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/)
National Institute of Mental Health (NIMH) (http://www.nimh.gov/)

Title: Epidemiologic Investigation of Putative Causal Genetic Variants—Coordinating Center (U01)

Announcement Type

New

Request For Applications (RFA) Number: RFA-HG-07-015

Catalog of Federal Domestic Assistance Number(s)
93.172, 93.242

Key Dates
Release Date:  August 17, 2007
Letter of Intent Receipt Date: October 19, 2007
Application Receipt Date: November 19, 2007
Peer Review Date: February/March 2008
Council Review Date: May 2008
Earliest Anticipated Start Date: July 1, 2008
Additional Information To Be Available Date (Url Activation Date): N/A
Expiration Date: November 20, 2007

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 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

Section I. Funding Opportunity Description

1. Research Objectives

Nature of the Research Opportunity

The purpose of this funding opportunity is to provide support for a Coordinating Center (CC) to serve as a centralized resource to facilitate and support the investigation, in well-characterized population studies, of genetic variants identified as potentially causally associated with complex diseases in genome-wide association (GWA) and other genetic studies, with the aim of widespread sharing of the resulting population-based descriptive and association data to accelerate the understanding of genes related to complex diseases.

For the purposes of this RFA, “well-characterized population studies” are defined as population-based  cohort studies or clinical trials with detailed existing information on demographics, health characteristics, environmental exposures, and disease risk factors and traits.  “Population-based’ is defined as broadly representative of and generalizable to the U.S. community-dwelling population, as opposed to most hospital- or clinic-based samples.  “Existing information” may be cross-sectional, if extensive, or, preferably, prospective and longitudinal.  “Variants identified as potentially causally associated,” or “putative causal variants,” are defined as genetic variants such as single nucleotide polymorphisms (SNPs), structural variants, or other genomic characteristics for which there is strong and convincing statistical, biological, and/or functional evidence of association with a disease or trait such that the variant is likely to play a role in etiology.  “Descriptive and association data” are group-level (not individual-level) data on prevalence and associations of putative causal variants derived from well-characterized population studies.

The goal of this funding opportunity is to provide centralized support and infrastructure for the studies supported by the RFA-HG-07-014, “Epidemiologic Investigation of Putative Causal Genetic Variants – Study Investigators,” which will utilize existing population-based cohort studies and clinical trials, and the investigators most familiar with their intricacies, to: 1) determine the population-based profile, or “epidemiologic architecture,” of putative causal variants, including prevalence in racial and ethnic subgroups of relevance to the U.S. population and magnitude of disease risk and associations with other health characteristics; 2) identify modifiers of gene-trait associations, particularly lifestyle factors or medication use; and 3) identify potential clues to the biological basis of an association by studying the relationship of the putative causal variants to phenotypic characteristics such as laboratory measures or imaging findings.

To ensure that the maximal scientific benefit is derived from this significant public investment, this funding opportunity aims to support rapid sharing of the resulting descriptive and association data with the broad scientific community for research use, through community resource databases such as dbGaP (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gap) or other databases to be developed within or outside this project. 

Background

The power and potential of large-scale GWA studies to identify genetic variants related to complex disease have been amply demonstrated with recent successes in macular degeneration, inflammatory bowel disease, diabetes, prostate cancer, breast cancer, and coronary disease.  Many of these studies have identified genes not previously postulated to be associated with a given disease, such as complement factor H with macular degeneration, or CDKN2A/B with type II diabetes, while others have identified regions not previously postulated to have much, if any genomic function, such as the “gene deserts” in the 8q24 region associated with prostate and breast cancer and in the 5p13.1 region associated with Crohn’s disease.  These findings, many of which have been convincingly replicated, raise important questions about the potential role of these variants in disease causation, or as markers of true causative variants.     

GWA studies are thus a crucial first step in the identification of genetic variants related to complex diseases, but they are only a first step.  Several subsequent phases of investigation are needed to eliminate potentially spurious associations, characterize the full spectrum of variants in an associated region, determine the impact of variants on gene function, and design appropriate intervention strategies.  Many proposals for initial GWA scans now include independent replication studies, fine mapping of associated regions, and identifying and typing rare variants found by targeted sequencing.  Once a small number of repeatedly associated, putative causal variants are isolated, however, investigation often shifts away from human populations to the laboratory, to examine experimentally the impact of variants on gene function in model systems.

