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: Microbiome of the Lung and Respiratory Tract in HIV-Infected Individuals and HIV-Uninfected Controls (U01)

Announcement Type
New

Request For Applications (RFA) Number: RFA-HL-09-006

Catalog of Federal Domestic Assistance Number(s)
93.838

Key Dates
Release Date: October 31, 2008
Letters of Intent Receipt Date: February 25, 2009
Application Receipt Date: March 25, 2009
Peer Review Date(s): June/July 2009
Council Review Date: August 2009
Earliest Anticipated Start Date: September 30, 2009 
Additional Information to be Available Date (Url Activation Date): Not Applicable
Expiration Date: March 26, 2009

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

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

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

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

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

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

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

Purpose

The purpose of this FOA is to characterize the microbiome of the lung (the airways and airspaces below the glottis as well as the lung parenchyma) alone or in combination with the microbiome of the nasal and/or oropharyngeal cavities in HIV-infected individuals and matched HIV-uninfected controls, including normal healthy controls, using molecular techniques to identify bacteria and if possible other organisms, e.g., viruses, cell-wall deficient organisms, protozoa and fungi.  The investigators should use robust high-throughput technology platforms to create data sets of sufficient quality and depth to allow the analysis of changes of the lung microbiota in HIV progression/complications. Molecular characterization technologies should include 16S rRNA gene sequencing and metagenomic shotgun sequencing.  

The data obtained will be used to examine the impact of changes in the respiratory microbiome on the pathogenesis and progression of HIV disease, HIV-related respiratory complications, and the effects of anti-HIV therapies.

Background  

The entire respiratory tract is constantly exposed to the external environment and serves as the portal of entry for many microbes.  It is in the airways and lungs that numerous pathogens, opportunistic organisms, and commensals first encounter the host defense system.  The characteristics and mix of organisms populating the respiratory tract, coupled with the state of local respiratory defenses (e.g., mechanical, immune, and non-immune) are key factors in determining whether a person remains healthy or develops acute, chronic, or latent infection.  Inflammation in the airways and lungs and how it progresses or is resolved affects not only local immune mediators and primary gas exchange functions, but may also have consequences for the whole immune system and the progression of diseases in other organs.

HIV-infected individuals are at very high risk of developing pneumonias caused by pathogenic and opportunistic microorganisms.  These respiratory infections frequently cause morbidity, and they are often life threatening.  They also may increase the rate of replication of HIV, accelerating the course of HIV disease.   HIV-infected individuals experience decremental losses of lung function following pneumonias which are not observed in normal, HIV-uninfected populations.  Furthermore, lung infections and microbial colonizations are suspected in the etiology of HIV-associated emphysema and pulmonary hypertension.  A new issue that is becoming increasingly more important is that lung infections may play a role in inducing the immune reconstitution syndrome seen in some HIV-infected patients following initiation of multi-drug antiretroviral regimens.

Objectives

Determining the lung microbiome will enable us to learn which microbes are present and where they are located.  Starting from this basic knowledge, we will be able to study how these microbes grow, interact among themselves, relate to other microbial species co-existing in the same niche and with the cells in the lung; and how they are altered by other environmental factors such as the physical environment and cigarette smoke.  This knowledge will enhance our understanding of the role of the lung microbiome in preserving health or causing disease and also in the divergent effects observed in HIV-infected versus uninfected individuals.  Knowledge of the lung microbiome and that of other components of the respiratory tract in health and diseased states may lead to the identification of predictors of disease progression and therapeutic targets for translation into better preventive and treatment strategies.  In the future it may also provide an opportunity to study gene-gene and gene-environment interactions under specific disease conditions and also interactions of the lung microbiome with microbial populations located elsewhere in the respiratory tract or other organs.  This program will support research on the human lung microbiome; animal research will not be supported under this FOA.

Research approaches

Investigators should determine which available technology is most appropriate for the analysis of the lung microbiome, for example, 16S rRNA gene sequencing and/or metagenomic shotgun sequencing.  Protocol consistencies among the groups funded under the FOA should be pursued.

