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: Clinical Centers for the Severe Asthma Research Program (SARP) (U10)

Announcement Type
New

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

Request For Applications (RFA) Number: RFA-HL-11-018

Catalog of Federal Domestic Assistance Number(s)
93.838

Key Dates
Release Date: May 26, 2010
Letters of Intent Receipt Date: September 15, 2010
Application Receipt Date: October 15, 2010
Peer Review Date: March 2011
Council Review Date: May 2011
Earliest Anticipated Start Date: July 1, 2011 
Additional Information To Be Available Date (Url Activation Date): Not Applicable
Expiration Date: October 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

Asthma affects 22 million people in the United States.  Although most patients have mild-to-moderate asthma that responds well to treatment, 5-10% exhibit severe disease. These account for more than half of the estimated $19.7 billion annual costs of asthma, which is the 5th most costly chronic disease. Severe asthma is an escalating public health problem world-wide. Severe in contrast to mild-moderate asthma is characterized by continuous rather than episodic symptoms, frequent exacerbations, progressive decline in lung function and limitations to physical activity despite aggressive therapy, including high-dose inhaled and systemic corticosteroids. These patients suffer higher morbidity and mortality, are largely insensitive to available therapies, and endure serious side effects from their intensive yet modestly effective treatments. Current understanding of these complex processes and attendant interactions is limited, thus improvements in care remain elusive.

Accumulating evidence suggests that severe asthma is heterogeneous in several dimensions including age of onset, sex, allergic response, comorbidities, patterns of inflammation, and response to treatment. Recognizing that severe asthma consists of groups of patients with distinct underlying phenotypes has important implications for how to target therapies, but the understanding thus far primarily derives from cross-sectional data. SARP will develop a new paradigm for the understanding of severe asthma and its sub-phenotypes, in children and adults, by defining disease at the molecular and cellular level longitudinally. There is a paucity of information on the evolution of pathobiology and disease presentation over time that makes it difficult to predict clinical course and optimal treatment. Disease definition will be characterized through identification and validation of phenotypic traits that are based on underlying pathobiology and pathophysiology rather than clinical manifestations which can lead to an oversimplified approach to diagnosis and treatment. Definition and phenotyping at the cellular and molecular level over time will provide a comprehensive understanding of the evolution of disease and serve as a rational basis for the design of mechanism-based diagnostic, prognostic and treatment strategies for severe asthma in children and adults.

This funding opportunity announcement (FOA) solicits applications to participate in the NHLBI Severe Asthma Research Program (SARP). The purpose of this new phase of SARP is to promote collaborative, multidisciplinary research using a mechanistic-based temporal approach to achieve the following objectives:

The following are examples of research questions and topics responsive to this FOA; however, applicants are not limited to the subjects mentioned and are encouraged to submit other topics pertinent to the objectives of this FOA.

Program Structure

SARP will include up to six Clinical Centers (CC), one Clinical Coordinating Center (CCC), and a Steering Committee (SC). Voting members of the SC will be principal investigators from the CCs (one vote per CC) and the CCC, the NHLBI project scientist, and the Chair, who will be appointed by NHLBI and vote only to break a tie.

Clinical Centers (CC): Clinical Center applications will propose research questions and strategy requiring a shared longitudinal protocol conducted across all participating centers and which will include common information on all SARP participants as well as research questions and strategy for a mechanistic study which may not require or be feasible in all centers, but will be conducted at the applicant’s center. The final shared longitudinal protocol will be developed or adapted by the Steering Committee from the protocols proposed by the successful applicants. For mechanistic study and longitudinal protocol design/planning purposes, each applicant may assume a multicenter participant pool and accrual pattern as described in this FOA. Mechanistic studies eventually may be combined or participants pooled to address collaborative research questions. Investigators must agree to use common guidelines and manual of procedures developed by the Steering Committee for all SARP studies. The fundamental aim of the research questions is to (1) characterize developmental molecular, cellular, and physiologic phenotypes and to further elucidate the pathobiology and pathogenesis of severe asthma and its sub-phenotypes; and (2) develop an integrated understanding of temporal changes in lung structure and function, pathobiology, exacerbations, asthma control, and quality of life in relation to pharmacotherapy and add dimensions of progression and outcome to our understanding of severe asthma. Cross-sectional studies or therapeutic efficacy trials will not be considered responsive to this FOA. Clinical Center applicants are required to (1) demonstrate current access to at least 50 subjects with severe asthma as defined by the American Thoracic Society (Am J Respir Crit Care Med 2000:162;2341-2351) and (2) demonstrate ability to recruit at least 125 subjects per year - for the first three award years - with persistent asthma as defined by the NAEPP EPR-3 Guidelines for the Diagnosis and Management of Asthma (see http://www.nhlbi.nih.gov/guidelines/asthma/) (60% severe of which 25% are children including preadolescents).

