PCORI Funding for Addressing Rare Diseases (US)

Applicants are strongly encouraged to propose individual or cluster randomized controlled trials; however, well-specified natural experiments and rigorous observational studies will also be considered. Other innovative CER designs, suited to rare disease research, may also be considered, as long as rigorous methods are proposed. Proposed studies should examine diverse populations with an overall sample size suitable to allow for precision in the estimation of hypothesized effect sizes and, as appropriate, analysis of heterogeneity of treatment effects. Note that given the smaller evidence base for some rare diseases, it is recognized that there may be greater uncertainty in effect size estimates than for more common conditions. Applicants are encouraged to pay special attention to issues of intervention implementation with an aim of facilitating widespread uptake of findings after study completion. However, strict implementation or dissemination studies will not be considered responsive, nor will studies focused on the development of research methods.

Priorities

• To be considered responsive, applicants must propose research that meets this PFA’S distinctive requirements and addresses at least one of the following National Priorities for Health:
  • Increase Evidence for Existing Interventions and Emerging Innovations in Health
    • Goal: Strengthen and expand ongoing CER focused on both existing interventions and emerging innovations to improve healthcare practice, health outcomes, and health equity.
  • Accelerate Progress Toward an Integrated Learning Health System
    • Goal: Foster actionable, timely, place-based, and transformative improvements in patient-centered experiences, care provision, and improved health outcomes through collaborative, multisectoral research to support a health system that understands and serves the needs and preferences of individuals.
  • Achieve Health Equity
    • Goal: Expand stakeholder engagement, research, and dissemination approaches that lead to continued progress toward achieving health equity in the United States.
  • Advance the Science of Dissemination, Implementation, and Health Communication
    • Goal: Advance the scientific evidence for and the practice of dissemination, implementation, and health communication to accelerate the effective sharing of CER results for public understanding and uptake into practice.
• Applicants will be asked to select one of these four National Priorities as primary, and if relevant, a secondary and/or tertiary National Priority in their Letter of Intent (LOI) and, if invited, full application.

Themes

• The Topic Themes, clustered into three groups, are as follows:
  • Populations
    • Improving outcomes for people with intellectual and developmental disabilities (IDD)
    • Promoting health for older adults
    • Promoting healthy children and youth
  • Health Behaviors
    • Addressing substance use
    • Addressing violence and trauma
  • Health Conditions
    • Addressing COVID-19
    • Addressing rare diseases
    • Improving cardiovascular health
    • Improving mental and behavioral health
    • Managing pain
    • Preventing maternal morbidity and mortality (MMM)
    • Promoting sleep health

Funding Information

• PCORI has allotted up to approximately $100 million under this PFA to fund high-quality comparative effectiveness studies that respond to research questions of interest.
• The proposed budget for studies under this initiative can include up to $12 million in direct costs.

Special Areas of Emphasis

• 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.
  • 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).
  • 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.
  • 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.

Research Requirements

• To be considered responsive, applications must do the following:
  • Describe comparators. Regardless of the approach being studied, all proposed research projects must compare at least two alternatives. If the applicant proposes usual care as a rational and important comparator in the proposed study, then it must be described in detail, coherent as a clinical alternative, and properly justified as a legitimate comparator.
  • Describe research that compares two or more alternatives, each of which has established efficacy and/or is in widespread use. PCORI expects the efficacy or effectiveness of each intervention to be known. If the efficacy or evidence base is insufficient, then data must be provided to document that the intervention is used widely.
  • Describe research that studies the benefits and harms of interventions and strategies delivered in real-world settings. PCORI is interested in studies that provide practical information that can help patients and members of the broader health and healthcare community make informed decisions about their health care and health outcomes.
  • Describe consultation with patients and members of the broader health and healthcare community about how the study is answering a critical question. PCORI expects applicants to explain the pertinent evidence gaps and why the project questions represent decisional dilemmas for patients, caregivers, clinicians, policy makers, and other healthcare system stakeholders. Describe why project outcomes are especially relevant and meaningful endpoints to patients and members of the broader health and healthcare community.

Eligibility Criteria

• In general, applications for the conduct of research and management of funding may be submitted by appropriate academic research, private sector research, or study-conducting entities. This may include, among others, agencies and instrumentalities of the Federal Government, nonprofit and for-profit research organizations, and colleges and universities.
• Per PCORI’s authorizing statute, every applicant must demonstrate capability to comply with the following conditions:
  • abide by the transparency and conflicts of interest requirements that apply to PCORI with respect to the research managed or conducted under contract;
  • comply with the PCORI methodological standards adopted by the Board of Governors;
  • consult, as appropriate, with the expert advisory panels for clinical trials and rare disease;
  • deposit de-identified data from the original research into a PCORI designated repository to facilitate data sharing, as appropriate; have appropriate processes in place to manage data privacy and meet ethical standards for the research;
  • comply with the requirements of PCORI for making the information available to the public;
  • and comply with other terms and conditions determined necessary by PCORI to carry out the research project.

Ineligibility Criteria

• Individuals are not permitted to apply.

For more information, visit PCORI.