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Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
National Heart, Lung, and Blood Institute (NHLBI), (http://www.nhlbi.nih.gov)

Title: Prematurity and Respiratory Outcomes Program (PROP) (U01)

Announcement Type
New

Request For Applications (RFA) Number:  RFA-HL-10-007

Catalog of Federal Domestic Assistance Number(s)
93.838

Key Dates
Release Date: March 10, 2009
Letters of Intent Receipt Date: May 4, 2009
Application Receipt Date: June 2, 2009
Peer Review Date(s): September/October 2009
Council Review Date: January 2010
Earliest Anticipated Start Date: April 1, 2010 
Additional Information To Be Available Date (Url Activation Date):  Not applicable http://www.nhlbi.nih.gov/funding/inits/faq-prop.htm (January 16, 2009)
Expiration Date: June 3, 2009

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

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

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

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

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

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

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

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose and Rationale  

To promote collaborative, innovative research to identify mechanisms and associated functional and molecular biomarkers of respiratory disease risk of premature infants ready for discharge from the neonatal intensive care unit (NICU).

Background

Increased survival of very premature infants is leading to increasing numbers of children with chronic lung disease.  Even late preterm infants (born up to six weeks early) have a readmission rate two to three times their term counterparts, and are more likely to suffer respiratory complications.  Impairment of lung function in premature infants can persist into adulthood, contributing to chronic respiratory diseases including asthma and emphysema.  With the rates of premature births increasing (12.7% in 2005, a 30% increase since 1981), efforts to improve strategies for managing low birth weight, fragile infants are an important public health goal. There are currently no objective measures that can be used to predict premature newborns that will have persistent respiratory problems after discharge from the hospital.  Given the high prevalence of respiratory morbidities in infants discharged from NICUs, strategies and tools to identify newborns at risk of low lung function and to reduce acute and chronic respiratory morbidity are urgently needed. 

It is estimated, for example, that 5,000-10,000 newborns each year develop bronchopulmonary dysplasia (BPD), with an incidence of up to 85% in preterm infants of very low birth weight (500-699g).  Because the lungs are less well-developed, preterm infants with and without BPD have life-long increased risk of death, re-hospitalization, and chronic and acute respiratory symptoms requiring therapy compared to term infants. 

Because BPD is a non-specific diagnosis based on a supplemental oxygen requirement at 36 weeks postmenstrual age, it is likely caused by many mechanisms; pathophysiology that contributes to respiratory morbidity may include airway obstruction, low lung volumes due to abnormal alveolarization, pulmonary hypertension, or apnea.  Currently, infants are not separated by objective measures to phenotype the underlying respiratory limitations. Better understanding of the different mechanisms and the characteristics of the premature infants associated with each mechanism would permit stratification of risk, better informed therapeutic choices, and possibly, markers for evaluating risk modification.

Purpose

This RFA intends to fill this need for understanding the underlying pathophysiology by supporting the investigation of the molecular mechanisms that contribute to acute and chronic respiratory morbidity of the premature infant.  The well phenotyped populations developed in this program will significantly increase the chance of studying groups with common pathophysiology and lay the groundwork for novel biomarker discovery.

The program will use the cooperative agreement mechanism and require multidisciplinary expertise including neonatologists/pulmonologists, and physiological, molecular, biological, or bioinformatics scientists.  Participating sites will plan and coordinate their own research and will develop and implement shared protocols for respiratory phenotyping and respiratory outcomes of the premature infant NICU graduate.  A Data Coordinating Center will manage data collection and provide support for standardization of definitions, clinical report forms, and analysis and will manage funds for multicenter projects selected by the Steering Committee.  We encourage leveraging of resources available through CTSAs and the NICHD Neonatal and Maternal-Fetal Research Networks.

Program Structure

PROP will consist of multiple Clinical Research Centers (CRC), one Data Coordinating Center (DCC), and a Steering Committee (SC). The first six months of the grant period will be for planning to permit the CRCs to conduct the necessary activities, individually and as a cooperative program, to be able to begin recruiting infants by the end of Year 1. 