Applicants should determine which sites, specimens, and methods are most suitable for sampling the lung microbiome alone or in combination with the nasal and/or oropharyngeal cavities in HIV-infected patients and HIV-uninfected controls.  In addition to investigating which bacteria may be present, applicants are urged to determine if it is possible to use inexpensive high-throughput methods to obtain good data on viruses, cell-wall deficient organisms, and fungi, and use this methodology and data to address hypothesis driven research questions.  

This is a multidisciplinary, highly collaborative program using the cooperative agreement mechanism (U01).  The grants will be ideal for multiple PIs.  Collaborations, standardization and sharing of data, and sharing and banking of biospecimens will be expected and enabled by a Data Coordinating Center (DCC), a Steering Committee made up of investigators, and NIH program staff.   The DCC will be expected to provide assistance to the Clinical/Sequencing Centers in maintaining quality control, facilitating data sharing, and program coordination. 

The program will require close collaborations among pulmonologists, molecular biologists, microbial geneticists, clinical investigators with access to HIV-infected and control populations, experts in microbiology and microbiome research who have high-throughput sequencing capabilities or access to sequencing centers, informatics experts, computational biologists, biostatisticians, as well as investigators who have expertise in basic and clinical research in HIV disease and infectious diseases.

Applicants must set aside $25,000/year in direct costs in all years for collaborative pilot studies among the FOA-funded Clinical/Sequencing Centers.  These must be outlined briefly in the grant application and will need to be developed in greater detail by the Steering Committee and reviewed and approved by the DSMB, and NHLBI.  The protocols for the pilot collaborative studies would be designed to extend research on the lung microbiome in HIV beyond what can be accomplished at one Clinical/Sequencing site.  The collaborative pilot studies should explore an area of research related to the lung microbiome that would require the population and other resources from at least one other collaborating Clinical/Sequencing Center.  

The Lung HIV Microbiome Program is intended to complement and take advantage of new technologies, especially large-scale sequencing, and the tools and infrastructure developed for the Roadmap Human Microbiome Project (HMP).  The mission of the HMP is to generate resources to enable comprehensive characterization of the human microbiota and analysis of its role in human health and disease.   This proposed NHLBI FOA is designed to explore an area that is not a current focus of the HMP. 

Applicants are strongly urged to form collaborations with Roadmap HMP investigators and when possible to leverage resources generated by the HMP Program.  Applicants should identify existing or readily accessible sets or collections of donor/samples, consented in a way consistent with HMP guidelines.

Applicants are urged to use resources available through the Clinical Translational Science Award (CTSA) program at their institutions, or through collaborations, to obtain additional expertise and reduce costs. 

Applicants are encouraged to form collaborations with investigators supported under the Longitudinal Studies of HIV-Associated Lung Infections and Complications program, RFA HL-07-008, who are conducting longitudinal investigations of HIV-related lung complications in HIV-infected cohorts http://www.lunghiv.com/.  Another resource that applicants are encouraged to use is the Lung Tissue Research Consortium (LTRC) http://www.ltrcpublic.com/.

Research topics

The following are examples of research topics responsive to this FOA.  These are examples only; applicants should not feel limited to the subjects mentioned and are encouraged to submit other topics pertinent to the objectives of this FOA.  

Research topics related to the Lung HIV Microbiome Program’s primary research aims (i.e., characterization and investigation of the lung microbiome in HIV-infected individuals and appropriately matched HIV-uninfected controls using molecular techniques) should be applicable to multicenter research, should address issues of clinical significance, and have a high potential to inform clinical practice.

Selected Research Examples:

Organization of NHLBI’s Microbiome of the Lung in HIV Program (Lung HIV Microbiome)

The Lung HIV Microbiome Program will be a cooperative network of up to four Clinical/Sequencing Centers, one Data Coordinating Center (DCC), and the Division of Lung Diseases, NHLBI.

Each Clinical/Sequencing Center is encouraged to use the multiple Principal Investigators (PI) option (see  http://grants.nih.gov/grants/multi_pi/index.htm); each Clinical/Sequencing Center is expected to  be comprised of a partnership between a lead Principal Investigator with expertise in pulmonary disease, especially HIV-associated pulmonary diseases and one or more lead Principal Investigators with expertise in microbiology and/or molecular techniques, genomics, metagenomic approaches and other high-throughput sequencing, or analytic, bioinformatics, and computational techniques, applicable to investigating the human microbiome.

