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
National Human Genome Research Institute (NHGRI), (http://www.genome.gov)

Title: Genome-wide Association Studies of Treatment Response in Randomized Clinical Trials – Study Investigators (U01)

Announcement Type
New

Update: The following update relating to this announcement has been issued:

Request For Applications (RFA) Number: RFA-HG-08-004

Catalog of Federal Domestic Assistance Number(s)
93.172

Key Dates
Release Date: August 19, 2008
Letters of Intent Receipt Date: October 13, 2008
Application Receipt Date: November 13, 2008
Peer Review Date(s): February/March, 2009
Council Review Date(s): May, 2009
Earliest Anticipated Start Date: July 1, 2009
Additional Information To Be Available Date (Url Activation Date): N/A
Expiration Date: November 14, 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(s) 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. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Receipt, Review and Anticipated Start Dates
         1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
   D.  Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
     A. Cooperative Agreement Terms and Conditions of Award
         1. Principal Investigator Rights and Responsibilities
         2. NIH Responsibilities
         3. Collaborative Responsibilities
         4. Arbitration Process
3. Reporting

Section VII. Agency Contact(s)
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 purpose of this funding opportunity is to support genome-wide association (GWA) studies in randomized clinical trials to identify genetic variants associated with response to treatments for conditions of clinical or public health significance.

For the purposes of this program, a treatment is defined as an intervention, whether involving drug, dietary, and/or lifestyle modification, that aims to reduce morbidity and/or prevent disease.  A randomized clinical trial is defined as an experimental study that assigns participants to one or more interventions with a known but unpredictable probability of each assignment and collects pre- and post-intervention data on pre-defined endpoints.  Population-based studies are encouraged; studies are not required to be hospital- or clinic- based.

The goal of this U01 program is to utilize existing clinical trial data and sample resources to: 1) identify genetic variants that influence an individual’s response to treatment; 2) determine whether specific treatments are more or less effective in groups defined by genotype; and 3) develop and disseminate innovative methods for adding genome-wide technologies to randomized clinical trials and interpreting the results in the context of a randomized treatment assignment. 

The value of existing epidemiologic data in large randomized trials will be increased substantially by the addition of GWA genotyping.  To ensure that the maximal scientific benefit is derived from this significant public investment, this funding opportunity aims to support rapid and widespread sharing of the resulting genotype data, combined with phenotype and exposure data provided by the Study Investigators according to their plans for data sharing, through community resources such as the Database of Genotype and Phenotype (dbGaP) of the National Center for Biotechnology Information  (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gap), consistent with the goals of NIH policies on data sharing in GWAS (http://grants.nih.gov/grants/gwas/).

Background

Patients are known to vary considerably in response to drug therapy and other interventions, both in magnitude of treatment effect and in risk of adverse events; much of this variation has been hypothesized to have a genetic basis.  Growing evidence supporting this hypothesis includes identification of variants in CYP2C9 and VKORC1 that explain roughly 40% of variation in warfarin dosage requirements, variants in ADRß2 that are strongly associated with response to bronchodilators in asthma, and variants in GRIK4 and HTR2A associated with response to citalopram treatment for depression.  Such findings are not limited to pharmacologic therapies; for example, variants in TCF7L2, KCNJ11, and PPAR? have been investigated in relation to the impact of lifestyle modifications on incidence of diabetes.  Adverse drug reactions have also been related to genetic variation, including variants in TPMT and treatment with purine antimetabolites, UGT1A1 and irinotecan therapy, and HLA-B*5701 and abacavir treatment.

Despite these initial successes, known variants generally explain a small proportion of the estimated genetic variability of response to many of these therapies.  Identification of variants related to treatment response to date has largely relied on candidate gene studies, much as did research in the genetics of complex diseases before the advent of GWA studies.  Studies of drug response have been slower to adopt the GWA approach.  Early pharmacogenomic studies have also placed an understandable emphasis on severe adverse drug reactions, which are generally too uncommon to permit accrual of the large series of cases needed for GWA studies.  In contrast, clinical improvement (or lack thereof) in response to treatment is a frequently occurring outcome in clinical trials, so that large numbers of responders and non-responders can readily be collected.  When treatment response can be assessed as a continuous trait, the power of GWA studies is even greater.

