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)  (http://www.nhlbi.nih.gov)

Title: Next Generation Genetic Association Studies (U01)

Announcement Type

New

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

Request For Applications (RFA) Number: RFA-HL-11-006

Catalog of Federal Domestic Assistance Number(s)
93.837, 93.838, 93.879

Key Dates
Release Date: March 15, 2010
Letters of Intent Receipt Date(s):
May 17, 2010 
Application Receipt Dates(s):
June 15, 2010
Peer Review Date(s): November 2010
Council Review Date(s):
January 2011 
Earliest Anticipated Start Date: April 2011  
Additional Information To Be Available Date (Url Activation Date): May 2010
Expiration Date:
June 16, 2010

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Table of Contents  


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
    A. Eligible Institutions
    B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Receipt, Review and Anticipated Start Dates
         1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
   D.  Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
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. Dispute Resolution 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

The purpose of this FOA is to build upon existing genomic study findings with functional information gained by assessing cellular profiles that are surrogates for disease phenotypes.  This FOA is threefold and proposals may include all three phases, but must include the second and third phase outlined below. Applicants may propose Phases I to III or II to III depending on the current state of induced pluripotent stem (iPS) generation and cell type differentiation technology needed  to meet their specific aims. First, NHLBI proposes a technology development phase whose goal is to utilize emerging iPS cell generation and differentiation technology to generate cell types relevant to HLBS diseases.  The second phase scales up this technology to generate cell lines in large numbers of samples.  The availability of such technology on a production scale will enable the third (implementation) phase that will  apply cellular reprogramming and molecular profiling to population-based samples and will integrate this information with existing genotypic and phenotypic data. The resulting data will allow assessment of how human genetic variation influences the activities of biological networks in cell-based models of disease.  Addressing this goal will require a multidisciplinary approach, consisting of teams including, but not limited to, epidemiologists, clinicians, population geneticists, stem cell and molecular biologists and bioinformaticians.

Nature of the Research Opportunity:

Genomic studies have been successful in identifying common disease-associated DNA variants, but they have provided relatively little direct insight into underlying causal mechanisms.  One way to overcome this limitation is to integrate information from  genomic studies with molecular surrogates for clinical phenotypes that can be assayed in cell-based models of disease derived from individuals of known genotype.  This research opportunity will utilize a phased approach to investigate how genetic variants identified in GWAS influence molecular phenotypes in such cell-based models of disease:

The goal is to add a functional dimension to existing genomic studies by combining cellular reprogramming strategies with molecular profiling and cellular assays, followed by integration of this information with existing genotypic data to assess how naturally occurring human genetic variation influences the activities of biological networks in cell-based models of disease.  This approach will require a multidisciplinary team; existing NHLBI genomic studies are well-suited to move into this area of genomic-based mechanistic research.

Pertinent Background Information:

Genetic variants and function:

Identifying genetic variation contributing to disease risk has been a major aim of genetic epidemiology.  Over the past three years, GWAS has been the most common approach to addressing this aim.  GWAS relevant to HLBS diseases and traits have been performed in asthma, atrial fibrillation, blood pressure, coronary disease, heart rate, myocardial infarction, peripheral arterial disease, idiopathic pulmonary fibrosis, pulmonary function and COPD, venous thromboembolism, hematological diseases, hypertension, blood pressure, as well as levels of HDL cholesterol, LDL cholesterol, total cholesterol, and triglycerides.  These Genome-wide association studies have been relatively successful in achieving this aim.  However, genomic studies have provided relatively little direct insight into the mechanisms underlying the gene–disease association.  One approach to overcome this limitation is to add functional information to genomic studies by selecting individuals with specific genetic variants and using cellular reprogramming strategies to create a cellular proxy of the disease  in the laboratory.  These cells can then be interrogated regarding functional and mechanistic hypotheses originating from genomic results.

iPS derived cells as models for disease:

Recent advances in stem cell biology have enabled generation of iPS cells from readily obtainable human tissue (for example, skin fibroblasts, blood cells and hair keratinocytes).  Human fibroblast cells from skin biopsies and human keratinocytes isolated from plucked hair have been successfully programmed to iPS cells, which can differentiate into cardiomyocytes and endothelial cells.  Recently, human iPS cell were generated from peripheral blood mononuclear cells of healthy volunteer and coronary artery disease patients.  These iPS cells can be differentiated into endothelial cells and have vasculogenic potential in vivo in tested animal models.  Additionally, viral and non-viral protocols for differentiating iPS cells into cell types relevant to HLBS disorders have been rapidly developing.  These differentiated cells provide the potential for use as disease models for  testing mechanistic hypotheses or drug and toxicology screening.  Efficiency of cellular differentiation protocols is also rapidly developing.  However, other cell types related to HLBS diseases or traits are also needed.  Furthermore,  the protocols for creating iPS cells from somatic cells and for differentiating iPS cells into specific cellular types as well as obtaining homogenous cell types are not yet amenable to high-throughput production.   

Integration of molecular profiling, cellular assays, phenotypic and genomic information:

The abundance of data derived from genomic studies, as well as that from gene expression and transcriptomics studies, has led to an interest in integrating data from disparate  sources.  The ability to integrate and analyze data from a variety of molecular profiles, biochemical and physiologic assays in concert with genetic, environmental, clinical and phenotypic data in cells with known genetic mutations  has not been explored and has the potential to reveal a more detailed picture of the underlying biochemical pathways to disease.  Thus, integrated analysis of these data may elucidate multiple molecular networks and pathways related to specific genetic variants that lead to disease. Ultimately, increasing our knowledge in this area may lead to the development of effective prevention and treatment strategies for both rare and common, complex heart, lung, blood, and sleep diseases and disorders.  

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

Deciphering the biological function of genes and gene networks identified through genomics has been a major challenge.  Many of these variants are located in intergenic or intronic regions or non-coding regions.  Furthermore, the functions of the genes and the mechanism of association to the diseases or traits are often unknown.  Although these genes have provided new biological insights, the functional link between associated variants and phenotypic traits and their effects on the pathways to diseases are unknown in most cases.  Even in cases of replicated associations, it is not clear that the identified variant is the actual functional variant and its effect on the pathway to disease is unknown in most cases.  The availability of cell-based models of human disease will enable testing of hypotheses based on genomic findings in relevant tissues.   Such interrogations will contribute information on molecular and cellular effects of genetic variation in humans.   In addition, it will generate new mechanistic hypotheses about disease causation.

Objectives of this research program:

The objectives of this research program are to (1) stimulate technology development for high-throughput iPS cell line generation and differentiation and (2) utilize this technology to follow up on genomic associations with additional mechanistic information gained from cellular models of disease.

A phased approach will be used to attain the aims of this proposal.  Phase I entails technological development to generate iPS cells from human samples well-phenotyped for HLBS disorders and risk factors and differentiate these iPS cells into specific cells relevant to HLBS diseases.   Phase II involves ramping up the technologies developed in Phase I for high-throughput generation of differentiated cells from iPS cells in population samples.  Capacity to reliably generate differentiated cells in hundreds to thousands of individuals should be demonstrated.  Phase III will include sample collection, integration of cellular reprogramming, molecular profiling, cellular assays and existing genotype, phenotype and environmental information to begin to assess functional significance of human genetic variation.  Phase III study designs should build upon or leverage prior knowledge from genomic studies or gene discovery studies, for example, by identifying the most informative subjects for subsequent investigation.  Applicants should organize their proposals in two to three phases; each phase will have its own research plan.  Applicants may propose Phases I to III or II to III depending on the current state of iPS generation and cell type differentiation technology needed  to meet their specific aims.  Applications will be considered non-responsive if they propose only Phase I and/or Phase II.  Each phase / research plan may be up to 12 pages in length for a total of 36 pages (if the application contains all three phases), and each phase will include one page for specific aims and statement of impact that the results of the proposed research will exert on the research field(s) involved.  Milestones will be associated with each phase to ensure adequate progress.   Milestones will be developed by the NHLBI in consultation with funded applicants, the steering committee and the OSMB.  Evaluation of progress toward milestones will enable decision making to maximize flexibility in approach in concert with rapidly changing technology.  