Clinical Research Centers (CRC):  A CRC can be a single institution or group of institutions with the capability of recruiting sufficient numbers of premature infants ready for discharge from the NICU to ensure robust pathophysiologic and molecular studies of acute and chronic respiratory disease risk.  Each CRC will be comprised of a multidisciplinary team that must include at least one clinician scientist (pediatric pulmonologist, neonatologist) and at least one laboratory scientist (physiologist, developmental/molecular biologist, geneticist, statistical geneticist, bioinformatics expert).  Additional key personnel such as recruiters, nurse coordinators, biostatisticians, and others should be specified.  CRCs may use the multiple principal investigator (PI) option (http://grants.nih.gov/grants/multi_pi); investigators can be either from the same institution or different institutions.

CRC applications must contain two components: (1) a research project that investigates one or more molecular mechanisms that contribute(s) to respiratory disease risk in premature neonates over the first year of life, and (2) a multicenter concept for biomarker discovery that can easily be applied in the routine clinical setting. In addition, it is strongly suggested that a proposal for uniform respiratory phenotyping and respiratory outcomes of neonates near the time of discharge from the NICU and in the year following discharge that could be utilized across all participating sites be included.

Applications in response to this FOA will require collaboration of pediatric pulmonologists/neonatologists with expertise in measurements of pulmonary outcomes, and physiological, molecular, biological, or bioinformatics scientists, who will develop pioneering hypotheses together. Each CRC will propose and conduct unique research with physiological/imaging, genetics/”omics” or other molecular biomarker studies at its site, but will also participate in a cooperative and interactive manner with all other CRCs that comprise the Steering Committee to develop common definitions of respiratory phenotypes and respiratory outcomes, and develop one to two multicenter projects. 

The proposed clinical measurements and sample collection should be to support the discovery of the proposed hypotheses of pathophysiological mechanisms and biomarkers that will characterize premature infants and predict which develop respiratory difficulties such as airway obstruction, inadequate alveolar growth, pulmonary hypertension, and/or apnea.  State-of-the art “omics” approaches such as genomics, epigenetics, transcriptomics, proteomics, metabolomics, or exploring the microbiome could be applied to the proposed pathophysiologic mechanisms and discovery of biomarkers that characterize and predict respiratory abnormalities in premature infants. The likelihood of discovering genetic/epigenetic causes of early onset lung disease is high in premature newborns, as environmental exposures over their short “life-time” are better defined.

Clinical tools such as infant pulmonary function testing, imaging, polysomnography, and echocardiography can be utilized in new, inventive ways to determine the underlying pathophysiological status of the at-risk premature infant and eventually lead to better prediction of appropriate therapeutic interventions.  Biospecimens could be from uniquely perinatal and non-invasive sources (amniotic fluid, placenta, and cord blood); from patients and parents, if available; as well as from more traditional sources (serum, urine, stool, and tracheal aspirates). 

Each CRC will be expected to recruit a minimum of 150 participants for physiologic and/or molecular biomarker studies and to share biospecimens and patient information with other members, so that data on 750 premature infant graduates will be available to the collaborating sites.  For the multicenter novel biomarkers proposals, the research design will need to consider feasibility and quality of biospecimen collection from other sites in calculations of sample size.  The Steering Committee will develop common recruitment, phenotyping procedures, and follow-up schedules.  Investigators should indicate in their application their willingness to collaborate on the development and use of standardized protocols for phenotyping and outcome data collection, identification of diagnostic studies, methods for biospecimen collection, data analysis, and their willingness to collaborate with NHLBI program staff in all aspects of the study.  The Steering Committee will evaluate the multicenter concepts proposed by each applicant and decide which one to two protocols will be developed for multicenter collaboration in biomarker discovery and potential for clinical application in the NICU setting.