Clinical Coordinating Center (CCC): The CCC will coordinate all SARP administrative and clinical research activities. The CCC Principal Investigator is expected to share in the scientific leadership of the SARP collaboration through the Steering Committee. In addition to activities presented below, it is anticipated that the CCC will enable the performance and productivity of SARP by identifying synergies and points of leverage with other federally sponsored projects (e.g., Clinical and Translational Award sites). The CCC is expected to provide the methodological, analytical, managerial, website, computer systems, logistical, and administrative expertise to support research and operational activities of SARP including: (1) collaborate in the design and analytic plans for a shared longitudinal protocol to be executed by all Clinical Centers; (2) manage and distribute funds to Clinical Centers to conduct the shared longitudinal protocol; (3) provide informatics support that is innovative and flexible to enable operations, administration and research activities; (4) manage and evaluate quality of data received from Clinical Centers and provide relevant reports to NHLBI, Steering Committee (SC) and Data and Safety Monitoring Board (DSMB); (5) monitor and evaluate shared longitudinal protocol execution and subject accrual and provide relevant reports to NHLBI, SC and DSMB; (6) develop manual of procedures for quality control, training and certification, data management, and regulatory compliance; (6) provide logistical support for meetings and teleconferences of the SC and its subcommittees, and DSMB; (7) provide support for preparing and submitting collaborative presentations and manuscripts; and (8) track progress of publications, including PubMed Central reference number, and presentations of findings. Applications for the CCC may be submitted by individuals at the same institution as an applicant for a CC grant under this FOA, but an individual may not be the PI of both a CC and CCC.

The NHLBI will be responsible for overall support, direction and oversight of SARP. The NHLBI Program Office and Office of Grants Management will oversee the overall direction and progress of SARP. In addition to regular grant stewardship, the NHLBI Project Scientist will be involved substantially with the awardees as a NHLBI partner, consistent with the Cooperative Agreement mechanism. The NHLBI will appoint the Data and Safety Monitoring Board, and the Steering Committee Chair.

A Steering Committee (SC) composed of the principal investigators of the Clinical Centers and the Clinical Coordinating Center, and the NHLBI Project Scientist will be the core governing body of SARP. The NHLBI will appoint a Steering Committee Chair to preside over SC meetings and serve as the SC representative. All major scientific decisions will be resolved by majority vote of the SC. Each Clinical Center (independent of multiple PIs), the Clinical Coordinating Center, the NHLBI will have one vote; the Steering Committee Chair will have a vote in case of a tie vote among the other SC members. It is anticipated that the SC will meet two times a month by telephone conference call and up to six times a year by in-person meetings. The SC has final responsibility for approving the longitudinal protocol and budget, and protocol revisions, before review by the DSMB. Subcommittees of the SC will be established to perform specific functions such as Publications and Presentations, Equipment, Quality Control, Regulatory Assurance, and Conflict of Interest Policy. The SC will monitor disclosures of financial interests and potential conflicts of interest among investigators and clinic coordinators according to NHLBI conflict of interest policy (see http://www.nhlbi.nih.gov/funding/policies/coi-res.htm), but such monitoring will not preclude investigators’ responsibility to report their financial disclosures to their respective grantee institutions. Grantee members of the SC will be required to accept and implement policies approved by the SC.

An independent Data and Safety Monitoring Board (DSMB), established by the NHLBI in accordance with NIH policies and with input from the SC, will monitor patient safety and review study performance. The DSMB will consist of a chair, clinicians with expertise in asthma management, scientists with expertise in asthma clinical research, bioethics, and biostatistics. An NHLBI scientist other than the NHLBI’s SARP Project Scientist will serve as the Executive Secretary to the DSMB. The DSMB will meet approximately semi-annually by teleconference or in-person meetings in Bethesda, MD. The DSMB will review serious adverse event reports on an ongoing basis, according to NHLBI policies. Following each meeting, the DSMB will submit recommendations to NHLBI regarding the continuation of clinical research projects. The NHLBI will address the recommendations and prepare a report for principal investigators that can be provided to their institutional review boards.

