Part I Overview Information

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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)
National Institute of General Medical Sciences (NIGMS), (http://www.nigms.nih.gov)

Title: High-Priority Phenotype and Exposure Measures for Cross-Study Analysis in Genome-Wide Association Studies (U01)

Announcement Type
New

Request For Applications (RFA) Number: RFA-HG-07-006

Catalog of Federal Domestic Assistance Number(s)
93.172, 93.859

Key Dates
Release Date:  March 20, 2007
Letters of Intent Receipt Date(s): April 17, 2007
Application Receipt Date(s): May 17, 2007
Peer Review Date(s): July/August 2007
Council Review Date(s): August 2007
Earliest Anticipated Start Date(s): September 30, 2007
Additional Information To Be Available Date (Url Activation Date): Not applicable
Expiration Date: May 18, 2007

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

• This funding opportunity will support identifying, developing, and disseminating readily standardized and implemented phenotypic and environmental exposure measures of public health significance suitable for addition to planned or ongoing genome-wide association (GWA) studies.
• The total amount to be awarded is approximately $8,500,000.
• Number of awards anticipated: 1.
• This opportunity will use the Cooperative Agreement (U01) award mechanism.
• Eligible organizations include: for-profit organizations; non-profit organizations; public or private institutions, such as universities, colleges, hospitals, and laboratories; units of State government; units of local government; eligible agencies of the Federal government; domestic Institutions; faith-based or community-based organizations.  Foreign institutions are not eligible to apply.
• Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with her/his institution to develop an application for support.
• Applicants may submit more than one application, provided they are scientifically distinct.
• See Section IV.1 for application materials.
• Telecommunications for the hearing impaired is available at: TTY 301-451-5936

Table of Contents

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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 and Review and Anticipated Start Dates
      1. Letter of Intent
    B. Sending an Application 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
    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

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Section I. Funding Opportunity Description

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1. Research Objectives

Nature of the funding opportunity

This funding opportunity will support identifying, developing, and disseminating readily standardized and implemented phenotypic and environmental exposure measures of public health significance suitable for addition to planned or ongoing genome-wide association (GWA) studies.

Background

Genome-wide association (GWA) studies measure hundreds of thousands of single nucleotide polymorphisms (SNPs) across the genome and relate them to common diseases and traits.  Once an individual’s genome has been comprehensively characterized in this way, it can potentially be related to any trait, not just the primary trait initially proposed for the GWA study, as long as these additional uses are consistent with the informed consent provided by study participants (such as the datasets that are and will be available through dbGaP [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gap]).

Despite the vast potential of multi-faceted GWA studies, very few studies include phenotypic and exposure data on a sufficiently wide variety of traits and diseases to enable such additional analysis.  Instead, most current GWA studies utilize a case-control or family design focusing on a single disease or group of related traits.  More importantly, the potential for cross-study comparisons is severely restricted by the lack of standardized or comparable phenotypic and environmental measures, despite the many risk factors (e.g., obesity, smoking, low socioeconomic status) common to multiple diseases.  At present, the only data elements in common across multiple studies proposed for GWA genotyping tend to be age, sex, and self-reported race/ethnicity (which are often defined differently across studies) and, less commonly, height or weight.

Standardizing or harmonizing data elements and associated controlled vocabularies is the focus of many current and planned efforts in bioinformatics.  Clinical groups have also developed standardized measures in specific conditions such as type 1 diabetes, tuberculosis treatment outcomes, and trauma.  While these efforts are crucial for developing future large-scale ontologies and databases, or for promoting in-depth research in specific conditions, most are not yet ready for application to the GWA studies being conducted now.  Applying all of them in a single study would be overwhelmingly complex, but including specific elements may be possible and desirable to permit cross-study comparisons.

This funding opportunity will support identifying, developing, and disseminating a relatively small subset of readily standardized and implemented measures in topic areas or domains related to the most common complex diseases.  These measures would serve as a “basic tool set” for phenotypic and environmental exposure assessment in GWA studies and other large-scale genomic research efforts that could then be applied to proposed or ongoing genome-wide studies.  Where similar measures have already been collected, availability of this basic tool set could facilitate converting existing measures to allow comparisons across existing studies.  Measurement tools may include assays based on stored biospecimens.  Choice of measurement tools will be based on objective scientific criteria such as validity, reproducibility, cost, and feasibility, and may include recommendations for different scenarios (such as data collection through questionnaires, interviews, or clinical examinations).

