It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Purpose

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 X02 and its companion RFA-AR-19-013 "Research Innovation for Scientific Knowledge (RISK) for Musculoskeletal Diseases (R61/R33)", 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 are evaluated to be highly innovative and most relevant to the RISK program, will be 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 encourages pre-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. Each area will be supported by separate FOAs, which are identical except the topic areas. This X02 pre-application FOA and companion RFA-AR-19-013 encourage applications related to the diagnosis, treatment, and prevention of musculoskeletal diseases and on improving patients quality of life. The musculoskeletal 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: http://www.niams.nih.gov/about_us/mission_and_purpose/long_range.asp.

The applicants are encouraged to consult with NIAMS program officials for selecting the correct FOA prior to submission of their application.

See Section VIII. Other Information for award authorities and regulations.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time.

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Amanda Boyce, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5055
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

For this specific FOA, the Pre-application attachment is limited to 3 pages.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

Type of Submission: Select Pre-Application.

Total Federal Funds Requested: Enter $0

Total Federal & Non-Federal Funds: Enter $0.

Estimated Program Income: Enter $0.

Pre-application

Describe the applicant’s innovative vision for, and the significance of, the biomedical or behavioral problem to be addressed. Applicants should make clear how the planned research is uniquely suited to the goal of the RISK program, rather than a traditional grant mechanism. No detailed scientific plan should be provided as the research plan will be evaluated in the R61/R33 application.

The applicant must conceal personal and institutional identities in the X02, avoiding any information that would allow reviewers to identity the PD/PI or collaborators. Specifically, if this essay contains the following type of information, it will be considered non-compliant and withdrawn:

• Names of the applicant/collaborators and their current or past institutional affiliations.
• Mention of applicant’s mentor/mentee relationships.
• Mention of applicant’s role in any committee/organization.
• Use of we, I, our, my, etc. in reference to a publication, meeting abstract, grant, prize/award, or established theory/hypothesis (e.g., James Watson writes "my theory of the double helix structure of DNA ).

The pre-application must include the following sections in the order given and with headings as shown below:

Project Title:

As reviewers will not be provided with the cover page of the pre-application, applicants should include the title at the beginning of the essay.

Concept Summary:

Scientific challenge: Describe the scientific problem or challenge that will be addressed. Include sufficient background information for non-experts to understand the intellectual framework surrounding the problem.

Scientific goal: Describe the goal of this project, including an explicit, testable hypothesis or process (e.g., new methods or tools) that will serve that goal.

Scientific premise: Describe the rationale/conceptual basis (i.e., evidence and logic) of the hypothesis/solution to the challenge.

Overall approach: Outline a general experimental strategy to test the hypothesis/solution. Assess the feasibility of the strategy and the technical risks involved. No details of experimental protocols necessary.

Expected outcomes: Describe the range of possible outcomes, explain their implications to the proposed goal.

Significance:

Describe the translational potential of the project, and how the results will translate the new knowledge, mechanisms, and/or techniques into new approaches for prevention, diagnosis, and treatment of musculoskeletal diseases. Describe how the outcomes of the project will change a research field significantly beyond incremental expansion of current knowledge. Describe how the planned research uniquely suits the stated goals of the RISK program.

Innovation:

Describe how the project represents a new and distinct direction for the field. Describe how the concept addresses the scientific challenge in a new and creative way, challenging existing paradigms, testing a hypothesis beyond the leading edge of the field, exploring an unusual biological phenomenon or unexpected previous result, or proving a new connection between existing bodies of knowledge. Describe how the project is a leap rather than the next logical step. For projects proposing to develop new technologies, describe how the proposed technology offers clear and significant improvement over currently available methods.

Literature references are not allowed. If references are included, the pre-application will be deemed non-compliant and withdrawn without review. To use published papers to support the proposed concepts and approaches, concisely describe the relevant points of the published work in the main body of the research proposal. Figures and illustrations may be included but must also fit within the three-page limit. Do not include links to websites to provide further information. No animations (movies) are allowed in any documents.

All instructions in the SF424 (R&R) Application Guide must be followed.

Profile - Project Director/Principal Investigator: Do not attach a biographical sketch. Applicants will receive an error message and should upload an attachment indicating that per FOA instructions a biosketch is not required.

Profile - Senior/Key Persons: Do not list additional Senior/Key Personnel.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

Not Applicable

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, and by components of participating organization, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

Pre-applications that are complete will be evaluated by a multidisciplinary group of outside experts, convened by NIAMS. An innovative feature of the review is that the applicant(s) and their institutional affiliations will be anonymous to the reviewers. Information about the applicant(s) and institution will be used for administrative purpose only. These will not be provided to reviewers, as the evaluation of pre-applications will focus on innovation and significance only. PD/PIs with the most outstanding pre-applications (those that best address the review criteria) will be notified of the opportunity to submit full applications for RFA-AR-19-013, Research Innovation for Scientific Knowledge (RISK) for Musculoskeletal Diseases (R61/R33).

RISK applications are meant to support pioneering - and possibly transforming - approaches that, if successful, will have a major impact on biomedical or behavioral research within the NIAMS mission areas. Accordingly, reviewers will emphasize the following:

• The importance of the scientific problem and potential impact of the research;
• The novelty and innovativeness of the concept;
• Evidence that the proposed research is of sufficient risk/potential impact that it is more suitable for the RISK program than for a traditional grant mechanism, and that the proposed research represents a new research direction.

Not Applicable

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to the FOA:

Does the application focus on translating new knowledge, mechanisms, and/or techniques into new approaches for prevention, diagnosis, and treatment of musculoskeletal diseases? Has the PD/PI convincingly argued that the outcomes of the project will go significantly beyond incremental expansion of current knowledge? If the proposed project is successful, will it open new avenues of research?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA:

Does the project propose to address the question in a new and creative way, challenging existing paradigms, testing a hypothesis beyond the leading edge of the field, exploring an unusual biological phenomenon or unexpected previous result, or proving a new connection between existing bodies of knowledge? Is the project taking risks rather than simply the next logical step? For projects proposing to develop new technologies, does the proposed technology offer clear and significant improvement over currently available methods?

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIAMS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• Will receive a written critique.

Applications will be assigned to NIAMS. Investigators whose X02 pre-applications are meritorious and relevant to the RISK program priorities will be notified of the opportunity to submit an R61/R33 application under RFA-AR-19-013.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Not Applicable

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

Not Applicable

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten on-time submission, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application processes and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Amanda Boyce, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin (NIAMS)
Telephone: 301-594-5055
Email: [email protected]

Kan Ma, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Phone: 301-451-4838
Email: [email protected]

Andrew Jones
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-435-0610
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Not Applicable.