Part I Overview Information

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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 NHLBI Asthma Network (AsthmaNet) (U10)

Announcement Type
New

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

• December 9, 2008 - See Notice (NOT-HL-09-112) a list of Frequently Asked Questions (FAQs) has been developed for this FOA.

Request For Applications (RFA) Number: RFA-HL-08-010

Catalog of Federal Domestic Assistance Number(s)
93.838

Key Dates
Release Date: June 19, 2008
Letters of Intent Receipt Date: December 30, 2008
Application Receipt Date: January 30, 2009
Peer Review Date(s): May-June 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: January 31, 2009

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

• Purpose. The purpose of this funding opportunity announcement (FOA), issued by NHLBI, NIH, is to invite applications to participate in the NHLBI Asthma Network (AsthmaNet), a clinical research network that will develop and conduct multiple clinical trials to address the most important asthma management questions and new treatment approaches in pediatric and adult populations. AsthmaNet is designed to promote cooperation and coordination, facilitate scientific exchange, provides training opportunities, and leverage resources. AsthmaNet will include multiple Clinical Centers and one Data Coordinating Center. The protocols will include clinical trials to evaluate and/or compare existing or new therapeutic approaches to asthma management as well as a limited number of proof-of-concept studies to advance the development of novel therapies and studies that investigate the mechanistic bases for interventions examined in AsthmaNet. This FOA solicits applications for clinical centers and runs in parallel with a separate FOA that solicits applications for the data coordinating center (see RFA-HL-08-011).
• Mechanism of Support. This FOA will utilize the cooperative agreement mechanism of support (U10).
• Funds Available and Anticipated Number of Awards. The total amount to be awarded for AsthmaNet (the Clinical Centers and the Data Coordinating Center) will be a maximum $104.8 million total costs for the project period. It is anticipated that up to 9 Clinical Centers under this FOA, and 1 Data Coordinating Center under the related FOA (see RFA-HL-08-011) will be awarded. As an optional program, and included in the total amount designated for AsthmaNet, up to 3 Clinical Research Skills Development Cores may be awarded to Clinical Centers participating in AsthmaNet if they apply for a CRSD core.
• udget and Project Period. The total project period for an application submitted in response to this FOA is 7 years. Out of the total funds for AsthmaNet and in response to this FOA, the NHLBI expects to award approximately $50.7 million total costs over seven years for up to 9 Clinical Centers for three functions: (1) $27.2 million total costs for core funds to provide infrastructure for implementing protocols and reporting findings; (2) $20.5 total costs to cover protocol start up costs, which will be awarded as restricted funds and released by NHLBI according to protocol needs and clinical center performance; and (3) up to $2.9 million total costs for Clinical Research Skills Development Core funds. In addition to the funds awarded directly by NHLBI to the Clinical Centers, protocol funds (approximately $40.3 million total costs) to execute and closeout clinical management trials, proof-of-concept studies and mechanistic studies will be part of the Data Coordinator Center’s grant award and will be distributed by the DCC to the Clinical Centers and the DCC in accordance with protocol budgets (see RFA-HL-08-011).
• Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
• Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
• Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application. Each clinical center is strongly encouraged to use the multiple principal investigators option, and each clinical center is expected to be comprised of a partnership between a lead principal investigator in pediatric asthma and a lead principal investigator in adult asthma. These investigators may be from either the same institution or different institutions.
• 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.
• Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates.
• Application Materials. See Section IV.1 for application materials.
• Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY 301-451-5936.

Table of Contents

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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

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Section I. Funding Opportunity Description

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1. Research Objectives

Purpose

The purpose of this funding opportunity, issued by NHLBI, NIH, is to invite applications to participate in the NHLBI Asthma Network (AsthmaNet), a clinical research network that will develop and conduct multiple clinical trials to address the most important asthma management questions and new treatment approaches in pediatric and adult populations. AsthmaNet is designed to promote cooperation and coordination, facilitate scientific exchange, provides training opportunities, and leverage resources. AsthmaNet will include multiple Clinical Centers and one Data Coordinating Center. The protocols will include clinical trials to evaluate and/or compare existing or new therapeutic approaches to asthma management as well as a limited number of proof-of-concept studies to advance the development of novel therapies and studies that investigate the mechanistic bases for interventions examined in AsthmaNet. This FOA solicits applications for Clinical Centers and runs in parallel with a separate FOA that solicits applications for the Data Coordinating Center (see RFA-HL-08-011).

This is a one time solicitation to support AsthmaNet for a 7-year project period.

Background

Asthma affects more than 22 million persons, and it is one of the most common chronic diseases of childhood. The burden of the disease is high to the individual who has asthma, to his/her family, and to the larger community. Asthma costs over $14 billion annually, with a majority of expenses related to urgent care, hospitalizations, and lost productivity. The NHLBI’s National Asthma Education and Prevention Program strives to reduce this burden through the development of clinical practice guidelines and educational programs. The NHLBI established two asthma clinical research networks (one for adult asthma, originating in 1993, and one for childhood asthma in 1999) to fill the gaps in science identified, in part, by the guidelines and to address newly arising areas of clinical concern in the management of asthma. The results of the networks studies have influenced subsequent revisions of the guidelines and identified new approaches for managing asthma. The most recent guidelines update, NAEPP Expert Panel Report-3: Guidelines for the Diagnosis and Management of Asthma (http://www.nhlbi.nih.gov/guidelines/asthma/index.htm), 2007, notes that significant strides have been made, but that challenges remain.