Phase I will place an emphasis on appropriate validation of iPS cells and their derivatives, evaluating the hetero/homogeneity of any cell populations and selecting cellular and molecular assays that are relevant to HLBS disorders.  Applications should focus on cell types, such as fibroblasts, keratinocytes and blood cells, which can be readily obtained from human subjects and stored for later conversion to iPS cells.  Focus should also be placed on differentiation protocols which generate tissues relevant to HLBS disorders, for example, cardiomyocytes, hepatocytes, adipocytes, alveolar epithelial, hematopoietic cells or vascular endothelia.

Phase II will emphasize efficiency and ease of tissue collection, cellular differentiation and profiling assays.  Tissue samples must be feasible to obtain from living human populations and must be easily obtained in samples from hundreds or thousands of individuals.  Assays for cellular differentiation should be efficient and amenable to high-throughput implementation.  Cellular profiling assays should be relevant to HLBS disorders, have high quality and reproducibility and be amenable to high-throughput implementation.  Studies should include provisions to archive and readily distribute both non-induced (e.g., primary) and iPS cells, as well as open sharing of protocols for generation of iPS cells and differentiation.

Responsive applications for Phase III must integrate molecular profiling, biochemical or physiologic assay data with existing genomic, phenotypic and environmental data to interrogate molecular and cellular effects of genetic variation associated with HLBS disorders and risk factors.  Phase III should address specific scientific hypotheses derived from genomic studies (GWAS, sequencing, candidate gene or linkage with follow up fine mapping).  Collection or measurement of additional patient level phenotypes or genotypes will not be supported.  Collection of tissues for iPS cell generation and differentiation will be supported, as will reconsent, cellular and molecular level phenotyping.  Examples of responsive research include, but are not limited to: 

Study design, sample size and selection should be informed by results from existing genomics studies.  Power calculations must be provided to support study design and sample size.  Protocols for the acquisition of tissue from subjects must include reconsent of participants for collection, induction, differentiation and distribution of cell lines as well as provisions to archive and readily distribute non-induced (e.g., primary) and iPS cells. Additionally, appropriate statistical methods and models for data integration and analysis must be included.

Multidisciplinary research teams should be formed and include personnel with expertise in stem cell biology, clinical medicine, epidemiology, population and statistical genetics, network modeling, bioinformatics, cell biology, genomics, and molecular profiling.   Grants will be phased U01s with clear milestones at each phase.   NHLBI will work closely with the OSMB and investigators to assess progress, evaluate milestones, and provide overall coordination and governance of this research program.  NHLBI staff will assess, based on attainment of milestones, state of the technology and investigator need, the feasibility of collaboration to develop and refine cellular differentiation and molecular profiling protocols during Phase II of the program.  All data generated in this program must be deposited and made available in electronic form into NCBI’s dbGaP (http://www.ncbi.nlm.nih.gov/gap) or other suitable data base.  All primary cells collected and iPS cells must be archived in a suitable repository agreed upon by the study investigators and NHLBI staff.  Both primary and iPS cells must be made available to the scientific community in a timely manner, agreed upon by the Steering Committee and NHLBI staff, once they have been adequately characterized. Investigators should provide assurance that the informed consent used to collect specimens explicitly allowed for data and specimen sharing.  Access to data will be overseen by the NHLBI Data Access Committee utilizing existing application procedures.

Program Organization:

The grants funded under this RFA will be U01 research grants.  Interaction among the participating investigators will be required, as well as significant involvement from NHLBI, over a five-year period to collect samples, generate iPS cell lines, differentiate cell types, complete molecular profiling and cell based experiments, perform integrative data analysis, and share data and results with the scientific community. 

1.  Internal Governance of Each Study

Each study will establish an internal organization by which they govern and oversee various components and phases of the study.  The three phases of the study should be clearly defined and activities coordinated.  Each phase may have a different PI or lead investigator; a contact PI should be designated for the entire project.  This organization will oversee and approve all protocols and procedures involved in the performance of the research and publication of findings.  Applicants should include a description of the organization, as well as a budget to cover monthly meetings and/or conference calls.

