Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (http://commonfund.nih.gov/) through the NIH Office of the NIH Director, Office of Strategic Coordination (https://commonfund.nih.gov/about.aspx). The FOA will be administered by the National Institute of General Medicine (NIGMS/NIH) (http://www.nigms.nih.gov/) on behalf of the NIH.
Funding Opportunity Title	Undiagnosed Diseases Gene Function Research (R21)
Activity Code	R21 Exploratory/Developmental Research Grant Award
Announcement Type	New
Related Notices	April 18, 2014 - This RFA has been reissued as RFA-RM-14-005. August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications. May 20, 2013 - See Notice NOT-RM-13-019. Notice Announcing List of Genes of Interest.
Funding Opportunity Announcement (FOA) Number	RFA-RM-13-003
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.310
Funding Opportunity Purpose	This Developmental Research Funding Opportunity intends to support gene function studies in collaboration with the Undiagnosed Diseases Network (UDN) building upon the NIH Intramural Research Program’s Undiagnosed Diseases Program (NIH-UDP). Responsive applications will propose to investigate the underlying genetics, biochemistry and/or pathophysiology of newly diagnosed diseases in association with the respective gene variant(s) identified through the UDN. In recent years, gene function studies combined with genetic and genomic analyses and metabolic studies have greatly improved diagnoses of these very rare diseases and advanced scientific knowledge of the underlying pathogenesis. This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact.

Posted Date	April 2, 2013
Open Date (Earliest Submission Date)	May 14, 2013
Letter of Intent Due Date(s)	May 14, 2013
Application Due Date(s)	June 14, 2013, by 5:00 PM local time of applicant organization. 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.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	October/November 2013
Advisory Council Review	January 2014
Earliest Start Date	April 2014
Expiration Date	June 15, 2013
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the 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

This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

The purpose of this Funding Opportunity Announcement (FOA) is to support gene function studies in collaboration with the Undiagnosed Diseases Network to investigate the underlying genetics, biochemistry and pathophysiology of newly diagnosed diseases (Diseases of Interest) in association with the respective gene variant(s) identified through the NIH-UDP. In recent years, gene function studies combined with genetic and genomic analyses and metabolic studies have greatly improved diagnoses of these very rare diseases and advanced scientific knowledge of the underlying pathogenesis.

Over the past decade, the NIH Office of Rare Diseases Research (ORDR, NCATS) has received thousands of inquiries regarding patients undiagnosed diseases. Of those individuals seeking assistance, 6% were found to have an undiagnosed disorder. The NIH-UDP began in May 2008 and has received approximately 6,300 inquiries over a four-year period. From these inquiries, the investigators were able to evaluate 2,300 medical records and admit 450 patients to the NIH Clinical Center for thorough, one-week evaluations. Over the four-years, diagnoses were made in approximately 100 patients. The NIH-UDP discovered and described two unknown diseases and identified 15 genes not previously associated with human disease. The ability to diagnose these rare and yet to be described diseases has been revolutionized by the use of genetic and genomic analyses combined with gene function studies that uncover the links among gene defects, patient phenotypes, and diseases.

The NIH-UDP has demonstrated that it can, in some cases, overcome the obstacles impeding traditional methods of diagnoses, capitalize on new technologies to reveal novel mechanisms of diseases, and expand the spectrum of explained human phenotypes and successfully diagnose patients with rare diseases. Building on the success of the UDP, the NIH is prepared to develop the existing UDP into a larger program with a greater commitment to the advancement of diagnosis of rare diseases. Part of this commitment is the expansion of the UDP into a network of clinical sites containing the NIH Intramural Research Program (NIH-UDP) and Extramural UDN Clinical Sites. These clinical sites together with the planned Undiagnosed Diseases Coordinating Center will comprise the Undiagnosed Diseases Network (UDN).

UDP patients present compelling research questions since clarification of the underlying genetics, biochemistry and physiology of these disorders will lead to a better understanding of their disease processes and those of related disorders. Advances in the science of genetics and genomics in medicine have made it possible to understand the causes and potential targets for treatment of some of these rare diseases. A critical step in the process leading to diagnosis and potential treatment of patients with these rare diseases is the investigation of gene function. These studies provide the causal link between the genetic defects and patient phenotypes. Over half of the UDP newly diagnosed diseases (Diseases of Interest) involve neurological dysfunction or developmental delay; the remaining phenotypes span metabolic, skeletal and inflammatory disease among others. A current list of UDP Diseases of Interest and the associated gene variant(s) linked to these diseases is provided on the UDP website.

With expansion of the UDP, the need for gene function studies will substantially increase. Recognizing the importance of this research, the UDN Program is planning to increase research on genes identified by UDN Clinical Sites. The Undiagnosed Diseases Gene Function Research FOA will be an important step in an expanding, multi-faceted approach to meet this growing demand. This funding opportunity and the related FOA (PA-13-076, Gene Function Studies to Investigate Rare and Undiagnosed Diseases (Admin Supp) ), will provide support for scientific research projects designed to investigate the function of variant genes and their related relevant biological pathway, disease or disease model.

Applications should not be limited to particular experimental methods but should employ a wide variety of investigative approaches. Applicants are expected to conduct integrated studies of individual genes in the relevant physiological/pathophysiological environment across any of several levels including molecular, cell, tissue, organ, and model organisms. Before submitting an application, investigators are strongly encouraged to use the NIH-UDP (UDP website) to establish collaborations and/or gain detailed information about the gene variant and associated clinical phenotype of the disease of interest. In addition, applicants can inquire about the availability of patient bio-specimens and other available resources for gene function studies.

