Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
This RFA is developed as a Roadmap initiative. All NIH Institutes and Centers participate in Roadmap initiatives. This RFA will be administered by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) on behalf of the NIH, http://www.niddk.nih.gov/.

Title: Discovery of Novel Epigenetic Marks in Mammalian Cells (R01)

Announcement Type
New

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.

Request for Applications (RFA) Number: RFA-RM-07-015

Catalog of Federal Domestic Assistance Number(s)
93.310

Key Dates
Release/Posted Date: November 14, 2007
Opening Date: January 14, 2008 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): January 14, 2008 NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Submission/Receipt Date(s): February 14, 2008
Peer Review Date(s): June/July 2008
Council Review Date(s): August  2008
Earliest Anticipated Start Date(s): September 30, 2008
Additional Information To Be Available Date (Activation Date): N/A
Expiration/Closing Date: February 15, 2008

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives


Section II. Award Information

1. Mechanism of Support

2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants

    A. Eligible Institutions
    B. Eligible Individuals
2. Cost Sharing or Matching
3. Other-Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information

2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Submission, Review, and Anticipated Start Dates
      A.1. Letter of Intent
    B. Submitting an Application Electronically to the NIH
    C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Sharing Research Data
    D. Sharing Research Resources
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices

2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contacts
1. Scientific/Research Contact(s)

2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

Nature of the Research Opportunity

The goal of this Funding Opportunity Announcement (FOA) is to stimulate the identification of novel epigenetic marks and establish their utility in mammalian cells. It is anticipated that the results of these studies would quickly be translated to global epigenome mapping in human cells. Epigenetic processes are critical to the normal development and function of multicellular organisms. Understanding these processes and in particular their susceptibility to perturbation may provide novel insights into disease pathogenesis and therapeutic approaches. This FOA is restricted to studies in mammalian cells which propose to identify novel epigenetic marks and validate their role in transcriptional silencing or activation. There is a companion announcement to this FOA, focused on discovery of putative epigenetic mechanisms in both mammalian and non-mammalian model systems, using the R21 mechanism (RFA-RM-07-016). In the long term, advances in these areas will enhance our ability to investigate, diagnose and ameliorate human disease with a significant epigenetic component.

The NIH Roadmap is an integrated vision to deepen our understanding of biology, stimulate interdisciplinary research teams, and reshape clinical research to accelerate medical discovery and improve human health. It is a collection of initiatives designed to pursue major opportunities and gaps in biomedical research that no single NIH institute could undertake alone but which the NIH as a whole can address. These initiatives are intended to have tremendous impact on the progress of medical research and to catalyze changes that will have a transforming effect on research to ultimately result in tangible benefits for public health (http://nihroadmap.nih.gov/).

The Roadmap Epigenomics Program is one of the new programs being launched under Roadmap 1.5 beginning in 2008. The program is being developed and implemented by a trans-NIH Epigenomics Working Group. The Working Group convened the “Epigenetics of Human Health and Disease Workshop” in March 2007 (Bethesda, MD) (http://nihroadmap.nih.gov/epigenomics/) and invited leading experts in the field of epigenetics from the United States, Canada and Europe to identify research opportunities and potential areas for international collaboration. Workshop participants identified the following priorities (1) establish a set of “reference epigenomes” based on genome-wide characterization of DNA methylation and multiple histone modification marks in multiple human cell types; (2) characterize the epigenetic states associated with major human diseases, response to environmental stressors, and stages of development; and (3) seek input from researchers in the international community to define standardized protocols and critical reagents requisite for utilizing cutting edge scientific approaches, and coordinate the informatics/data technology platforms and output formats for publicly accessible data generated by the Roadmap Epigenomics Program.