A Timeline and Milestones section must be included in the Specific Aims of the research plan and will be included in the page limit for the Research Plan. The timeline should describe the expected progression of the research activities over the life of the project. Project milestones should be identified along the timeline. Milestones should be well described, quantifiable, and scientifically justified. The NHLBI will use the milestones, the annual progress reports, and other measures of productivity and success to judge the progress, impact, and value of the program.

The immense amount of data generated from this FOA lends itself to collaborative analysis efforts.  Investigators are encouraged to establish collaboration and are required to share cell lines, protocols, phenotypic, environmental and genotypic data with the scientific community, with appropriate protections for participant confidentiality.  Ultimately, data and cell lines generated in this program will be made available to the greater scientific community through dbGAP or other suitable database and a publicly accessible repository.  Plans for sharing and public access to data and cell lines generated in this program should be stated in the application; final plans must be mutually agreed upon by the steering committee and NHLBI staff.  Early and open access to data and cell lines generated through this program is desirable.  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. 

2.  Steering Committee for Overall Program

The Steering Committee for the entire program, comprised of each PI, a Co-PI from each study, and NHLBI Scientific staff will identify issues that have broad applicability across the program.  Initial recommendations regarding program level organization, consistency across studies in areas which would benefit from a coordinated research effort will be made by the Steering Committee.  Such recommendations might involve areas such as standardized aspects of informed consent, data analysis techniques, data sharing and publications policy, sample collection and protocol development.  Applicants should budget for meetings to be held twice a year in Bethesda. 

There is no plan to fund a separate Program Coordinating Center to organize Steering Committee meetings.  Therefore, the task of organizing Steering Committee calls and in person meetings will rotate among funded studies.  Each study will be asked to assume this role for a one-year period.  Each applicant should budget for the cost of organizing monthly Steering Committee teleconference calls and in person meetings twice yearly for a period of one year. 

3.  Observational Safety and Monitoring Board

An independent program-wide Observational Safety and Monitoring Board (OSMB) will be appointed by the Director of NHLBI.  Members of the OSMB will advise the Institute regarding protocol safety, participant burden and successful achievement of milestones for each project.  Each study should budget for the PI and one Co-PI to travel to Bethesda once a year to attend OSMB meetings.

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

Section II. Award Information


1. Mechanism of Support

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

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

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

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

2. Funds Available

NHLBI intends to commit approximately $76 million in total costs over a 5-year period to fund 5-8 new grants in response to this FOA.  Applicants may request a project period up to five years.  Each budget year may not exceed the following direct cost thresholds: Year One $500,000, Year Two $825,000, Years Three, Four and Five $1,500,000. The total direct cost threshold must not exceed $5,825,000 and total cost must not exceed $9,500,000 for each applicant over the entire project period.

The estimated amount of funds available for support of 5-8  projects awarded as a result of this announcement is $6 million for fiscal year 2011. Future year amounts will depend on annual appropriations.

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

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

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her 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 program support.

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

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

Multidisciplinary research teams should be formed and include personnel with expertise including but not restricted to stem cell biology, clinical medicine, epidemiology, population and statistical genetics, network modeling,  bioinformatics, cell biology, genomics, and molecular profiling.  Each Phase of the grant will require different expertise and may be lead by a different PI.  Coordination between the phase specific teams and overall leadership plans should be outlined in the research plan for each phase.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

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

Required: Resubmission applications are not permitted in response to this FOA. 

Renewals. Renewal applications are not permitted in response to this FOA. 

Section IV. Application and Submission Information


1. Address to Request Application Information

The current 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

Prepare all applications using the PHS 398 application forms and in accordance with the PHS 398 Application Guide (http://grants.nih.gov/grants/funding/phs398/phs398.html).

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

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

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

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from foreign organizations must:

In addition, for applications from foreign organizations:

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

Applications with Multiple PDs/PIs 

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

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

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, the section of the Research Plan entitled “Multiple PD/PI Leadership Plan”, must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators. 