Identifying and applying such a “uniform” or “preferred” set of data elements for GWA studies could substantially enhance their value for research in a variety of common, complex diseases.  It could also identify a key subset of measures to be collected in large-scale prospective cohorts of genes and environment and in ongoing biorepositories or “biobanks.”

Scientific Knowledge to be Achieved

This research program will identify readily standardized and implemented phenotype and exposure measures for use in GWA studies.  Success in this effort will facilitate more efficient use of GWA data to understand genetic influences on incidence of, and morbidity and mortality from, common diseases, on trait variation, and on responses to environmental exposures, including drugs or other therapies, and lifestyle factors.

Objectives of this Research Program

• Define 15-20 high priority phenotypic and exposure domains for GWA studies, such as cancer, pulmonary disease, anthropometrics, lifestyle factors, or medication use;
• For each domain, identify standardized measures available or under development and recommend 10-15 high priority measures to consider for inclusion in GWA studies;
• Disseminate the recommendations broadly to research communities involved in genome-wide and related studies.

Types of Research and Experimental Approaches that are being sought

This announcement solicits applications for a specialized center to develop a “basic tool set” for phenotypic and exposure measures for use in GWA studies.  The methods should be proposed by the applicant to maximize the validity and usefulness of the information obtained, but would in general be expected to include consulting with ongoing bioinformatic efforts within and outside of NIH such as Biomedical Informatics Research Network (BIRN), Cancer Biomedical Informatics Grid (caBIG), Human Phenome Project, Inventory and Evaluation of Clinical Research Networks (IECRN) of the NIH Roadmap, National Electronic Clinical Trials and Research (NECTAR), the National Health Information Network (NHIN), and the Pharmacogenetics and Pharmacogenomics Database (PharmGKB), reviewing current literature, and establishing working groups with broad and domain-specific expertise as needed to develop consensus recommendations on readily standardized and implemented measures.  “Domain” is used here to refer to a group of related measures typically relevant to a particular disease or set of exposures.

The awardee will be responsible for establishing a process to define criteria to select high-priority domains and criteria for evaluating measures within domains, and implementing the process to develop a “basic tool set” that will be widely disseminated.  It is anticipated that the process will include an over-arching working group as well as domain-specific working groups, and will involve working closely with NHGRI program staff.  The over-arching working group should identify and agree on criteria for prioritizing domains for GWA studies and criteria for evaluating specific phenotypic or exposure measures within each domain, and should make the final recommendations to NHGRI  about domain priorities and specific elements of the “tool box” after reviewing recommendations made by the awardee and, for specific elements, domain-specific working groups.  Criteria for prioritizing domains and evaluating specific measures within each domain should be proposed by the applicant.  Examples of criteria for prioritizing domains include evidence for strong genetic influence on the domain, evidence for environmental modification of genetic influence or genetic modification of environmental effects, and public health significance.  Criteria for evaluating measures may include aspects such as validity, reproducibility, cost, feasibility, and burden to participants, recognizing that these criteria may vary across domains.  Where appropriate, the awardee should leverage ongoing activities in each specific domain by engaging the respective communities, including relevant NIH Institutes and Centers, and reusing established data elements where possible.  Domain-specific efforts should be proposed to refine prioritization criteria, review available measures, and develop standard instruments for collecting new data and approaches for harmonizing existing data.  The applicant should propose criteria for selecting the over-arching and domain-specific working group members, such as expertise needed, but should not propose specific individuals for membership.  One or more NIH staff with relevant expertise may participate in the domain-specific working groups.  It is anticipated that the Project Scientist will be a voting member of the over-arching working group.