Critical analysis of the NIH epigenetic research portfolio revealed a limited investment in disease-focused research (except cancer); limited tools to measure epigenetic changes across the genome; and limited approaches to mapping reference epigenomes. Moreover, a consensus reached by participants at multiple epigenetic focused meetings was that the research community would greatly benefit from the development of an organized, integrated, publicly accessible database of signature epigenetic profiles of human stem cells, differentiating cells, differentiated cells, and tissues (http://cancerres.aacrjournals.org/cgi/reprint/65/24/11241; http://www.landesbioscience.com/journals/epigenetics/article/heindelEPI1-1.pdf). The integration of sequence variation data from genomic and HapMap (http://www.genome.gov/10005339) data and other components of DNA that will be cataloged by the NIH ENCODE program (http://www.genome.gov/10005107) with the NIH Roadmap epigenomic data will result in a database developed and maintained by the National Center for Biotechnology Information (NCBI) that will be a resource for researchers working to unravel the components of disease and dysfunction in addition to providing important information about health and normal processes.

There are five components of the Roadmap Epigenomics Program. Four of these are being announced concurrently. The RFA numbers and titles are as follows: RM-07-013, Reference Epigenome Mapping Centers; RM-07-014, Epigenomics Data Analysis and Coordination Center (EDACC); RM-07-011 (R01) and RM-07-012 (R21) Technology Development in Epigenetics; and RM-07-015 (R01) and RM-07-016 (R21) Discovery of Novel Epigenetic Marks in Mammalian Cells. A fifth component, addressing the Epigenetics of Human Health and Disease, will be announced in FY2008.

The goals of the Roadmap Epigenomics Program are to establish multiple sets of comprehensive reference epigenomes; develop new reagents and tools for epigenetic research; identify public resources for purified, high quality stem cells, differentiated cells, and tissues; provide publicly accessible data as well as new tools for data integration; and conduct research on novel hypotheses on epigenetic roles in human health and disease.

It is anticipated that the Roadmap Epigenomics Program will make significant impacts on understanding: 1) human health by assessing cell/tissue variation in epigenetic marks during stem cell differentiation, development, aging, and environmental responsiveness; and 2) human disease by potential identification of biomarkers, and novel therapeutic targets and tissue regeneration strategies.

Purpose

The purpose of this funding announcement is to establish and validate novel pathways of stable, differential silencing and activation of gene expression in mammalian cells. A companion announcement, using the R21 mechanism (RFA-RM-07-016), is focused on discovery of potential epigenetic marks in model systems. In the long term, advances in these areas will enhance our ability to investigate, diagnose and ameliorate human disease with a significant epigenetic component.

Background

The organization of DNA into chromatin presents the cell with the opportunity to use powerful regulatory mechanisms broadly defined as epigenetics. Increasing evidence demonstrates epigenetic mechanisms are linked to gene activation, gene silencing and chromosomal instability. Epigenetic processes act in cell specific, temporally regulated manners to direct normal development, organogenesis, tissue formation, differentiation and aging. Epigenetics is an emerging frontier of science that involves the study of changes in the regulation of gene activity and expression that are not dependent on gene sequence. For purposes of this program, epigenetics refers to both heritable changes in gene activity and expression (in the progeny of cells or of individuals) and also stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable. While epigenetics refers to the study of single genes or sets of genes, epigenomics refers to more global analyses of epigenetic changes across the entire genome. Epigenetics is an emerging basic field of science as evidenced by the exponential increase in basic epigenetic research literature citations observed between 1990 and 2006. A similar pattern of escalating citations is now being documented with epigenetics and diseases, and multiple disease focused research initiatives and grants that have been awarded by the NIH in recent years.

Epigenetic regulation of gene transcription apparently plays a pivotal role in the governance of normal and disease development through dynamic transcriptional activities from gametogenesis through embryonic and neonatal stages, and continuing throughout adolescence, adulthood and elderly stages/old age. The growth of epigenetic research in human health, aging and disease is rapidly evolving and has reached a critical point where opportunities exist to make significant inroads in understanding how epigenetically regulated transcription directs normal development, differentiation, specialized tissue/organ function, and aging, as well as a number of disease processes. Multiple lines of study focusing on epigenetic mechanisms have begun to yield information about the normal regulation of transcription and human health.

