The Patient-Centered Outcomes Research Institute (PCORI) intends to issue a PCORI Funding Announcement (PFA) on August 12, 2025, seeking to fund high-quality, patient-centered comparative clinical effectiveness research (CER) studies that focus on rare diseases. This preannouncement provides potential applicants additional time to identify collaborators; obtain patient and stakeholder input on potential studies; and develop responsive, high-quality proposals.

Research Initiative Highlights

PCORI uses the National Institutes of Health's definition of a rare disease, defined as a condition that affects fewer than 200,000 individuals in the United States. Though each disease is rare individually, it is estimated that there are more than 10,000 rare diseases affecting about 30 million Americans. People with many different types of rare diseases and their caregivers often experience similar challenges such as finding reliable information and relevant resources, receiving an accurate diagnosis and gaining access to adequate and appropriate care. This Topical PFA will solicit applications proposed to address patient-centered CER questions that will fill important rare disease research gaps. Applications addressing critical decisional dilemmas that span multiple rare diseases are encouraged.

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 one of the below SAEs should identify the area that is best associated with their research approach:

1. Approaches to symptom management for individuals with rare disease: As few rare diseases have curative treatments and many patients with a rare disease focus their efforts on managing their disease symptoms, PCORI is interested in funding CER comparing symptomatic care, particularly for symptoms that occur in multiple rare diseases. Some examples include behavioral and symptom relief treatments/techniques for sleep disturbance, pain, pruritus and comorbid mental health diagnoses (e.g., anxiety and depression). 
2. Approaches for timely diagnosis of rare diseases: Between three and 15 years is a common timeline for receiving a correct rare disease diagnosis, with an average of approximately five years. During this period, frequently referred to as the “diagnostic odyssey,” individuals may experience numerous care visits, a multitude of tests and procedures and inaccurate or missed diagnoses. PCORI is interested in CER studies comparing approaches to decrease the length of the diagnostic odyssey — for example, by comparing genetic testing approaches for newborns with serious illnesses of unknown cause.  
3. Approaches to improving care delivery for individuals with rare diseases: Care delivery for those with rare diseases is influenced by many system-level factors that impact patients, families and caregivers. Challenges are not necessarily condition-specific, which allows for a focus on cross-cutting issues and outcomes to increase the potential for research impact. PCORI is interested in funding CER comparing strategies to address these challenges and improve care delivery for individuals with rare diseases. Some examples include models of care for children with rare disease transitioning to adult care; case management models, including family-based care management models designed to reduce caregiver burden or stress; and approaches to improving primary care for individuals with rare disease unable to access care in specialty centers, including care coordination models or telemonitoring/digital health tools.

Applications addressing cross-cutting issues that include more than one rare disease diagnosis are encouraged, but studies focusing on a single rare disease are also acceptable. Individual- or cluster-randomized controlled trials are preferred; however, well-specified natural experiments, well-designed prospective or retrospective observational studies, and other innovative CER designs suited to rare disease research will also be considered if rigorous methods are proposed. 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. Studies focused on the development of research methods will not be considered responsive. Applicants proposing retrospective observational studies must use and demonstrate access to existing data sources such as registries, patient-powered networks or data networks (e.g., PCORnet®).

Comparators can be systems and/or clinical approaches, which may be pharmacological or nonpharmacological interventions. Comparators targeted to rare disease patients and/or their caregivers are acceptable. Interventions with established efficacy in the general population or interventions developed or adapted for those with rare diseases may be acceptable. 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 or similar situation may be responsive, but the level of adaptation must be minimal, clearly described and justified a priori.

Applicants should consider, as appropriate, the full range of 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 dollars and 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 cost maximum. For additional information, please see the full announcement upon posting.