Yet much remains to be learned from well-characterized human population samples in which putative causal variants have been, or could be, assayed.  Important clues to gene function may be identified by examining associations with related or intermediate phenotypes such as hormone levels or bone density.  In addition, the potential population impact of variants of interest may be poorly described by the often highly-selected or otherwise non-representative groups of cases in whom they were initially identified.  The “epidemiologic architecture” of these putative causal variants—their population prevalence; prevalence in racial and ethnic subgroups; population ancestry and stratification; associated relative risk of rigorously-defined, incident disease; consistency of association across subgroups defined by age, sex, race/ethnicity, or exposures; and potential modifiability of associated risk— is rarely pursued in depth in population studies once a genotype-phenotype association is identified, even for candidate genes.  This information is critical, however, to determining the health implications of a given variant and the priority it should receive for identifying and testing interventions to reduce its associated risk.  This information may also be quite valuable in exploring gene function, since the epidemiologic approach of genetic investigation, starting from observed phenotypic characteristics and moving more proximally to gene pathways and sequence variants, complements the laboratory approach of moving from DNA sequence to function to phenotype.

Detailed investigation of putative causal genetic variants on a population basis might be facilitated by simply cataloguing potentially available studies and encouraging collaboration, but the complexity of these datasets is such that the epidemiologic investigators who develop and routinely work with them remain uniquely positioned to conduct and interpret such analyses.  Although no single group of investigators can fully mine the massive potential of these large-scale datasets, and consequently the wide sharing of de-identified individual data continues to be strongly encouraged, not all studies are suitable for widespread sharing of genotype-phenotype data on individual participants.  In contrast, widespread sharing of summary association data should present few if any obstacles.

More importantly, defining the risk associated with a specific genotype is essentially an epidemiologic problem, similar to characterizing any other risk factor, and requires a detailed understanding of bias, confounding, and interaction.  Such investigations may best be undertaken by experienced epidemiologists using data from the large-scale population studies they have designed and carried out as they are most familiar with the complexity of these datasets, including the potential biases involved in participant recruitment, exposure assessment, and follow-up.  Clinical trials, particularly primary prevention trials, may provide similarly representative and well-characterized population samples, with the added value of randomized interventions that may suggest potential avenues for modifying genotype-phenotype associations.

Scientific Knowledge to be Achieved

This funding opportunity and the RFA-HG-07-014, “Epidemiologic Investigation of Putative Causal Genetic Variants – Study Investigators,” will form a collaborative program to provide detailed, population-based information on genetic variants with strong evidence for a causal role in complex diseases and traits.  The program will do so in a rapid and cost-effective manner by assaying these variants in representative population samples already well-characterized for a number of phenotypic traits and exposure variables, and will provide the resulting descriptive and association data in a readily interpretable manner for use by the scientific community.  It will also provide detailed and standardized descriptions of the participating population studies and clinical trials, such as numbers of subjects, their demographics, dates of recruitment and examination, length of follow-up, and types of interview and examination data, so that studies most suitable for the investigation of a specific trait can be rapidly identified both by investigators participating in this program and those outside of it wishing to collaborate.

Objectives of this Research Program

This RFA will support a Coordinating Center (CC) to facilitate and support multiple Study Investigators and their investigative groups with population-based epidemiologic and analytic expertise, and affiliated with existing population studies, to investigate and disseminate information on the epidemiologic architecture of putative disease-associated genetic variants.  The solicitation, HG-07-014, “Epidemiologic Investigation of Putative Causal Genetic Variants – Study Investigators,” will support the genotyping and primary data analysis efforts of investigative groups participating in the program.  The participating institutes anticipate funding 3-5 investigative groups under HG-07-014.

Investigative groups will work together and with the CC to develop criteria and methods for identifying highly-replicated, putative causal variants suitable for detailed epidemiologic pursuit within individual population studies.  Vigorous and productive debate will likely ensue on the evidence needed to justify extensive population characterization of a variant, such as number of independent replications, number of subjects studied and consistency of associations, and number or type of traits associated.   These discussions will provide valuable guidance to the studies participating in this program and to population studies in general. 

