NIH – Research Innovations for Scientific Knowledge (RISK) for Musculoskeletal Diseases (R61/R33 Clinical Trial Not Allowed)

July 23, 2018 by School of Medicine Webmaster

In 2004, the NIH Office of Director launched a series of funding mechanisms, including the Pioneer (DP1), New Innovator (DP2), and Transformative Research (TR01) awards, aiming at boosting the support for high risk and high innovation projects.  Several NIH ICs also offered their own mechanisms to promote innovative research, e.g., EUREKA (multiple ICs), Avant-Garde Award (NIDA), BRAINS (NIMH), ONES (NIEHS), etc.

The NIAMS Research Innovation for Scientific Knowledge (RISK) initiative, consisting of this R61/R33 and its companion PAR-18-865 Research Innovation for Scientific Knowledge (RISK) for Musculoskeletal Diseases (X02), reflects NIAMS’s recognition of the need to enhance support of originality, creativity and risk-taking in its mission relevant research areas.  Through the RISK initiative, NIAMS envisions supporting bold and eclectic ideas. The RISK initiative serves as a complement to the other NIH research project mechanisms.  It intends to capture and support innovative ideas of high potential value, especially those in their early stage of development that may not fare well otherwise in peer review, thus accelerating the discovery process.  The RISK initiative itself intends to innovate by incorporating new features and processes in the X02 review, e.g., applicant’s anonymity.

Investigators whose X02 pre-applications were evaluated to be highly innovative and most relevant to the RISK program, will have been notified of the opportunity to submit an R61/R33 application to RFA-AR-19-013 (R61/R33). The R61/R33 is a two-phase application. The R61 Phase will provide up to two years of support to perform critical experiments that rigorously test the proposed concept.  These critical experiments should unambiguously support or reject the central hypothesis.  The outcomes of these critical experiments will be the main determining factor for the activation of the R33 Phase, which will provide up to one additional year of support to further validate and explore the innovative concept.

Specific Objectives

This FOA solicits biphasic applications for innovative research within the NIAMS mission, specific to musculoskeletal diseases.  The FOA focuses on pursuing unusual observations, testing imaginative hypotheses, investigating creative concepts, and building new paradigms, all of which deviate significantly from the current prevailing theories and practice.  The FOA is particularly designed to encourage the submission of projects that may be considered too risky, premature, controversial, or unconventional for other NIH mechanisms. The initiative intends to support disease-focused translational studies, up to, but not including, first in human studies. This FOA is not intended to support clinical trials.

Examples of areas of NIAMS interest in innovative research include, but are not limited to, the following:

  • Proposes a new area of inquiry, e.g., an unexpected function of cells or molecules associated with mechanism of disease;
  • Uses or develops a completely unexplored approach to solving a longstanding important challenge or obstacle;
  • Is substantially different from research already being pursued;
  • Introduces a new paradigm or challenges prevailing paradigms/assumptions;
  • Looks at existing problems or issues from a new perspective;
  • Seeks unconventional approaches that are outside the mainstream;
  • Could change established practice or create new fields;
  • Could yield new avenues of investigation;
  • Is more than an incremental advance on published data;
  • Is not the next logical step or continuation of a previous research project.

The following attributes will not be viewed negatively if:

  • The proposed work is still in the early stage of development;
  • The theory or hypothesis has scant precedent or lacks preliminary data;
  • The outcome of the proposed study is unpredictable;
  • The premise of the study contradicts existing paradigms/assumptions.

The RISK initiative will support the two main scientific areas of NIAMS mission, 1) musculoskeletal diseases and 2) the skin and rheumatic diseases. This FOA and companion PAR-18-865 solicit bi-phasic applications related to the diagnosis, treatment, and prevention  of musculoskeletal diseases and on improving patients’ quality of life.  The musculosketeal disease portfolios include Cartilage and Connective Tissue, Clinical Research and Diagnostic Tools for Osteoarthritis and Bone Quality, Muscle Development and Physiology, Muscle Disorders and Therapies, Musculoskeletal Tissue Engineering and Regenerative Medicine, Orthopaedic Research, Osteoporosis and Metabolic Disorders of Bone, and Rare Diseases and Integrated Physiology of Bone. Detailed descriptions can be found in NIAMS Long-Range Plan page at:

Deadlines:  April 9, 2019; January 9, 2020


Filed Under: Funding Opportunities