Data Coordinating Center (DCC):  The DCC will provide statistical leadership and expert assistance in concept development and feasibility assessment. The DCC will facilitate all aspects of recruitment including harmonization of procedures across sites, consent form templates, development and programming of case report forms, preparation of materials for submission to local IRBs, manuals of operation, oversight of protocol and protocol amendments, web-based data entry, serious adverse event reporting, coordinator and other staff training, common phenotyping elements, and clinical database management.  The DCC will oversee a biorepository. The DCC will also organize meetings and calls of the Steering Committees, Data and Safety Monitoring Board (DSMB), and PROP joint annual meetings; design and maintain written materials and a website to support PROP; and distribute funds for multicenter collaborative studies. The DCC will provide relevant reports to the NHLBI and DSMB.  The DCC should have appropriate expertise for neonatal studies.

Applicants for the DCC should present a description of plans to: 

  1. Maintain a common data set.
  2. Provide data management, including quality control and development of forms.
  3. Provide data analysis plans and other statistical support.
  4. Develop needed databases and implement a web-based system to coordinate program activities.
  5. Provide support in designing and conducting joint protocols.
  6. Provide support for and monitor clinical center start up procedures.
  7. Maintain quality control and monitor performance of the Clinical Centers and other central units.
  8. Provide procedures and training to clinical center staff, answer questions as needed, and take a leadership role in resolving issues and problems as they arise during the study.
  9. Monitor that all clinical centers use informed consent documents that contain all necessary elements and that informed consent is obtained properly for all participants.
  10. Prepare and distribute report (e.g., adverse event report compilation and distribution; clinical center recruitment performance).
  11. Provide coordination of DSMB, Steering Committee, and Research Site subcommittee teleconferences, meetings, and reports as needed.
  12. Provide support for preparing and submitting joint presentations and joint publications.

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

NHLBI, with input from the Steering Committee, will determine the multicenter collaborations that will be conducted by the PROP CRCs; up to $575,000 additional direct costs/year in Years 2-5 will be distributed by the DCC.

Steering Committee:  The Steering Committee will have responsibility for overall scientific direction of the PROP, for evaluating multicenter collaborative research opportunities, data sharing and publication, and for devising ancillary studies that may include new investigators in program activities.  The CRC PIs, the DCC PI, and the NHLBI Project Scientist will serve on a Steering Committee for the PROP.  The Steering Committee will be chaired by one of the site investigators or an outside expert selected by the NHLBI.  The Chair will have one vote, as will each of the other site PIs, the DCC PI, and the NHLBI Project Scientist.  The Steering Committee will meet by conference call monthly, in person for an implementation meeting at the start of the project period to agree upon common definitions of respiratory phenotypes, clinical and biospecimen data collection, and definitions of respiratory outcomes, and up to twice a year throughout the project period. Each applicant must budget funds for attending these meetings.

A DSMB will be responsible for monitoring the funded projects and will report to the Director of the NHLBI.  The DSMB will be appointed by the Director, NHLBI to provide overall monitoring of progress, interim data and safety issues.  Therefore, applicants should not appoint DSMB members in advance of the peer review, or even inquire about the interest of possible DSMB members, because anyone so contacted would not be eligible to serve as a member of the peer review committee that will evaluate the applications for scientific merit.  An NHLBI scientist other than the NHLBI’s PROP Program Scientist will serve as the Executive Secretary to the DSMB.  The DSMB will meet approximately semi-annually by teleconference call or in-person meetings in the Greater Washington D.C./Baltimore region.

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

Applicants should not submit plans for an External Advisory Committee, nor should they propose specific names of individuals for the DSMB in their application.

Planning Phase: The project period for the PROP will be five years, with the first six months serving as a planning phase.  The Steering Committee will meet at the start of the project period, assess the needs of the program, and develop a plan for collection of data and biospecimens, data handling, and collaborations.  The collaborative plan will be reviewed by the Steering Committee, which will make recommendations to the NHLBI.

