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Key Dates

  • PFA Opens
    May 7, 2024
  • Applicant Town Hall
    Watch the Recording
  • Letter of Intent (LOI) Deadline
    June 4, 2024; 5 pm (ET)
  • LOI Status Notification
    July 2, 2024
  • Application Deadline
    Sept. 4, 2024; 5 pm (ET)
Apply Here

This Topical PCORI Funding Announcement (PFA) seeks to fund high-quality patient-centered comparative clinical effectiveness research (CER) projects that focus on rare diseases.

Research Initiative Highlights

Consistent with the National Institutes of Health and the Food and Drug Administration, PCORI uses the Orphan Drug Act definition of a rare disease: a condition that affects fewer than 200,000 people in the United States. Although each disease is rare individually, it is estimated that more than 10,000 rare diseases affect about 30 million people in the United States and that 80 percent of rare diseases are genetic in origin. People with many different types of rare diseases, and their caregivers, often face similar challenges such as finding information and resources, getting an accurate diagnosis, and accessing adequate 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 an SAE 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 that compares symptomatic care, particularly for symptoms that occur in multiple rare diseases. Some examples include behavioral and symptom relief treatments and techniques for sleep disturbance, pain, pruritis, and comorbid mental health diagnoses (e.g., anxiety, depression).
  2. Approaches for timely diagnosis of rare diseases: Between 3 and 15 years is a common timeline for receiving a correct diagnosis of rare disease; the average is approximately 5 years. During this period, frequently referred to as the “diagnostic odyssey,” individuals may experience numerous care visits, multiple tests and procedures, and inaccurate or missed diagnoses. PCORI is interested in CER studies that compare 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 affect 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 that compares 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 a rare disease who are unable to access care in specialty centers, including care coordination models or telemonitoring and digital health tools.

Applications that address cross-cutting issues that include more than one rare disease diagnosis are encouraged, but studies focused 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 be considered if rigorous methods are proposed. Applicants are strongly encouraged to assess issues of intervention implementation to facilitate widespread uptake of findings after completion of the study. Toward that end, hybrid type 1 and hybrid type 2 designs may be appropriate. Applicants who propose 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. Interventions with established efficacy in the general population or interventions developed or adapted for those with rare diseases may be acceptable. Applications that propose novel interventions and/or aim 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 or similar situations may be responsive, but the level of adaptation must be minimal, clearly described, and justified a priori.

Applicants should propose well-justified outcomes that are clinically meaningful and considered important by patients and that can be affected by the proposed intervention within the study duration. 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. For more information, visit the Patient-Centered Economic Outcomes page on our website.

This funding announcement will accept applications with direct costs up to $12 million 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, 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.

Download Full Announcement

Key Dates

Online System Opens
May 7, 2024
Applicant Town Hall
View Event
Letter of Intent Deadline
June 4, 2024, 5 pm (ET)
Letter of Intent Status Notification
July 2, 2024
Application Deadline
Sept. 4, 2024, 5 pm (ET)
Merit Review
Nov. 2024
Awards Announced
April 2025
Earliest Start Date
Aug. 2025

Funds and Project Period

Funds Available Up To
Approximately $100 million
Total Direct Costs
Up to $12 million
Maximum Project Period
Up to five years

To Apply for This Opportunity

  1. Read the full funding announcement
  2. Follow the process outlined in the Submission Instructions
  3. Submit a Letter of Intent
  4. Submit an application (if invited)

Applicant Resources

Write Your LOI

Submit Your Application

Required Application Templates

Additional Applicant Resources


Health Conditions Health Conditions These are the broad terms we use to categorize our funded research studies; specific diseases or conditions are included within the appropriate larger category. Note: not all of our funded projects focus on a single disease or condition; some touch on multiple diseases or conditions, research methods, or broader health system interventions. Such projects won’t be listed by a primary disease/condition and so won’t appear if you use this filter tool to find them. View Glossary
Populations Populations PCORI is interested in research that seeks to better understand how different clinical and health system options work for different people. These populations are frequently studied in our portfolio or identified as being of interest by our stakeholders. View Glossary
Award Types