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

New Engagement Resource and Expectations: PCORI’s Foundational Expectations for Partnerships in Research

In 2024, PCORI released updated guidance for engagement in research, PCORI's Foundational Expectations for Partnerships in Research. Project teams are expected to address PCORI’s Foundational Expectations when applying for PCORI research funding, developing project and engagement plans for awarded projects and reflecting on engagement during a project to improve and strengthen engagement over time. There will be flexibility in how applicants may address the Foundational Expectations. Additional information, guidance and resources can be found on the PCORI website. 

Key Dates

Online System Opens

Aug. 12, 2025, 9 am (ET)

Applicant Town Hall

Aug. 19, 2025; 12 - 1 pm (ET)

View Event

Letter of Intent Deadline

Sept. 23, 2025, 5 pm (ET)

Letter of Intent Status Notification

Oct. 21, 2025, 5 pm (ET)

Application Deadline

Jan. 13, 2026, 5 pm (ET)

Merit Review

March 2026

Awards Announced

July 2026

Earliest Start Date

November 2026

Funds and Project Period

Funds Available Up To

Up to $60 million

Total Direct Costs

Up to $12 million

Maximum Project Period

Up to five years

AI Generated success prediction

1. Patient-Centeredness and Stakeholder Engagement

PCORI places a strong emphasis on research that prioritizes outcomes meaningful to patients. Successful applications often demonstrate:

Active involvement of patients, caregivers, and other stakeholders throughout the research process.

Focus on patient-reported outcomes such as quality of life, symptom management, and functional status.

Engagement strategies that ensure the research addresses real-world patient needs.

2. Comparative Clinical Effectiveness Research (CER)

PCORI funds studies that compare two or more healthcare interventions to determine which works best for specific populations. Successful proposals typically:

Address evidence gaps in clinical decision-making.

Utilize diverse study designs, including randomized controlled trials and observational studies.

Aim to inform healthcare choices by comparing benefits and harms of interventions.

3. Real-World Applicability

Research conducted in real-world settings enhances the generalizability of findings. PCORI favors studies that:

Are implemented in diverse healthcare environments.

Reflect routine clinical practice.

Include populations that are representative of those affected by the health issue under study.

4. Methodological Rigor

Adherence to PCORI's Methodology Standards ensures the credibility of research findings. Successful applications demonstrate:

Robust study designs with appropriate controls.

Clear statistical analysis plans.

Strategies to minimize bias and confounding factors. 

5. Focus on Health Equity

Addressing disparities in healthcare outcomes is a priority for PCORI. Successful proposals often:

Target underserved or vulnerable populations.

Incorporate interventions aimed at reducing health disparities.

Engage community partners to ensure cultural relevance and acceptability. 

6. Collaborative Partnerships

Collaborations between research institutions and community organizations enhance the relevance and impact of research. PCORI supports projects that:

Leverage the strengths of multiple stakeholders.

Promote co-learning and shared decision-making.

Foster sustainable partnerships beyond the life of the project.

Notable Examples of PCORI-Funded Projects

Maternal Health Equity Studies: PCORI awarded $80.5 million to four large studies addressing maternal health disparities. These projects are co-led by academic and community partners and focus on interventions that tackle both clinical and social determinants of health. 

Health Systems Implementation Initiative (HSII): Through HSII, PCORI funded 25 projects with a total of $37 million to implement evidence-based interventions in health systems. Projects include improving antibiotic prescribing practices and integrating weight loss programs into primary care.

Tips for Prospective Applicants

Engage Stakeholders Early: Involve patients, caregivers, and clinicians from the outset to ensure the research addresses their priorities.

Demonstrate Real-World Impact: Highlight how the study's findings will be applicable in everyday clinical settings and benefit diverse populations.

Ensure Methodological Soundness: Align your study design with PCORI's Methodology Standards to enhance the credibility of your research.pcori.org

Address Health Disparities: Design interventions that are culturally sensitive and aim to reduce inequities in healthcare outcomes.

Foster Collaborative Relationships: Build partnerships with community organizations and other stakeholders to enrich the research process and outcomes.