It is not the intent of this program to have each proposal for assay and analysis of a putative causal variant vetted or voted upon by the group; rather, a general framework will be developed for selecting variants to be investigated and population samples in which to investigate them, and for analyzing, synthesizing, disseminating, and interpreting the resulting data.  It will be important to balance the advantages of group consideration and prioritization against the speed and flexibility of pursuit possible within an individual study, so that research would neither be unnecessarily slowed nor undesirably duplicated.  Adherence to the agreed-upon framework will be strongly encouraged to ensure efficiency and pursuit of highest-priority science, and will be monitored program-wide by immediate reporting to the Steering Committee of plans to assay a specific variant within a specific study or a specified subgroup of participants, and by periodic in-depth discussion of key findings and lessons learned.  Strengths and weaknesses of the framework will be evaluated by the Steering Committee and an Expert Scientific Panel (ESP, see below) and modified as needed.

Once approaches for identifying variants suitable for epidemiologic pursuit are generally agreed upon, subsequent investigation will proceed predominantly within individual investigative groups to include: 1) identifying appropriate studies and participants within studies to be assayed and the relevant phenotypic and exposure data to be used in analyses; 2) retrieving existing samples, performing whole genome amplification and/or transformation of cryopreserved cells on a limited number of highest-priority samples if needed, and isolating, quantifying, and aliquoting highest-priority DNA samples if not already funded to do so; 3) conducting genotypic and other evolving genomic assays (such as gene expression in transformed lymphoblasts) as needed to characterize the reported association; 4) analyzing the resulting data in detail, in relation to all or nearly all the relevant phenotypic and covariate/exposure, and population ancestry data available; 5) synthesizing the results into a readily comprehensible form; 6) disseminating the descriptive and association data in user-friendly formats through standard databases such as dbGaP; and 7) inviting collaborations with outside investigators for further functional or translational research.  The CC is expected to be most actively involved in steps 5-7 above, particularly in developing program-wide approaches to data synthesis and presentation that facilitate collaboration and comparability across participating studies, as well as promoting accessibility and ease of use for investigators outside the program.  The CC may also assist individual investigative groups in steps 1 and 4, and will work with all participating groups to develop the framework for all the steps above.

Applications in response to this RFA should propose approaches to synthesis and presentation that maximize information on population impact and potential gene function, while minimizing spurious findings and difficulty sifting through the resulting analyses.  Innovative bioinformatic approaches for identifying and displaying potentially important findings should be proposed and applied program-wide, as appropriate, to increase the ease of use of the descriptive and association results, particularly for users unfamiliar with the studies from which they were derived.  Sharing of expertise and experience in this and other areas across investigative groups, facilitated and encouraged by the CC and NHGRI, will be a major goal of this collaborative program, with the intent of developing best practices for rapid investigation of putative causal variants and making the resulting findings available and understandable to investigators from a wide range of disciplines.

Applications should also propose methods for coordination among investigative groups, analysis within and across participating studies (to be conducted by the investigative groups and/or the CC as appropriate), synthesis of findings, cataloguing the characteristics of participating studies, and invitations to collaborate with participating studies.  Applicants should propose information to be collected from investigative groups to describe their studies, such as source population, eligibility criteria, informed consent and consultation process, recruitment methods, percent participation, losses to follow-up, and numbers and demographics of participants currently in the population study or proposed for inclusion, as well as specific provisions of current informed consent and IRB approvals for dissemination of grouped descriptive and association data and any restrictions on research use of the data.  Information to be collected and disseminated on biospecimens should include type, quality, and amount of biospecimens available; biospecimen source (tissue, blood, urine, etc); methods for collection (surgical excision, fine needle aspiration, phlebotomy, etc), aliquoting and tracking; storage conditions; DNA extraction methods; methods for whole genome amplification or cell transformation as applicable, as well as DNA quantity and quality and methods used to assess them. 

Applications should describe how this information will be collected from investigative groups, compiled and formatted, and provided to databases such as dbGaP, as well as approaches for reaching consensus on program-wide approaches to providing these data.  Although rigid uniformity across all participating studies may be neither feasible nor desirable, common approaches should be pursued to the degree possible to promote efficiency, ease of use, and comparisons across studies. 

Investigative groups funded through RFA-HG-07-014 will in general be expected to have the experience and expertise to characterize their studies, and to perform and provide descriptive and association analyses in an agreed-upon format.  In some instances, however, investigative groups may need guidance and assistance from the CC in performing these functions.  The CC should be prepared to assist as needed, providing appropriate expertise both for performing analyses and for developing the necessary analytic capabilities within the investigative groups.  The CC will also propose and implement approaches for evaluating quality of available data, DNA, documentation, and analyses provided by the investigative groups for submission to dbGaP and similar databases.  Although it is expected that databases such as dbGaP will be the primary vehicle for disseminating information about and from these studies to the scientific community, other approaches may be appropriate and desired.  Development of new tools and databases for providing such information will be supported under this RFA; these tools should be made freely available to the scientific community during the course of this award and provisions proposed for turning their maintenance over to a suitable archive at the end of the grant period. 