Leveraging existing clinical trial resources for genome-wide research also provides opportunities to explore the implications of generating genetic information in the context of delivering a controlled intervention.  Analysis and release of genomic data in such settings, for example, may be complicated by the need for masking of treatment assignment until the trial is completed.  Incorporation of point-of-care models, where prevention or treatment strategies are selected based on a patient’s genotype, have not been widely explored.  Empirical data on the expectations of and reactions from study participants regarding such approaches, including the return of genetic information from genome-wide studies, are lacking.

Scientific knowledge to be achieved

This funding opportunity and the related FOA RFA-HG-08-005, “Genome-wide Association Studies of Treatment Response in Randomized Clinical Trials – Coordinating Center,” will form a collaborative program to identify genetic variants associated with response to treatments for conditions of clinical or public health significance.  Where appropriate and feasible, studies will reduce false positive associations through suitable replication and follow-up strategies.  By working collaboratively to share expertise and experience across studies, investigators within this program will develop best practices for incorporating genome-wide studies in clinical trials, including approaches for establishing needed infrastructure for genomic research.  The resulting data and best practices will be widely shared as research tools with the scientific community.

Objectives of this research program

This program will support multiple investigative groups to conduct GWA studies on existing DNA samples and data from roughly 2,000 participants per treatment arm in randomized controlled clinical trials.  Each Study Investigator will be supported to provide high-quality DNA to an NHGRI-designated genotyping facility for GWA genotyping, and to submit extensive phenotype and exposure data to the program’s CC (funded separately through RFA-HG-08-005, “Genome-wide Association Studies of Treatment Response in Randomized Clinical Trials – Coordinating Center,”) and dbGaP for distribution through open and controlled processes in accordance with NIH-wide GWAS policies.  Awardees will be supported to analyze genotype-treatment associations and disseminate the results to the scientific community.  They will also work collaboratively with the program’s CC, NHGRI, and each other to develop methods for analyzing gene-treatment associations and their modifiers, incorporating genomic studies into clinical trials, and disseminating data and results.  Although it is expected that data analysis and dissemination must await unmasking of treatment assignment, and hence completion of the clinical trial, applicants who can demonstrate that analysis and dissemination can proceed in an ongoing trial without threatening the trial’s integrity will be eligible to apply.  Data and samples must be ready for submission within nine months of award, and for unmasked analysis within 12 months of award.

Consistent with a goal of leveraging existing studies, awardees under this initiative will be expected to coordinate productively with related efforts supported by NIH, such as the NIH Pharmacogenetics Research Network (http://www.pharmgkb.org/network/pharmacogenetics_research_network.jsp) and the PhenX Toolkit (https://www.phenx.org/Default.aspx?tabid=36), and related non-NIH funded activities, as applicable.  This will ensure that the exposures and response phenotypes are described in the most consistent and complete a manner possible and that standards and guidelines for conducting genome-wide studies in randomized clinical trials are harmonized as well as possible.

Each application should clearly define: the public health significance and genetic complexity of the trait(s) and treatment(s) proposed for study; the need for a genome-wide association study, as proposed in the application; the strength of the evidence for a genetic component for the trait; the anticipated size of a detectable genetic effect; and the power of the proposed sample to detect it.  Adequacy of informed consent for GWA studies and for controlled but widespread data access (described below) should be clearly described, along with timelines for unmasking of treatment assignment and any restrictions on research use of the data.  The organization, governance structure, funding, and history of the study, including expectations of, and commitments (explicit or implicit) made to and by study participants, clinicians, and investigators, should also be clearly described. 

Applications should include documentation of access to biospecimens and data from the parent clinical trial(s), and evidence of close interaction and coordination with the organizational structure of the parent trial(s), to ensure that use of specimens is consistent with the consents and sample/data access procedures already in existence.  Although it is expected that most trials proposed for genome-wide study under this FOA will be completed, unmasked, and published or in the press, applications proposing use of samples from ongoing trials should provide a clear plan for coordination and avoidance of overlap or duplication of existing trial infrastructure such as data monitoring committees, steering committees, and publication procedures.