Selected research examples include, but are not limited to: 

This FOA is intended to support only human studies.  Applications that include animal studies will not be considered responsive. Patient registries alone, without a hypothesis to be tested, will not be responsive.  Retrospective studies will not be considered responsive, and clinical trials are not the intent of this FOA.    

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

Section II. Award Information

1. Mechanism of Support

This funding opportunity will use the Research Project Cooperative Agreement (U01) award mechanism(s). In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

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

2. Funds Available

The estimated amount of funds available for support of up to 5 Research projects and 1 DCC as a result of this announcement is $1.5 million for fiscal year 2010.  Future year amounts are expected to be commensurate with the commencement of recruitment into clinical protocols, and will depend on annual appropriations.

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

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

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

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions
 
The following organizations/institutions are eligible to apply:

1.B. Eligible Individuals

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

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

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. 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.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Number of Applications.  Applicants may submit only one application on which they are the PI or part of a multiple PI team.

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

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

Section IV. Application and Submission Information

1. Address to Request Application Information

The 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.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs 

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

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

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

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

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

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

3. Submission Dates and Times

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

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date: May 4, 2009
Application Receipt Date: June 2, 2009
Peer Review Date(s): September/October 2009
Council Review Date: January 2010
Earliest Anticipated Start Date: April 1, 2010

3.A.1. Letter of Intent

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

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

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

The letter of intent should be sent to:

Chief, Review Branch
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892
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
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892
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

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

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

6. Other Submission Requirements and Information

This FOA will require collaboration of pediatric pulmonologists and neonatologists with expertise in neonatal pulmonary outcomes and molecular, biological, or bioinformatics scientists, who will together propose innovative hypotheses to be tested, develop protocols for clinical data collection, novel use and analysis of functional measurements, and biospecimen collection, and will share and analyze data to create predictive models for respiratory outcomes. Use of the Multiple PI mechanism is strongly encouraged.  Awardees must agree to the “Cooperative Agreement Terms and Conditions of Award” in Section VI.2.A “Award Administration Information.” 

Clinical Research Center Principal Investigators will be required to declare a minimum effort of 2.4 calendar months, and will be required to participate on the Steering Committee as described in Section VI.2.A.  If the Multiple PD/PI approach is chosen, the minimum effort can be distributed across all PIs, if this will be sufficient to support the science. 

Clinical Research Center applicants at sites that have Clinical and Translational Awards CTSAs or sites that have Maternal and Fetal Medicine Unit or Neonatal Networks (supported by NICHD) are strongly encouraged to describe in their applications how they will leverage these resources to support the research proposed for this FOA.

Research Plan Page Limitations

Applications must contain the following sections, in order, with page limits where indicated:  (1) Documentation of Commitment to the Program (1 page); (2) Research Plan (25 pages); (3) Strategy for respiratory phenotyping and outcome measures (2 pages); and (4) Applicant Group Qualifications, Organization and Administration (10 pages).  Each section is described below:

1.  Documentation of Commitment to the Program (1 Page)

The application must include a written commitment, signed by the Principal Investigator(s) and the applicant institution, to participate in the Program, including serving on the Steering Committee, adhering to Steering Committee policies and decisions, accepting the participation and assistance of NHLBI staff in accordance with the guidelines described in Section VI.2.A. Cooperative Agreement Terms and Conditions of Award.

2.  Research Plan (25 pages)

The research plan should propose a single center project that can be completed by the Clinical Research Center in four years (after an initial six-month planning period).  Clinical Research Center applications will contain two components: (1) an innovative research project to identify mechanisms and associated functional and molecular biomarkers that will predict risk of respiratory disease in the first year of life, which can be accomplished at the PIs institution (22 pages), and (2) a multicenter concept for biomarker discovery that would be collaborative across at least three CRCs in PROP, that can easily be applied in the routine clinical setting (3 pages).

