Expanding the opioids system modeling efforts to more comprehensively address fentanyl, stimulants use, polysubstance use and associated outcomes.(U01) Clinical Trials Not Allowed | RFA FD 21 022

Opportunity Information: Apply for RFA FD 21 022

This grant opportunity (RFA-FD-21-022) is a cooperative agreement from the U.S. Department of Health and Human Services, Food and Drug Administration (FDA), focused on strengthening and expanding FDA's existing opioid-related system modeling so it better reflects the current realities of the overdose crisis. The central idea is that older models that mainly track prescription opioids or heroin trends are no longer sufficient on their own, because fentanyl and other synthetic opioids, rising stimulant use, and widespread polysubstance use have changed how overdose risk emerges and how prevention strategies perform in the real world. The project is intended to produce a more comprehensive, data-informed modeling framework that can represent these interacting epidemics and generate insights relevant to public health and regulatory decision-making, without conducting clinical trials.

The core purpose of the work is to model the dynamics of fentanyl, stimulants (such as methamphetamine and cocaine), and polysubstance use, and to explicitly represent how these substances interact with opioid use, misuse, opioid use disorder, and treatment pathways. In practical terms, the funded research is expected to move beyond single-substance assumptions and capture how people transition between use patterns (for example, opioid-only use to opioid-plus-stimulant use), how market changes like fentanyl contamination affect overdose mortality, and how these patterns influence treatment need and treatment outcomes. A key emphasis is overdose deaths: the FDA is seeking a model that can better explain and project opioid overdose mortality in an environment where fentanyl and co-use with stimulants are increasingly common and may amplify risk in ways that standard opioid-only models fail to capture.

Another major component is evaluating, through modeling, how polysubstance use and synthetic opioids might change the effectiveness of harm reduction and overdose-prevention strategies. The opportunity highlights the need to quantify how interventions perform under newer conditions, such as fentanyl prevalence and frequent co-ingestion of stimulants and opioids. This could include modeling how strategies like naloxone distribution, fentanyl test strips, expanded access to medications for opioid use disorder, safer-use education, or other prevention approaches might prevent deaths differently when overdoses involve multiple substances or when fentanyl drives rapid respiratory depression and reduces the time available for rescue. The intent is not just to list interventions, but to build a system model capable of estimating downstream outcomes and tradeoffs under different scenarios and assumptions.

A secondary purpose is to identify and implement feasible ways to incorporate mental health into the modeling effort. This reflects the reality that mental health conditions can influence substance initiation, escalation, relapse risk, treatment engagement, and mortality outcomes, and that these factors may interact with polysubstance use in important ways. The FDA is looking for practical approaches that can be implemented in a system model, meaning methods that can be supported by available data sources and that can meaningfully improve the model's ability to represent real-world patterns, rather than purely conceptual additions.

Administratively, this is a discretionary funding opportunity using a cooperative agreement (U01), which typically means substantial federal involvement during the project, such as collaboration with FDA staff on priorities, data alignment, model structure, and deliverables. Clinical trials are explicitly not allowed, reinforcing that the work is intended to be modeling-focused, drawing on existing data and established analytic and simulation methods rather than testing interventions in human subjects in a trial format. The program anticipates making one award, with an award ceiling of $1,250,000. The assistance listing (CFDA) number is 93.103, and the activity category is described broadly as consumer protection and research and development, consistent with FDA's mission and the modeling and policy-relevant orientation of the work.

Eligibility is broad and includes many types of organizations that could credibly build and validate complex public health models. Eligible applicants include state, county, and local governments; public and private institutions of higher education; federally recognized tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; and other applicants as allowed by the opportunity's additional eligibility language. This wide eligibility reflects the interdisciplinary nature of the work, which may require expertise spanning epidemiology, health economics, systems science, substance use research, mental health, and policy evaluation.

In short, the opportunity funds an expansion of FDA's opioid system modeling to reflect fentanyl-driven overdose dynamics, increasing stimulant involvement, and polysubstance use, with a strong focus on understanding and projecting overdose deaths and on estimating how prevention and harm-reduction strategies might work differently under these evolving conditions. It also encourages adding a mental health dimension in a feasible, data-grounded way so the model can better represent the interconnected drivers of risk, treatment engagement, and outcomes across the broader substance use landscape.

• The Department of Health and Human Services, Food and Drug Administration in the consumer protection, food and nutrition, science and technology and other research and development sector is offering a public funding opportunity titled "Expanding the opioids system modeling efforts to more comprehensively address fentanyl, stimulants use, polysubstance use and associated outcomes.(U01) Clinical Trials Not Allowed" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.103.
• This funding opportunity was created on Mar 12, 2021.
• Applicants must submit their applications by May 17, 2021. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $1,250,000.00 in funding.
• The number of recipients for this funding is limited to 1 candidate(s).
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501(c)(3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For profit organizations other than small businesses, Small businesses, Others (see text field entitled Additional Information on Eligibility for clarification).

Apply for RFA FD 21 022

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