The lead Principal Investigators may be from either the same institution or different institutions.  Clinical/Sequencing Centers may also include satellite recruitment and protocol implementation sites (that is, additional recruitment sites at a different location from the Clinical/Sequencing Centers).

Program Coordination

The studies supported by this FOA will not use a common study protocol. However, after awards are made, investigators may wish to collaborate on developing and reporting using standardized definitions and criteria (e.g. pneumonia, pulmonary hypertension, categorizing microbes) and variables, such as pulmonary function tests, chest computed tomography, smoking status, quality of life, and population characteristics.   The use of common study variables, criteria, and protocols to facilitate meta-analysis of the studies when possible is highly encouraged.

Investigators should indicate in their application their willingness to collaborate on the development and use of standardized protocols, where applicable, identification of diagnostic and other criteria, methods, data analysis, and their willingness to collaborate with NHLBI program staff in all aspects of the study. The cooperative agreement mechanism will be used and a Steering Committee formed to facilitate collaboration (see Section VI.2.A, Cooperative Agreement Terms and Condition of Award.)

Each awardee is responsible for all aspects of conducting the research.

A Data Safety Monitoring Board (DSMB) will be responsible for monitoring the funded projects and will report to the Director of the NHLBI. Therefore, applicants should not appoint DSMB members in advance of the peer review, or even inquire about the interest of possible DSMB members, because anyone so contacted would not be eligible to serve as a member of the peer review committee that will evaluate the applications for scientific merit.

The NHLBI - will be substantially involved with the awardees in a partnership. The NHLBI Program Scientist will monitor patient recruitment and study progress, ensure a policy for the disclosure of conflicts of interest, and assure adherence to NHLBI policies. NHLBI will appoint a DSMB and appoint a chairperson of the Steering Committee.  The Steering Committee will be an important body for this project. 

Clinical/Sequencing Centers - Clinical/Sequencing Centers will be responsible for conducting their own individual project proposed in their grant applications and for participating in the development and prioritization of common protocols for harvesting biospecimens and for genetic analysis of the lung microbiome.  Each Clinical/Sequencing Center must be able to design their project and be able to store the biospecimens and store and analyze the data generated.  The Clinical/Sequencing Centers will be required to collaborate with the DCC and the other Clinical/Sequencing centers that are part of the Lung HIV Microbiome Program.   Applicants must agree to share data and biospecimens.  They will be responsible for conducting the research (subject recruitment and implementation of all study procedures), analyzing and interpreting research results, and disseminating research findings.  Clinical/Sequencing Centers will also be responsible for working with the DCC to develop common definitions and setting milestones.   Each Clinical/Sequencing Center will be required to participate in a cooperative and interactive manner with all other Clinical/Sequencing Centers and the DCC in all aspects of the program.

Both the Clinical/Sequencing site and staff and the DCC staff must have appropriate training and experience for working safely with biologically hazardous specimens that may contain HIV and other dangerous microbial agents.  They must indicate which steps they will take to safely acquire, process, ship, store, and distribute biologically hazardous specimens that contain HIV and other infectious agents.

Each awardee will be required to attend Steering Committee meetings in which study plans, findings, and issues of common interests and concerns will be shared and discussed. Each applicant must include in his/her budgets funds for attending these meetings. For budgeting purposes, the applicants should assume that, in-person meetings will be convened three times during the first funding year and twice a year for each funding year thereafter.  Applicants should assume for budgeting purposes that the meetings will be for two days in the Washington, DC, metro area and will require the attendance of the Principal Investigators and one other person.  Funds should also be included for the two principal investigators to attend a one day meeting of the DSMB in Bethesda, Maryland each year.

The Data Coordinating Center (DCC) - The DCC will support the individual projects at each of the sites and will support the development and implementation of the agreed upon common protocols at each of the sites.  The DCC will be responsible for keeping an inventory of all biospecimens collected at the various centers.  The DCC will need expertise in the management and analysis of large data sets (e.g., metagenomic datasets) and be able to store and manipulate these so that they will be able to support the Clinical/Sequencing Centers collaborations with other sites supported by the FOA and with other programs and investigators, e.g., the Roadmap HMP.  The DCC will provide support for quality control, especially for collaborative protocols.  The DCC will also coordinate all meetings and conference calls including preparation of printed materials to be used at the meetings/conference calls.