The description of the planning period should include activities required to ensure that recruitment can begin by the end of Year 1, such as finalizing protocols, obtaining pilot data if needed, obtaining IRB approval, establishing research collaborations with other sites, completing coordinator training, and ordering necessary supplies. 

The research plan for Years 2-5 will include a description of the clinical study design, including hypotheses, study objectives, target population, total number of subjects required at the site (for the research project) and across the Program (for the multicenter concept), anticipated duration of recruitment and data analysis, and a description of the statistical analysis plan.  The Research Plan should describe the patient population and recruitment resources including experience with recruitment of neonates available at the Research Center site that would benefit the Program, including CTSA, Maternal Fetal Medicine Unit, and/or Neonatal Network resources.  The research plan should propose specific milestones that could be used to evaluate success of the project throughout the duration of funding. 

All proposals will include a data sharing plan, and any proposal including genome-wide association studies will comply with the NIH GWAS policy (http://grants.nih.gov/grants/gwas/)  Novel genetic variants identified should also be shared (e.g., through dbSNP -- http://www.ncbi.nlm.nih.gov/projects/SNP/). 

3. Strategy for respiratory phenotyping and outcome measures (2 pages)

The clinical research center should propose a strategy for how the NICU graduates in the program should be phenotyped for respiratory status at the time of discharge from the NICU and what/how/and when respiratory outcomes should be measured in the year of follow-up across all sites in collaborative projects.  This will be used for program planning of PROP by NHLBI and the Steering Committee.

4. Applicant Group Qualifications, Organization and Administration, Including Cores (10 pages)

The applicant institution and PI(s) must document clinical and research collaborative experience of neonatology and pulmonology, an established program of neonatal and pulmonary follow up of premature infants, and prior experience in recruitment (minimum of 30/year), and retention (at least 80%) of infant study participants.

Detailed data on the population available for each proposed study (single site and multicenter) should include at a minimum the following:

Neonatology (in the past year):

1.  Number of births per year.

2.  Number of neonatal ICU admissions per year.

a.  Of these, how many had a birth weight<1500 grams.

b.  Of these, how many had a birth weight <1000 grams.

c.  Number of admissions inborn.

d.  Number of patients outborn/transported.

3.  Average daily census in NICU.

4.  Average Length of Stay in NICU.

5.  Number of patients requiring ventilatory support.

a.  CPAP only (without mechanical ventilation).

b.  Ventilator.

c.  Extra corporeal membrane oxygenation (ECMO).

6.  Number of discharges with a diagnosis of bronchopulmonary dysplasia (BPD).

Pulmonology (in the past year):

1.  Total number of admissions for whom the pediatric pulmonary service assumed major clinical responsibility

a.  Average daily census of patients on the pediatric pulmonary service

b.  Number of new patients admitted each year (“new” refers to those who are being seen by pulmonologists for the  first time)

c.  Average length of stay of patients on  the pediatric pulmonology service:

2.  Number of consultations by pediatric pulmonologists on other inpatients

a.  Number of consultations provided to the NICU

b.  Number of consultations provided to the PICU

3.  Number of outpatient visits

a.  Number of new consultations for NICU graduates

b.  Number of NICU graduates

Clinical Facility/Service (in the past year):

The expertise of the functional/molecular scientist(s) must also be provided.  

The applicant must provide a clear and concise plan in narrative and/or diagrammatic form that depicts the interrelationships among the members of the team or group, their relevant experience and expertise, and the contribution of each to fulfillment of the objectives of this RFA. 

The applicant must provide a plan to ensure the maintenance of close cooperation and effective communication among members of the applicant’s group and evidence of the capability of the applicant organization to participate and interact effectively in cooperative, multi-center clinical research.