Putative causal variants assayed under RFA-HG-07-014, as well as methods used for assaying them and relevant quality control metrics, should be collected by the CC on a frequent basis in a standard format as agreed upon program-wide.  Applications should describe approaches to collecting and disseminating this information through databases such as dbGaP. 

Pooling of analyses and harmonization of phenotypes across investigative groups are not expected to be major components of this program as most analyses are expected to be done by and within investigative groups.  On occasion, however, there may be scientific advantages to such analyses, and the CC should be prepared to facilitate and conduct them as needed. 

The CC funded by this RFA will manage the logistics of the program in collaboration with the NIH Program Office, including organizing meetings and teleconferences, distributing materials, recording draft minutes for Program Office review, etc.  The CC will also be responsible for obtaining reports and other information from the investigative groups and preparing reports for review by NIH program staff, outside advisors including the ESP, etc.

Investigative groups will be responsible for study design, genetic assays, and analysis of their individual studies.  The CC will be responsible for providing support and assistance to accomplish the goals of the program, including providing support and assistance to investigative groups to accomplish their goals.  Applicants should describe their experience in working as part of a research consortium or other collaborative activities that included both laboratory and clinical/epidemiologic partners.

The CC will work collaboratively with investigative groups and NCBI to provide information on study characteristics and descriptive and association data for distribution through dbGaP.  The program may support a variety of study designs derived from existing population studies, including cohort studies and clinical trials. Applicants should describe analytic challenges related to these various designs and challenges in combining the resulting data, as well as approaches to minimizing biases.

The exact boundaries of the activities of the CC, the investigative groups, and NCBI are not possible to predict at this time, and will depend in large degree on the capacities and experience of the investigative groups.  These responsibilities will need to be negotiated once the project is funded and underway, and may change as scientific opportunities present themselves.  Applicants should describe their willingness to be flexible in assuming or relinquishing responsibilities as program needs arise.

Funding will be provided to support methodologic development and collaborative activities such as developing a framework for selecting variants to be investigated and population samples in which to investigate them, and for analyzing, synthesizing, disseminating, and interpreting the resulting data.  No participant recruitment or direct data collection for use in genome-wide studies (such as questionnaires, examinations, or laboratory measures) will be supported by this RFA. 

A detailed analytic plan should address issues related to the large amount of descriptive and association data to be generated such as multiple testing, assessing complex interactions, and evaluating the potential impact of population ancestry/history and stratification.

Program Organization

The award funded under this RFA will be a cooperative agreement (see Section VI.2.A. Cooperative Agreement Terms and Conditions of Award).  The solicitation: “HG-07-014, Epidemiologic Investigation of Putative Causal Genetic Variants – Study Investigators,” will support the investigative groups assaying putative causal variants and providing descriptive and association data from participating population studies.  Close interaction among awardees and the NIH will be required to develop appropriate strategies and tools to carry out this program.  The awardees will meet as a Steering Committee, which will include the Principal Investigators from each investigative group, the CC, and the NIH Project Scientist. 

The Steering Committee will examine approaches to identifying variants most suitable for follow-up in large-scale population studies, balancing cost and efficiency of approach with timeliness and scientific innovation.  Consensus guidelines will be developed regarding the level of evidence needed to justify investigation of the epidemiologic architecture of a variant in a large population study, and how these guidelines might differ depending on the nature of the variant (prevalence, magnitude of effect, postulated mechanism), the associated trait, or the population in which it is likely to be best characterized.  The Steering Committee will also identify strengths and weaknesses of the various participating studies in terms of traits and covariates available for investigation, and suggest best uses for specific studies, such as examining the impact of a particular intervention on a given genotype-phenotype association, or the risk of a specific trait associated with a given variant.  The CC will catalog this information across studies and disseminate it through standard databases such as dbGaP, a program website as appropriate, and other means. 