Alterations in normal gene silencing and activation result in inappropriate patterns of gene expression, adversely affecting phenotypic plasticity and resulting in a broad spectrum of tissue dysfunction and disease outcomes, including but not limited to multiple cancers, autoimmune diseases, neurodegenerative disorders, respiratory disorders, and behavioral disorders. The integration of epigenetics with genetics and environmental influences will be necessary to fully understand mechanisms of complex human diseases. Epigenetic mechanisms which are responsible for temporal and tissue specific activation or silencing of gene transcription include: DNA methylation of CpG islands in promoters and other regions of the genome; chromatin remodeling and higher order chromatin structural alterations; post-translational ATP-dependent modifications which include methylation, acetylation, ubiquination, and phosphorylation of histone tail domains; and gene silencing through RNAs thought to escort epigenomic apparatus to specific genomic loci. There are conceivably additional epigenetic mechanisms that have not yet been discovered or elucidated.

Normal development and aging are also directed by epigenetic processes. Programmed transcriptional activation and de-activation directs the phenotypic plasticity of totipotent stem cells into specialized cells and tissues. Human embryonic stem cells are derived from the inner cell mass of the blastocyst and possess an unlimited capacity for self renewal with the potential to give rise to all differentiated cells in the developing embryo. Epigenetic mechanisms are responsible for governing the programmed patterns of gene expression and silencing that direct differentiation of embryonic stem cells into the specialized cells and tissues (e.g., neurons, muscle cells, hepatic cells, etc.) that are the component of the various organs and tissues that constitute the human body. Recent data indicate that developmental nutrition in combination with environmental exposures may alter gene expression via alteration of epigenetic marks. This altered gene expression in many cases is permanent giving rise to increased susceptibility to disease later in life and even across generations.

Epigenetic research has enormous potential for significantly improving health outcomes through the discovery/development of novel:

Objectives

For the purposes of this FOA, reference epigenomes are the epigenetic profiles from specific  cell types that direct gene transcription in a manner that defines the characteristic expression profile and therefore phenotype of the cell or tissue. Transient, stimulus-associated regulation of gene expression may share many of the same pathways and proteins, but for the purposes of the epigenome project only those that result in stable alteration in transcriptional potential of a cell will be considered epigenetic marks. There are several well established epigenetic marks that restrict gene expression resulting in characteristic cellular phenotypes of fully differentiated cells and tissues. DNA methylation and methylation of a number of lysine residues in histone H3 are both well established epigenetic marks which play a role in lineage progression, genetic imprinting, and tumor development. This FOA will solicit proposals to establish the validity of other mechanisms as epigenetic marks in mammalian cells. Studies in yeast, worms, and flies have been crucial as models in which to identify potential new mechanisms of genetic regulation and confirm their potential as epigenetic marks. Thus, these model systems have been used to advantage to provide much of what we know about eukaryotic development and in particular the epigenetic mechanisms employed in that process. The current FOA is distinct from this field of endeavor in that it is focused solely on the establishment of epigenetic marks as valid mechanisms in mammalian cells and tissues. Thus, proposed studies must demonstrate that the marks are characteristic of a defined functional state, that they can be measured reliably, and that they can act on a genomic scale in mammalian cells.

Some examples of areas of epigenetic mark discovery of particular interest are outlined below. These examples illustrate some potential avenues of research, but do not constitute an all inclusive list.

Proposed research should include studies to assess both the stability of putative epigenetic marks and a functional readout of the effect of a change in the epigenetic state of the putative mark. Global mapping of novel marks is beyond the scope of the current FOA, but it is anticipated that results from this initiative would be rapidly translated to genome wide mapping in human tissues through Roadmap funded epigenomics centers.