5.  Additional submission requirements for the preparation of the Detailed Budget

Research Centers

The budget for the first year, which includes a 6-month planning phase, should include a minimum of 2.4 calendar months effort for the applicant PI or a minimum of 2.4 calendar months combined effort for all PIs if the multiple PI strategy is used, a 0.5 FTE clinical study coordinator, travel funds for two 2-day Steering Committee meetings in Bethesda, MD, for the PI and coordinator, travel funds for 2-3 days of coordinator training, and additional items as needed.  Direct costs in Year 1 cannot exceed $150,000.  

For Years 2-5, all costs required for the proposed research must be included in the application and be fully justified.  The budget must include support for a 0.75 FTE clinical study coordinator; a minimum of 2.4 calendar months effort for the applicant PI or a minimum of 2.4 calendar months combined effort for all PIs if the multiple PI strategy is used.  The budget should include the costs associated with identification, screening, and recruitment of subjects and, if indicated, controls; the costs of obtaining, processing, and storage of biological specimens; and the costs associated with the analyses required for the physiologic and/or molecular/biologic aims of the research.  Travel costs for two Steering Committee meetings per year in Bethesda should be included for two to three members of the Research Center, including at least one PI and the coordinator. If CTSA resources are to be used, and a fee is charged, please note this in the budget.  Direct costs in Years 2-5 cannot exceed $350,000 per year.  

The elements of patient-related research costs should be clearly identified, and included both as a per-patient amount, and a total amount.  Patient-related funds can be moved by NHLBI after award from one site to another to adjust for variability in recruitment or other needs that might arise.  Indirect costs (facilities and administration) are not permitted to be included in patient-related research costs.  In addition, IRB fees are not permitted to be paid from direct costs in NIH grants.  They are considered to be indirect costs.    

For multicenter concept proposals, the budget must include the costs associated with coordination of biospecimen collection from all patients to be recruited, not just the number of patients that are expected from the applicant site.  Costs may include those associated with shipping specimens, images, or other material; staff time to develop operational and training manuals, analyze recordings, specimens, or images and report the results; any storage capability required at the sites; travel for one Steering Committee meeting per year in Bethesda, MD; and other components as required.  These budgets, which should be on separate budget pages, are for planning purposes only; the NHLBI, with input from the Steering Committee, will determine the multicenter collaboration configuration, with up to $575,000/year in Years 2-5 allocated by the DCC and be additional to the administrative costs of the DCC.    

Data Coordinating Center 

Applicants for the centralized DCC should present a description of plans to: 

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

The DCC staff should have appropriate expertise and experience in project management, biostatistics, epidemiology, database management, and sample collections.  Prior experience in complex collaborative studies is desired.  The DCC Principal Investigator and other key staff should have knowledge of neonatal outcomes, respiratory clinical studies, repositories, and biomarker/“omics” research.  The DCC is expected to have online data entry capabilities; analytic and computational modeling; informatics expertise; and expertise in web-based data management.

Appendix Materials

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

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

Resource Sharing Plan(s)

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

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

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

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

Section V. Application Review Information

1. Criteria

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

2. Review and Selection Process

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

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

The following will be considered in making funding decisions:

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

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

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

Significance.  Does the project address an important problem or a critical barrier to progress in the field?  If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved?  How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Are the rationale and scientific merit of the proposed studies well developed and feasible?  If implemented, is it likely that the proposed studies will advance the field of neonatal-pulmonary medicine?

Investigator(s).  Are the PD/PIs, collaborators, and other researchers well suited to the project?  If Early Stage Investigators or New Investigators, do they have appropriate experience and training?  If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?  If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Does the Principal Investigator(s) have adequate expertise in and a documented history of contributions to the field of human neonatal-pulmonary medicine or neonatal functional/molecular biomarkers?  Does the Principal Investigator have prior experience with collaborative research?  Does the Principal Investigator have prior experience with successful timely recruitment and retention of neonatal subjects?