The 2007 release of the NHLBI’s strategic plan (http://apps.nhlbi.nih.gov/strategicplan/) and the anticipated end of the current funding period for the asthma networks prompted the Division of Lung Diseases, NHLBI, to conduct a workshop with leaders in pulmonary research, clinical trial design, and biostatistics to obtain advice on a network structure that would sustain the past success of the lung networks while meeting future clinical research needs. The result of the workshop was to strongly endorse the concept of networks and to encourage the following network objectives: maintain the focus on improving clinical care but allow more flexibility in the type of research questions to advance the development of novel therapies and accelerate translational research; develop mechanisms to facilitate and promote scientific exchange across networks and other clinical research programs; structure networks to maximize programmatic and scientific efficiency; promote shared use of resources and standardization among networks; promote training; and facilitate rapid dissemination of research findings to the medical community (see http://www.nhlbi.nih.gov/meetings/workshops/network-wkgp-exesum.htm). The NHLBI’s plans for promoting the shared use of resources and the promotion of programmatic and scientific efficiency coincide with the expansion of the NIH Roadmap of Medical Research initiative to Re-engineer the Clinical Research Enterprise through the Clinical and Translational Science Award program (see www.ctsaweb.org).

Research objectives

The primary aim of AsthmaNet is to address important clinical management questions in asthma, mainly through Phase II and Phase III clinical trials. The emphasis will be on clinical trials 12-20 months in duration that help identify optimal therapies for a variety of asthma phenotypes, genotypes, and racial and ethnic backgrounds. A limited number of clinical trials of longer duration may be considered. The knowledge gained will inform clinical practice and future updates to the NAEPP clinical practice guidelines. The secondary aim is to conduct small proof of concept studies that have an objective of advancing novel asthma therapies and to conduct studies that investigate the mechanistic bases for interventions in AsthmaNet clinical trials. The knowledge gained will advance the development and application of novel therapies and treatment approaches. The merger of the pediatric and adult networks into one AsthmaNet will enhance scientific exchange and stimulate research that addresses questions on the similarities, differences, and relationships between childhood and adult asthma.

Research approaches

Over the 7-year project period, the AsthmaNet will conduct approximately 8-10 clinical trials relevant to the primary research aims, and at least 2-4 proof of concept or mechanistic studies. The exact number of protocols supported in the 7-year program will depend on the nature and extent of the investigations proposed by the AsthmaNet Steering Committee (SC) and the availability of funds. The first protocol will be initiated within the first year of the award period; in subsequent years, 2-4 protocols will be conducted simultaneously over the project period. All protocols should be completed within the 7-year duration of AsthmaNet.

The AsthmaNet Steering Committee will develop the protocols collectively; all protocols will be approved by the Protocol Review Committee. Of the total protocols conducted, at least one should be targeted to children 0-4 years of age, one to children 5-11 years of age, and one to patients who have severe asthma. Protocols that address issues across age groups or across the spectrum of disease severity should also be included. AsthmaNet protocols may be selected or adapted from the studies proposed by the successful applicants in response to this FOA, but a decision to fund a particular Clinical Center will not commit the AsthmaNet to develop that applicant’s specific protocol.

All centers are expected to participate in all protocols related to the primary research aim; at least 4 centers are expected to participate in proof-of-concept or mechanistic studies.

Funds to support the Clinical Centers for execution of the protocols will be part of the Data Coordinating Center grant award and be distributed to the Clinical Centers by the Data Coordinating Center on a per patient basis and according to the approved protocol budgets developed by the Steering Committee. All Clinical Centers must be willing to follow this funding arrangement for each protocol.

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 AsthmaNet’s primary research aims (i.e., Phase II or III clinical management trials) should be applicable to multicenter research; should address issues of clinical significance and have a high potential to inform clinical practice guidelines; and should be trials not likely to be conducted by commercially supported research. The clinical management trials should be powered for clinically important endpoints (such as, for example, the kind identified by clinical practice guidelines). Examples of research topics include, but are not limited to, the following:

• What treatments are the most effective strategies for young children (<4 years of age) with different levels of symptoms severity (e.g., comparative studies of drugs for asthma)?
• What added value and role does the treatment of co-morbidities have in improving asthma control (e.g., allergic rhinitis, chronic sinusitis, obesity, obstructive sleep apnea)?
• Does tailoring therapy to specific asthma genotypes/phenotypes lead to more effective asthma management?
• Are different treatments optimal at different points across the age span and, if so, what contributes to differential responses?
• What treatment for severe asthma improves asthma outcomes?
• What are the comparative advantages of non-pharmacologic vs. pharmacologic interventions?

The emphasis will be on trials of 12-20 months in duration, although a limited number of trials of longer duration may be considered.

Examples of mechanistic study topics related to AsthmaNet’s secondary research aims include, but are not limited to, use of -omics analyses (e.g., gene expression profiles, peripheral blood transciptome) to interpret the biologic and clinical significance of treatment response (e.g. response to corticosteroids); evaluation of predictors of response to treatment; examination of the role of imaging to assess disease progression and treatment response; profiling molecular and cellular events that regulate disease progression or modify treatment response.

Examples of proof of concept study topics related to AsthmaNet’s secondary research aims include, but are not limited to, studies that advance the use of novel therapies through small studies testing the feasibility and efficacy of novel drugs or new therapeutic approaches, such as: evaluation of oligodeoxynucleotides containing CpG motifs in at risk infants; use of statins, imatinib mesylate, or VEGF inhibitors in severe asthma; use of predictive biomarkers or genotype/phenotype characterizations to select or adjust treatment.