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 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."  This is a one-time solicitation to fund SARP for six years. It is expected that mechanistic studies and longitudinal protocol will be completed within the six-year time period. Plans beyond the current funding period are indefinite.

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

The total amount of funding that NHLBI expects to award for SARP (for up to six clinical centers and one CCC) is $31.5 million for a project period of six-years. Designated funding levels are subject to change at any time prior to award, due to unforeseen budgetary, administrative, or scientific developments.

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. 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.

Applications are expected to include a multidisciplinary team that is comprised of asthma clinician-scientists and scientists with expertise in areas such as immunology, pulmonary physiology, molecular genetics, molecular phenotyping, imaging, and bioinformatics. The Principal Investigator will be responsible for the scientific and technical direction of the Clinical Center.

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.

Resubmissions.  Resubmission applications are not permitted in response to this FOA.

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

Awards for a Clinical Center and a Clinical Coordinating Center will not be made to the same Principal Investigator to ensure that data analyses and data acquisition are performed independently.  

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.

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: September 15, 2010
Application Receipt Date(s): October 15, 2010
Peer Review Date(s): March 2011
Council Review Date(s): May 2011
Earliest Anticipated Start Date(s): July 1, 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 Research Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 7214, MSC7924
Bethesda, MD 20892-7924 (Express mail 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).

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 Research Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 7214, MSC7924
Bethesda, MD 20892-7924 (Express mail 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

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

Qualifications and Experience. Applicants should describe qualifications and experience in the appropriate narrative sections of the application and in biosketches. Applicants must have the necessary experience (e.g., investigative bronchoscopy, induced sputum, bronchoprovocation challenges) and expertise to conduct clinical research in children and adults with severe asthma to address objectives of this FOA. Applicants should have an established research program in severe asthma and demonstrated leadership in the conduct of clinical research in children and adults with severe asthma.

Budget Plans. Applicants should consider the following guidance in preparing the PHS 398 budget page forms. All costs in the proposed budget should include appropriate justification. It is estimated that this budget will cover appropriate percentage of effort for asthma clinician-scientists, basic scientists and other key personnel (e.g., clinical coordinator); travel costs for approximately up to six trips each year to attend Steering Committee meetings in Bethesda, MD; other travel related to SARP operations; and costs associated with proposed mechanistic study. Do not include budget for shared longitudinal protocol (see below). The budget should not exceed direct costs up to $380,000 in first year, and $450,000 in direct costs per year in years 2-6.

Research Plan Page Limits. Applicants should use the following guidance, in addition to the instructions accompanying the PHS 398 form. Applicants should submit a research plan with the following sections, in order, with page limits where indicated: (1) Collaboration Commitment (2 pages), (2) Specific Aims (1 page), (3) Research Strategy (12 pages). The additional sections (4–15) of the Research Plan should follow the Table of Contents and instructions provided in PHS 398 form.

1.     Collaborative Commitment to the Program (limited to two pages). Applicants should state their willingness to (1) participate in all Steering Committee meetings, which may include conference calls two times a month and in-person meetings at least six times a year; (2) participate in a collaborative and interactive manner with other Clinical Centers, the Clinical Coordinating Center, and the NHLBI in all aspects of SARP, including sharing of biospecimens and data; (3) use common guidelines and manual of procedures developed by the Steering Committee for all SARP studies; and (4) accept fee for service reimbursement from the Clinical Coordinating Center to execute the shared longitudinal protocol according to budget approved by the Steering Committee and NHLBI. Applicants are encouraged to describe any special expertise or unique strengths they can offer to the collaborative effort (e.g., genetics/epigenetics, –omics technology/platforms, imaging, bioinformatics, patient adherence strategies, dissemination activities). Applicants from an institution that has a General Clinical Research Center (GCRC) or Clinical and Translational Science Award (CTSA) funded by the NIH National Center for Research Resources are expected to present a plan for collaborating to engage relevant services/expertise. A plan might include utilization of (1) facilities for investigative procedures (e.g., bronchoscopy, sputum induction, bronchoprovocation); (2) imaging core; (3) bioinformatics core; (4) biospecimens storage; (5) recruiting and characterizing patients; and (5) mutual development of training opportunities in translational research, e.g., SARP’s dynamic phenotyping and mechanistic research in humans provides unique opportunity for training basic and clinical scientists.