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

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

3. Submission Dates and Times

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

3.A. Receipt, Review and Anticipated Start Dates
Letter of Intent Receipt Date: May 17, 2010
Application Receipt Date:  June 15, 2010
Peer Review Date: November 2010
Council Review Date: January 2011
Earliest Anticipated Start Date: April 2011

3.A.1. Letter of Intent

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

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

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Director, Office of Scientific Review
Division of Extramural Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 7214, MSC 7924
Bethesda, MD 20892-7924
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 forms found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

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

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

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

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


3.C. Application Processing

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

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

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

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at NIH Grants Policy Statement.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: 1) are necessary to conduct the project, and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)

6. Other Submission Requirements

Applications should address all three phases of research.  Applicants must include Phases II and III in their research plan.  Applications will be considered non-responsive if they only include Phase I and/or Phase II.  Clear expertise in stem cell biology, generation and differentiation of iPS cell lines must be demonstrated in Phases I and II.  Expertise in clinical sciences, epidemiology, genomics, biostatistics, and bioinformatics should be demonstrated in the design and execution of all three phases.  Different teams and/or PIs may lead different phases.  Clear coordination and leadership must be demonstrated across the three phases.

A Timeline and Milestones section must be included in the Specific Aims of the research plan and will be included in the page limit for the Research Plan. The timeline should describe the expected progression of the research activities over the life of the project. Project milestones should be identified along the timeline. Milestones should be well described, quantifiable, and scientifically justified. The milestones should be regarded as criteria for evaluating the progress and direction of the research project and should not be just a restatement of the specific aims. During the project period, the applicant will be expected to refer to these milestones in his or her annual progress reports. The NHLBI will use the milestones, the annual progress reports, and other measures of productivity and success to judge the progress, impact, and value of the program. Applicants should write the milestones assuming that a scientifically literate non-expert will use them to evaluate the progress that has been achieved. Applications lacking this information will be not be reviewed.

Because each phase of the project is an individual component and requires different expertise, each component/phase may have up to 12 pages for the research plan.  Thus, for this RFA, the maximum number of pages devoted to the research plan in the entire grant application is 36 if all three phases are included.   

Awards will be made as cooperative agreements (U01s).  Therefore, awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information."  Interaction among the participating investigators will be required, as well as significant involvement from NHLBI, over a five-year period to accomplish the program aims.  A Steering Committee, comprised of each PI, a Co-PI from each study, and NHLBI Scientific staff, will identify issues that have broad applicability across the program.  Initial recommendations regarding program level organization, consistency across studies in areas which would benefit from a coordinated research effort will be made by the Steering Committee.   Applicants should budget to attend  meetings to be held twice a year  There is no plan to fund a separate Program Coordinating Center to organize Steering Committee meetings.  Therefore, the task of organizing Steering Committee calls and in person meetings will rotate among funded studies.  Each study will be asked to assume this role for a one year period.  Each applicant should budget for the cost of organizing monthly Steering Committee teleconference calls and in person meetings twice yearly in Bethesda for a period of one year.

PHS398 Research Plan Sections

All application instructions outlined in the PHS398 Application Instructions are to be followed, with the following additional requirements:

Budget

This FOA uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). 

Appendix Materials

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

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

Resource Sharing Plan(s)

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

(a) Data Sharing Plan: Investigators seeking $500,000 or more in direct costs in any year are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

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

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

The Scientific Review panel will assess the reasonableness of the resource sharing plan or the rationale for not sharing resources. However, reviewers will not factor the proposed resource sharing plan into the determination of scientific merit or the priority score.  The assessment of the review committee will be considered by Program staff of the funding organization when making recommendations about funding applications.  The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590). See Section VI.3., “Reporting.”

Specific Instructions for Foreign Applications

All foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096.

Section V. Application Review Information


1. Criteria

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

2. Review and Selection Process

Review Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NHLBI and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

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

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability.  As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system. 

Overall Impact

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five scored review criteria, and additional review criteria (as applicable for the project proposed). 

Scored Review Criteria

Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each.  An application does not need to be strong in all categories to be judged likely to have major scientific impact.  For example, a project that by its nature is not innovative may be essential to advance a field.