The DCC will initiate and coordinate activities to promote standardization of lung microbiome research vocabularies and methodologies and coordinate Lung HIV Microbiome activities with NHLBI bioinformatics programs.  These should be developed to be compatible with Roadmap HMP whenever possible. 

The DCC will be responsible for arranging meetings and conference calls, preparing reports, implementing a web-based system to coordinate joint program activities, and facilitating the sharing of data and specimens.  The DCC will provide data management and quality control, develop forms, and maintain common data sets.  The DCC will be expected to provide statistical support in designing and conducting collaborative protocols and in analyzing data.  The DCC will also support specimen banking activities, as needed, and activities associated with preparing and submitting presentations and publications. The DCC will provide support to the Clinical/Sequencing Centers in monitoring the milestones developed by the investigators.

The DCC will provide editorial and meeting coordination for manuscript preparation, coordination of the activities of the Steering Committee, Data and Safety Monitoring Board (DSMB), and overall study coordination and quality assurance.

The DCC staff should have appropriate expertise and experience in project management, genomics, genomic sequencing data collection, biostatistics, epidemiology, database management, and sample collections.  Prior experience in complex collaborative studies is desired.  The DCC Principal Investigator and other key staff should have knowledge of HIV/AIDS, pulmonary clinical studies, repositories, and microbiome research.  The DCC is expected to have online data entry capabilities; analytic and computational modeling; informatics expertise; and expertise in web-based data management.

Applicants for the centralized DCC should present a description of plans to:  (1) provide data management, including quality control and development of forms; (2) maintain a common data set; (3) develop needed databases and implement a web-based system to coordinate program activities; (4) provide statistical support; (5) provide support in designing and conducting joint protocols; (6) support specimen banking activities; (7) provide support for preparing and submitting joint presentations and joint publications; (8) provide coordination of meetings and reports as needed; (9) provide administrative support services for a DSMB for the Clinical/Sequencing Centers (estimate 4 centers); and (10) provide assistance for interacting and harmonizing with Roadmap HMP projects.   The application should include funds to support the DSMB. 

Applications for the DCC may be submitted by individuals located at the same institution as an applicant for a Clinical/Sequencing Center site grant submitted under this FOA, but an individual may not be the Principal Investigator of a Clinical/Sequencing Center grant and the DCC.

For budgeting purposes, the applicants should assume that, in-person steering committee meetings will be convened three times during the first funding year and twice a year for each funding year thereafter.  Applicants should assume for budgeting purposes that the meetings will be for two days in the Washington, DC, metro area and will require the attendance of the Principal Investigator and three other persons.

The DCC is also responsible for covering the costs for DSMB teleconferences and in-person meetings (includes travel of the DSMB members to the meeting and honorarium).  These should be included in the DCC budget.  For budgeting purposes the it is anticipated that the  DSMB, estimated to include 5-7 members, will meet approximately semi-annually - one telephone conference call and one, one day in-person meeting in Bethesda, Maryland each year.

A Steering Committee (SC) Awardee(s) agree to the governance of the study through a Steering Committee.  The Steering Committee will be composed of the Principal Investigators of the Clinical/Sequencing Centers (both the clinical and sequencing segments), the Data Coordinating Center (DCC), and the NHLBI Project Scientists. The NHLBI will appoint a Study Chair who may be independent of the Clinical/Sequencing Centers and the DCC to preside over Steering Committee meetings and serve as the Steering Committee representative.  All major scientific decisions will be determined by majority vote of the Steering Committee.   Each Clinical/Sequencing Center, the DCC, the NHLBI will have one vote; the Study Chair will have a vote in case of a tie vote among the other Steering Committee members.  Note that although each Clinical/Sequencing Center’s two or more lead Principal Investigators are expected to participate in all Steering Committee meetings, each Clinical/Sequencing Center has just one vote. 