Organization of NHLBI’s Asthma Network (AsthmaNet)

AsthmaNet will be a cooperative network of up to nine clinical centers, one Data Coordinating Center, and the Division of Lung Diseases, NHLBI.

• Each Clinical Center is strongly encouraged to use the multiple principal investigators (PI) option (see http://grants.nih.gov/grants/multi_pi/index.htm); at a minimum, each Clinical Center is expected to be comprised of a partnership between a lead principal investigator with expertise in pediatric asthma and a lead principal investigator with expertise in adult asthma. The investigators may be from either the same institution or different institutions. Clinical Centers may also include satellite recruitment and protocol implementation sites (that is, additional recruitment sites at a different location than the Clinical Centers). Clinical Centers will be responsible for proposing and prioritizing protocols, participating in protocol development, preparing protocol budgets in collaboration with the Data Coordinating Center, conducting the research (subject recruitment and implementation of all study procedures), analyzing and interpreting research results, and disseminating research findings. Clinical Centers will also be responsible for working with the Data Coordinating Center to develop common definitions and standardization across protocols wherever appropriate. Each Clinical Center will be responsible for a Clinical Research Skills Development Core that helps young investigators develop skills and experience to progress to more senior status. Each Clinical Center will be required to participate in a cooperative and interactive manner with all other Clinical Centers and the Data Coordinating Center in all aspects of the network.
• The Data Coordinating Center will support protocol development (e.g., statistical support, assistance in defining analytical approaches for clinical trial design), data collection and analysis, editorial and meeting coordination for manuscript preparation, coordination of the activities of the Steering Committee, Protocol Review Committee, and Data and Safety Monitoring Board, drug acquisition and distribution, and overall study coordination and quality assurance. The Data Coordinating Center will be responsible for distributing protocol funds to the Clinical Centers for the implementation of protocols. The Data Coordinating Center will also initiate and coordinate activities to promote standardization of asthma research vocabularies and methodologies and coordinate AsthmaNet activities with NHLBI bioinfomatics programs. See RFA-HL-08-011 for more details describing the responsibilities of the AsthmaNet Data Coordinating Center.
• The NHLBI will be responsible for organizing and providing overall support for the AsthmaNet. The NHLBI Program Office and Office of Grants Management will be responsible for the overall management of AsthmaNet. In addition to regular grant stewardship, the NHLBI Project Scientists will be involved substantially with the awardees as a NHLBI partner, consistent with the Cooperative Agreement mechanism. The NHLBI will appoint the Protocol Review Committee, the Data Safety and Monitoring Board, and the Study Chair.
• A Steering Committee (SC) composed of the principal investigators of the Clinical Centers (both adult and pediatric asthma), the Data Coordinating Center, and the NHLBI Project Scientist will be the main governing body of AsthmaNet. The NHLBI will appoint a Study Chair who may be independent of the Clinical Centers and the Data Coordinating Center to preside over SC meetings and serve as the SC representative. All major scientific decisions will be determined by majority vote of the SC. Each Clinical Center, the Data Coordinating Center, the NHLBI will have one vote; the Study Chair will have a vote in case of a tie vote among the other SC members. Note that although each Clinical Center’s two lead principal investigators (one with expertise in adult asthma, one with expertise in pediatric asthma) are expected to participate in all SC meetings, each Clinical Center has one vote. It is anticipated that the SC will meet two times a month by telephone conference call and 6 times a year by in-person meetings. The SC will have primary responsibility for the general organization of AsthmaNet, prioritizing proposed topics for investigations, finalizing clinical 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 protocols will be proposed and prioritized by the SC. For each protocol, one Clinical Center will take the lead responsibility for drafting the protocol and budget, although the entire SC will provide input and will be responsible for assuring development of a common protocol to be implemented by the Clinical Centers. The SC has final responsibility for approving protocols, protocol budgets, and protocol revisions, before review by the PRC or DSMB. Subcommittees of the SC will be established to perform specific functions such as Publications and Presentations, Equipment, Quality Control, Assurance committee, 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. Awardee members of the SC will be required to accept and implement policies approved by the SC.
• An independent Protocol Review Committee (PRC), established by the NHLBI with input from the SC, will provide peer review for all protocols---clinical management trials, proof-of-concept studies, and mechanistic studies. The PRC will consist of a chairperson and scientists with expertise in asthma clinical research, pulmonology, allergy/immunology, clinical trial design, biostatistics, asthma genetics, enabling technologies, outcome measures, and other areas of expertise as needed. Because the PRC serves as an independent group advisory to the NHLBI, AsthmaNet investigators will not communicate with PRC members regarding study issues, except as authorized by the PRC’s Executive Secretary. The PRC will use review criteria similar to those used in NIH study sections (e.g. innovation, significance, scientific merit, feasibility, and appropriateness of budget), and will make recommendations directly to the NHLBI on the scientific merit of the protocol. Two phases of review are anticipated for all protocols--clinical management protocols, proof of concept, and mechanistic studies: (1) the PRC will review short protocol concepts proposed by the SC to assess innovation, scientific significance and priority among various topics under consideration, relevance to the AsthmaNet objectives and NHLBI mission and policies, and appropriateness to proceed with development of a full protocol; (2) the PRC will review full protocol proposals for scientific merit, feasibility, and appropriateness of budget. The PRC may recommend approval, disapproval, approval with contingencies, or request revisions. Submitted clinical management protocols are permitted a maximum of two reviews, analogous to NIH large grant submission policy. The PRC will provide a written critique of each proposal and a final recommendation to the NHLBI. All study protocols performed by AsthmaNet will be recommended by the PRC and approved by the NHLBI before implementation.
• An independent Data Safety and 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 trials, bioethics, and biostatistics and clinical trial design and coordination. An NHLBI scientist other than the NHLBI’s AsthmaNet Project Scientists will serve as the Executive Secretary to the DSMB. The DSMB will meet approximately semi-annually by telephone conference call 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 each study. 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

