Addressing Substance Use Topical PCORI Funding Announcement -– Cycle 2 2024

This topical PCORI funding announcement (PFA) seeks to fund high-quality patient-centered comparative clinical effectiveness research (CER) projects that focus on people with substance use disorders or individuals who use/misuse substances.

Research Initiative Highlights

Among those age 12 or older in the United States, around 60 percent reported current use of tobacco products, nicotine, alcohol, or an illicit drug in 2022. Nationally, more than 48 million people age 12 or older were diagnosed with a substance use disorder in 2022; of these people, an estimated 76 percent received no treatment. Rates of both diagnosed substance use disorders and of overdose have escalated in recent years. This topical PFA will solicit applications focused on substance use/misuse and substance use disorders.

PCORI is particularly interested in applications focusing on substance use/misuse and substance use disorders in high-need and/or underserved populations, including but not limited to rural populations, low-income populations, sexual/gender minorities, racial/ethnic minorities, pregnant persons, individuals involved with the justice system, youth, older adults, and persons with co-occurring mental and physical health conditions. Applications may propose CER studies of prevention, screening, harm reduction, treatment, and recovery approaches for substance use/misuse and substance use disorders at the individual, community, or systems level to improve patient-centered substance use–related outcomes. At least one primary outcome must focus on substance use. PCORI is interested in both long- and short-term outcomes; however, long-term follow-up of 12 months is desired.

Substances of interest include but are not limited to alcohol, opioids, nicotine, and polysubstance use. For this PFA, “substance” refers to any psychoactive compound with the potential to cause health and social problems including the development of a substance use disorder (e.g., alcohol, nicotine, cannabinoids, opioids, depressants, stimulants, hallucinogens). Substance use disorder is defined as meeting criteria in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), for one or more drugs or alcohol. Proposals focused on gambling or other addictive behaviors, or proposals with psychedelic substances as therapeutic interventions, are not responsive to this PFA.

Applications proposing novel interventions and/or aiming to develop new technologies (such as mobile apps) or decision support tools/aids will be considered nonresponsive. Adaptations of efficacious interventions used in the general population may be responsive, but the level of adaptation must be clearly described and well justified a priori.

PCORI is particularly interested in submissions that address the following special areas of emphasis (SAEs). The purpose of identifying these SAEs is to encourage submissions to these areas, not to limit submissions to these topics. Applicants addressing an SAE should identify the area that is best associated with their research approach.

1. Evidence-Based Strategies to Advance Equity in the Prevention and Treatment of Substance Use Disorders: Historically underserved and underresourced populations experience significant disparities in outcomes and inequities in access to the continuum of care for substance use/misuse and substance use disorders. PCORI is interested in evidence-based approaches that advance health equity—and strongly recommends the inclusion of individuals with lived experience contributing to the design of the study. Examples of studies are community-centered recovery models, trauma-informed care, evidence-based behavioral interventions, and peer support interventions.
2. Evidence-Based Interventions for Overdose Prevention: Overdose deaths remain a national crisis, with over 75 percent of overdose deaths involving opioids and nearly half involving multiple drugs. PCORI is interested in patient-centered CER of system-, community-, and individual-level interventions to reduce negative overdose-related health outcomes and deaths, particularly for historically marginalized and underresourced populations. Examples of studies may include harm reduction strategies, multilevel interventions and approaches that increase linkage to medications for opioid use disorder (MOUD).
3. Strategies to Reduce Nicotine and Tobacco Use in Disproportionally Affected Populations: Despite quit attempts and longer-term cessation increasing over the past two decades, considerable disparities remain in the prevalence of nicotine and tobacco use across races and ethnicities as well as the prevalence of key indicators of smoking cessation (e.g., quit attempts and use of cessation therapies). PCORI is interested in funding patient-centered CER that assesses different forms, doses, durations, and delivery of treatments, particularly when they focus on disparities and health equity. Examples of studies may include school-based initiatives, digital therapeutics, and pharmacotherapy approaches.

Applicants are strongly encouraged to propose individual- or cluster-randomized controlled trials; however, well-specified natural experiments and well-designed observational studies will also be considered. Proposed studies should examine large and diverse populations with an overall sample size that will allow precision in the estimation of hypothesized effect sizes and, as appropriate, analysis of population subgroups that may include heterogeneity of treatment effects. Applicants are encouraged to pay special attention to intervention implementation, with an aim of facilitating widespread uptake of findings after completion of the study. However, strict implementation or dissemination studies will not be considered responsive, nor will studies focused on the development of research methods. Applicants should propose well-justified substance use–related outcomes that are clinically meaningful, considered important by those with lived experience, and can be affected by the proposed intervention within the study duration. Objective outcome measures are encouraged where appropriate, and self-report outcomes should be sufficiently justified and validated.

Applicants should consider, as appropriate, the full range of substance use-related clinical and patient-centered outcomes data relevant to patients and other stakeholders. PCORI’s Principles for the Consideration of the Full Range of Outcomes Data in PCORI-Funded Research inform the expectations for applicants and the corresponding evaluation of applications submitted in response to this PFA.

This funding announcement will accept applications with direct costs up to $12 million and up to five years in duration. For this PFA, applicants may request coverage of patient care costs (including medical products, procedures, and care services) for potential funding by PCORI. These costs are included as part of the overall direct costs.

PCORI encourages all investigators interested in applying to use this inquiry form to submit questions and request to speak with a PCORI Program Officer.