Each application should clearly define the source population, eligibility criteria, consent process, participant recruitment and randomization methods, percent participation, follow-up procedures, retention rates over time, and numbers and demographics of participants currently in the study and expected to be available one year after the anticipated award date (anticipated to be July, 2009).  Numbers (and methods of ascertainment) of confirmed or possible cases of a variety of complex diseases and traits of public health importance, available at the time of submission and expected to be available one year after award, should also be described.  Each application should also define the subgroup of study participants proposed for genome-wide study under this FOA, including inclusion and exclusion criteria, availability of sufficient biospecimens to permit the required genotyping, and any potential biases in subject selection or phenotypic/exposure assessment.

Each application should also clearly describe the types, quality and completeness of the available phenotype and environmental exposure data.  Type, quality, and amount of biospecimens available on participants to be studied under this FOA should be explicitly described, including source, methods of collection, aliquoting and tracking; storage conditions; DNA extraction methods; and DNA quantity and quality (and methods used to assess them).  Prior experience in using the biospecimens for research should be described.  Applicants may provide suggestions on choice of genotyping platform, but genome-wide technologies and platforms will be selected by the NHGRI.

A detailed analytic plan should address issues related to the large amount of genome-wide data to be generated such as multiple testing and assessing complex interactions.  The potential impact of population ancestry/history and stratification on genome-wide analyses should be discussed regardless of the population chosen for study, and means for minimizing the effects of population stratification proposed.  The analytic plan should detail methods to address false positive genome-wide results and adjust for multiple testing, as well as assessing interactions with treatment assignment and other analytic challenges presented by GWA studies in randomized clinical trials.

A research program of this type raises important questions on ethical, legal, and social issues (ELSI) that fall within the mandate of NHGRI’s ELSI Research Program (www.genome.gov/ELSI).  Applicants interested in pursuing such questions are encouraged to contact the ELSI Research program staff (http://www.genome.gov/ELSI/#Staff) to discuss research opportunities in this important area and explore the possibility of submitting an application in response to to PA-08-012, “Ethical, Legal and Social Implications (ELSI) Regular Research Program (R01),” (http://grants.nih.gov/grants/guide/pa-files/PA-08-012.html) or PA-08-013, “Ethical, Legal and Social Implications (ELSI) Regular Research Program (R03)" (http://grants.nih.gov/grants/guide/pa-files/PA-08-013.html). 

Even for treatments that show a clear population-wide benefit, particular population subgroups, such as those defined by race and ethnicity, may exhibit differences in treatment benefits or harms.  The highest programmatic priority will be given to trials that include participants representative of the U.S. population, address conditions or treatments of public health importance, and provide extensive phenotypic and exposure information.  Availability of suitable replication populations will also be an important consideration, though replication in an adequately-sized randomized trial, testing the same interventions in the same populations, may be difficult to achieve.  Applicants may propose other approaches to replication with suitable justification and scientific rigor, such as replication of gene-treatment associations in unbiased observational studies.  Investigators without replication components identified and available at the time of application should clearly document relevant ongoing collaborations and describe a plan to establish additional collaborations as needed to permit replication of findings.

This initiative will not support recruitment of human subjects, collection of human specimens, collection of medical or phenotype data, or studies using animal models.  Applications that otherwise include recruitment of human subjects, collection of human specimens, or collection of medical or phenotype data; or studies using animal models, will be considered non-responsive and returned to the applicant.  Genotyping costs will be supported with separate funding to NHGRI-designated genotyping facilities; applicants should not include these costs in their applications.

Evidence of appropriate informed consent for genome-wide studies and sharing of previously collected data through dbGaP, or a plan for reconsent, should be provided at the time of application submission.  Only applications describing protection of participants’ privacy and confidentiality will be considered.