Approaches to analysis and synthesis of data and documentation will be shared and reviewed in Steering Committee meetings, using summary data derived from the participating studies themselves.  The Steering Committee will propose and agree upon approaches for release of analytic results, to be standardized as much as feasible across participating studies and provided as rapidly as possible, in both a summary, user-friendly form and a more detailed, comprehensive form.  These results will be compiled by the CC and provided to the scientific community through databases such as the open-access portion of dbGaP or others to be developed through this program.  Appropriate embargoes on submission of publications from these findings, consistent with NHGRI and NIH guidelines, will be applied although the summary information itself will be disseminated as soon as it is generated.  Dates of completion of genotyping, of completion of descriptive and association analyses, and of deposition for dissemination will be reported by the investigative groups to the CC for tracking and monitoring program productivity and publication exclusivity periods.  Sharing of genotype or phenotype data on individual study participants in databases such as the controlled access portion of dbGaP will not be necessary to participate in the program, but will be strongly encouraged in keeping with NHGRI and NIH policies.

The Steering Committee will meet in person three times per year and monthly on conference calls as needed to share information on data resources, methodologies, analytical tools, as well as data and preliminary results.  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, 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 such as bioinformatics, public health, social sciences, and translational research where appropriate. The cost of 3-4 persons from the CC to attend these meetings, as well as the costs associated with arranging and participating in monthly conference calls, should be included in the proposed research budget.  

Data from this RFA are expected to be handled so as to increase the value of the significant public investment in genotyping and investigating the epidemiologic architecture of variants in the participating population studies.  NHGRI intends that descriptive study materials and descriptive and association data generated through genotyping efforts supported in this RFA will be widely shared with the scientific community for research uses through NIH-supported databases such as the open access portion of dbGaP.  Although NHGRI expects these materials and data to be available through a database such as dbGaP, they do not intend dbGaP, or any single database, to become the exclusive source of this program’s data; other databases, public web sites, and/or publication in the scientific literature are suitable additional venues for data dissemination. 

Applicants for this CC RFA should indicate their willingness to cooperate with Study Investigators supported under RFA HG-07-014 and with NHGRI in the development and design of research and analysis methods, procedures, policies and strategies to be applied in this program. Applicants should also describe prior experience in working as part of a research consortium or other collaborative activities to meet individual study and collaborative goals

This initiative will not support additional recruiting of human subjects for genome-wide studies or collecting medical or phenotype data to develop or broaden the existing study.  Applications that include recruiting human subjects or collecting medical or phenotype data to develop or broaden the existing study will be considered non-responsive and returned to the applicant.

Proof of appropriate informed consent and/or IRB approval for serving as the CC in this collaborative program to use previously collected data and biospecimens for genetic research, and to share the resulting association data, should be provided at the time of application submission. Only applications describing protection of participants’ privacy and confidentiality will be considered.

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

Section II. Award Information

1. Mechanism(s) of Support

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

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

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see https://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

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".

There are no plans at present to reissue this RFA.

2. Funds Available

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.

Section III. Eligibility Information

Failure to meet an eligibility criterion by the time of an application deadline will result in the return of the application without review, or even though the application may be reviewed, will preclude the agency from making an award.

1. Eligible Applicants

1.A. Eligible Institutions

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

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

2. Cost Sharing or Matching

Cost sharing is not required.

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

3. Other-Special Eligibility Criteria

N/A

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at https://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: 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 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
Letter of Intent Receipt Date: October 19, 2007
Application Receipt Date: November 19, 2007
Peer Review Date(s): February/March, 2008
Council Review Date: May, 2008
Earliest Anticipated Start Date: July 1, 2008

3.A.1. Letter of Intent

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

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

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

The letter of intent should be sent to:

Erin M. Ramos, 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: 301-496-7531
FAX: 301-480-2770
Email: ramoser@mail.nih.gov

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 https://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

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: https://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 https://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 https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements

Special Application Requirements

Applicants must address the following when preparing applications in response to this RFA. Items A–D in the application (Specific Aims, Background and Significance, Preliminary Studies, and Research Design and Methods) should not exceed 25 pages.

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

The applicant must address human subjects issues, including potential barriers to sharing summary genotype-phenotype descriptive and association data generated through this funding opportunity, as well as barriers to sharing phenotypic/exposure and genetic data from individual participants, if such sharing is proposed by a Study Investigator, with the broad scientific community.

Applicants are expected to have obtained appropriate Institutional Review Board (IRB) and any other required approvals for sharing association data with NIH and for submitting association results to a shared data resource as described under “Plans for Sharing Research Data.”