2.     Specific Aims (limited to one page). The application must include detailed Specific Aims for the proposed shared longitudinal protocol and mechanistic study. This section should discuss the synergy of the unique mechanistic study and shared longitudinal protocol, and the innovation and potential impact of the findings.

3.     Research Strategy (limited to a total of 12 pages for both the longitudinal protocol and mechanistic study). Applicants will propose (1) research questions and strategy requiring a shared longitudinal protocol conducted across all participating centers and which will include common information ( baseline characterization and 36- to 48-month follow-up data collection may vary by age) on all SARP participants and (2) research questions and strategy for a mechanistic study which may not require or be feasible in all centers, but will be conducted at the applicant’s center. The fundamental aims are (1) to temporally characterize molecular, cellular and physiologic phenotypes and to further elucidate the pathobiology and pathogenesis of severe asthma and its sub-phenotypes; and (2) to develop an integrated understanding of temporal changes in lung structure and function, pathobiology, exacerbations, asthma control and quality of life in relation to pharmacotherapy and add dimensions of progression and outcome to our understanding of severe asthma. The eventual shared longitudinal protocol conducted by SARP will be selected or adapted by the Steering Committee from the protocols proposed by the successful applicants. Mechanistic studies may eventually be combined or participants pooled to address collaborative research questions. Cross-sectional studies or therapeutic efficacy trials will not be considered responsive to this FOA.

Investigators must agree to use common guidelines and manual of procedures developed by the Steering Committee for all SARP studies. It is expected that all clinical research will be performed in a manner consistent with NIH clinical research policies and the United States Food and Drug Administration guidelines. The research strategy should follow generally the instructions in the PHS 398 application form, e.g., hypotheses/research questions, background, methods, analytic plan, and consideration of potential difficulties or ease of implementation across SARP clinical centers. Research strategy for the longitudinal protocol and mechanistic study must be clearly distinguishable. For planning purposes, each applicant will assume a participant pool and accrual pattern consistent with this FOA. That is, applicants are required to demonstrate (1) current access to at least 50 subjects with severe asthma as defined by the American Thoracic Society (Am J Respir Crit Care Med 2000:162;2341-2351) and (2) ability to recruit at least 125 subjects per year - for the first three award years - with persistent asthma as defined by the NAEPP EPR-3 Guidelines for the Diagnosis and Management of Asthma (see http://www.nhlbi.nih.gov/guidelines/asthma/ (60% severe of which 25% are children including preadolescents). Total accrual projected for applicant’s center should be presented using the PHS 398 Targeted/Planned Enrollment Table. All participants enrolled in SARP will undergo baseline characterization and shared longitudinal protocol.

Budget Plan for Shared Longitudinal Protocol: A detailed budget is not required for the research questions and strategy requiring a shared longitudinal protocol, but applicants should provide a summary budget for their proposed longitudinal protocol using a simple budget table rather than the PHS 398 budget page forms; the budget pages should be inserted immediately after Research Strategy, but are not included in the page limit of the Research Plan. The budget should indicate the total direct costs of conducting the proposed shared longitudinal protocol (e.g., including baseline characterization and 36- to 48-month follow-up data collection in approximately 2250 participants over six-years) across all Clinical Centers (assuming six CCs). Accrual should begin within six-months of award. The budget does not need to include Clinical Coordinating Center costs (e.g., forms development, coordinator training, and data collection, quality control and analyses). The budget should include all per-patient costs associated with the conduct of the proposed longitudinal protocol (e.g., recruitment, investigative procedures for enrollment and follow-up visits, participant reimbursements, study personnel, and equipment and supplies). These per-patient costs should include any protocol related study personnel costs over and above the proposed staff in the Clinical Center Budget (see above). Costs of drugs (e.g., evoked phenotype, pharmacologic characterization) or laboratory tests that are not clinically indicated (i.e., are not eligible for third-party reimbursement as part of routine clinical care) should be part of the per-patient costs of executing the protocol. Applications should identify the potential source(s) for any drugs or substances that are required in the proposed protocol that are currently unavailable commercially. If the proposed protocol includes obtaining biospecimens, the applicant should delineate the cost of obtaining the samples and shipping them to a central laboratory in the per-patient budget, as well as the estimated cost of analyzing the specimens in a central laboratory. For budget preparation, it can be assumed that the equipment necessary to perform bronchoscopy, induced sputum, spirometry, methacholine challenge, exhaled nitric oxide, height and weight, and computer data entry already is available. However, any equipment that may be unique to the proposed study should be included in the budget. Longitudinal protocol funds (approximately $4.0 M over six year project period) will be distributed by the Clinical Coordinating Center.