Program Organization

The awards funded under this FOA will be cooperative agreements (see Section VI.2.A. Cooperative Agreement Terms and Conditions of Award).  Close interaction among awardees and the NIH will be required to develop appropriate strategies and tools to carry out this program.  The Study Investigators, Coordinating Center (CC), and NHGRI will meet as a Steering Committee three times a year, and by conference call on an ongoing basis, to identify and address common genotyping and analytic issues and explore opportunities for synergy among studies.  Existing phenotypic and exposure data, as well as quality and quantity of DNA and related biospecimens, will be assessed and documented by each awardee in a standard format, as agreed upon by the Steering Committee and Expert Scientific Panel for all participating trials.   Information on study design, characteristics, and available data and DNA will be compiled by each investigative group and provided to the CC funded under companion RFA-HG-08-005 for public dissemination in a user-friendly manner. 

Study Investigators will have primary responsibility for analyzing genotype and phenotype data from their own studies, but may receive advice or assistance from the CC as needs arise and funding permits.  The CC will be responsible for cross-study functions, such as harmonizing data across studies, leading any cross-study analyses, and organizing the logistics of the collaborative program.

Subcommittees and working groups may be established, such as a Genotyping group or an Analysis group.  Key co-investigators, and pre- and postdoctoral trainees, in addition to the PIs, are eligible to attend these meetings.  PIs are encouraged to include investigators and trainees who are members of under-represented minority groups and those from different but related disciplines such as computational biology, social sciences, public health, and translational research where appropriate.  The cost of 3-4 persons to attend these meetings (anticipated to occur roughly three times per year), as well as the costs associated with monthly conference calls, should be included in the proposed research budget.  Collaborative activities with related research programs, both NIH-funded and non-NIH funded, will be sought and my involve additional committee involvement and joint meetings.  Applicants should describe their willingness to participate actively in such activities and propose relevant programs with which they might spear-hear collaborations.  To achieve the goals of this program, highest priority should be given to collaborations that emphasize genome-wide studies and randomized clinical trials.

To achieve the goals of this program, all de-identified, individual-level phenotypic, environmental exposure and genotypic data proposed for analysis will be made available to the scientific community through a controlled access process managed by NIH.  Further, summary data and other non-identifying information such as study protocols, descriptions, and publications will be made openly available through a public web site and publication in the scientific literature.  Development and dissemination of methods and best practices for incorporating genomic studies in clinical trials, including approaches for establishing needed infrastructure for genomic research, will be another important product of this collaborative program.

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

Section II. Award Information


1. Mechanism of Support

This funding opportunity will use the NIH U01 Cooperative Agreement award mechanism(s).

The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.  

This FOA uses “Just-in-Time” information concepts.  It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). 

This funding opportunity will use a cooperative agreement award mechanism.  In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

There are no plans at present to reissue this FOA.

2. Funds Available

The estimated amount of funds available for support of 3-5 projects awarded as a result of this announcement is $2,300,000 for fiscal year 2009.  Support for genome-wide genotyping will be provided separately to a genotyping facility selected by NHGRI.  Future year amounts for these awards will depend on annual appropriations.

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 IC(s) 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.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

NIH grants policies as described in the http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs 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 PDs/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

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

3. Other-Special Eligibility Criteria

Applicants are not permitted to submit a resubmission application in response to this FOA. 

Renewal applications are not permitted in response to this FOA. 

Applicants may submit more than one application, provided each application is scientifically distinct.

Section IV. Application and Submission Information


1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. 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

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

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:

In addition, for applications from foreign organizations:

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 PD/PIs are proposed, use the Face Page-Continued page to provide items 3a – 3h for all PD/PIs. NIH requires one PD/PI be designated as the “contact PD/PI” for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the “Contact PD/PI, et. al.” The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed 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” 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, and should include communication plans, process for making decisions on scientific direction, 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.

Additional information is available in the PHS 398 grant application instructions.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date: October 13, 2008
Application Receipt Date: November 13, 2008
Peer Review Date(s): February/March, 2009
Council Review Date: May, 2009
Earliest Anticipated Start Date: July 1, 2009

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 in Section IV.3.A.