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1. Mechanism of Support

This funding opportunity will use the Cooperative Agreement (U10) award mechanism(s).
The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

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

This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award." This is a one time solicitation to fund AsthmaNet for 7 years. It is expected that all protocols will be completed within the 7-year time period. Plans beyond the current funding period are indefinite.

2. Funds Available

The total amount of funding that NHLBI expects to award for AsthmaNet (for up to 9 clinical centers and 1 DCC) is $104.8 million for a project period of 7 years. Designated funding levels are subject to change at any time prior to award, due to unforeseen budgetary, administrative, or scientific developments.

The NHLBI anticipates awarding up to 9 Clinical Centers in response to this FOA, and one Data Coordinating Center in response to a separate FOA (see RFA-HL-08-011). Out of the total funds for AsthmaNet and in response to this FOA, the NHLBI expects to award approximately $50.7 million total costs over 7 years for up to 9 Clinical Centers for three functions: (1) $27.2 million total costs for core funds to provide infrastructure for implementing protocols and reporting findings; (2) $20.5 total costs to cover protocol start up costs, which will be awarded as restricted funds and released by NHLBI according to protocol needs and clinical center performance; and (3) up to $2.9 million total costs for Clinical Research Skills Development Core funds.

In addition to the funds awarded directly by NHLBI to the Clinical Centers, protocol funds (approximately $40.3 million total costs) to execute and closeout clinical management trials, proof-of-concept studies and mechanistic studies will be part of the Data Coordinator Center’s grant award and will be distributed by the DCC to the Clinical Centers and the DCC in accordance with protocol budgets (see RFA-HL-08-011).

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

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

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

Section III. Eligibility Information

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1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education
• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Small Businesses
• For-Profit Organizations (Other than Small Businesses)
• State Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribally Designated Organizations
• County Governments
• City or Township Governments
• Special District Governments
• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• U.S. Territory or Possession
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Regional Organizations
• Other(s):
  • Eligible Agencies of the Federal Government

1.B. Eligible Individuals

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

Each Clinical Center application is strongly encouraged to use the multiple PD/PI option. Additional information on the implementation plans, policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

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.

Among the disciplines appropriate for Clinical Center investigators are pulmonary medicine, allergy and immunology, pharmacology, pharmacogenetics, molecular and cellular biology, development of therapeutics, and clinical trial design and implementation.

The applications are expected to include a lead PI with expertise in pediatric asthma and a lead PI with expertise in adult asthma who will share leadership of the Clinical Center. These two PIs may be from the same institution or different institutions. Failure to list these two PIs using the multiple PI option will be considered unresponsive to this RFA and the application will be returned without review. Even if the application is reviewed, failure to meet eligibility requirements will preclude the NHLBI from making an award. The two PIs (adult asthma and pediatric asthma) will share the authority and responsibility 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

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

Renewal applications are not permitted in response to this FOA.

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

Awards for a Clinical Center and a DCC 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

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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) 710-0267, Email: [email protected].

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.

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.

Multiple PIs at different institutions must identify which institution will be the applicant institution and use the traditional subcontract mode for other PIs.

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: December 30, 2008
Application Receipt Date: January 30, 2009
Peer Review Date(s): May-June 2009
Council Review Date: August 2009
Earliest Anticipated Start Date(s): September 30, 2009

3.A.1. Letter of Intent

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

• Descriptive title of proposed research
• Name, address, and telephone number of the Principal Investigator
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

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: [email protected]

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:

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: [email protected]

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 or renewal 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 or renewal award.

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

Awards will also be made under the Cooperative Agreement Terms and Conditions of Award noted in Section VI. 2. A.

6. Other Submission Requirements and Information

Qualifications and Experience. Applicants should describe qualifications and experience in the appropriate narrative sections of the application and in biosketches. Participation in AsthmaNet will be a complex and time-consuming undertaking. Applicants for Clinical Centers must have the necessary experience and expertise to conduct clinical studies in patients with asthma. Applicants should have an established research program in asthma and demonstrated leadership in the design and conduct of clinical trials in pediatric and adult asthma. An appropriate time commitment is expected from the principal investigators and any co-investigators at each Clinical Center; it is estimated that 60% total FTE for the combined leadership of principal investigators and co-investigators in adult and pediatric asthma will be required. Because the AsthmaNet Clinical Centers will use the multiple PI option, a Leadership Plan must be included in the research plan section of the application (see below).

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 AsthmaNet program. Applicants are encouraged to describe any special expertise or unique strengths they can offer to the collaborative effort (e.g., innovative clinical trial design, genetics/genomics/proteomics, bioinformatics, team leadership and training, patient adherence strategies, 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 meetings, which may include conference calls two times a month and in-person meetings at least six times a year. Applicants should discuss their willingness, and that of the institutions involved, to accept fee for service reimbursement from the Data Coordinating Center to implement protocols according to budgets approved by the SC and NHLBI for each protocol. Clinical 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.