Plan for Sharing Research Data

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

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

The applicant is expected to provide specific plans for data sharing and data release in the application.  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 NHGRI has identified this program as a community resource project.  As such, the program aims to function openly by making all descriptive and association data (not necessarily individual genotype and phenotype data) available to the scientific community in a timely manner prior to publication, with suitable restrictions for protection of human research subjects.  The NHGRI is committed to creating a resource founded on the principle of no-cost, rapid, and complete release of genotype-phenotype association data for use by investigators throughout the global scientific community.  All participants in the 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 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.

Publication Policy:

NHGRI expects that beginning on the date that descriptive and association data on a given variant are released for distribution through a database such as dbGaP, there will be a period of nine months during which Investigators retain the exclusive right to submit publications developed with the data and samples they contributed.  During this nine-month period of publication exclusivity, the dates of which will be identified and tracked by the CC, other users will have access to the summary data, but be admonished not to submit for publication any results or analyses derived from the use of any program data within that period without consent of the Investigator.  Investigators will be encouraged to shorten the period of exclusivity at their own discretion.  NHGRI may request a shorter period of exclusivity.  The NHGRI 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 NHGRI expects that data generated under the support of this RFA and conclusions derived directly 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 that would prevent use of or block access to any genotype-phenotype data developed with support of this RFA.  The NHGRI 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 (https://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 datasets and dbGaP could substantially diminish the utilization of information and the potential public benefit they could provide.

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 https://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm and https://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, https://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

As this program is a community resource project, NHGRI expects that not only data, but also resources generated during the course of the program, such as guidelines, best practices, 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.  

Section V. Application Review Information

1. Criteria

The following will be considered in making funding decisions:

Additional criteria for award will include:

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:

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?

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?  Are the proposed plans for providing operational and analytic coordination and support likely to promote productive collaborations and provide maximal scientific value?  Are the proposals for collecting, collating, and disseminating information from investigative groups on study characteristics and descriptive and association analyses adequate?  Are the proposed plans to share data in a timely manner likely to provide maximal scientific value for identifying the potential causal role of genes strongly associated with complex diseases?

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? Does the application propose novel approaches or methods for collecting and disseminating information from investigative groups on study characteristics and descriptive and association analyses?  Valid statistical and computational methods for accomplishing this may represent sufficient innovation for this RFA.

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

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

2.A. Additional Review Criteria:

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

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

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 E on Human Subjects in the PHS Form 398).

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.

The NHGRI 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 applicant is encouraged to provide specific plans for data release in the application. 

Program staff will be responsible for the administrative review of the plan for sharing data. The adequacy of the data 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 sharing plan with the awardee before recommending funding of an application. The final negotiated version of the data sharing plan will become a condition of the award of the cooperative agreement. The effectiveness of the data sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

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 https://grants.nih.gov/archive/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 are expected to 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 July 1, 2008.

Section VI. Award Administration Information

Additional criteria for award will include:

The awardee must agree to the “Cooperative Agreement Terms and Conditions of Award” in Section VI.2.A. “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 (https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.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

The NHGRI 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.

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 (https://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 (https://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 the NIH U01 Research Project Cooperative Agreement award mechanism, 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 meeting the project requirements of RFA-HG-07-015 and 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 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.  However, the role of NIH staff will be to facilitate and not to direct the activities.  It is anticipated that decisions in all activities will be reached by consensus of the program and that NIH staff will be given the opportunity to offer input to this process.  The Project Scientist will participate as a member of the Steering Committee and will have one vote.  The Project Scientist will have the following substantial involvement:

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 the Project Scientist.

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

The NCBI is substantially involved.   NCBI manages and maintains data security for dbGaP.  They will work with the CC and the Study Investigators as needed to ensure data integrity and clarify data definitions.

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, analyze, and coordinate studies of putative causal variants. The awardees from RFAs HG-07-014 and HG-07-015 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 under RFAs HG-07-014 and HG-07-015.  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. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

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.  The CC should budget for travel funds for Expert Scientific Panel members and appropriate CC personnel to attend meetings in Bethesda twice a year.

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 will also be required.

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

Section VII. Agency Contacts

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

1. Scientific/Research Contacts:

Erin M. Ramos, 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: 301-496-7531
FAX: 301-480-2770
Email: ramoser@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

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).

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 (https://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 https://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.

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 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at https://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 (https://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 https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

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).

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 https://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 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 https://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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