Periodic reconvening of the over-arching working group may be needed to assess progress and promote consistent approaches across domains where appropriate.  Careful attention will be needed to keep working groups focused and on task and to encourage adopting a selected, streamlined tool set of existing measures, recognizing that compromises may be needed to develop a feasible, cost-effective set of measures.  A standardized format should be developed that can be readily adopted by all users to facilitate data exchange.  Applicants should propose approaches for encouraging adoption of proposed elements, such as vetting with relevant professional organizations, NIH Institutes and Centers, and other experts, and plans for dissemination in a variety of formats (publication, web-based, etc) for use in GWA studies.  It is anticipated that finalizing the overall approach, prioritizing domains, and developing measures for the 2-4 highest-priority domains, would be completed in the first year, with 6-8 more domains completed in the second year, and the final 6-10 in the third year.

It is anticipated that the specialized center supported by this announcement will work closely with representatives of the funding agency in finalizing and adapting research approaches, identifying working group members, deciding which domains to pursue, and finalizing the “tool set” for dissemination.   Moderate-priority domains may be pursued if additional funding is available for specific domains from other NIH Institutes or Centers.  The specialized center will be expected to cooperate closely with the funding agency representatives.

It is anticipated that successful completion of this project will require a number of face-to-face meetings with working groups and other experts.  At least one-half of the meetings with the over-arching and domain-specific working groups should be planned for the Washington DC area.

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

This research program will not support primary data collection, or analysis of individual-level data.

Section II. Award Information

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1. Mechanism(s) of Support

This funding opportunity will use the Cooperative Agreement (U01) award mechanism. The duration of the award is expected to be three years. Requested amount should be no more than $5,600,000 direct costs for the three-year period.

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

The NIH U01 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator 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". We expect this to be a one-time award.

2. Funds Available

• NHGRI expects to award approximately $8,500,000 in total costs through this announcement, through a 3-year award;
• NHGRI anticipates making one award;
• The expected amount for the individual award is approximately $5,600,000 direct costs;
• The anticipated start date is September 30, 2007, and period of performance is September 30, 2007 to September 29, 2010.

NHGRI intends to commit approximately 1,900,000 dollars in FY 07 to fund one new and/or competing continuation grant in response to this RFA. An applicant may request a project period of up to three years and a budget for direct costs up to 1,200,000 dollars in FY07 and 2,200,000 dollars per year in FY08 and FY09.

Although the financial plans of the IC 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.

Section III. Eligibility Information

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1. Eligible Applicants

1.A. Eligible Institutions

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

• For-profit organizations
• Non-profit organizations
• Public or private institutions, such as universities, colleges, hospitals, and laboratories
• Units of State government
• Units of local government
• Eligible agencies of the Federal government
• Domestic Institutions
• Faith-based or community-based organizations

Foreign institutions are not eligible to apply.

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.

2. Cost Sharing or Matching

Cost sharing is not required.

The most current Grants Policy Statement can be found at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing

3. Other-Special Eligibility Criteria

Experience managing or working with content experts, professional groups, or consensus panels using evidence-based approaches is required.

Experience conducting epidemiologic or genome-wide association studies may be helpful but is not required.

Bioinformatics expertise may be helpful but is not required.

Section IV. Application and Submission Information

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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) 710-0267, Email: [email protected].

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 on line 2 of the face page of the application form and the YES box must be checked.

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(s): April 17, 2007
Application Receipt Date(s): May 17, 2007
Peer Review Date(s): July/August 2007
Council Review Date(s): August 2007
Earliest Anticipated Start Date(s): September 30, 2007

3.A.1. Letter of Intent

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

• Descriptive title of proposed research
• Name, address, and telephone number of the Principal Investigator
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

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:

Emily L. Harris, 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)
Telephone: 301-594-6524
FAX: 301-435-1580
Email: [email protected]

3.B. Sending an Application to the NIH

Applications must be prepared using the research grant applications 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: [email protected]

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3.C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the NHGRI. Incomplete and 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 http://grants.nih.gov/grants/policy/policy.htm.

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 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 continuation 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/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

6. Other Submission Requirements

Special Application Requirements

In addition to the brief “Plan for Sharing Research Data” described below, applicants should describe methods for disseminating the “basic tool set” and experience in disseminating such products as part of the Research Plan Sections A-D.

