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 Heart, Lung, and Blood Institute (NHLBI/NIH), (http://www.nhlbi.nih.gov)

Title:  Genome-Wide Association Studies to Identify Genetic Components that Relate to Heart, Lung, and Blood Disorders (R01)

Announcement Type
New

Request For Applications (RFA) Number: RFA-HL-06-012

Catalog of Federal Domestic Assistance Number(s)
93.233, 93.837, 93.838, 93.839

Key Dates

Release Date: February 16, 2006
Letters of Intent Receipt Date(s): March 21, 2006 
Application Receipt Dates(s):  April 20, 2006
Peer Review Date(s): July 2006 
Council Review Date(s): August, 2006 
Earliest Anticipated Start Date: September 30, 2006
Additional Information To Be Available Date (Url Activation Date): Not  Applicable
Expiration Date:  April 21, 2006 

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
  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

The purpose of this RFA is to identify genetic variants related to heart, lung, and blood disorders and their risk factors by utilizing rapidly developing methods of genome-wide association in existing human studies.  Data from this effort will contribute to knowledge of the underlying genetic components, their interaction with each other and the environment, and the biochemical pathways which contribute to complex heart, lung blood and cardiopulmonary related sleep disorders (HLBS).   Results have the potential to identify novel predictors of disease, new therapeutic interventions, prevention strategies and treatments, as well as predictors of response to treatment.

Nature of the research opportunity:

Translating the contribution of genomic variation to the development and progression of complex heart, lung and blood disorders, into effective, new or improved diagnostic tools and treatments is a high priority for the National Heart, Lung, and Blood Institute (NHLBI).  Such translation must begin with a strong knowledge base, to provide a firm foundation for research and for the generation and testing of new hypotheses that can contribute directly to the development of new tools and approaches to prevent and manage disease. The Institute has a long tradition of supporting population, family and clinic based studies and trials in which individuals have been extensively phenotyped.  The addition of large scale genotyping information to existing databases from these studies would provide unparalleled resources for assessing genetic contributions to heart, lung, blood, and cardiopulmonary sleep disorders.  Many studies of HLBS phenotypes appear particularly suited for application of the newly available tools enabling rapid and relatively inexpensive typing of hundreds of thousands of single nucleotide polymorphisms (SNPs) needed for genome-wide association (GWA) studies.  To address the need for translation of genomic discoveries to heart, lung, and blood disorders research to clinical care, NHLBI recognizes the importance of developing a variety of mechanisms for investigators to conduct genetic and genomic studies of HLBS phenotypes in existing population, family and clinical studies.  This RFA will provide an opportunity for investigators to obtain and share genomic data from their existing studies and perform GWA studies.

Pertinent Background Information: 

Many heart, lung, and blood diseases are multi-factorial and complex in their presentation, progression, and outcome.  They are influenced by the interaction of multiple genetic and environmental factors, making it challenging to identify genetic components responsible for the cause, severity, and progression of these common diseases.  Genome-wide association is one method to address this challenge.  The use of new genomic technology based on data from the HapMap project shows promise for identification of SNPs which may influence common HLBS diseases.  The strategy does not rely on hypothesis-based approaches, but does require detailed information on SNPs, their patterns of linkage disequilibrium and a well-characterized (for both phenotype and environment) sample.  Genome-wide association offers improved power to detect genetic variation as well as genetic interactions with other genes and the environment contributing to complex HLBS disorders. 

Until recently, the cost and effort required to characterize the large number of SNPs in the human genome have been major impediments to conducting genome-wide association studies.  With improved knowledge of linkage disequilibrium patterns to select a smaller set of informative SNPs (tagSNPs), and recent reduction of genotyping costs, it is now feasible to conduct genome-wide association analyses in existing studies using a variety of designs, such as cohort, clinical and family studies.   The addition of dense SNP genotyping to the existing wealth of information on disease incidence, risk factors, environmental exposures and responses to clinical treatment will provide unparalleled resources for unraveling the complex etiology of HLBS disorders.

Scientific knowledge to be achieved through research supported by the special program:

Dissecting the genetic architecture of complex heart, lung, blood and cardiopulmonary sleep disorders will provide valuable information to further investigate gene function and its role in the pathogenesis and progression of disease and response to therapy.  Further, this information may be used to develop new treatment strategies that maintain or restore health, prevent or retard progression of existing disease and predict individual risk of disease and response to treatment. 