It is anticipated that the Steering Committee will meet at least once a month by telephone conference call – subcommittees may have more frequent calls, as needed - and it is anticipated that the Steering Committee will meet two-three times a year in-person.  The Steering Committee will have primary responsibility for the general organization of the Lung HIV Microbiome Program, standardizing vocabulary, methodology, and forms, prioritizing proposed topics for joint investigations, finalizing protocols, facilitating the conduct and monitoring of the studies, reporting study results in a timely manner, and working with the NHLBI to promote dissemination of the findings.  Topics for the joint protocols will be proposed and prioritized by the Steering Committee.  

The entire Steering Committee will provide input and will be responsible for assuring development of a common protocol(s) in areas to be implemented by the Clinical/Sequencing Centers.  The Steering Committee has final responsibility for approving joint protocols and protocol revisions before review by the DSMB.

Subcommittees of the Steering Committee will be established to perform specific functions as needed.

An independent Data Safety and Monitoring Board (DSMB) A Data and Safety Monitoring Board will be appointed by the Director, NHLBI to provide overall monitoring of progress, interim data and safety issues; the Steering Committee will nominate members for this Board.   An NHLBI scientist other than the NHLBI’s Lung HIV Microbiome Program Scientists will serve as the Executive Secretary to the DSMB.  An independent Review Committee, established by the NIH, will provide peer review for technical aspects of the program and for new protocols. Because the Board serves as an independent group advisory to the NIH, study investigators will not communicate with Board members regarding study issues, except as authorized by the Board’s Executive Secretary. 

The Monitoring Board will meet approximately semi-annually by telephone conference call or in-person meetings in Bethesda, Maryland.

The collaborative protocol and governance policies will call for the continued submission of data centrally to the coordinating center for a collaborative database; the submittal of copies of the collaborative datasets to each principal investigator upon completion of the study; procedures for data analysis, reporting and publication; and procedures to protect and ensure the privacy of medical and genetic data and records of individuals. The NIH Project Scientist, on behalf of the NIH, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the Steering Committee.

Applicants for both the Clinical/Sequencing Centers and the Data Coordinating Center are encouraged to establish links and utilize existing resources including those listed below, but other resources not mentioned here may also be appropriate. 

Links to

NIH Roadmap Human Microbiome Project (HMP) http://nihroadmap.nih.gov/hmp/grants.asp

The Lung Tissue Research Consortium (LTRC) http://www.ltrcpublic.com/.

Longitudinal Studies of HIV-Associated Lung Infections and Complications program, RFA HL-07-008 http://www.c-tasc.com/Projects.html

Clinical and Translational Science Awards (CTSA) http://www.ncrr.nih.gov/clinical_research_resources/clinical_and_translational_science_awards/funding_guidelines.asp

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 Cooperative Agreement U01 award mechanism(s). 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."

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). 

2. Funds Available

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

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

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

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

Each Clinical/Sequencing Center is recommended to use the multiple Principal Investigators (PI) mechanism.  Each Clinical/Sequencing Center is expected to be comprised of a leadership team that includes at least a Principal Investigator with expertise in pulmonary disease, especially HIV-associated pulmonary diseases, and one or more lead Principal Investigator(s) with expertise in microbiology and/or molecular techniques, genomics, metagenomic approaches and other high-throughput sequencing, or analytic, bioinformatics, and computational techniques, applicable to investigating the human microbiome.   These investigators may be from either the same institution or different institutions.    

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

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

Renewal applications are not permitted in response to this FOA

No animal studies permitted in response to this FOA.

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

Section IV. Application and Submission Information


1. Address to Request Application Information

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

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

2. Content and Form of Application Submission

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

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

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

Foreign organizations are not eligible to apply to this FOA, however, domestic institutions may form consortia and enter into subcontracts with Non-domestic (non-U.S.) entities (Foreign Organizations) if need can be demonstrated – foreign subcontracts use the same criteria as are used for justifying foreign grants.

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

Applications from foreign organizations must:

In addition, for applications from foreign organizations:

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

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs 

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

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

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

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

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

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

3. Submission Dates and Times

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

3.A. Receipt, Review and Anticipated Start Dates
Letter of Intent Receipt Date: February 25, 2009
Application Receipt Date: March 25, 2009
Peer Review Date(s): June/July 2009
Council Review Date: August 2009
Earliest Anticipated Start Date: September 30, 2009

3.A.1. Letter of Intent

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

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

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

The letter of intent should be sent to:

Chief, Review Branch
Division of Extramural Research 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 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).

