NIH High-Risk High Reward Research Program  

Bethesda,  MD 
United States
  • Booth: 215

Welcome to the NIH's High-Risk High Reward Research Program!

The High-Risk, High-Reward Research (HRHR) program supports exceptionally creative scientists pursuing highly innovative research with the potential for broad impact in biomedical, behavioral, or social sciences within the NIH mission. Preliminary data are not required. The program's four constituent NIH Director's awards provide a diverse set of funding opportunities. Each of the four awards - the Pioneer, New Innovator, Transformative Research, and the Early Independence awards have various eligibility requirements and each recognize that great science comes from a variety of backgrounds. They highly encourage applications from scientists from diverse backgrounds, scientific areas and eligible institutions.

Funding opportunity announcements are typically released each spring! Visit the HRHR website for more details and to signup for the HRHR listerv to be notified when funding is available!


HRHR Program Overview Video

 Press Releases

  • The National Institutes of Health awarded 106 grants to support highly innovative and broadly impactful biomedical or behavioral research by exceptionally creative scientists through the Common Fund’s High-Risk, High-Reward Research program. Supported research this year includes understanding how long-term memory might be encoded in the shape of folded DNA in our neurons, mining data from unconventional sources to reveal social determinants of suicide, establishing new paradigms to address the functional consequences of health disparities in drug development, and looking at the impact of high school and collegiate athlete injuries on long-term health. The 106 awards total approximately $329 million over five years, pending availability of funds.

    The High-Risk, High-Reward Research program catalyzes scientific discovery by supporting highly innovative research proposals that, due to their inherent risk, may struggle in the traditional peer-review process despite their transformative potential. Program applicants are encouraged to think “outside the box” and pursue trailblazing ideas in any area of research relevant to the NIH’s mission to advance knowledge and enhance health.

    “The science put forward by this cohort is exceptionally novel and creative and is sure to push at the boundaries of what is known,” said NIH Director Francis S. Collins, M.D., Ph.D. “These visionary investigators come from a wide breadth of career stages and show that groundbreaking science can happen at any career level given the right opportunity.”

    The High-Risk, High-Reward Research Program is part of the NIH Common Fund, which oversees programs that pursue major opportunities and gaps throughout the research enterprise that are of great importance to NIH and require collaboration across the agency to succeed. The High-Risk, High-Reward Research program manages the following four awards, including two awards aimed specifically to support researchers in the early stages of their careers:

    • The NIH Director’s Pioneer Award, established in 2004, challenges investigators at all career levels to pursue new research directions and develop groundbreaking, high-impact approaches to a broad area of biomedical, behavioral, or social science.
    • The NIH Director’s New Innovator Award, established in 2007, supports unusually innovative research from early career investigators who are within 10 years of their final degree or clinical residency and have not yet received a research project grant or equivalent NIH grant.
    • The NIH Director’s Transformative Research Award, established in 2009, promotes cross-cutting, interdisciplinary approaches and is open to individuals and teams of investigators who propose research that could potentially create or challenge existing paradigms.
    • The NIH Director’s Early Independence Award, established in 2011, provides an opportunity to support exceptional junior scientists who have recently received their doctoral degree or completed their medical residency to skip traditional post-doctoral training and move immediately into independent research positions.

    Unique to this year was the addition of two special-focus areas:

    • Amyotrophic Lateral Sclerosis (ALS) – The Common Fund and National Institute of Neurological Disorders and Stroke (NINDS) partnered to support the Accelerating Leading-edge Science in ALS (ALS2) initiative as an opportunity to support ALS research through several Transformative Research Awards, including one award with support from National Institute of General Medical Sciences (NIGMS). The initiative aims to dramatically advance the understanding of what triggers and drives the rapid progression of ALS.
    • COVID-19 – Due to the public health emergency, the Transformative Research Award and Early Independence Award issued additional funding opportunities for COVID-19-related research on the prevention of, preparation for, or response to coronavirus SARS-CoV-2 using funds provided through the CARES Act.

    NIH issued 10 Pioneer awards, 64 New Innovator awards, 19 Transformative Research awards (10 general, four ALS-related, and five COVID-19-related), and 13 Early Independence awards for 2021. Funding for the awards comes from the NIH Common Fund, NIGMS, National Institute of Mental Health, and the NINDS.


    About the NIH Common Fund: The NIH Common Fund encourages collaboration and supports a series of exceptionally high-impact, trans-NIH programs. Common Fund programs are managed by the Office of Strategic Coordination in the Division of Program Coordination, Planning, and Strategic Initiatives in the NIH Office of the Director in partnership with the NIH Institutes, Centers, and Offices. More information is available at the Common Fund website:

    About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

    NIH…Turning Discovery Into Health®


  • The Pioneer Award
    For scientists with outstanding records of creativity pursuing pioneering approaches to major challenges....