Objectives of this research program:

The NHLBI supports a number of studies and programs that investigate the genetics of complex diseases, as well as several contracts and resources to facilitate gene identification and variation discovery. In addition, various Institutes at NIH, as well as other government agencies, also support gene discovery programs and infrastructure such as the International HapMap Project.  The current need is for investment in the efficient use of these resources and data to link genetic variation to the development and/or progression of disease.  This initiative requires the use of extensive, currently available HLBS phenotypes and risk factors coupled with state of the art strategies for gene discovery to elucidate the genetics of complex disease. 

This RFA will support investigators to implement innovative strategies for genome-wide association studies in existing population, cohort, clinical and family studies.  Studies may seek to identify associations of genes with the presence of one particular HLBS disorder and may examine interactions among genetic and environmental factors; susceptibility for multiple conditions; or associations of genes with disease risk factors, disease incidence, or therapeutic responsiveness.   A diversity of participant populations regarding age, sex, and race/ethnicity will be supported under this RFA.  Investigators should have access to existing sources of DNA from such population studies.   Funding will be provided for genotyping and data analysis.  This solicitation will fund measurement of genomic data on available samples from existing human studies and analysis of those data.   No recruitment, additional phenotyping, or sample acquisition will be supported by this RFA.

Each application must clearly define a plan for selection of the population, study design, genotyping platform and proposed analyses.  Proposed analyses should be described in detail, including any plan for assessing gene-by-gene interaction, gene by environment interaction, and pleiotropy;  the impact of population ancestry/history and stratification on GWA analyses should be discussed. A detailed analytic plan should address any relevant issues associated with a large amount of GWA data such as multiple testing, assessing complex interactions (e.g., gene by gene, gene by environment including gene by drug, pleiotropy, epistasis).  The impact of unobserved population substructure, population history and ancestry should be addressed regardless of the population chosen for study.  Power calculations must be provided to justify sample size needed to detect putative disease variants with a variety of allele frequencies and effect sizes, i.e., from rare alleles with large effect to common alleles with small (as little as 5% or less of the variance) effect size.  The analytic plan should detail methods to address false positives and adjust for multiple testing.

Choice of population and study design should be dictated and justified by the scientific questions addressed in each application, such as the disease or risk factor epidemiology.   This RFA may support a variety of study designs derived from existing population, family and clinical studies including, but not limited to, case-control, cohort, case-cohort, family based, sequential sampling and DNA pooling.  The applicant must justify the study design chosen based on the epidemiology and biology of the disease(s) and/or risk factor(s) as well as the population under study.  Equal emphasis should be placed on the justification for choice of cases and controls.

Applicants should describe the significance and complexity of the primary phenotype(s) and the need for a high throughput whole genome association study.  A description of the prevalence of the trait or disorder in the population and its impact on public health and clinical care should be included.  Applicants should provide evidence for a genetic effect on the primary phenotypes under consideration and describe the anticipated size of a detectable genetic effect.   Applicants should describe their plans for replication and follow-up studies if an association is found, including current availability of a suitable replication sample.

Choice of genotyping platform, number of SNPs and method of choosing SNPs should be discussed with respect to the proposed study population, study design, analytic plan and biology and epidemiology of the disease or phenotype.  Data on error rates for the proposed genotyping platform, and a clear plan for quality control of genotypes and methods for addressing false positives should be included in the application. 

Applicants should clearly outline a plan for data quality control (QC), database development, documentation, data storage and retrieval, i.e., bioinformatics.  Such a plan must clearly describe the mechanisms used to fully integrate genomic, clinical and/or epidemiological data.  The bioinformatics platform should provide tools for data integration and interpretation and data sharing. The computing platform and data set developed for dissemination should be capable of integration and interoperability with existing platforms and data bases.  The bioinformatics system plan should address critical functions including maintenance of clinical data set security and integrity, protection of participants’ privacy and confidentiality, electronic accountability and verification of informed consent, tools to facilitate data integration and interpretation and plans for data sharing including methods for attribution of disseminated data.

Program Organization: 

The grants funded under this RFA will be R01 research grants.  Interaction among the participating investigators is required over a three-year period to perform genotyping, genome-wide association analysis and share data and results with the scientific community.  Applicants should plan to attend grantee meetings, normally held in the Metropolitan Washington, D.C. area 2 times per year and bimonthly by conference calls to share information on genotyping, methodology and preliminary results.  Grantee meetings will also be attended by NIH staff. Key co-investigators and pre- and postdoctoral trainees, in addition to the PIs, are eligible to attend these meetings. The cost of up to 3 people to attend these meetings, as well as the costs associated with one conference call including 20 participants, should be included in the proposed research budget.