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 Research 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.C. Application Processing

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

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

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

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

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

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

6. Other Submission Requirements and Information

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

Qualifications and Experience. An appropriate time commitment is expected from the Principal Investigators and any co-investigators at each Clinical Center. Because the Lung HIV Microbiome Program Clinical/Sequencing Centers will use the multiple PI option, a Leadership Plan must be included in the research plan section of the application (see below).  Use of multiple PIs is strongly suggested.

Collaboration.  Applicants should state their general support of collaborative research and their willingness to participate in a collaborative and interactive manner with other Clinical Centers, the Data Coordinating Center, and the NHLBI in all aspects of the Lung HIV Microbiome Program.  Applicants are encouraged to describe any special expertise or unique strengths they can offer to the collaborative effort (e.g., innovative study design, genetics/genomics, bioinformatics, computational biology, team leadership, and dissemination activities).

Applicants must agree, if awarded, to accept the “Cooperative Agreement Terms and Conditions of Award” in Section VI. 2. A.  “Award Administration Information.”

Applicants should indicate their willingness to attend all Steering Committee and other meetings, which may include conference calls at least once a month and in-person meetings at least 2-3 times a year.

Clinical/Sequencing Center applicants should be able to interact with the Data Coordinating Center to transmit and edit data and should discuss their capability to participate in a distributed data entry system.

Study Population.  Applicants should demonstrate (with reference to specific, objective sources of data on the size of the available population[s]) access to a sufficient number of patients to accomplish their proposed protocols.  The application should include a description of the pool of potential study participants, including the age range, ethnic/racial and gender distributions and recruitment sources.

The application should include a brief description of anticipated problems with recruitment and plans for addressing these problems, including letters of support if additional groups will be used.  Note that proposed solutions to recruitment problems may not include requesting additional funds.  

Links with NIH resource centers.  Applications from institutions that have a General Clinical Research Center (GCRC) or Clinical and Translational Science Award (CTSA) funded by the NIH National Center for Research Resources should identify the resources that could be available to support the proposed Lung HIV Microbiome Program Clinical/Sequencing Center, commenting particularly on those aspects that will enhance their programmatic and scientific efficiency.  In such a case, a description of the GCRC or CTSA and how the applicant proposes interacting with it should be included, as well as a letter of agreement from either the GCRC/CTSA Program Director or PI.

Applicants should indicate how they link to other NIH-supported programs including the Roadmap Human Microbiome Project, NHLBI-supported AIDS research programs such as HL-07-008 - Longitudinal Studies of HIV-Associated Lung Infections and Complications, the NHLBI Lung Tissue Research Consortium (LTRC), NHLBI-supported COPD research studies, and NIAID-supported AIDS cohort research programs.

Research Plan Page Limitations

Research Plan: Applicants should submit a research plan with the following subsections: Multiple PI Leadership Plan, Research Protocol Plan, Data and Biospecimen sharing plan, Dissemination Plan, and Budget.    

Subsection 1: Multiple PI Leadership Plan (maximum 2 pages). The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts.  The roles and administrative, technical, and scientific responsibilities for the program should be delineated for the PIs and other collaborators.  If budget allocation is planned, the distribution of resources to specific components of the project or the individual PIs should be delineated (in the event of an award, the requested allocation may be reflected in a footnote in the NOGA). See the Multiple Principal Investigator website for more information http://grants.nih.gov/grants/multi_pi/index.htm.

Subsection 2: Research Plan (maximum total 27 pages)

Subsection 3: Dissemination Plan.  The Data Coordinating Center will be responsible for coordinating the dissemination of Lung HIV Microbiome research findings and relevant protocol materials.  Accordingly, the DCC applicants in response to this FOA will propose a dissemination plan.  Clinical/Sequencing Center applicants to this FOA for Lung HIV Microbiome Program should indicate here their willingness to collaborate with the DCC and other Steering Committee members in dissemination efforts (preferably less than, but no more than, a maximum of 1 page).    