The goal of this research FOA is to obtain mechanistic understanding of (1) what these genes do in the context of physiology and/or pathophysiology of the disease of interest, (2) whether and how the genetic variation affects gene expression and function particularly as it relates to the disease phenotype, and (3) whether and how particular genes and their specific variants are involved in the disease pathogenesis. Several of the genes on the list may have pleiotropic functions or function in known pathways that may or may not be relevant to the newly diagnosed disease of interest. Highest priority will be given to those proposals that can provide new mechanistic insight into gene function relevant to the disease of interest.

Examples of research may include, but are not limited to:

• Functional characterization of the genes and their variants using integrated omic approaches (genomics, transcriptomics, proteomics, metabolomics, phenomics, etc.) to examine the mechanism leading to the disease phenotype (gene x gene, gene x environment, epigenetics, etc.).
• Examination of spatiotemporal expression patterns of the genes and their protein products, their upstream and downstream regulation, protein interactions and signaling partners to understand the potential contribution of the gene variants to the respective Diseases of Interest.
• Use of model organisms (including mice, flies, zebrafish, worms, and yeast) to assess the contribution of the gene variant to the disease etiology, pathophysiology and phenotype.
• Exploration of the contribution of the disease-related gene variants to abnormalities in gene expression or function in patient bio-specimens.

Investigators interested in applying to this Funding Opportunity Announcement should plan to discuss scientific and technical issues with UDP investigators prior to submission of an application. Potential applicants should go to the UDP website where they will find a list of gene variants of interest to the UDN and contact information to provide the applicant with a link to investigators of the UDP. .

The awards funded under this FOA will be Developmental Research Funding Opportunities (see Section VI.2. Terms and Conditions of Award).

Gene function research often requires building investigative teams that cross scientific disciplines. UDN productivity will depend on investigator collaboration in sharing of research plans; identifying commonalities in approaches, barriers, and solutions; and developing common resources such as educational, reporting, and evaluative tools. Shortly after award, the Gene Function awardees will be introduced to other UDP investigators in the network through the UDN Coordinating Center and will be encouraged to participate in network meetings to share in the development of new strategies to address the common network goals. Awardees will be able to learn about the clinical methods and technology applied and in turn they will share their approaches and progress in defining the functions of the specific genes of interest to the network. Through this collaboration the Network will provide improvements in both the diagnosis and treatment of rare diseases.

Funding Instrument	Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed	New The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The total amount of funds available for this award is approximately $650,000 for FY14 contingent upon receiving scientifically meritorious applications. Three to five awards are anticipated in FY14.
Award Budget	Application budgets should not exceed $250,000 total costs per year in FY14 and FY15 and must reflect the actual needs of the proposed project.
Award Project Period	The total award period for this FOA is 2 years (FY14 through FY15).

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

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)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are 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 and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the 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:

Donna Krasnewich, M.D., Ph.D.
National Institute of General Medical Sciences (NIGMS)
Telephone: 301-594-0943
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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

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

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

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

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

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

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

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims: List each aim and how it supports the Objectives of this Research Program as described in Section I. Funding Opportunity Description.

Research Strategy: In describing the research strategy, list a wide variety of investigative approaches. Applicants should describe integrated studies of individual genes addressing relevant physiological and pathophysiological conditions. These integrated studies may take place across several levels including molecular, cell, tissue, organ, and model organisms. Investigators are strongly encouraged to visit the NIH-UDP (UDP website) to gain detailed information about the gene variants and associated clinical phenotypes of the diseases of interest to the UDP before submitting an application. In addition, applicants are encouraged to use the contact information provided at the website to communicate with investigators of the UDP to discuss scientific and technical issues prior to submission of an application. Applicants can inquire about the availability of patient bio-specimens and other available resources for gene function studies.

The goal of this research FOA is to obtain mechanistic understanding of (1) what these genes do in the context of physiology and/or pathophysiology of the disease of interest, (2) whether and how the genetic variation affects gene expression and function, particularly as it relates to the disease phenotype, and (3) whether and how particular genes and their specific variants are involved in the disease pathogenesis. Applications will receive the highest priority for providing mechanistic insight into gene function relevant to the disease of interest.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Data from the UDN are expected to be handled so as to increase the value of the significant public investment in the creation and operation of the Network. Consistent with achieving the goals of the UDN program, the data sharing plan should describe how final research information such as protocols, methods, biological results, descriptions, bioinformatics tools, and publications will be shared among the UDN, made available through an open access section of a database such as dbGAP, other public websites, as well as with the research community at large. Any barriers to achieving such data sharing should be addressed. For additional information on the NIH Data Sharing Policy, see http://grants.nih.gov/grants/policy/data_sharing/.

The NIH also requires the timely sharing of biomedical resources by grant recipients. The resources sharing plan should also describe how unique research resources will be distributed, e.g., through the institution, a repository, or national coordinating center. For information regarding research resources sharing, see http://grants.nih.gov/grants/sharing.htm. Information regarding the sharing of model organisms can be found at http://grants.nih.gov/grants/policy/model_organism/.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

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.

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 by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NHGRI Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

Innovation

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?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

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?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

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).

Resource Sharing Plans

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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Human Genome Research, 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:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact/priority score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate National Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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.

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

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described 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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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.

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Phone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

Donna Krasnewich, M.D., Ph.D.
National Institute of General Medical Sciences (NIGMS)
Telephone: 301-594-0943
Email: [email protected]

Carson R. Loomis, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 919-541-7592
Email: [email protected]

Rudy O. Pozzatti, Ph. D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-402-0838
Email: [email protected]

Nicole Fleisher
Grants Management Team Leader
National Institute of General Medical Sciences
Telephone: 301-594-3923
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.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.