The immense amount of data generated from this RFA lends itself to collaborative analysis efforts.  Investigators are encouraged to establish collaboration and share phenotypic, environmental and genotypic data with the scientific community, with appropriate protections for participant confidentiality.  Ultimately, data generated in this program will be made available to the greater scientific community.  For the purpose of this RFA only, curated data will be delivered to the NHLBI after quality control protocols are completed. Completion of quality control protocols is not to exceed 6 months following receipt or completion of raw genotyping data.  The NHLBI will make these data available to the scientific community 1 year after receipt of the curated data set.   Additional collaborative efforts and data sharing efforts are encouraged to maximize the quality and quantity of scientific output from these data.  Investigators are encouraged to propose an infrastructure that facilitates such collaboration.

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

This initiative will not support the recruitment of human subjects, collection of human samples, collection of phenotypic or medical data, or studies using animal models.  Applications that include recruitment of human subjects, collection of human samples, collection of phenotypic and/or medical data will be considered non-responsive and returned to the applicant.

Proof of appropriate informed consent for the previously collected data must be provided at the time of application submission.  Only applications describing protection of participants’ privacy and confidentiality will be considered.

Section II. Award Information


1. Mechanism(s) of Support

This funding opportunity will use the R01 research grant award mechanism(s).
As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses just-in-time concepts. It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular budget format described in the PHS 398 application instructions. Otherwise follow the instructions for non-modular research grant applications.

2. Funds Available

NHLBI intends to commit approximately $20 million in total costs ($8 million in FY2006) to fund 4-6 new and competing continuation grants in response to this RFA.  An applicant may request a project period of up to 3 years.  Funds for genotyping should be requested in the first year.  The anticipated start date for awards is September 30, 2006.  

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size of each award will also vary.  Although the financial plans of the NHLBI 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.

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

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

1.B. Eligible Individuals

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

2. Cost Sharing or Matching

As defined in the current NIH Grants Policy Statement, this program does not require cost sharing (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).  

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

3. Other-Special Eligibility Criteria
 
Section IV. Application and Submission Information


1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

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

2. Content and Form of Application Submission

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

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form, and the YES box must be checked.

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

Proposed research should provide a unique research opportunity not available in the U.S.

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): March 21, 2006 
Application Receipt Dates(s):  April 20, 2006
Peer Review Date(s): July 2006 
Council Review Date(s): August 2006 
Earliest Anticipated Start Date: September 30, 2006

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:

Chief, Review Branch
Division of Extramural Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 7214, MSC 7924
Bethesda, MD 20892-7924 (Express zip: 20817)
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email: nhlbichiefreviewbranch@nhlbi.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 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:

Chief, Review Branch
Division of Extramural Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 7214, MSC 7924 (Express zip: 20817)
Bethesda, MD 20892-7924
Telephone: (301) 435-0270
FAX:  (301) 480-0730
Email: nhlbichiefreviewbranch@nhlbi.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: 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 NHLBI. Incomplete and non-responsive applications will not be reviewed. If the application is not responsive to the RFA, NIH staff may contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next appropriate NIH review cycle.

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.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

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/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements

This initiative will support the utilization of currently available phenotypic data related to HLBS disorders to implement novel strategies for genome-wide association studies.  Each applicant may submit only one application as PI.   

Specific Instructions for Modular Grant applications.
Applications requesting up to $250,000 per year in direct costs must be submitted in a modular budget format. The modular budget format simplifies the preparation of the budget in these applications by limiting the level of budgetary detail. Applicants request direct costs in $25,000 modules. Section C of the research grant application instructions for the PHS 398 at http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step guidance for preparing modular budgets. Applicants must use the currently approved version of the PHS 398. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm.

Plan for Sharing Research Data

As the work scope of this RFA lends itself to a multidisciplinary collaborative approach, investigators are encouraged to actively pursue collaborations and share phenotypic, environmental and genotypic data with the scientific community subject to appropriate protections for participant confidentiality.   

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

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

For the purpose of this RFA only, curated phenotypic, genotypic and pedigree (if appropriate) data will be delivered to the NHLBI after quality control protocols are completed.  Completion of quality control protocols is not to exceed 6 months following receipt or completion of raw genotyping data.  The NHLBI Program Staff will work closely with investigators to ensure reasonable timelines for receipt of the curated data set.  The NHLBI will make these data available to qualified scientific investigators with IRB approval 1 year after receipt of the curated data setAdditional collaborative efforts and data sharing efforts are encouraged to maximize the quality and quantity of scientific output from these data. 