  • The NIH Director’s Pioneer Award (DP1 mechanism), established in 2004, supports highly innovative researchers at any career stage who propose bold research projects with unusually broad scientific impact. To be considered “pioneering,” the proposed research must reflect ideas that are substantially different from those being pursued in the investigator’s research program or elsewhere. No detailed experimental plan or detailed budget is expected, and the major component of the application is a five-page essay describing the project and its innovation and significance, the investigator’s history of being highly innovative, and why the proposed project is suitable for the award. Three letters of reference must also be provided and discuss the applicant’s scientific innovativeness and creativity.

    • Open to all career stages
    • Single PI only
    • No preliminary data required
    • Must be new scientific research direction
    • Minimum of 51% research effort in first 3 years
    • Letters of Reference required
    • $700,000 in direct costs per year for up to 5 years
  • The New Innovator Award
    For exceptionally creative early career scientists proposing innovative, high-impact projects...

  • The NIH Director’s New Innovator Award (DP2 mechanism), established in 2007, supports highly innovative research from promising Early Stage Investigators (defined as those within 10 years of completing their terminal research degree or postgraduate clinical training and who have not yet received substantial NIH support). No detailed experimental plan or preliminary data are required. The major component of the application is a 10-page essay describing (1) the significance of the problem/challenge being addressed; (2) the general approach to be taken to address the problem/challenge; (3) why the project is unusually innovative; and (4) the qualities and experiences of the investigator that make him/her especially well-suited to pursue such research.

    • Single PI only
    • Must have Early Stage Investigator status (completed doctoral degree or postgraduate clinical training within last 10 years and never received a substantial NIH independent research award)
    • No preliminary data required
    • Minimum of 25% research effort
    • $1.5 million in direct costs split into two multi-year segments
  • The Transformative Research Award
    For individuals or teams proposing groundbreaking, unconventional research with the potential to create new scientific paradigms...

  • The NIH Director’s Transformative Research Award (R01 mechanism), established in 2009, supports exceptionally innovative and/or unconventional research projects with the potential to create or overturn fundamental paradigms. Multiple Principal Investigators and large budget applications are welcome. Though the application uses the standard R01 application, the requested information is very different from the standard R01. No detailed experimental plan or preliminary data are required. In the “Research Strategy” component, the investigators are asked to describe the challenge or problem being addressed, why it is important, and why the proposed approaches to addressing this major challenge or problem are unusually innovative. In addition, the investigators are asked to use the “Specific Aims” component to distill their proposal into a one-page summary in which they explicitly address the challenge, innovation, and impact of what they propose and the rationale of their approach.

    • Open to all career stages
    • Open to individuals or teams
    • No preliminary data required
    • Research effort commensurate to project needs
    • Anonymized review process
    • Flexible budgets
    • No prior approval required for large budget requests
  • The Early Independence Award
    For exceptional junior scientists bypassing postdoctoral training to launch independent research careers...

  • The NIH Director’s Early Independence Award (DP5 mechanism), established in 2011, accelerates the entry of exceptional junior investigators (within 15 months after or 12 months before receiving their terminal research degree or completing postgraduate clinical training) into positions of independent research by omitting the traditional postdoctoral training period. The review places a strong emphasis on the qualities of the investigator and the environment provided by the host institution.

    • Single PI only
    • Must complete doctoral degree or clinical training between June 1, 2021 and September 30, 2023
    • Must be in non-independent research position at time of application submission
    • Limit of 2 applications per institution
    • Preliminary data not required
    • Requires 9.6 months of research effort each year for first 2 years
    • Requires 3-5 Letters of Reference
    • $250,000 direct costs per year for up to 5 years
  • High-Risk High Reward Flyer
    A description of the program's four funding opportunities for biomedical research...

  • The NIH Common Fund’s High-Risk, High-Reward Research program ( supports exceptionally creative scientists pursuing highly innovative research with the potential for broad impact in biomedical or behavioral science. The program’s four constituent awards provide a diverse set of funding opportunities. A description of the four initiatives supported by this program.
  • HRHR Program Comparisons
    A tabular comparison of the four programs of the HRHR High-Risk High Reward Program...

  • A comparison table addressing the components of the four funding initiatives - Pioneer, New Innovator, Transformative Research, and Early Independence awards. The table addresses eligibility criteria, target groups, application requirements including preliminary data, research strategy, budget, reference letters, and the percetn effort required.

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