Studies of regulatory mechanisms controlling the establishment of epigenetic marks, or activation and repression of individual genes by transcription factors are not responsive to this FOA.  Potential applicants are encouraged to contact NIH staff (see program contacts) to discuss the appropriateness of proposed research to the goals of this FOA.

Technical Assistance Workshop

NIH will conduct a Technical Assistance Workshop and videoconference in Research Triangle Park, NC, on December 7, 2007. This will allow potential applicants to discuss and clarify any issues related to this RFA with NIH staff. Detailed information about the workshop (e.g., time, location, videoconference information, etc.) will be available on the Roadmap Epigenomics Program website at http://nihroadmap.nih.gov/epigenomics, and will also be posted to the NIH Guide. Potential applicants will be able to ask questions of program staff involved in managing the program, both in-person and by teleconference during the workshop, but are encouraged to submit their questions or comments in advance of the meeting by sending an email to epigenomics@nih.gov.

Evaluation

As part of good program management, NIH assesses the implementation and effectiveness of its programs using evaluation tools and techniques. Grantees may be asked to provide information for program evaluation purposes, both locally and at the national level. Such information may be used in evaluations of the Epigenetic Mark Discovery projects, as well as the “Mid-Course” review of the entire Roadmap Epigenomics Program. Note that the Roadmap Epigenomics Program Mid-Course evaluation will be directed by the Epigenomics Working Group (EWG). Applicants are advised to review the additional details on evaluation that are provided in Section IV.6. Application and Submission Information, “Other Submission Requirements.”

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information


1. Mechanism(s) of Support

This funding opportunity will use the NIH Research Project (R01) grant mechanism.

The applicant will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses “Just-in-Time” information concepts. It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are a U.S. organization and are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 5.4, “Modular Budget Component,” of the Application Guide). 

U.S. applicants requesting more than $250,000 in annual direct costs and all foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096, August 23, 2006. 

2. Funds Available

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the Institutes and Centers (ICs) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

NIH grants policies as described in the NOT-OD-05-004.

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution 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.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach that clearly does not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a single PD/PI or multiple PD/PI grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for multiple PD/PI grants will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PD/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

Cost sharing is not required.

The most current Grants Policy Statement can be found at: http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#matching_or_cost_sharing

3. Other-Special Eligibility Criteria

Applicants may submit more than one application, provided they are scientifically distinct.

Section IV. Application and Submission Information


To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/applicants/apply_for_grants.jsp and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

PDs/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.

Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:

1)   Organizational/Institutional Registration in Grants.gov/Get Registered

2)   Organizational/Institutional Registration in the eRA Commons

3)   Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

Both the PD/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo: Telephone 301-435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

The SF424 (R&R) application has several components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/Apply includes all applicable components, required and optional. A completed application in response to this FOA includes the data in the following components:

Required Components:

SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist

PHS398 Modular Budget or Research & Related Budget, as appropriate (See Section IV.6., “Special Instructions,” regarding appropriate required budget component.)
Research & Related Budget (required for foreign applications)

Optional Components:

PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

Foreign Organizations Non-domestic (non-U.S.) Entity)

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600260.

Applications from foreign organizations must:

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact” PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of “PD/PI.” Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the “Credential” field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership of the project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” (Section 14 of the Research Plan Component in the SF424 (R&R)), must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, allocation of resources, publications, intellectual property issues, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs, and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form. 

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only. Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

Applications Involving federal Agencies

“The requests from federal agencies, including the NIH intramural program, will not include any salary and related fringe benefits for career, career conditional or other federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative costs).

In general, the budget requests will be limited to the incremental costs required for carrying out the proposed work.  These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. While support for extramural collaborators may be requested in a separate grant application, funds can be requested for services by an external investigator or contractor as a subcontract/consortium including the applicable indirect (F&A costs) of the contractor/collaborating institution.

Justification must be provided for all requested support and for the Federal employees who will be committed to the project although no funds are requested in the application.

Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.”