The letter of intent should be sent to:

Lucia A. Hindorff, PhD, MPH
National Human Genome Research Institute
5635 Fishers Lane
Suite 4076, MSC 9305
Bethesda, MD 20892-9305 (U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (express/courier service; non-USPS service)

Email: hindorffl@mail.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the forms found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Rudy Pozzatti, PhD
National Human Genome Research Institute
5635 Fishers Lane
Suite 4076, MSC 9305
Bethesda, MD 20892-9305 (U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (express/courier service; non-USPS service)
Telephone: 301-496-7531
FAX: 301-435-1580
Email: pozzattr@mail.nih.gov

3.C. Application Processing

Applications must be received on or before the application receipt date described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed.  Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute Incomplete and/or non-responsive applications will not be reviewed.

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.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

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. The Grants Policy Statement can be found at 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 award if such costs: 1) are necessary to conduct the project, and 2) 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 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 NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.)

6. Other Submission Requirements and Information

Applicants should address the following when preparing applications in response to this FOA:

Applicants are expected to document access to existing DNA specimens and phenotypic data from an existing human randomized clinical trial.  Consistent with their plans for data sharing, data and specimens should be available for sharing with program-designated Genotyping Facilities within nine months of award, and for unmasked analysis within 12 months of award.  Applicants should describe all relevant phenotypic and environmental exposure measures from the study.  Applicants should provide strong justification for the choice of population and sampling design.

Human Subjects (as part of item E in the application)

The applicant should address human subjects issues, including sharing phenotypic and genetic data from individual participants with the broad scientific community.

Applicants are expected to demonstrate that the informed consent for the existing study population(s) allows for the genetic study proposed and the sharing of phenotypic and genetic data with the broad scientific community.  If this is not the case, a plan should be proposed for obtaining reconsent including IRB approval, or an IRB waiver of reconsent for data sharing, and a specific budget for reconsent should be provided.  Plans for reconsent, including consent forms, must be approved by the NHGRI Program Director prior to implementation.  Any restrictions on data use (such as limitations to a specific disease or condition or to non-commercial investigators) should be clearly described.  Restrictions on data use will be considered in the selection process.

Applications that include recruiting human subjects, collecting human specimens, and/or collecting phenotypic or medical data will be considered non-responsive and returned to the applicant.

Applicants being considered for an award are expected to have in place appropriate Institutional Review Board (IRB) and any other required approvals when sharing individual-level data with NIH and when submitting DNA specimens, or specimens from which DNA will be extracted, to an NIH-designated central genotyping facility.  Applicants being considered for an award will also be required to document IRB approval and institutional certification for submitting individual-level phenotype and exposure data and genotyping results to dbGaP as described in NIH GWAS policies under “Plans for Sharing Research Data,” or applicants may document IRB approval for a reconsent process.  The investigator and institution contributing data will be expected to make the following assurances:

Plan for Sharing Research Data

All applicants are expected to include a plan for sharing research data in their application.  The reasonableness of the data sharing plan 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 applicant is expected to provide specific plans for data sharing and data release in the application and expected to indicate whether they are willing to abide by the current NIH data release policy, as described below (see “Resource Sharing Plans,” section 3).

The NIH is committed to the principle of rapid data release to the scientific community.  This principle was initially implemented during the Human Genome Project and has been recognized as leading to one of the most effective ways of promoting the use of the genome sequence data to advance scientific knowledge.  At a meeting in Ft. Lauderdale, FL that was co-sponsored by the Wellcome Trust and NHGRI in January 2003, the concept of rapid data release by genomic sequence data producers was reaffirmed, and the attendees strongly recommended applying the practice to other types of data produced by “community resource projects.” The attendees recognized, however, that different issues, particularly with respect to data validation, would be involved in the development of appropriate release practices for different types of data.  Since they also recognized that sustaining the practice of rapid, prepublication data release by community resources requires that the interests of all involved - including the data producers, data users, and funding agencies - be addressed, they emphasized the need to develop a tripartite system of responsibility.  The report from the Ft. Lauderdale meeting can be found on the Wellcome Trust website at: http://www.wellcome.ac.uk/doc_wtd003208.html.