An objective of the AsthmaNet is to accelerate translation of study findings to the scientific community and clinical practice as well as stimulate identification of salient research questions from experiences in clinical practice. Applicants should indicate willingness to work, through the AsthmaNet, with the NHLBI Division of the Application of Research Discoveries (DARD), whose mission is to promote the development and implementation of evidence-based guidelines in partnership with individuals, professional and patient communities, and health care systems and to communicate research advances effectively to the public, and to bridge the gap between research and practice through knowledge networks. DARD is in the early planning stages of developing a Pulmonary Knowledge Network (PKN) which will serve as a knowledge and communication resource for researchers and clinicians. Examples of potential PKN-related collaborative opportunities may include, but are not limited to: (1) use of a web-based virtual collaborative work environment to exchange information and ideas, such as new research findings, to other researchers and clinicians, communication from practicing clinicians to researchers that inform and shape the research agenda, and interactive discussion groups to stimulate ideas and answer important questions from the research and clinical communities; (2) automated methods for rapidly identifying relevant research findings that can be integrated into the guidelines development process to ensure that guidelines are updated regularly; (3) promotion of standardized methodologies for reporting research findings to facilitate more rapid and efficient translation of research findings into clinical practice; and (4) contribution to data repositories and evidence tables that can be accessed by clinicians and researchers.

Study Population. Applicants should demonstrate (with reference to specific, objective sources of data on the size of the available population) access to a sufficient number of patients to accomplish their portion of the proposed protocols. It is anticipated that each Clinical Center should have access to a minimum of 600 children and 600 adults who have asthma, and access to at least 100 persons who have severe asthma. The application should include a description of the pool of potential study participants, including the age range, ethnic/racial and gender distributions (approximately 50 percent women and 25 percent minorities), and recruitment sources. It is not anticipated that all eligible patients will be enrolled in research protocols at any one time, and it is possible that an individual patient may be enrolled in more than one study over the AsthmaNet project period.

Patient access may be accomplished by establishing links with other groups (e.g., other health care providers in the community, such as pulmonary/allergy practices, primary care practitioners, pediatricians, and health maintenance organizations) in addition to the applicant’s institution. If links with other groups are anticipated, the application should include a plan with appropriate letters of support that describes (1) how the applicant Clinical Center will link to and operate with the other groups and (2) how the Clinical Center will monitor the quality of the other group’s performance (recruitment and, if applicable, patient visits and data collection).

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 AsthmaNet Clinical 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 letter of agreement from either the GCRC/CTSA Program Director or PI.

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

Subsection 1: Multiple PI Leadership Plan (maximum 2 pages). The governance and organizational structure of the leadership team (the PI with expertise in pediatric asthma and the PI with expertise in adult asthma) 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: Protocol Plan (maximum total 28 pages) The protocol plan should include proposals for two distinct clinical management trial protocols (maximum 11 pages each) and two distinct, brief protocol concepts (maximum 2.5 pages each), and, positioned at the beginning of the protocol plan, an overview/abstract of the key objectives and design features of the four protocol proposals (maximum 1 page). Refer to Section I.1. Research Objectives/ Research Approaches of this FOA for a discussion of appropriate research topics. It is expected that all protocols will be performed in a manner consistent with NIH clinical research policies and the United States Food and Drug Administration guidelines.

The two clinical management trial protocol proposals (maximum 11 pages each) should include one pediatric asthma management trial and one adult asthma management trial. Applicants are encouraged to explore, within the context of their proposed protocols, new technologies that could lead to improvements in treatments, monitoring of asthma control and disease progression, or prediction of response to therapy. Each protocol proposal should generally follow the instructions in the PHS 398 application form (revised 11/2007; http://grants.nih.gov/grants/forms.htm) and should include a rationale (i.e., scientific and clinical practice justification for the proposed research), research aims, outcome measures (indicating appropriate objective and patient-centered measures of primary and secondary outcomes), study design and timetable, and a description of the study population with sample size calculations and an estimate of the expected distribution of female and minority participants. The applicant should indicate for each protocol how many study participants are available in the applicant’s center and how many will be required from the entire AsthmaNet to conduct the protocol.

A budget for each protocol should be presented, using a budget table or spreadsheet rather than the PHS 398 budget page forms; the budget pages are not included in the page limit. The budget should indicate the total direct costs of implementing the proposal across all Clinical Centers, not just at the applicant’s Clinical Center. Present the budget in direct costs only; do not include any administrative cost. The budget does not need to include Data Coordinating Center costs (e.g., for drug distribution, forms development, coordinator training, and data collection, quality control and analysis). The protocol budget should include all per-patient costs associated with the conduct of the proposed study (recruitment, procedures for enrollment, randomization, and follow-up visits, participant reimbursements, drugs, study personnel, PI oversight, manuscript preparation, and equipment and supplies). These per-patient costs should include any study personnel costs over and above the proposed staff in the Clinical Center Core Budget, see Subsection 5 Budget). Costs of drugs 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 conducting 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 blood or tissue samples, 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 the purposes of these proposed protocol budgets, it can be assumed that the equipment necessary to perform spirometry, exhaled nitric oxide, methacholine challenge, height and weight, and computer data entry are already available. (Such basic equipment is expected to be used for multiple protocols, and their purchase will be managed out of the initial project year’s protocol dollars.) However, any equipment that may be unique to the proposed protocol should be included in the proposed protocol budget.

