness correlated with two cultural constructs across countries: uncertainty avoidance and power distance. Our findings show that more responsive adoption of similar policies saves many lives, with important implications for the design and implementation of responses to future outbreaks.

Reducing opioid use disorder and overdose deaths in the United States: A dynamic modeling analysis.

Opioid overdose deaths remain a major public health crisis. We used a system dynamics simulation model of the U.S. opioid-using population age 12 and older to explore the impacts of 11 strategies on the prevalence of opioid use disorder (OUD) and fatal opioid overdoses from 2022 to 2032. These strategies spanned opioid misuse and OUD prevention, buprenorphine capacity, recovery support, and overdose harm reduction. By 2032, three strategies saved the most lives: (i) reducing the risk of opioid overdose involving fentanyl use, which may be achieved through fentanyl-focused harm reduction services; (ii) increasing naloxone distribution to people who use opioids; and (iii) recovery support for people in remission, which reduced deaths by reducing OUD. Increasing buprenorphine providers' capacity to treat more people decreased fatal overdose, but only in the short term. Our analysis provides insight into the kinds of multifaceted approaches needed to save lives.

Behavioral dynamics of COVID-19: estimating underreporting, multiple waves, and adherence fatigue across 92 nations.

Effective responses to the COVID-19 pandemic require integrating behavioral factors such as risk-driven contact reduction, improved treatment, and adherence fatigue with asymptomatic transmission, disease acuity, and hospital capacity. We build one such model and estimate it for all 92 nations with reliable testing data. Cumulative cases and deaths through 22 December 2020 are estimated to be 7.03 and 1.44 times official reports, yielding an infection fatality rate (IFR) of 0.51 percent, which has been declining over time. Absent adherence fatigue, cumulative cases would have been 47 percent lower. Scenarios through June 2021 show that modest improvement in responsiveness could reduce cases and deaths by about 14 percent, more than the impact of vaccinating half of the population by that date. Variations in responsiveness to risk explain two orders of magnitude difference in per-capita deaths despite reproduction numbers fluctuating around one across nations. A public online simulator facilitates scenario analysis over the coming months. © 2021 System Dynamics Society.

Data Needs in Opioid Systems Modeling: Challenges and Future Directions.

INTRODUCTION: The opioid crisis is a pervasive public health threat in the U.S. Simulation modeling approaches that integrate a systems perspective are used to understand the complexity of this crisis and analyze what policy interventions can best address it. However, limitations in currently available data sources can hamper the quantification of these models. METHODS: To understand and discuss data needs and challenges for opioid systems modeling, a meeting of federal partners, modeling teams, and data experts was held at the U.S. Food and Drug Administration in April 2019. This paper synthesizes the meeting discussions and interprets them in the context of ongoing simulation modeling work. RESULTS: The current landscape of national-level quantitative data sources of potential use in opioid systems modeling is identified, and significant issues within data sources are discussed. Major recommendations on how to improve data sources are to: maintain close collaboration among modeling teams, enhance data collection to better fit modeling needs, focus on bridging the most crucial information gaps, engage in direct and regular interaction between modelers and data experts, and gain a clearer definition of policymakers' research questions and policy goals. CONCLUSIONS: This article provides an important step in identifying and discussing data challenges in opioid research generally and opioid systems modeling specifically. It also identifies opportunities for systems modelers and government agencies to improve opioid systems models.