The NIH has identified this program as a community resource project.  As such, the program aims to function openly by making all data available to the scientific community in a timely manner prior to publication, with suitable restrictions for protection of human research subjects.  The NIH is committed to creating a resource founded on the principle of no-cost, rapid, and complete release of genotype-phenotype datasets for use by investigators throughout the global scientific community who, along with their institutions, certify their agreement with NHGRI and NIH policies (“Approved Users”).  All participants in this program are expected to promote NHGRI and NIH policies on data access, publication, and intellectual property summarized below, and describe their methods for doing so in the application.  NHGRI will establish mechanisms to monitor data use in agreement with these policies.

The NHGRI, in consultation with the program Steering Committee, will make all final decisions concerning program policies.  All program policies are subject to change by the NHGRI as deemed necessary to sustain program principles and priorities, or to ensure the highest standards for responsible research conduct within program operating procedures.

Data Access: The program Database within dbGaP will comprise two sections: open access and controlled access.  Information describing the phenotype data, such as the variables measured and protocols used to collect the data and specimens, but not the phenotype dataset itself, will be made available in the open access part of dbGaP.  Project Datasets (genotype data as well as genotype-phenotype datasets along with pre-computed analyses of them) will be available through the controlled access section of dbGaP.  Although all Project Datasets from funded applications will be made available through the controlled access section of dbGaP, the NIH does not intend dbGaP to become the exclusive source of these Project Datasets.

The genotype data generated for each specimen, plus unidentified phenotype and exposure data, are expected to be deposited in the controlled access section of dbGaP as soon as both the phenotype and exposure data submitted by Study Investigators and the genotype data have passed appropriate data quality assessments; quality standards will be developed by the program Steering Committee in collaboration with NCBI and NHGRI.  Simple, unadjusted genotype-phenotype associations (“pre-computes”) will be calculated and posted in dbGaP, along with a listing of all variants known to be in strong linkage disequilibrium with variants showing significant association with a phenotype or trait.  Other analyses, such as annotated information on genes and genomic features in identified regions of interest, may be provided as well.

Access to Project Datasets through dbGaP will be provided for research purposes through the NHGRI Data Access Committee (DAC).  To become an Approved User, investigators seeking data from the controlled access section of dbGaP will submit a Data Use Certification that is co-signed by the designated Institutional Official, for approval by the NHGRI DAC.  The Data Use Certification will include a brief description of the proposed research use of the requested Project Dataset(s).  As part of the Data Use Certification, investigators will stipulate that they will: use the data only for the approved research use; protect data confidentiality; follow all applicable laws and any local institutional policies and procedures for handling Project data; not attempt to identify individual participants from whom data within a dataset were obtained; not sell or share any of the data elements from datasets obtained from the project Database with third parties, other than sharing with their own research staff who have agreed to dbGaP policies; and provide annual progress reports on research.  Access to a Project Dataset through dbGaP will be approved by the DAC following: completion of the Data Use Certification; and confirmation that the proposed research use is consistent with any constraints identified by the Study Investigators who submitted the data to dbGaP.

The terms and conditions governing data access for research use of Project Datasets for investigators supported through this program and NIH will be identical to those for any other member of the scientific community seeking to become an Approved User, except that a Study Investigator may be able to identify individual participants in her or his own study and may share her or his own data with third parties at her or his discretion.  All submitted specimens provided to NHGRI-designated Genotyping Facilities by Study Investigators for use within this project will be returned or destroyed following the completion of the specified genotyping services according to the procedures set by the contributing study site.

Publication Policy: Consistent with the proposed policy on data sharing in GWAS, the NIH expects that beginning on the date that a Project Dataset is released for distribution through a database such as dbGaP, there will be a period of up to twelve months during which Investigators retain the exclusive right to submit publications developed with the data and samples they contributed.  During this twelve-month period of publication exclusivity, Approved Users will have access to data, but will agree not to submit for publication any results or analyses derived from the use of any Project Dataset within that period without consent of the Investigator.  Submission of publications using genotype data only that may be available through databases such as dbSNP is permissible during this period.   Investigators will be encouraged to shorten the period of exclusivity at their own discretion.  NHGRI may request a shorter period of exclusivity.  The NIH expects that, in all resulting oral or written publications, disclosures, or publications, all investigators who access these datasets will acknowledge the Investigator(s) who conducted the original study and the funding organization(s) that supported the work.

