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 Institute of Child Health and Human Development (NICHD), (http://www.nichd.nih.gov/)

Title: NICHD Cooperative Multicenter Neonatal Research Network

Announcement Type
This announcement for the NICHD Neonatal Research Network (NRN) is a reissue with modifications of RFA-HD-00-010, released on April 3, 2000.

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

Request For Applications (RFA) Number: RFA-HD-04-010

Catalog of Federal Domestic Assistance Number(s)
93.865

Key Dates
Release Date: March 4, 2005
Letters of Intent Receipt Date(s): June 22, 2005
Application Receipt Dates(s): July 22, 2005
Peer Review Date(s): October/November 2005
Council Review Date(s): January 2006
Earliest Anticipated Start Date: April 1, 2006
Additional Information To Be Available Date May 16, 2005 (Url Activation Date): A workshop on the RFA will be held on May 16, 2005 in conjunction with the Pediatric Academic Societies Annual Meeting in Washington, DC. The presentation will be available at (http://www.nichd.nih.gov/RFA/HD-04-010/Workshop.htm).
Expiration Date: July 23, 2005

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 and Review and Anticipated Start Dates
        1. Letter of Intent
      B. Sending an Application to the NIH
      C. Application Processing
    4. Intergovernmental Review
    5. Funding Restrictions
    6. Other Submission Requirements

  Section V. Application Review Information
    1. Criteria
    2. Review and Selection Process
      A. Additional Review Criteria
      B. Additional Review Considerations
      C. Sharing Research Data
      D. Sharing Research Resources
    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

The National Institute of Child Health and Human Development (NICHD) invites applications from investigators willing to participate with the NICHD under a cooperative agreement in an ongoing multicenter clinical program designed to perform interventional and observational clinical studies in newborn infants, particularly low birth weight infants. The model of multi-site clinical centers for research is the gold standard for conducting clinical research. The objective of this program is to facilitate the advancement of neonatal care by establishing a network of academic centers that, by rigorous patient evaluation using common protocols, can study the required numbers of patients and can provide answers more rapidly that individual centers acting alone.

The infrastructure is set up for the ideal randomized double-blinded placebo controlled trial with the ability to follow short term (clinical effect) and long term (neurodevelopmental outcome) measures. The infrastructure is also set up for observational, longitudinal studies in the neonatal intensive care unit setting. Many randomized clinical trials involve the need for baseline information regarding disease incidence and outcome, which is available from the generic database of neonates < 1,500 grams birth weight in the current Neonatal Research Network. This initiative will foster conducting multicenter trials in the neonatal population.

The NICHD Program Staff will assist Principal Investigators of the Neonatal Research Network (NRN) and the Advisory Board in identifying research topics of high priority, and in designing and implementing protocols in the evaluation of optimum management in the areas targeted for research.

It is anticipated that approximately 13 to 16 clinical centers will be involved in the program.

Background

The primary objective of the Neonatal Research Network (NRN) is to advance the field of Neonatal-Perinatal Medicine by establishing and maintaining a network of academic centers that perform multi-center clinical protocols in a rigorous manner to investigate the safety and efficacy of treatment and management strategies to care for newborn infants, including low birth weight infants.

In an attempt to respond to the need for well-designed clinical trials in neonatal medicine, NICHD established a Neonatal Research Network in 1986. Seven university units were selected from among respondents to an RFA. The Network Steering Committee, which consists of representatives from each Clinical Center, NICHD staff, and data center staff, evaluated several controversial issues for study. It then selected certain priority areas in which to develop protocols for randomized clinical trials. Protocols on the prevention of sepsis, intraventricular hemorrhage, pulmonary hypertension, surfactant administration, and outcome and resource requirements for very low birth weight (VLBW) infants were initiated. In addition, the Network established a generic database of infants less than 1,500 grams at birth. During the second grant period of the Neonatal Research Network (1991-1996), clinical trials were initiated on the prevention or treatment of chronic lung disease (CLD), intraventricular hemorrhage, retinopathy of prematurity, and persistent pulmonary hypertension. Studies of VLBW maturity and postnatal growth, the sequelae of the fetal drug exposure, and a standardized follow-up program also were initiated. During the third Neonatal Research Network funding period (1996 – 2001), intraventricular hemorrhage, retinopathy of prematurity, the treatment of persistent pulmonary hypertension, parenteral glutamine, indomethacin, erythropoietin, inhaled nitric oxide, postnatal steroids, ventilation management strategies, and outcome at follow-up were addressed. During the fourth cycle (2001-present), 16 clinical sites performed studies in the areas of necrotizing enterocolitis, inhaled nitric oxide, whole body cooling for asphyxia, benchmarking practices for bronchopulmonary dysplasia, phototherapy for extremely low birth weight infants, continuous positive airway pressure in the delivery room, candidal infections, neonatal infections, pneumococcal vaccine in very low birth weight infants, and follow up of high risk infants.