3. Submission Dates and Times

Applications must be received on or before the receipt date described below. See Section IV.3.A. for details.

3.A. Submission, Review, and Anticipated Start Dates

Opening Date: January 14, 2008 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): January 14, 2008
Application Submission/Receipt Date(s): February 14, 2008
Peer Review Date(s): June/July 2008
Council Review Date(s): August 2008
Earliest Anticipated Start Date(s): September 30, 2008

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Philip F, Smith, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases
Democracy 2, Room 689
6707 Democracy Blvd.
Bethesda, MD 20892-5460

Telephone: (301) 594-8816
Fax: (301) 480-3503
Email: smithp@mail.nih.gov

A letter of intent is not required for the funding opportunity.

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp and follow steps 1-4. Note: Applications must only be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review (CSR) and responsiveness by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Incomplete and non-responsive applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR receives the Grants.gov acknowledgments. The AOR and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status in the Commons.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an “Introduction” describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing renewal (formerly “competing continuation”) award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See the
NIH Grants Policy Statement.

6. Other Submission Requirements

Applicants must budget funds for travel of the PD/PI and up to one additional investigator to attend an annual investigators’ meeting in Washington D.C.

This initiative is part of a broader program in Epigenomics funded as part of the NIH Roadmap.  In order to fulfill requirements for oversight of the Epigenomics Program as a whole, NIH staff may have to present status reports on individual initiatives to coincide with NIH Office of the Director timeframes.  Thus, in addition to the annual progress report required at the time of submission of the noncompeting continuation application, awardees may be required to submit additional progress updates at a time to be determined by NIH. Program staff will use information from reports, site visits, etc. to evaluate each grantee’s progress and the success of the overall program. Progress will also be evaluated with the assistance of external advisors at the annual meeting and at the mid-course review of the entire Roadmap Epigenomics Program (see “Management and Evaluation” below).

To accelerate progress in the field of epigenomics, grantees will be expected to participate actively and openly in at least one grantee meeting per year. Substantial information sharing is critical to the program, so how an applicant plans to achieve this would be considered as a term and condition of the award; failure to openly share information will be considered in continued funding, consistent with achieving the goals of the program. It is understood that some information developed under the grants will be proprietary and cannot be shared immediately without damaging the commercialization potential of the technology. Applicants should describe their plans for participating in the grantee meetings and for managing the intellectual property concerns in the context of those meetings and other opportunities for information sharing. Other investigators in the field (i.e., not supported under this program) may be invited to participate in these workshops, but their agreement to share information substantially will be a prerequisite to their participation. Applicants should request travel funds in their budgets for the principal investigator and up to one additional lead investigator to attend the annual meeting.

Management and Evaluation

The project management team will evaluate the grants through annual progress reports and through annual All Hands Roadmap Epigenomics Program meetings starting in year 1 of the award. PIs of funded projects will be required to attend at least one grantee meeting per year  for project evaluation and to facilitate technology transfer to the other components of the Roadmap Epigenomics Program. The annual meeting may include program staff, external advisors, and PIs from all funded awards in the Roadmap Epigenomics Program.

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD/PI(s) to fill in his/her Commons User ID in the “PROFILE – Project Director/Principal Investigator” section, “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

Warning: Please be sure that you observe the direct cost, project period, and page number limitations specified above for this FOA. Application processing may be delayed or the application may be rejected if it does not comply with these requirements.

PHS398 Research Plan Component Sections

Items 2-5 of the PHS398 Research Plan component are limited to 25 pages. While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporating "Just-in-Time" information concepts, and with the following additional requirements:

Special Instructions for Modular Grant applications

R01 applications from U.S. institutions/organizations requesting up to $250,000 per year in direct costs (excluding consortium F&A costs) must be submitted in a modular budget format. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm. When submitting a modular budget, the applicant organization will include only the PHS398 Modular Budget component. See Section 5.4 of the SF424 (R&R) Application Guide for further instructions regarding the use of the PHS398 Modular Budget component.