Intellectual Property Policy: The NIH expects that data generated by this FOA and conclusions derived directly from the data therefrom, will remain freely available, without any licensing requirements, for uses such as, but not necessarily limited to, markers for developing assays and guides for identifying new potential targets for drugs, therapeutics, and diagnostics.  The intent is to discourage the use of patents in a manner that would prevent use of or block access to any genotype-phenotype data developed with support from this FOA.  The NIH encourages broad use of these Project Datasets that is consistent with a responsible approach to management of intellectual property derived from downstream discoveries as outlined in NIH’s Best Practices for the Licensing of Genomic Inventions and the NIH Research Tools Policy (http://grants.nih.gov/grants/intell-property_64FR72090.pdf).

The filing of patent applications and/or the enforcement of resultant patents in a manner that might restrict use of these Project Datasets and dbGaP could substantially diminish the utilization of information and the potential public benefit they could provide.  Approved Users and Investigators supported by this FOA, and their institutions, should acknowledge the program’s IP Policy, the goal of which is to ensure the greatest possible public benefit from Project Datasets.

Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information".

Research Plan Page Limitations

Items 2–5 in the application (Specific Aims, Background and Significance, Preliminary Studies, and Research Design and Methods) should not exceed 25 pages.

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CDs only. Include five identical CDs in the same package with the application.  (See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.)

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.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible.  A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition.  For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

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 (NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm  and 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, http://grants.nih.gov/grants/funding/2590/2590.htm).  See Section VI.3. Reporting.

As this program has been identified as a community resource project, NIH expects that not only data, but also resources generated during the course of the program, such as analytic methods and data standards, will be made rapidly available to the research community and that sharing plans should follow the same principles and spirit as the rapid data release policy.  The applicant should provide specific plans for resource sharing and distribution in the application.

Specific Instructions for Foreign Applications

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.

Section V. Application Review Information


1. Criteria

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

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 NHGRI and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

The following will be considered in making funding decisions:

Additional criteria for award will include:

Quality and quantity of DNA and other biospecimens available for GWA genotyping

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 meritorious 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?

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?  Are the study design and population chosen appropriate for the aims proposed? Are the proposed plans to share data in a timely manner adequate? Have the sources and generalizability of study subjects been clearly described, have any potential biases in subject selection been identified, and are the applicants’ approaches for minimizing these biases appropriate? Are the proposed plans to share data in a timely manner likely to provide maximal scientific value for identifying genes related to complex diseases and their treatments consistent with meeting the aims of this program?  

Innovation: Is the project original and innovative? For example: 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 this area? What advantages does this data set offer over others in terms of approaches to data management and data analysis? What advantages does it offer for replication and follow-up studies to identify causative genetic variants and develop diagnostic, preventive, or therapeutic strategies? What is the richness of the dataset for future studies that may be based on other phenotypes or benefit from information on environmental exposures?

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 PD/PI(s) investigative team bring complementary and integrated expertise to the project, including randomized clinical trials, biostatistics, epidemiology, genetics/genomics and ELSI of genomic research, as applicable?  Are the investigators willing to collaborate with each other, the NIH, and related existing efforts, including other NIH-funded and non-NIH-funded programs in genome-wide studies and randomized clinical trials, consistent with meeting the aims of this program?  

Environment: Do(es) the scientific environments 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? Is the bioinformatics infrastructure sufficient to accomplish the goals of the project? Have the investigators documented their ongoing or future access to data and samples from the clinical trial in a highly-effective collaborative relationship, and their ability to commit the biospecimens and samples, in consultation with appropriate decision-makers, to participate in this FOA?

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 rating:

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 Research Plan section on Human Subjects in the PHS 398 instructions).

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 Research Plan section on Human Subjects in the PHS 398 instructions).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five points described in the Vertebrate Animals section of the Research Plan will be assessed.