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

Approach.  Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?  Are potential problems, alternative strategies, and benchmarks for success presented?   If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for (1) protection of human subjects from research risks, and (2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Are there adequate and feasible plans for managing the proposed studies and for recruitment and retention of study participants?  Does the applicant adequately address potential obstacles, limitations and problem-solving strategies with respect to these activities?  Are the milestones proposed appropriate?

Environment.  Will the scientific environment in which the work will be done contribute to the probability of success?  Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed?  Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?  Is there evidence that the institution has a track record in supporting collaborative clinical investigations? Are there institutional resources that will be leveraged (CTSAs, NICHD networks)?

Potential for Collaboration.  Would the project proposed benefit from collaborative interactions with the program (PROP)?  Will the proposal allow flexibility in collaboration with the program?  Will the investigators bring valuable areas of expertise to the program that will maximize flexibility for the program?  Does the application describe prior successful collaborative research?

Potential Multicenter Proposals. What is the quality of the multicenter concept for biomarker discovery? What is the likelihood that that concept could (or would) be applied in a routine clinical setting? If the application contains a proposal for uniform respiratory phenotyping and respiratory outcomes of neonates near the time of discharge from the NICU and in the year following discharge, what is the quality of that proposal?

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

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

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

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

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

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

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

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

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

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

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/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 study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the Steering Committee. 

Awardee(s) agree to the governance of the study through a Steering Committee. Steering Committee voting membership shall consist of the principal investigators (i.e., cooperative agreement awardees), the NHLBI Project Scientist, the Chairperson, and the DCC PI.  Meetings of the Steering Committee will ordinarily be held by telephone conference call or in the metropolitan Washington Area.

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

Upon completion of the project, awardees are expected to put their intervention materials and procedure manuals into the public domain and/or make them available to other investigators, according to the approved plan for making data and materials available to the scientific community and the NHLBI, for the conduct of research at no charge other than the costs of reproduction and distribution.

Awardees will retain custody of and have primary rights to their data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. The collaborative protocol and governance policies will call for the continued submission of data centrally to the coordinating center for a collaborative database; the submittal of copies of the collaborative datasets to each principal investigator upon completion of the study; procedures for data analysis, reporting and publication; and procedures to protect and ensure the privacy of medical and genetic data and records of individuals. The NHLBI Project Scientist, on behalf of the NHLBI, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the Steering Committee.

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

2. A.2. NIH Responsibilities
 
An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

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

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

The NHLBI reserves the right to withhold funding or curtail the study (or an individual award) in the event of (1) failure to develop or implement a mutually agreeable collaborative protocol, (2) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control, (3) major breach of the 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 end of the award. 

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

Additionally, an agency program official or NIH program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.  The assigned program director may also serve as an NIH Project Scientist.

2.A.3. Collaborative Responsibilities

Awardees agree to the governance of the Program (PROP) through the Steering Committee.  Membership will include, at a minimum, the Research Center PIs, the PI of the Data Coordinating Center, and the NHLBI Project Scientist.  A representative Data Coordinating Center will be an ex officio member.  The Steering Committee Chair will be appointed by NHLBI.  Additional members may be added by majority vote of the Steering Committee.

Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

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

Section VII. Agency Contacts

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

1. Scientific/Research Contacts:

Carol J. Blaisdell, M.D., F.A.A.P.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Dr., 10042
Bethesda, MD 20892
Telephone: (301) 435-0222
Email: [email protected]

2. Peer Review Contacts:

Chief, Review Branch
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892 (Express Mail Zip: 20817
Telephone: (301) 435-0270
FAX: 301-480-0730
Email: [email protected]

3. Financial or Grants Management Contacts:

Natasha Hurwitz
Grants Management Specialist
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7132
Bethesda, Md.  20892-7926 (Express Mail Zip 20817)
Telephone: (301/435-0163)
Email:  [email protected]

Section VIII. Other Information

Required Federal Citations

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

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

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

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

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, state and federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

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

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

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/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: (1) 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 (2) 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.

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

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

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

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

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

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

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

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

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NIH Funding Opportunities and Notices


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