Applicants should describe prior experience managing or working with content experts, professional groups, or consensus panels.

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

Plan for Sharing Research Data

In the context of this application, the term “data” refers to the supporting information that was collected to develop the “tool set,” such as results of literature searches and summaries of validity, reliability, and feasibility, if available, of measurements that were considered. Applicants 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 will be provided, and the mode of data sharing.  It is anticipated that these supporting data will be shared throughout the performance period, as recommendations for each domain are completed. 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.

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.

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/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.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.

Section V. Application Review Information

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1. Criteria

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

The following will be considered in making funding decisions:

• Scientific merit of the proposed project as determined by peer review
• Availability of funds
• Relevance of program priorities

The awardee must agree to the “Cooperative Agreement Terms and Conditions of Award” in Section VI.2.A. “Award Administration Information.”

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NHGRI in accordance with the review criteria stated below.

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

• Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score.
• Receive a written critique.
• Receive a second level of review by the National Advisory Council for Human Genome Research.

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 study address a breadth of phenotypes and exposures, including clinical outcomes, treatments, traits, risk factors, and risk modifiers?

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?  Does the applicant propose adequate methods for identifying key stakeholders and experts, selecting and convening working groups, and facilitating and monitoring progress of the working groups? Does the applicant propose state-of-the-art methods for working with content experts and expert groups and for evaluating, standardizing, harmonizing, and implementing phenotypic and exposure measures? Does the applicant propose adequate methods for quickly identifying and resolving problems that the working groups encounter? Does the applicant propose adequate methods for vetting the recommended tool sets, encouraging their adoption, and disseminating them?

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?

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)? Does the investigative team have experience managing or working with content experts, professional groups, or consensus panels using evidence-based approaches? Does the investigative team have experience conducting large epidemiologic or genetic epidemiologic studies, in which phenotype and exposure are collected and analyzed? Does the investigative team have experience in bioinformatics related to standardizing or harmonizing data?

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

N/A

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.

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.

In the context of this application, the term “data” refers to the supporting information that was collected to develop the “tool set,” such as results of literature searches and summaries of validity, reliability, and feasibility, if available, of measurements that were considered. Applicants 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 will be provided, and the mode of data sharing. It is anticipated that these supporting data will be shared throughout the performance period, as recommendations for each domain are completed.

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

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/grants/policy/nihgps/part_ii_5.htm#availofrr and

http://www.ott.nih.gov/policy/rt_guide_final.html). 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. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a 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. Reporting.

3. Anticipated Announcement and Award Dates

It is anticipated that awards will be made by September 30, 2007.

Section VI. Award Administration Information

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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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

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

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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.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/grants/policy/nihgps_2003/NIHGPS_part9.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 (U01), 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 defining the details for the project within the guidelines of RFA-HG-07-006 and for performing the scientific activities. The Principal Investigator will agree to accept close coordination, cooperation, and management of the project as described under “NIH Responsibilities.”  Specifically, the Principal Investigator will:

• Determine approaches, design protocols, set project milestones, and implement the protocol;
• Provide a detailed plan to the NHGRI Program Official that describes how prioritizing, identifying, evaluating, and standardizing measures, and vetting and disseminating the “tool set” will occur;
• Revise and update approaches, protocols, and milestones as more experience is gained in developing the “tool set”;
• Provide high-quality documentation of the study protocol and other information that will be sufficient for key stakeholders and potential users of the “tool set” to understand the rationale and details of the final recommendations;
• Provide to the NHGRI Program Official proposed members for working groups;
• Schedule, convene, and document working group meetings, consultations, and other approaches used to develop the phenotypic/exposure tool set;
• Facilitate and monitor progress of working groups;
• Identify quickly any problems that working groups encounter and propose methods for resolving them to the Project Scientist;
• With the concurrence of the NHGRI Project Scientist, implement agreed-upon methods for resolving problems;
• Provide to the NHGRI Project Scientist all draft literature reviews, working group guides, consensus documents, and other written materials to be used for the project;
• Request guidance from the Project Scientist in prioritizing and selecting measures for the final “tool set”;
• Schedule and attend regular meetings (in person or by phone) with the Project Scientist;
• Adhere to policies regarding data access, publication, and intellectual property established by NHGRI;
• Submit periodic progress reports as described in Section VI. 3. Reporting.