The two brief protocol concept proposals (maximum 5 page total; 2.5 pages for each brief protocol concept proposal) should include a concept proposal for (1) a mechanistic study that will investigate the biological, mechanistic significance of the intervention in one of the applicant’s proposed clinical management protocols; and (2) either a concept proposal for a proof-of-concept study that has an objective of advancing novel asthma therapies or a concept proposal for a clinical management trial on either severe asthma or a study that examines management across the spectrum of disease severity . The brief protocol concept proposals should include a brief description of the rationale for the proposal, research aims, general study design and methods, and study population. No budget information is required for the brief concept proposals.

Subsection 3: Clinical Research Skills Development Core Plan (CRSDC) (maximum 3 pages) AsthmaNet presents a rich environment for young investigators to be exposed to and develop additional research skills and to assist them in progressing to more senior status. To assist the AsthmaNet awards in enhancing the developmental environment for their new clinical investigators, the NHLBI will provide up to $30,950 direct costs to each Clinical Center each year for the seven year project period that will be dedicated to implementing a Clinical Research Skills Development Core Plan.

The CRSDC is intended for staff investigators with limited clinical research experience, including fellows and junior faculty members, but not investigators who have had previous (not currently active) K series awards. The CRSDC support is in addition to the infrastructure and protocol costs for AsthmaNet, and may include such activities as seminars, courses, and/or participation in AsthmaNet Steering Committee meetings, developmental experiences with new research technologies and skills, cross-disciplinary opportunities, and translational research. The CRSDC should ensure that the new clinical investigators receive the mentoring they need to foster their research careers.

Each Clinical Center application should include a plan for training junior investigators in clinical research (maximum 3 pages) and a budget (see Budget Plan section of the application (subsection 5). Each Clinical Center application should include the following elements in the CRSDC plan: A description of the level of potential trainees, the type of experiences and skill development planned for the trainees that will promote progress to more independent researcher status, the nature and extent of mentoring, how the activities will be coordinated with activities of participating senior investigators, how overlap or duplication of existing training opportunities at the applicant institution will be avoided, and evaluation measures for the success of the training plan. In addition, the application should describe at least one distinct training opportunity the Clinical Center can offer AsthmaNet as a whole, since the AsthmaNet will encourage training collaborations among the clinical centers. For Clinical Centers that have access to an NIH funded CTSA, the CRSDC plan should describe specifically how the Clinical Center’s CRSDC will interface with the CTSA, and should include a letter of support from the CTSA Director.

The CRSDC plan will be evaluated separately from the Research Plan, and the application’s priority score should not be affected by the evaluation of the CRSDC plan. Rather, the reasonableness of the CRSDC plan will be considered either acceptable for funding at the requested level or not acceptable. See Section 2.b. Additional Review Considerations for considerations in evaluating the CRSDC. Continued funding for the CRSDC beyond the first project year will depend on NHLBI administrative review of performance in implementing the plan, as reported in the annual progress report.

Subsection 4: Dissemination Plan. The DCC will be responsible for coordinating the dissemination AsthmaNet research findings and relevant protocol materials. Accordingly, the DCC applicants in response to RFA-HL-08-011 will propose a dissemination plan. Applicants to this FOA for AsthmaNet Clinical Centers should indicate here their willingness to collaborate with the DCC and other SC members in dissemination efforts (preferably less than, but no more than a maximum 1 page).

Subsection 5: Budget Plans. Budget information for three separate budgets (Clinical Center Core, Clinical Research Skills Development Core, and Protocol Start-up Costs) should be provided using the PHS 398 Budget Page Forms. (These are distinct from the proposed protocol budget requested in the Research Protocol Plan described in Subsection 2).

Core Budget: Clinical Center applicants should consider the following issues regarding Clinical Center core budgets. All costs in the proposed budget should include appropriate justification. The underlying concept of the AsthmaNet is that a group effort is essential to maintain the infrastructure required to perform multiple clinical trials. Based on this approach, it is estimated that the individual Clinical Centers will require a minimum level of effort to sustain the organizational aspects of the AsthmaNet. It is estimated that this core budget will cover a minimum of 60% total effort for the combined leadership (PI and any Co-investigators); appropriate percentage of effort for other key personnel essential for core infrastructure over the course of the project period (e.g. clinical coordinator), keeping in mind that protocol funds (see below) will also include study personnel required to execute protocols over and above personnel proposed in the core budget); travel costs for approximately six trips each year to attend Steering Committee meetings in Bethesda, MD, and other travel related to AsthmaNet operations. Each Clinical Center should submit one core budget that incorporates both the pediatric asthma and adult asthma components of the center. The total should not exceed $222,000 direct costs in year one, which will be a 9-month project year, and should not exceed $295,000 direct costs per year in years 2-7 (all of which will be 12-month project years). If the Clinical Center 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.

Clinical Research Skills Development Core (CRSDC) Budget: A separate budget page for the CRSDC should be submitted; each Clinical Center applicant may request up to $30,950 direct costs each year for the seven year project period. Costs allowable for inclusion include salary support for the CRSDC leader and other senior investigators and staff participating in mentoring activities (it is expected, for example, that the Leader will devote a minimum of 5 percent effort, and active involvement by the PI and other senior investigators is strongly encouraged); travel costs for new investigators, supplies and equipment to support developmental activities, costs for courses, seminars, workshops, and other activities directly related to the development plan. All costs requested should be justified with respect to developmental activities and may not be used to supplement the costs of research proposed in the rest of the Clinical Center application. Salary support for the new investigators is neither needed nor allowable, since the CRSDC is intended to serve new clinical investigators who occupy positions and receive salary support from other sources.

