The scale of opioid harms in the US and globally requires urgent action to improve efforts to reduce such harms. Evidence on the number of people with opioid use disorder (OUD) is critical to quantify opioid agonist treatment (OAT) coverage and the scale-up required to reduce drug related deaths in the population.

Administrative databases linked at the individual-level have great power to inform prevalence estimates, examine rare outcomes, and explore subgroup and context specific variations of OAT. To date, there has been relatively limited use of data linkage in US OUD and OAT research, in part reflecting challenges and concerns about ethics and feasibility. Yet many of these challenges equally exist – and have been managed – in other countries. The fragmented and particularly complex US healthcare system presents additional complications, but there are examples of US jurisdictions that have managed to overcome these.

The TRANSFORM team will undertake a first of its kind multi-jurisdictional study using data linkages in the US (Rhode Island, Wisconsin, Colorado, and Massachusetts), Australia (New South Wales), and the United Kingdom (Scotland). The two non-US sites involve leading researchers globally who will be able to leverage the data and methods in those jurisdictions to apply to the four US sites and develop resources that can then be applied to other US jurisdictions.

This work will generate crucial new data on the prevalence of OUD and characterize jurisdiction-specific impacts of OAT across settings and clinical contexts. Mathematical modeling will provide jurisdiction-specific information about where the greatest impacts of enhanced OAT access on mortality can be achieved, to inform practice, policy, and advocacy. Analytic code and resources for estimating prevalence, analyzing linked data, and developing jurisdiction-specific models will be made freely available. This will increase understanding of and capacity for these study designs to be implemented in other jurisdictions across the United States and globally.

The overall study objective is to transform the evidence base on the prevalence of OUD and the impact of OAT as a strategy to prevent opioid harm. Specific aims include:

1. Generate robust OUD prevalence estimates;
2. Examine the impact of OAT on overdose and all-cause mortality in different OAT populations, treatment systems, and jurisdictions (these data will inform the statistical and population modelling in Aims 1 & 3, respectively); and
3. Determine the population-level impact of existing and expanded access of OAT provision on fatal overdose and all-cause mortality among people with OUD in select jurisdictions.

The TRANSFORM team will undertake a first of its kind multi-jurisdictional study using data linkages in the US (Rhode Island, Wisconsin, Colorado, and Massachusetts), Australia (New South Wales), and the United Kingdom (Scotland). The two non-US sites involve leading researchers globally who will be able to leverage the data and methods in those jurisdictions to apply to the US sites and develop resources that can then be applied to other US jurisdictions.

Project Collaborators External

Design and Method

The proposed study will utilize existing, population-based cohorts of people with OUD. Linked administrative data on cohorts will be available from six jurisdictions: four in the US (Rhode Island, Wisconsin, Massachusetts, Colorado), Scotland and Australia. The project will facilitate translation of lessons learned from the US jurisdictions into publicly available code and documentation, building capacity for new resources and similar studies to be conducted in other US jurisdictions.

Aim 1: Generate robust OUD prevalence estimates, illustrating potential for use in other jurisdictions

We will estimate the current prevalence of OUD in each setting using MPEP - a Bayesian statistical modeling approach that we are developing100 that has been only partially applied in the United States2,3. We will use evidence generated by Aim 2 to estimate the number of PWOUD who have not entered OAT within 3-5 years and thereby the total prevalence of OUD. We will refine and extend the methodology, provide additional tests of validity and consistency of evidence, and produce training materials and statistical code that are transferable to any jurisdiction with linked administrative data sets.

Aim 2: Examine the impact of OAT on overdose and all-cause mortality in different OAT populations, treatment systems and jurisdictions

We will characterize and quantify OAT impact on fatal overdose and all-cause mortality among PWOUD in each jurisdiction. The inclusion of four US and two international sites (Australia and Scotland) provides a unique opportunity to directly compare the impacts and patterns of OAT in different populations, treatment systems, and jurisdictions, providing crucial evidence on the real-world impacts of OAT given varying treatment models and modes of delivery. In addition to providing evidence for programmatic reform, these data are essential to inform prevalence estimation (Aim 1) and the construction and calibration of dynamic mathematical models (Aim 3).

Aim 3: Determine the population-level impact of existing and expanded access of OAT provision on fatal overdose and all-cause mortality among people with OUD in select jurisdictions

We will evaluate the population-level impact of existing and expanded access to OAT provision on fatal overdose and all-cause mortality among PWOUD in each jurisdiction using simulation modeling. We will develop a dynamic, microsimulation mathematical model of OAT use and mortality among PWOUD. The microsimulation model will track each individual, leveraging individual-level data and population heterogeneity obtained through cohort data. The model will be parameterised and calibrated using data from each jurisdiction, including population size estimates (Aim 1), impact of OAT on mortality (Aim 2), and national/state surveillance data.

Benefits

This project will contribute to improvements in the health of people who use drugs using existing data, as intended under RFA-DA-22-037. It has significant translational potential. It will demonstrate the benefits of linking administrative data sources in the US (and elsewhere) to generate more robust estimates of the prevalence of OUD, and the current and potential future impact of OAT. The lessons learnt and cases developed here will provide tools and training materials and be exemplars for other US sites. We will seek supplementary NIH funding for other US sites joining in a second wave of prevalence estimation exercises. We will extend and develop prevalence estimation methods to incorporate additional covariates that characterize the PWOUD population. In future projects, we can formalize use of our methods to estimate changes in prevalence over time, assess how to use our methods to impute prevalence in geographical areas that lack linked cohort data, and generate national and regional prevalence estimates. And importantly, as the drug supply changes, we will be poised to estimate prevalence of emerging drugs (including stimulants, xylazine and other drugs that may emerge). Future projects can extend our models to assess other drug related harms (HIV, HCV, suicide) and assess the impact and potential of other interventions (e.g., needle and syringe programs, supervised consumption rooms)