Foreign organizations may not submit modular budgets. See NOT-OD-06-096.

Appendix Materials

NIH has published new limitations on grant application appendix materials to encourage applications to be as concise as possible while containing the information needed for expert scientific review. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html.

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Note: While each section of the PHS398 Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to monitor better formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

Foreign Organizations (Non-domestic (non-U.S.) Entity)

Plan for Sharing Research Data

Technology and data sharing overview

To achieve the goals of this program, projects funded by this RFA are expected to share technological advances and research data. For example, depending on the precise nature of the project, sharing can take place in various ways. Examples of such approaches are described in greater detail in the sections that follow and are consistent with achieving the goals of this program. The PIs of funded projects will be expected to share technological advances and information with other PIs funded by the Roadmap Epigenomics Program through active and open participation in at least one grantee meeting per year. The PIs of funded projects will be also be expected to share technological advances and information with epigenetics researchers as a whole and thus need to give thought as to an appropriate intellectual property management plan necessary to facilitate this sharing.

The precise content of data sharing plans will vary, depending on the data being collected and how the investigator is planning to share the data.  Applicants who are planning to share data should describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

All applicants are expected to include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. Program staff will be responsible for overseeing the data sharing policy and for assessing the appropriateness and adequacy of proposed data-sharing plans. Applicants are encouraged to discuss data sharing plans with their program contact prior to submitting their application.

Sharing with other Roadmap Epigenomics Program Grantees

To accelerate progress in the field of epigenomics, grantees will be expected to participate actively and openly in at least one grantee meeting per year. Substantial information sharing is critical to the program, so how an applicant plans to achieve this would be considered as a term and condition of the award; failure to openly share information will be considered in continued funding consistent with achieving the goals of the program. It is understood that some information developed under the grants will be proprietary and might not be shared immediately without damaging the commercialization potential of the technology. Applicants should describe their plans for participating in the grantee meetings and for managing any applicable intellectual property concerns (see below) in the context of those meetings and other opportunities for information sharing. Other investigators in the field (i.e., not supported under this program) may be invited to participate in these workshops, but their agreement to share information substantially will be a prerequisite to their participation. Applicants should request travel funds in their budgets for the principal investigator and up to one additional lead investigator to attend the annual meeting.

Intellectual Property Management Plan

Certain research plans will require collaboration and coordination between investigators at different institutions, some of whom may not be NIH funding recipients and who may have pre-existing intellectual property obligations to third parties. It is anticipated that commercial embodiments of the results of such research may incorporate single inventions shared by several institutions, or multiple inventions each from a separate institution. Therefore, prior to funding, grant applicants are expected to address, for example, how they will coordinate patent prosecution and licensing activities, if necessary to enable a licensee to access the bundle of intellectual property needed to take a product to market on commercially viable terms. Suggested strategies include: (1) assigning intellectual property rights to related inventions to an invention management firm; (2) designating one organization to take the lead on patenting and licensing related inventions; and (3) agreeing in advance that if multiple parties are to independently license-related inventions, the total of stacked royalties will not exceed a predetermined percentage rate. The technology transfer/ intellectual property management/licensing officer or equivalent of the PI's institution is expected to submit an intellectual property management plan, including at least those elements above. Alternatives to the suggested strategies, which accomplish the same goals, will be considered. Intellectual property management plans are a just-in-time requirement and do not need to be included in the grant application but plans will be required before a grant can be awarded. The applicant's institution should avoid exclusively licensing those inventions that are research tools unless either: (1) the field of use of the exclusive license is restricted to commercial use; or (2) the exclusive licensee will make the research tool available on reasonable terms. Applicants are directed to the NIH policy on the dissemination of biological research resources (“research tools”) http://grants.nih.gov/grants/intell-property_64FR72090.pdf.