Protocol Start-Up Cost Budget: Each Clinical Center should also submit one budget for protocol start up and staffing costs, which should include costs to cover additional staffing, over and above the core, (e.g., clinical research coordinators, data entry personnel) required to start up and implement multiple protocols over the project period. This protocol start up and staffing budget should not exceed $88,000 direct costs in year 1 (which will be a 9-month project year) and $235,000 direct costs in each subsequent year (all of which will be 12-month project years). These funds will be awarded as restricted protocol funds and released by NHLBI according to protocol needs and clinical center performance.

In addition, funds for the Clinical Centers execution (e.g., equipment, study procedure costs, participant costs) and closeout of AsthmaNet protocols (clinical management trials, proof of concept and mechanistic studies) will be initially awarded to the AsthmaNet Data Coordinating Center and subsequently distributed to the Clinical Centers on a fee for service basis as delineated in the specific protocol budgets. These protocol execution costs may not be eligible for full facilities and administrative costs (F&A); the study personnel will generally be reimbursed separately from the fee for service agreements.

For budget allocation purposes within the grantee Institution(s), the Clinical Center can report the amount of protocol dollars awarded to the Clinical Center by the end of each project year. The actual amount of protocol funds awarded and released to each Clinical Center will be determined by the protocol budgets proposed by the AsthmaNet Steering Committee and approved by the AsthmaNet Protocol Review Committee and the NHLBI and by performance (e.g. number of enrolled and randomized patients). 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 NGA.

All AsthmaNet 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. Continuation and level of funding for each Clinical Center will be based on actual enrollment and overall performance.

Research Plan Page Limitations

The research plan is limited to a maximum of 34 pages, which includes the following subsections: Leadership Plan (2 pages); Research Protocol Plan (28 pages total: 1 page overview; 22 pages for 2 clinical trial protocols at 11 pages each; 5 pages for 2 concept proposals at 2.5 pages each); Clinical Research Skills Development Core (3 pages); Dissemination Plan (1 page). Budget pages are not included in the page limitation.

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

Appendix Materials

All paper PHS 398 applications 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 the RFA HL-08-011 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 the AsthmaNet Clinical Centers 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 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 AsthmaNet research resources such as Manual of Operations, study manuals, case-report forms, phenotype ascertainment instruments 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 in response to RFA-HL-08-011. Clinical Center applicants in response to this FOA should indicate here their willingness to cooperate with this resource sharing.

Section V. Application Review Information

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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:

• Undergo a selection process in which only those applications deemed to have the highest scientific and technical merit, generally the top half of applications under review, will be discussed and assigned a priority score.
• Receive a written critique.
• Receive a second level of review by National Heart, Lung, and Blood Advisory Council.

The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Willingness, and evidence of potential, to participate collaboratively in all aspects of the AsthmaNet program.
• Willingness to participate in NHLBI Division of Application of Research Discoveries (DARD s) dissemination and education programs.
• Agreement to accept the Cooperative Agreement Terms and Conditions of Award delineated in this FOA (see Section VI. 2. A).
• Geographic balance of Clinical Center awardees.
• Diversity of study populations among Clinical Center awardees.
• Program balance among proposed research protocols and balance of scientific expertise among investigators.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a 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? Do the proposed research protocols address issues of clinical importance?

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? Are the protocols powered sufficiently to address important objective and patient-centered endpoints (for example, but not limited to, outcomes or biomarkers identified by NAEPP clinical practice guidelines)? Does the applicant acknowledge potential problem areas and consider alternative tactics? Does the proposed research reflect a need for the AsthmaNet research network structure? Is the leadership approach (described in the Multiple PI Leadership Plan), 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 PIs? For the proposed study population(s), is there evidence of adequate access to recruit and enroll at least 600 children and 600 adults who have asthma, and 100 people who have severe asthma for participation in protocols? Are anticipated problems with recruitment adequately identified and addressed? Are there unique strengths at the applicant institution(s) in recruiting minority participants or participants with a specific level of asthma severity? Is there evidence of strong experience in recruiting AND retaining study participants in 12-18 month long studies? Is there experience in promoting adequate adherence to study protocols among study participants?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)? Is there an established asthma research program and strong experience in conducting clinical trials? 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 network structure?

Does the Leadership Plan for Multiple PIs describe a strong organizational structure for the leadership team (the PI with expertise in pediatric asthma and the PI with expertise in adult asthma) and the research project, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support? Is there evidence of the applicant institution’s history of collaborative research? Are institutional resources including personnel, space, special laboratory facilities adequate to support the proposed research and collaboration in a network structure?

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).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five points described in the Vertebrate Animals section of the Research Plan will be assessed.

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.

Clinical Research Skills Development Core: The reasonableness of the proposed Clinical Research Skills Development Core and requested level of funding will be evaluated as either acceptable or unacceptable. The evaluation will be separate from and will not enter into the AsthmaNet application priority score. The Clinical Research Skills Development Core will be evaluated for its effectiveness in developing the skills and clinical research capabilities of new investigators. This will include an evaluation of:

Senior Investigators: Does the applicant provide evidence of appropriate credentials and success records of the Principal Investigator, Core Project Leader, and other participating senior investigators as researchers and trainers.