Subsection 4:  Budget Plans.  Budget:  Applicants should consider the following issues regarding Clinical/Sequencing Center budgets.  All costs in the proposed budget should include appropriate justification.  If an application proposes PIs from separate institutions, the application should use the traditional subcontract mode with appropriate budgets. Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

For multiple PIs, if budget allocation is planned, the distribution of resources to specific components of the project should also be delineated in the leadership plan.  In the event of an award, the requested allocations may be reflected in a footnote on the NOGA.  

All Lung HIV Microbiome Program awards will be subject to administrative review annually through the NIH non-competing continuation (Type 5) reports.  More frequent review will be performed if necessary.  The DSMB will provide advice to the Institute on progress towards achieving sequencing milestones, progress in recruitment, follow-up, data acquisition, data and biospecimen management and sharing, protocol changes, quality control, adequacy of power, safety and confidentiality.  Continuation and level of funding for each grant will be based on overall performance.

Summary of Page Limitations:

Leadership Plan - 2 pages
Research Plan - 27 pages
Dissemination Plan – 1 page

Applications received that exceed these page limitations will be returned without review.

Appendix Materials

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

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

Resource Sharing Plan(s)

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

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief one-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/.

All Data Coordinating Center applicants in response to this FOA are expected to include a plan for sharing research data and submitting Genome-Wide Association Studies data to the NIH-designated GWAS data repository.  All Clinical/Sequencing Center applicants in response to the Lung HIV Microbiome Program FOA (RFA HL-09-006) are expected to indicate their willingness to participate in data sharing and submitting Genome-Wide Association Studies (GWAS) data to the NIH-designated GWAS data repository in accordance with the NIH GWAS policy. 

The precise content of the data-sharing plan ultimately developed by the Data Coordinating Center will vary, depending on the data being collected and how the investigators in the Steering Committee are planning to share the data.  The reasonableness of the data-sharing plan proposed by the Data Coordinating Center applicants 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.

It is expected that Lung HIV Microbiome Program research resources such as Manual of Operations, study manuals, forms, microbial sequence data, will be made available to the public after publication of study findings (e.g., through the National Technical Information Service, see http://www.ntis.gov/index.aspx).

The Data Coordinating Center applicants will include a plan for sharing these resources.   Clinical/Sequencing Center applicants in response to this FOA should indicate here their willingness to cooperate with this resource sharing.

Specific Instructions for Foreign Subcontracts

All foreign subcontracts must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096, August 23, 2006.

Section V. Application Review Information


1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

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

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by 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 following will be considered in making funding decisions:

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, and weighted as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a meritorious priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? For applications designating multiple PDs/PIs, is the leadership approach, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PDs/PIs? Is it likely that the projects proposed in the application can be completed within the five year time-frame of the FOA?

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 PD/PI(s) and other key personnel 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? Do the PD/PI(s) and investigative team bring complementary and integrated expertise to the project (if applicable)? Does the Leadership Plan for Multiple PIs describe a strong organizational structure for the leadership team?

Environment: Do(es) the scientific environment(s) 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 rating:

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

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan section on Human Subjects in the PHS 398 instructions).

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

Applications including foreign consortia: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed.  This applies only to foreign subcontracts proposed in applications submitted by domestic organizations in response to this FOA.  Grant applications from foreign organizations will not be accepted.

2.C. Resource Sharing Plan(s)   

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

3. Anticipated Announcement and Award Dates

Earliest Anticipated Start Date: September 30, 2009  

Section VI. Award Administration Information


1. Award Notices

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

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

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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

2. Administrative and National Policy Requirements

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/archive/grants/policy/nihgps_2003/index.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

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

2.A. Cooperative Agreement Terms and Conditions of Award

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

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

2. A.1. Principal Investigator Rights and Responsibilities

The PD(s)/PI(s) will have the primary responsibility for all aspects of the study, including any modification of 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 recommendation of the Steering Committee. 

Study investigators are encouraged to publish and to release publicly and disseminate results and other products of the study, in accordance with study protocols and governance. Within three years of the end of the period of NIH support for the project, data not previously released and other study materials or products not previously distributed are to be made available to individuals who are not study investigators, provided such release is consistent with the study protocol and governance and with 2.A.2, paragraph 3 below. In addition, study investigators must establish a plan for making data sets and materials available to the scientific community and to the NIH immediately upon completion of the three year period following the end of the period of NIH support.