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: Regardless of the amount requested, investigators 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/.

All Clinical Coordinating Center applicants in response to the RFA-HL-11-030 should include a plan for sharing research data and submitting Genome-Wide Association Studies data to the NIH-designated GWAS data repository. All Clinical Center applicants in response to this FOA should indicate their willingness to participate in data sharing and submitting Genome-Wide Association Studies (GWAS) data to the NIH-designated GWAS data repository. The precise content of the data-sharing plan ultimately developed by the Clinical 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 Clinical 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 SARP research resources such as Manual of Operations, study manuals, case-report forms, phenotype ascertainment tools, and 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.asp). The Clinical Coordinating Center applicants will include a plan for sharing these resources in response to RFA-HL-11-030. Clinical Center applicants in response to this FOA should indicate here their willingness to cooperate with this resource sharing.

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? Do the proposed research questions address the objectives of this FOA to temporally characterize molecular, cellular and physiologic phenotypes and to further elucidate the pathobiology and pathogenesis of severe asthma and its sub-phenotypes; and (2) to develop an integrated understanding of temporal changes in lung structure and function, pathobiology, exacerbations, asthma control and quality of life in relation to pharmacotherapy and add dimensions of progression and outcome to our understanding of severe asthma?

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? Do the investigators have available an established severe asthma research program and do they have strong experience in conducting clinical research? Are the administrative abilities of the PI and study coordinator well suited for participating in multi-center studies? Is there evidence of strong commitment to a multicenter, transdisciplinary collaborative program?

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? Does the proposed research reflect a need for the SARP structure? Is there evidence demonstrating current access to (1) at least 50 subjects with severe asthma as defined by the American Thoracic Society and (2) demonstrated ability to recruit at least 125 subjects per year - for the first three award years - with persistent asthma as defined by the NAEPP EPR-3 Guidelines (60% severe of which 25% are children including preadolescents)? Are anticipated problems with recruitment adequately identified and addressed? Are there unique strengths at the applicant institution(s) in recruiting children and adult minority participants with severe asthma?

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?  Is there evidence of the applicant institution’s history of collaborative research? Are institutional resources including personnel, space, and special laboratory facilities adequate to support the proposed research and collaboration in a collaborative multicenter program?

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 in response to this FOA.

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

Revision Applications.  Not applicable to 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.  Foreign applications are not permitted for this FOA.

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); (3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html; and (4) The Clinical Coordinating Center will prepare public-use files for sharing research resources, such as methods of procedures, study manuals, case-report form templates, patient-centric diary templates and phenotype ascertainment instruments (e.g., National Technical Information Service -- http://www.ntis.gov/).

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:

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/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 Principal Investigator will have the primary responsibility for: all aspects of the research plan, including participating in overall development of protocol and budget in collaboration with the Steering Committee, modifying protocol if indicated, recruiting protocol participants, executing the longitudinal protocol, assuring quality of protocol participant care and protocol adherence, assuring the accurate and timely transmission of data collected in conjunction with the CCC, analyzing and interpreting data, preparing publications, and working with the CCC and NHLBI to disseminate research findings. Clinical Center PIs also will be responsible for working with the Steering Committee to (1) to develop common guidelines and Methods of Operations for all SARP studies; (2) identify core constructs (e.g., asthma severity, control, responsiveness to therapy) for developing clinical asthma history and phenotype ascertainment tools, standardized procedures and outcome measures, and when possible harmonize phenotypes that apply uniformly to children and adults where appropriate; and (3) Promote collaboration across SARP to develop a comprehensive framework for evaluating the effectiveness of SARP, and for defining indicators (metrics) that SARP is achieving proposed goals.