Sharing Research Resources

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

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

When studies proposed in a response to this RFA are related to pharmacogenetics or pharmacogenomics (involve drugs, genes, and diseases), data should be deposited into PharmGKB, the NIH-funded database for genotype-phenotype knowledge with a focus on drug responses (http://www.pharmgkb.org/).  PharmGKB curates four types of data: (1) genotype data collected on human subjects, ranging from a few SNPs to whole-genome datasets, (2) phenotype data sets associated with drug response, collected at the molecular, cellular, organ or organismal level, and linked to associated genotype data, (3) curated pathways related to drug response built manually through a consensus process involving experts in the field, and (4) curated literature on gene-drug interactions, managed principally by the in-house scientific curators at PharmGKB.  PharmGKB has mechanisms for accepting genotype and phenotype data from all users.  PhD-level scientific curators work with submitters to ensure that the data columns are well-documented scientifically and do not compromise the privacy or security of study subjects (i.e. identifying fields are removed and potentially identifying information is made less precise). 

Section V. Application Review Information


1. Criteria

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

The following will be considered in making funding decisions:

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NHLBI 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?  

Has the applicant included a plan to share the data set and any analytical strategies and tools amongst the other investigators funded in the program? 

Has the applicant included a plan to share data to the broader scientific community?  Has the applicant proposed an adequate plan to provide a Limited Access Data Set to the NHLBI?

Has the applicant adequately addressed issues regarding intellectual property, human subjects and HIPAA, informed consent and implications for sharing data, tools and results?  

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)?

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

2.A. Additional Review Criteria:

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

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

Informed Consent Documentation:  Adequacy of consent (obtained for the existing data set) for proposed genetic research and ability to share genetic data with the scientific community will be assessed during peer review.  Applicants should refer to the NHLBI guidelines for consent:

Consent for tissue in repository http://www.nhlbi.nih.gov/funding/policies/repos-gl.htm

Consent for tissue sharing/genetics http://www.nhlbi.nih.gov/funding/policies/tissue.htm

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.   Adequate representation of women, children and minorities will be evaluated across the program as a whole, not for each specific application.

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 may be assessed by the reviewers. Program staff will be responsible for the administrative review of the plan for sharing research data and resources. The funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing. 

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps/part_ii_5.htm#availofrr and http://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 of the funding institute 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
Not applicable

Section VI. Award Administration Information


1. Award Notices

After the peer review of the application is completed, the 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/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

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

3. Reporting

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


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:

Cashell E. Jaquish, Ph.D.
Division of Epidemiology and Clinical Applications
National Institutes of Health
6701 Rockledge Drive
Room 8170, MSC 7934
Bethesda, MD 20892-7934
Telephone: (301) 435-0447
FAX: (301) 480-1455
Email: cj68r@nih.gov

Dina N. Paltoo, Ph.D., M.P.H.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Rockledge II, Room 9180
Bethesda, MD 20892
Telephone: (301) 435-0513
FAX: (301) 480-1336
Email: paltood@nhlbi.nih.gov

Ahmed A.K. Hasan, M.D., Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
Rockledge II, Room 10180
MSC 7950
6701 Rockledge Drive
Bethesda, MD  20892-7950
Phone: 301-435-0064
FAX: 301-480-1046
Email: hasana@nhlbi.nih.gov

Susan Banks-Schlegel, Ph.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
Rockledge II, Room 10018
MSC 7952
6701 Rockledge Drive
Bethesda, MD  20892-7952
Phone: 301-435-0202
FAX: 301-480-3557
Email: schleges@nhlbi.nih.gov

2. Peer Review Contacts:

Chief, Review Branch
Division of Extramural Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 7214, MSC 7924
Bethesda, MD 20892-7924 (Express zip: 20817)
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

3. Financial or Grants Management Contacts:

Teresa Marquette
Grants Operations Branch
National Heart, Lung, and Blood Institute
Rockledge II, Room 7152
6701 Rockledge Drive
Bethesda, MD 20892
Telephone: (301) 435-0144
FAX: (301) 480-3310
Email: MarquetteT@nhlbi.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 (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.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research” (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

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

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

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

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. 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://www.nih.gov/about/publicaccess/ and view the Policy or other Resources and Tools including the Authors' Manual (http://www.nih.gov/about/publicaccess/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 http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to 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 PA 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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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