Significance.  Does the project address an important problem or a critical barrier to progress in the field?  If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved?  How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s).  Are the PD/PIs, collaborators, and other researchers well suited to the project?  If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training?  If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?  If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation.  Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions?  Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense?  Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach.  Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?  Are potential problems, alternative strategies, and benchmarks for success presented?   If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment.  Will the scientific environment in which the work will be done contribute to the probability of success?  Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed?  Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? 

Additional Review Criteria

As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

Protections for Human Subjects.  For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects  and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children.  When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals.  The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information, see http://grants.nih.gov/grants/olaw/VASchecklist.pdf.

Biohazards.  Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmission Applications.  Resubmission applications are not permitted for this FOA.

Renewal Applications.  Renewal applications are not permitted for this FOA.

Revision Applications.  Revisions are not allowed for this FOA.

Additional Review Considerations

As applicable for the project proposed, reviewers will address each of the following items, but will not give scores for these items and should not consider them in providing an overall impact/priority score.

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

Select Agents Research. Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans.  Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable:  1) Data Sharing Plan (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

Budget and Period Support.  Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Selection Process

The following will be considered in making funding decisions:

NIH considers the following in evaluating Center grant applications:

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information


1. Award Notices

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

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

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

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The Cooperative Agreement “Kiosk” may also be a useful resource (see http://db2dev.od.nih.gov/oer/programs/coop/index.htm)

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

2.A. Cooperative Agreement Terms and Conditions of Award

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

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

2. A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for all aspects of the study, including study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the Steering Committee.

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

2. A.2. NIH Responsibilities

An NIH Project Scientist [or “Project Coordinator,” or “Project Collaborator,” or “Intramural Scientist”] will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. The NHLBI Project Scientist will serve on the Steering Committee; NHLBI scientist(s) may serve on other study committees, when appropriate.  The NHLBI Project Scientist (and other cited NHLBI scientists) may work with awardees on issues before the Steering Committee, and as appropriate, other committees, for example: development and implementation of data and sample sharing plans, informed consent issues, sample collection, protocol development, quality control, data analysis and publication, and preparation and development of solutions to major problems such as efficiency and yield of iPS differentiation protocols.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

2.A.3. Collaborative Responsibilities

Awardee(s) agree to governance, through voting and decision making, of the program through a Steering Committee.  Steering Committee voting membership shall consist of the principal investigators (i.e., the cooperative agreement awardees)  and the NHLBI Project Scientist.  Monthly meetings of the Steering Committee will ordinarily be held by telephone conference call.  In person meetings should be held twice yearly in Bethesda.

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.

2.A.4. Dispute Resolution 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 Dispute Resolution. A Dispute Resolution 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 dispute resolution procedure does not alter 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 the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

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

Section VII. Agency Contacts


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

1. Scientific/Research Contacts:

Cashell E. Jaquish, Ph.D.
Division of Cardiovascular Sciences  
National Heart, Lung and Blood Institute
National Institutes of Health
Room 8170, MSC 7934
Bethesda, MD 20892-7934
Telephone: (301) 435-0447
FAX: (301) 480-1455
Email: jaquishc@nhlbi.nih.gov

Weiniu Gan, Ph.D.
Division of Lung Diseases
National Heart, Lung and Blood Institute
Two Rockledge Center, Suite 10164
6701 Rockledge Dr. MSC 7952
Bethesda, Maryland 20892-7952
Telephone:  (301) 435-0202
Email:  ganw2@nhlbi.nih.gov

Pankaj Qasba, Ph.D.
Program Director,
Blood Diseases Branch
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute, NIH
6701 Rockledge Dr, MSC 7950
Bethesda, MD 20892-7950
Telephone:  301-435-0050 
Fax:  301-480-0867 
E-mail: qasbap@nhlbi.nih.gov

2. Peer Review Contacts:

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

3. Financial or Grants Management Contacts:

Teresa Marquette
Office of Grants Management
Division of Extramural Research Activities

National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 7128, MSC 7926
Bethesda, MD 20892-7926
Telephone: (301) 435-0166 
FAX: (301) 435-5462
Email: marquettet@nhlbi.nih.gov

Section VIII. Other Information


Required Federal Citations

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

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

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

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

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule.

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

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

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

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

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

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

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

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-116.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

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

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

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

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

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

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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

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


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