The Clinical Coordinating Center Principal Investigator will be responsible for the overall function of the CCC, which is to coordinate, administer, and support all SARP research activities. The CCC PI will be responsible for oversight of longitudinal protocol development, data collection, data safety and confidentiality, quality assurance, data analysis, coordination of data distribution, and implementation of all data sharing plans. The CCC PI will be responsible for the distribution of longitudinal protocol funds to the Clinical Centers (see “Funds Available” in Section II. 2.). The CCC PI will be responsible for coordination of the activities of the Steering Committee, Data and Safety Monitoring Board, and coordinating manuscript preparation.

Support or other involvement of industry or any other third party in the SARP protocol 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 NHLBI. Awardees must follow NHLBI policy concerning third party agreements (http://www.nhlbi.nih.gov/funding/policies/thirdparty.htm).  

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

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. The assigned program director may also serve as the NIH Project Scientist. SARP will have an NIH Project Scientists who will also serve as program director; he/she will share participation in overall Steering Committee activities. Several procedures are in place to manage potential conflict of interest by project scientist (PS) administering the cooperative agreement. These include: the PS adhere to stringent NIH ethics rules and financial disclosure reporting to eliminate overt and perceived conflict of interest; PS is prohibited from observing scientific review of competing applications from an investigator with whom they have published in the last three years; recommendations from PS about budgetary requests (e.g., carryover, administrative supplements, no-cost extensions) are reviewed and approved by supervisors (e.g., Branch Chiefs, Division Director, and Institute Director); recruitment progress is reviewed by study independent staff (quarterly within the Division; quarterly or semi-annually by the DSMB and supervisory staff; PS may be asked to leave the room during DSMB reviews of studies; recommendations made by PS in annual progress reports are reviewed by grant specialists with a separate Division (Office of Grants Management); PS will not seek co-authorship of primary publications and will obtain approval by Branch Chief to participate in secondary publications.

The NHLBI Project Scientist 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 potential changes in the protocol, data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment). The NHLBI Project Scientist, on behalf of the NHLBI, will have the same access, privileges, and responsibilities regarding the collaborative data as the other members of the Steering Committee.

The NHLBI reserves the right to terminate or curtail any SARP study (or an individual award) in the event of (1) failure to develop or implement mutually agreeable collaborative longitudinal protocol; (2) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (3) major breach of a protocol or substantive changes in the agreed-upon protocol with which NHLBI cannot concur; (4) attaining of a major study endpoint before schedule with persuasive statistical significance, or (5) human subject ethical issues that may dictate a premature termination.

Annual continuation and level of funding for each Clinical Center will be based on NHLBI review of accrual, scientific progress and overall performance, determined as part of the NHLBI review of the annual non-competing continuation grant progress reports submitted by awardees.

2.A.3. Collaborative Responsibilities

Awardees agree to the governance of studies through a Steering Committee (SC). All Principal Investigators, an NHLBI representative, and a Chairperson, to be appointed by the NHLBI, will comprise the SC. All major scientific decisions will be determined by majority vote of the SC. Each Clinical Center, the Clinical Coordinating Center, and the NHLBI Project Scientist will have one vote; the Chair will have one vote in case of a tie. It is anticipated that SC meetings will be held twice a month by conference call and six times a year in person.

A Data and Safety Monitoring Board (DSMB) will be appointed by the Director, NHLBI to provide overall monitoring of study performance, interim data, and safety issues. The Steering Committee may nominate members for the DSMB. DSMB meetings will ordinarily be held in Bethesda. An NHLBI scientist, other than the NHLBI Project Scientist, shall serve as Executive Secretary to the DSMB.


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:

Robert Smith, Ph.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Bethesda, MD 20892-7952
Telephone: (301) 435-0202
Email: smithra3@nhlbi.nih.gov

Patricia Noel, Ph.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 10042
Bethesda, MD 20892-7952
Telephone: (301) 435-0202
FAX: (301) 480-3557
Email:
noelp@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, MSC7924
Bethesda, MD 20892-7924 (Express mail zip: 20817)
Telephone: (301) 435-0270
FAX: 301-480-0730
Email:
nhlbichiefreviewbranch@nhlbi.nih.gov

3. Financial or Grants Management Contacts:

Dianna Jessee
Office of Grants Management
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 7170, MSC 7926
Bethesda, MD 20816-7926
Telephone: 301-435-0154
FAX: 301-451-5462
Email: jessed@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/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-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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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