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 DHHS, PHS, and NIH policies.

2. A.2. NIH Responsibilities

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

The NIH Project Scientist will serve on the Steering committee; he/she or other NIH scientists may serve on other study committees, when appropriate. The NIH Project Scientist (and other NIH scientists) may work with awardees on issues coming before the Steering Committee and, as appropriate, other committees, e.g., recruitment, intervention, follow-up, quality control, adherence to protocol, assessment of problems affecting the study and possible changes in protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment.

Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property issues is assigned to NHLBI staff other than the Project Scientist. The responsibility for final decision making may reside with Senior Institute management, separate organizational components and/or oversight committees. Because it is anticipated that the Project Scientist will participate in activities that rise to a level of involvement that results in conflicts of interest, for example, co-publication, etc., other staff members such as direct line supervisors and/or other Senior NHLBI Program management staff will serve as agency Program Officials and will be responsible for the normal scientific and programmatic stewardship of the award. The NHLBI policy on authorship and manuscript review of NHLBI sponsored extramural research protects against conflicts of interest with the Program Officer.

The NIH reserves the right to withhold funding or curtail the study (or an individual award) in the event of (a) failure to develop or implement  independent, site specific, or  mutually agreeable collaborative protocols; (b) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (c substantive changes in the agreed-upon protocols;  or (d) human subject ethical issues.

Support or other involvement of industry or any other third party in the study -- e.g., participation by the third party; involvement of study resources or citing the name of the study or NIH support; or special access to study results, data, findings or resources – may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NIH.

Additionally, an agency program official or NIH 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 the governance of the study through a Steering Committee. Steering Committee voting membership shall consist of the principal investigators (i.e., cooperative agreement awardees), the NIH Project Scientist, and the Chairperson. Meetings of the Steering Committee will ordinarily be held by telephone conference call or in the metropolitan Washington D.C. area. 

A Data and Safety Monitoring Board will be appointed by the Director, NHLBI, to provide overall monitoring of interim data and safety issues; the Steering Committee will nominate members for this Board. Meetings of the Data and Safety Monitoring Board will ordinarily be held in Bethesda. An NIH scientist other than the NIH Project Scientist shall serve as Executive Secretary to the Board.  An independent Review Committee, established by the NIH, will provide peer review for technical aspects of the program and new protocols. Because the Board serves as an independent group advisory to the NIH, study investigators will not communicate with Board members regarding study issues, except as authorized by the Board’s Executive Secretary.

The collaborative protocol and governance policies will call for the continued submission of data centrally to the coordinating center for a collaborative database; the submittal of copies of the collaborative datasets to each principal investigator upon completion of the study; procedures for data analysis, reporting and publication; and procedures to protect and ensure the privacy of medical and genetic data and records of individuals. The NIH Project Scientist, on behalf of the NIH, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the Steering Committee.

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. Arbitration Process

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

Sandra Colombini Hatch, M.D.
Lung Biology and Disease Branch
Division of Lung Diseases
National Heart, Lung and Blood Institute
6701 Rockledge Dr. MSC 7952
Bethesda, Maryland 20892-7952
Telephone:   (301) 435-0222
Fax: (301) 480-3557
Email:   Hatchs@nhlbi.nih.gov

Hannah H. Peavy, M.D.
Lung Biology and Disease Branch
Division of Lung Diseases
National Heart, Lung and Blood Institute
6701 Rockledge Dr. MSC 7952
Bethesda, Maryland 20892-7952
Telephone:   (301) 435-0222
Fax: (301) 480-3557
Email:   peavyh@nhlbi.nih.gov

2. Peer Review Contacts:

Chief, Review Branch
Division of Extramural Research 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:

Ms. Ryan Lombardi
Division of Extramural Research Activities

National Heart, Lung, and Blood Institute
Room 7154, MSC 7926
6701 Rockledge Drive
Bethesda, MD 20892-7926 (Express zip: 20817)
Telephone: (301) 435-0144
FAX: (301) 451-5462
Email: lombardr@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. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/.
Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

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

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

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

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

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

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

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

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

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

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

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

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

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

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The Loan Repayment Program (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 percent of their time (at least 20 hours per week based on a 40-hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.


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NIH Funding Opportunities and Notices


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