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: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. 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. Resource Sharing Plan(s)   

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score, unless noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing.

3. Anticipated Announcement and Award Dates

It is anticipated that awards will be made by July 1, 2009.

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 his or her Summary Statement (written critique) via the 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.

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 (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the 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 Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

The NIH has identified this program as a community resource project.  As such, the program aims to function openly by making all data available to the scientific community in a timely manner prior to publication, with suitable restrictions for protection of human research subjects.  NIH has established a common data release policy for GWA studies, and all awardees and their institutions will be expected to agree to the policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the Notice of Award. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

2. A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for:

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

2. A.2. NIH Responsibilities

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. ·      

The assigned program director may also serve as an NIH Project Scientist.

2.A.3. Collaborative Responsibilities

Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to develop appropriate strategies and tools to design, perform, and analyze GWA studies in randomized clinical trials.  The Study Investigator and CC awardees and the Project Scientist will meet as the program Steering Committee in person three times per year and monthly or more frequently by conference call as needed to share information on data resources, methodologies, analytical tools, as well as data and preliminary results.   Key co-investigators and pre- and postdoctoral trainees, in addition to the PIs, will be eligible to attend Steering Committee meetings.  PIs are encouraged to include investigators and trainees who are members of under-represented minority groups and those from different, but related, disciplines.   

The Steering Committee will serve as the main scientific body of the program.  The Steering Committee will be responsible for coordinating the activities being conducted by the program.  The Steering Committee membership will include one NHGRI Project Scientist and the P.I. from each awarded cooperative agreement.   Awardees utilizing the multiple PI/PD option will designate a single voting PI to serve on the Steering Committee.  The Steering Committee may add additional members, and other government staff may attend the Steering Committee meetings as desired.  It is anticipated that additional coordination mechanisms may be set up with other U.S. and international groups that may collaborate with the program.   Each full member will have one vote.

To address particular issues, the Steering Committee may establish working groups as needed, which will include representatives from the program and the NIH and possibly other experts.  Awardees agree to work collaboratively to:

Expert Scientific Panel

An Expert Scientific Panel (ESP) will evaluate the progress of the program.  The ESP will provide recommendations to the National Advisory Council for Human Genome Research about the progress and scientific direction of all components of the program. 

The ESP will be composed of four to eight senior scientists with relevant expertise, although the membership may be enlarged permanently or on an ad hoc basis as needed.  The ESP will meet at least twice a year; some meetings may be conducted by telephone conference.  At least once a year, there will be a joint meeting with the Steering Committee to allow the members of the both the ESP and the Steering Committee to interact directly.  Twice a year the ESP will make recommendations regarding progress of the program to the National Advisory Council for Human Genome Research about changes, if any, which may be necessary in the program.

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit electronic quarterly reports that describe the status and progress for all aspects of the study.  The quarterly report will be used as a management tool for the NIH and the program’s Steering Committee.   Reporting on cost and investigator/staff effort will also be required.

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

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 Contacts:

Lucia A. Hindorff, PhD, MPH
National Human Genome Research Institute
5635 Fishers Lane
Suite 4076, MSC 9305
Bethesda, MD 20892-9305 (U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (express/courier service; non-USPS service)
Email: hindorffl@mail.nih.gov

2. Peer Review Contacts:

Rudy Pozzatti, PhD
National Human Genome Research Institute
5635 Fishers Lane
Suite 4076, MSC 9305
Bethesda, MD 20892-9305 (U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (express/courier service; non-USPS service)
Telephone: 301-496-7531
FAX: 301-435-1580
Email: pozzattr@mail.nih.gov

3. Financial or Grants Management Contacts:

Ms. Cheryl Chick
National Human Genome Research Institute
5635 Fishers Lane
Suite 4076, MSC 9306
Bethesda, MD 20892-9306 (U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (express/courier service; non-USPS service)
Telephone: 301-435-7858
FAX: 301-402-1951
Email:ChickC@mail.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 (45CFR46) 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.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/

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 http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, 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 new PHS Form 398; 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 Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award.  For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

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) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

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. 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 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 NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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.


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NIH Funding Opportunities and Notices


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