Substance Use PCORI Funding Announcement -- Cycle 3 2026

Substance Use PCORI Funding Announcement -- Cycle 3 2026 is sponsored by Patient-Centered Outcomes Research Institute. Funds research to improve the quality and relevance of evidence regarding substance use and its treatment.

## Notice of Upcoming PCORI Funding Announcement * **Applicant Town Hall** * **Letter of Intent (LOI) Deadline** * **LOI Status Notification** * **Application Deadline** The Patient-Centered Outcomes Research Institute (PCORI) intends to issue a PCORI Funding Announcement (PFA) on **Aug.

4, 2026**, seeking to fund high-quality, patient-centered comparative clinical effectiveness research (CER) projects that focus on substance use/misuse and substance use disorders. This preannouncement provides potential applicants with additional time to identify collaborators, obtain patient and stakeholder input on potential studies and develop responsive, high-quality applications. ## Research Initiative Highlights In 2024, 48.

4 million people aged 12 or older in the United States were diagnosed with a substance use disorder, and approximately 58% reported current use of tobacco products, nicotine, alcohol or illicit drugs. However, an estimated 81% of those classified as needing substance use treatment did not receive it, resulting in significant morbidity, mortality and social and economic costs for individuals, families and communities.

Recent data suggest more than 80,000 overdose deaths annually. These burdens are borne unevenly, creating variability in the delivery and outcomes of care. This Topical PFA will solicit applications focused on addressing substance use/misuse and substance use disorders.

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. Substances of interest include but are not limited to alcohol, opioids, nicotine and polysubstance use.

PCORI is particularly interested in applications focusing on substance use/misuse and substance use disorders in populations with high incidence, prevalence or burden, or that experience lower access to or effectiveness of interventions.

Applications may propose patient-centered CER studies of prevention, screening, 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.

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

Studies proposing the inclusion of e-cigarettes as an intervention comparator will be considered low priority; however, interventions intended to reduce the use of e-cigarettes would be responsive to this funding announcement. In addition to encouraging investigator-initiated patient-centered CER proposals, 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 Prevention and Treatment of Substance Use Disorders:** PCORI is interested in evidence-based approaches that advance the prevention and treatment of substance use disorders in populations with high incidence, prevalence or burden, or that experience lower access to or effectiveness of interventions.

PCORI strongly recommends that study designs include contributions from individuals with lived experience. Studies may include community-centered recovery models, trauma-informed care and evidence-based behavioral interventions. 2.

**Evidence-Based Interventions for Overdose Prevention:** PCORI is interested in patient-centered CER of system-, community- and individual-level interventions to reduce overdose-related health outcomes and deaths for individuals with substance misuse or substance use disorders, particularly for populations at increased risk of substance misuse or lower access to evidence-based treatment, or for whom there is evidence of reduced effectiveness of interventions.

Examples of studies may include multilevel interventions and approaches that increase linkage to medications for opioid use disorder. 3. **Strategies To Reduce Nicotine and Tobacco Use:** PCORI is interested in funding patient-centered CER that assesses different forms, doses, durations and delivery of nicotine/tobacco reduction strategies, and increasing access to nicotine/tobacco reduction strategies.

Examples of studies may include school-based initiatives and pharmacotherapy approaches. Note that studies proposing the inclusion of e-cigarettes as a comparator will be considered a low priority. However, interventions intended to reduce the use of e-cigarettes would be responsive to this funding announcement.

4. **Treatment Strategies Addressing the Intersection of Poor Sleep and Substance Misuse/Substance Use Disorder:** PCORI is interested in evidence-based strategies that address the common co-occurrence of poor sleep and substance misuse/substance use disorder.

Given the limited number of interventions targeting both substance use and sleep outcomes, applications may focus on interventions with demonstrated efficacy or widespread use in one primary domain (sleep or substance use).

However, they should also include at least one key statistically powered secondary outcome in the other domain and provide a strong theoretical justification if there is no existing evidence of efficacy or widespread use for the other domain. Studies may consist of multicomponent interventions, systems-level approaches and behavioral interventions addressing co-occurring sleep disturbance and substance misuse.

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 be powered with an overall sample size adequate for the precise estimation of hypothesized effect sizes and, where appropriate, for assessing heterogeneity of treatment effect.

Applicants are encouraged to pay special attention to issues of intervention implementation with an aim of facilitating widespread uptake of findings after completion of the study by utilizing hybrid effectiveness-implementation approaches. However, studies that are strictly focused on implementation or dissemination studies will not be considered responsive, nor will studies focused on the development of research methods.

Applicants should propose well-justified and validated outcomes that are clinically meaningful and considered important by patients and that can be affected by the proposed interventions during the study period. 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.

In PCORI-funded research, patients and other healthcare partners are expected to meaningfully contribute their lived experience or professional expertise to ensure studies are patient-centered, relevant and useful for healthcare decision making. Applicants must address PCORI’s Foundational Expectations for Partnerships in Research — an evidence-based framework supported by tools and resources to guide effective engagement strategies.

View additional details on each of the Foundational Expectations. This funding announcement will accept applications with direct costs of up to $12 million dollars and of up to five years in duration. For this funding announcement, 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. For additional information, please see the full announcement upon posting. PCORI encourages all investigators interested in applying to please contact PCORI at pfa@pcori.

org to schedule a consultation. * Is Your CER Study Responsive to PCORI’s Funding Announcements? * What You Need To Know To Apply * Foundational Expectations for Partnerships in Research * PCORI’s Portfolio of Funded Research * Population Insights Reports Powered by PCORnet®") Letter of Intent Deadline Letter of Intent Status Notification August 2027 (Subject to Change) ## Funds and Project Period