National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
The RISK program will support the two main scientific areas of NIAMS mission, 1) musculoskeletal diseases and 2) the skin and rheumatic diseases. This R61/R33 application and the companion X02 pre-application (PAR-18- 866) encourage applications related to skin and rheumatic diseases.
The X02 is the highly recommended (not required) first step in the application process for this FOA. Potential applicants should read both FOAs.
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 this FOA.
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.
No late applications will be accepted for this Funding Opportunity Announcement
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
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.
There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.
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-18-866 "Research Innovation for Scientific Knowledge (RISK) for Skin and Rheumatic 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., principal investigator 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-19-012 (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.
This FOA solicits biphasic applications for innovative research within the NIAMS mission, specific to skin and rheumatic 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:
The following attributes will not be viewed negatively if:
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-18-866, solicit bi-phasic applications related to the diagnosis, treatment, and prevention of skin and rheumatic diseases and on improving patients’ quality of life. The rheumatic diseases portfolios include Arthritis Biology, Systemic Autoimmune Diseases Biology, Rheumatic Diseases Genetics and Translational Research, Clinical Rheumatic Diseases, and Rheumatic Diseases Biopsychosocial Research (including PROMIS and fibromyalgia). The skin diseases portfolios include Keratinocyte Biology and Diseases, Immunobiology and Immune Diseases of Skin, Skin Repair, Regeneration and Pigmentation, and Extracellular Matrix Biology and Diseases. 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.
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
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.
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.
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.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
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.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
All instructions in the SF424 (R&R) Application Guide must be followed.
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.
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 skin and rheumatic diseases. Describe how the outcomes of the project will change a research field significantly beyond incremental expansion of current knowledge.
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.
Compatibility with the goals of the RISK Program:
Describe how the planned research is uniquely suited to the stated goal of the RISK program, rather than a traditional grant mechanism.
R61 (Phase 1):
An R61/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Do not include links to websites to provide further information. No animations (movies) are allowed in any documents.
Applicants should include one or more critical experiments for rigorously testing the proposed innovative concept/hypothesis. These experiments must be scientifically justified, specific, quantifiable, and feasible. Applicants should state explicitly the results that support, reject, or are inconclusive regarding testing of their concept/hypothesis. Reviewers will be specifically asked to evaluate the soundness of these critical experiments as an assessment of the feasibility of the study, and the outcome of these critical experiments will be the central factor determining whether the R33 Phase will be activated.
R33 (Phase 2):
Although the Research Strategy for the R33 Phase is expected to be broad and speculative due to the unpredictable nature of the explorative research in the R61 Phase, the research plan for the R33 phase of the award should be described in enough detail for reviewers to evaluate the merit of this component of the application, based on anticipated results.
The following modifications also apply:
All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:
All instructions in the SF424 (R&R) Application Guide must be followed.
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.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement .
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
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.
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.
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.
Research Innovation for Scientific Knowledge (RISK) for Skin and Rheumatic Diseases 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. An R61/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Accordingly, reviewers will emphasize the following:
Reviewers will assign a single impact score for the entire application, which includes both the R61 and R33 Phases.
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 skin and rheumatic 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?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
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?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?
Specific to this FOA:
Has the applicant proposed the required critical experiment(s) for testing the innovative idea? Can these experiments unambiguously test the hypothesis at hand, and are they feasible? Are the proposed outcomes of the critical experiments well-defined with quantifiable measures that are appropriate for assessing the success of the R61 Phase of the award? Are the proposed critical experiments sufficient to determine if the project succeeded in accomplishing its specific aims? Is it clear how the R33 Phase of the study will develop and expand once the R61 Phase is completed?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.
For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.
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