Recruitment: Is the quality of the methods by which trainees are to be recruited and selected, including the plans to recruit women and minority individuals appropriate to the aims of the proposed studies. Are high quality trainees available to participate in the proposed research.

Development Plan: Are the plans provided for developing the skills of trainees; are the types of skill and technologic development proposed of appropriate quality to promote progression to more independent researcher status? Is there evidence of sufficient and clearly defined mentoring activities? Are proposed training activities well coordinated with participating senior investigators? Will steps be taken to avoid overlap or duplication with existing training opportunities at the applicant institution? Is there evidence of a distinct training opportunity to offer AsthmaNet as a collaborative training project?

Impact: Is the quality of the plan for measuring the effectiveness of the training program, including progression to more independent status appropriate for the proposed program?

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.

• Data Sharing Plan. [http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm]
• Sharing Model Organisms. [http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html]
• Genome Wide Association Studies (GWAS). [http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html]

Clinical Center applicants in response to this FOA are not required to submit resource sharing plans. The AsthmaNet Data Coordinating Center applicants in response to RFA HL-08-011 will submit data sharing and resource sharing plans. Clinical Center applicants should indicate willingness to work with the Data Coordinating Center in implementing a resource sharing plan on behalf of the AsthmaNet.

3. Anticipated Announcement and Award Dates

Not Applicable.

Section VI. Award Administration Information

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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 14 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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

2. Administrative and National Policy Requirements

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

The 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 AsthmaNet studies, including proposing protocols, participating in their overall development, preparing protocol budgets in collaboration with the DCC, modifying proposals if indicated, recruiting study participants, conducting the research, assuring quality of study participant care and protocol adherence, assuring the accurate and timely transmission of data collected in conjunction with the DCC, analyzing and interpreting data, preparing publications, and working with the DCC and NHLBI to disseminate research findings. Clinical Center PIs will also be responsible for working with the DCC to develop common definitions and standardization across protocols wherever appropriate.

The Data Coordinating Center Principal Investigator will be responsible for the overall function of the DCC, which is to coordinate, administer, and support all AsthmaNet research activities. The DCC PI will be responsible for oversight of protocol development, drug acquisition and distribution, data collection, data safety and confidentiality, quality assurance, data analysis, coordination of data distribution, and implementation of all data sharing plans. The DCC PI will be responsible for the distribution of protocol funds to the Clinical Centers (see Funds Available in Section II. 2. RFA-HL-08-011). The DCC PI will be responsible for the editorial and meeting coordination for manuscript preparation, coordination of the activities of the Steering Committee, Protocol Review Committee, and Data and Safety Monitoring Board.

Support or other involvement of industry or any other third party in the AsthmaNet studies 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.

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

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.

AsthmaNet will have two NIH Project Scientists who will also serve as program directors; they will share participation in overall Steering Committee activities. Several procedures are in place to manage potential conflict of interest by project scientists (PS) administering the cooperative agreement. These include: the project scientists adhere to stringent NIH ethics rules and financial disclosure reporting to eliminate overt and perceived conflict of interest; PS are 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; semi-annually or quarterly 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 lead authorship of primary publications and will obtain approval by Branch Chief to participate in secondary publications.

The NHLBI Project 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 potential changes in the 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). The NHLBI Project Scientists, 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 an AsthmaNet study (or an individual award) in the event of (1) failure to develop or implement mutually agreeable collaborative 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 actual recruitment 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 the study through a Steering Committee (SC). All Principal Investigators 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 Data Coordinating Center, and the NHLBI Project Office will have one vote; the Chair will have one vote in case of a tie. Note that although each Clinical Center’s two principal investigators (one with expertise in adult asthma, one with expertise in pediatric asthma) are expected to participate in all SC meetings, each Clinical Center has one vote. It is anticipated that SC meetings will be held twice a month by conference call and six times a year in person.

An independent Protocol Review Committee (PRC) will provide peer review for each AsthmaNet protocol. The PRC will be appointed by and be advisory to the NHLBI. It will consist of a chairperson, and Executive Secretary who is an NHLBI scientist other than the NHLBI Project Scientist, and scientists with expertise in clinical trial design, biostatistics and data coordinating center management, asthma clinical management and research in adults and pediatrics, bioethics, and other areas of expertise as needed. Because the Board serves as an independent group advisory to the NHLBI, study investigators will not communicate with Board members regarding study issues, except as authorized by PRC Executive Secretary. The PRC will evaluate protocols proposed by the SC based on the significance of the questions to be addressed, scientific merit and innovation of the experimental design and approach, feasibility, appropriateness for the Network and consistency with NHLBI missions and policies. The PRC will provide a written critique of each proposal and a final recommendation to the NHLBI. All study protocols performed by the AsthmaNet will be recommended by the PRC and approved by the NHLBI before initiation.

A Data 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 Scientists, shall serve as Executive Secretary to the DSMB.

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 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

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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:

Virginia S. Taggart, M.P.H.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Bethesda, MD 20892-7952
Telephone: (301) 435-0202
Email: [email protected]

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: [email protected]

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: [email protected]

3. Financial or Grants Management Contacts:

Ryan Cherise Lombardi, M.S.M.
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
Room 7154, MSC 7926
6701 Rockledge Drive
Bethesda, MD 20892-7926
Telephone: (301) 435-0144
FAX: (301) 451-5462
Email: [email protected]

Section VIII. Other Information

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

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

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

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

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

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

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-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 PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

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

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

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