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

The Project Scientist is a scientist of the NHGRI staff who will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination.  The role of the Project Scientist will be to facilitate and not direct the activities.  It is anticipated that the Project Scientist will be given the opportunity to offer input to key design and problem-solving issues. The Project Scientist will have the following substantial involvement:

• Review a detailed plan submitted by the Principal Investigator that describes how prioritizing, identifying, evaluating, and standardizing measures, and vetting and disseminating the “tool set” will occur; suggest appropriate modifications; and recommend approval of the final plan;
• Review and recommend approval of updates to approaches, protocols, and milestones;
• Attend regular meetings (in person or by phone) with the awardee;
• Participate in deciding optimal research approaches and protocol designs;
• Work with awardee to identify potential working group members;
• Review proposed working group members; and suggest appropriate modifications;
• Provide timely recommendation for approval to final recommendations for prioritizing domains and selecting measures for the final “tool set,” after appropriate consultation with the Principal Investigator and within NHGRI;
• Review progress of working groups and recommendations for resolving problems that the working groups encounter; suggest appropriate modifications; and recommend approval of the plan for resolution;
• Review drafts of literature reviews, working group guides, consensus documents, working group products, and other written materials to be used for the project; suggest appropriate modifications; and recommend approval of the final materials;
• Provide advice in the management and technical performance of the award;
• Participate in data analyses, interpretations, and, where warranted, co-authorship of the publications of results;
• Review drafts of plans for vetting proposed measures with professional and other relevant organizations, and for encouraging use and dissemination; suggest appropriate modifications; and recommend approval of the final materials;
• Work with awardee to identify approaches for promoting the availability of the resources developed in the course of this program to the scientific community at large;
• Retain the option to recommend withholding or reducing support to the awardee if the project fails to achieve its goals or comply with the Terms and Conditions of Award;
• Serve as a liaison to the NIH and as an information resource for the awardee about genome research activities;
• Report periodically on the progress of this research program to the Director of NHGRI and to the National Advisory Council for Human Genome Research.

Additionally, an NHGRI Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned Program Official may also serve as an NHGRI Project Scientist. The Program Official may withhold or reduce support to the awardee if the project fails to achieve its goals or comply with the Terms and Conditions of Award. The Program Official will be responsible for reviewing and approving:

• A detailed plan submitted by the Principal Investigator that describes how prioritizing, identifying, evaluating, and standardizing measures, and vetting and disseminating the “tool set” will occur;
• Updates to approaches, protocols, and milestones;
• Final recommendations for prioritizing domains and selecting measures for the final “tool set”;
• Plan for resolving problems that the working groups encounter;
• Literature reviews, working group guides, consensus documents, working group products, and other written materials to be used for the project;
• Final plans for vetting proposed measures with professional and other relevant organizations, and for encouraging use and dissemination.

Other NHGRI staff may assist the awardee as designated by the Program Official.

2.A.3. Collaborative Responsibilities

One or more NIH staff with relevant expertise may participate in the domain-specific working groups.  It is anticipated that the Project Scientist will be a voting member of the over-arching working group.

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 awardee 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. 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

Awardee will be required to submit quarterly reports that describe the progress on recruiting working group members and identifying key stakeholder groups, “tool set” development by the over-arching and domain-specific working groups and awardee, and disseminating the “tool set.”  These reports will be used as a management tool for NHGRI to identify early any correctable problems.  Awardee will also be required to submit final reports for each domain and for the overall “tool set.”  Reporting on cost will also be required.

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts

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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:

Emily L. Harris, 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)
Telephone: 301-594-6524
FAX: 301-435-1580
Email: [email protected]

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: [email protected]

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: [email protected]

Section VIII. Other Information

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Required Federal Citations

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.

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 (http://publicaccess.nih.gov/publicaccess_Manual.htm).

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 RFA 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 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.