After completion of the initial review, NIH program staff will be responsible for any additional administrative review of any plans for sharing data. The adequacy of such data sharing plans will be considered by program staff of the funding organization when making recommendations about funding applications. The final accepted data sharing plan will become a term and condition of the award. The effectiveness of the data sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590).

See Section VI.3. Award Administration Information, “Reporting.”

Sharing Research Resources

NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590). See Section VI.3. Award Administration Information, “Reporting.”

As the Roadmap Epigenomics Program is a community resource program, NIH expects that not only data, but also resources generated during the course of the program should be made rapidly available to the research community and that sharing plans should follow the same principles and spirit as the proposed rapid data release policy. The applicant should provide specific plans for resource sharing and distribution in the application. The reasonableness of data sharing plans will be assessed by the reviewers. However, reviewers will not factor the proposed resources sharing plan into the determination of scientific merit or the priority score. The adequacy of resources sharing plans will be considered by the funding organization when making recommendations about funding applications. The presence of a resources sharing plan will be part of the terms and conditions of the award. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm. See Section VI.3. Award Administration Information, “Reporting.”

Section V. Application Review Information


1. Criteria

Only the review criteria described below will be considered in the review process.

The following will be considered in making funding decisions:

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the Center for Scientific Review (CSR) in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

Receive a second level of review by the appropriate national advisory council or board.  

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application.

Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the application address the goals and objectives outlined in the RFA? Is the potential advance resulting from the proposed work likely to have broad application to the field of epigenetics research?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? For applications designating multiple PDs/PIs, is the leadership approach, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PDs/PIs? For applications designating multiple PDs/PIs, does the Leadership Plan ensure that there will be sufficient coordination and communication among the PDs/PIs? Are the administrative plans for the management of the research project appropriate, including plans for resolving conflicts?

Innovation: Is the project original and innovative? Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for epigenetic research?

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

2.A. Additional Review Criteria

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. See the “Human Subjects Sections” of the PHS398 Research Plan component of the SF424 (R&R).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated. See the “Human Subjects Sections” of the PHS398 Research Plan component of the SF424 (R&R).
 
Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the adequacy of the plans for their care and use will be assessed. See the “Other Research Plan Sections” of the PHS398 Research Plan component of the SF424 (R&R).

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget and Period of Support: The reasonableness of the proposed budget and the appropriateness of the requested period of support in relation to the proposed research may be assessed by the reviewers. The priority score should not be affected by the evaluation of the budget.

Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing.

2.D. Sharing Research Resources

NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps/part_ii_5.htm#availofrr and http://grants.nih.gov/grants/intell-property_64FR72090.pdf). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. The final data and resource sharing plans will become a term and condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590). See Section VI.3. Award Administration Information, “Reporting.” 

3. Anticipated Announcement and Award Dates

Not applicable.

Section VI. Award Administration Information


1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access their Summary Statement (written critique) via the NIH eRA Commons

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

2. Administrative and National Policy Requirements

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.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

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. See Section IV.5., “Funding Restrictions.” 

3. Reporting

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

Section VII. Agency Contacts


We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contact(s):

Philip F, Smith, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases
Democracy 2, Room 689
6707 Democracy Blvd.
Bethesda, MD 20892-5460

Telephone: (301) 594-8816
Fax: (301) 480-3503
Email: smithp@mail.nih.gov

2. Peer Review Contact(s):

Richard Panniers, Ph.D.
Division of Molecular and Cellular Systems
Center for Scientific Review, Room 2198
6701 Rockledge Drive
Bethesda, MD 20892
Telephone: (301) 435-1741
Email: pannierr@csr.nih.gov

3. Financial/Grants Management Contact(s):

Mary K. Rosenberg
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 745
Bethesda, MD 20892
Telephone: (301) 594-8891
FAX: (301) 480-3504
Email: mr239s@nih.gov

Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (“NIH Policy for Data and Safety Monitoring,” NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research” (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process, please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov/ and view the Policy or other Resources and Tools, including the Authors' Manual.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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 Parts 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.