Scope

There are a number of controversial issues in neonatology that might be clarified by multicenter collaborative research. Funded Principal Investigators will cooperate with the NICHD Program Scientist in identifying research topics of high priority and in designing protocols appropriate to the evaluation of superior, or even optimal management in these areas. The participating Neonatal Research Network members will be designated as “Clinical Centers” which will recruit, assess and treat subjects under the supervision of the respective Clinical Center Principal Investigator. The data center, which is funded under a separate RFA, will have primary responsibility for data management and analysis for Network research in collaboration with the Steering Committee.

The NICHD expects to enable the Network to initiate new protocols within the first year of the next award period. The topics of these protocols will be decided cooperatively by the Steering Committee with advice from the Advisory Board. Areas of potential projects include but are not limited to:

Ongoing protocols such as the generic data base and follow up study will continue.

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

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity will use the NIH Cooperative Clinical Research U10 award mechanism(s). As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. The anticipated award date is April 1, 2006.

The NIH (U 10 ) is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

2. Funds Available

The NICHD intends to commit approximately $6.4 million in total costs [Direct plus Facilities and Administrative (F & A) costs] in FY 2006 to fund 13 to 16 new and/or competing continuation grants in response to this RFA. An applicant may request a project period of up to five years and a budget for direct costs up to $180,000 per year.

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. At this time, it is not known if this RFA will be reissued.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-05-004.html.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

Clinical centers must have a minimum of 500 admissions per year in the neonatal intensive care unit. No more than 30 percent of the infants should be outborn. Large perinatal services will be given preference over combined services composed of a small inborn unit with a large transfer population s. Organizations should have academically oriented divisions of neonatology. The need for continuous and active communication among sites dictates that only institutions in the United States are eligible to apply. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their 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 programs.

2. Cost Sharing or Matching
Not applicable

3. Other-Special Eligibility Criteria

The NICHD invites applications both from current members of the NRN Network (competing renewal applications) and from prospective members (new applications). The following items must be addressed satisfactorily for an applicant to be eligible for consideration as a Network site.

Academic Productivity

Provide evidence of research productivity by the clinical center in previous or ongoing clinical trials, especially those of a cooperative or multicenter design. Contributions in key areas of research development and design, patient recruitment, retention and study completion, data collection and analysis, and track record of publications should be included in the application.

Applicants who are current Neonatal Research Network members should describe their participation and contribution to the network in detail including patient enrollment in studies, involvement in trials and their particular contribution to the trials (principal investigator at site, trial subcommittee), standing subcommittee activities including chairmanship or vice chairmanship, and publications. New applicants must describe their recent experience and participation in randomized clinical trials. Specific roles (principal investigator, participating site, steering committee, writing committee, trial design and development) should be described for each study. Publications should be listed that resulted from participation in the studies.

Neonatology Staffing

Participants must be based at a level III/IV neonatal intensive care units that admits inborn and outborn infants. There must be at least four full time, board certified in neonatal perinatal medicine, academically oriented neonatologists. A complete description of the neonatal staff's training and qualifications in clinical care and research is required. Participation in clinical trials and clinical research should be highlighted. The principal investigator should be a practicing neonatologist and should describe their clinical, research, administrative and academic commitments. One neonatologist must be designated as an alternate principal investigator who is able to serve in the absence of the PI. Appropriate biographical sketches should be submitted with the application for the alternate PI and site neonatologists. Sites with neonatology staff at more than one clinical center must provide evidence of collaboration on recent trials including publications resulting from these studies.

Population Available for Clinical Trials

Applicant clinical centers must have at least 500 admissions per year. No more than 30 percent of admissions should be outborn. In order to provide peer reviewers with the specific neonatal population available for study at the clinical site (s), include information regarding admissions over the designated two-year period (2002-2003) in tabular format:

Number of births
Number of NICU admissions
NICU admissions < 1500 grams birth weight
NICU admissions < 1000 grams birth weight
NICU transport admissions
Average daily census for the NICU
Average daily census for intermediate care/special care nursery
Average NICU length of stay
Number of patients receiving CPAP only
Number of patients receiving ventilator care
Number of ECMO cases
Number of surgical cases

For sites with more than one clinical center, please include each site's information in a separate column. Large perinatal centers are ideal and may be given preference over multi-site arrangements. If a multi-site center has a long standing, well-documented collaboration and interaction among institutions, this should be clearly stated in the application. Eligibility and enrollment in previous clinical trials should be included in the application.

In addition, the patient population served by the NRN must be characterized by demographics, obstetric parameters, and payment status. Indications must be given of the proportions of various subgroups, including minorities, that have been eligible and actually have been randomized, in previous or current clinical trials. In addition, centers with ongoing clinical trials should report those patients eligible for NRN studies (not competing with institutional research).

Maternal Fetal Medicine Unit

The clinical center should be located in an institution with a maternal fetal medicine service for delivery of high-risk pregnancies. Perinatologists should be active in clinical research and a history of collaboration between neonatology and Perinatology towards excellent clinical care, database accessibility, and research productivity should be included in the application. The application should include a letter of collaboration along with a biographical sketch of a maternal fetal medicine collaborator. The application must include in tabular form the following information from 2002-2003 detailing maternal population for potential neonatal studies:

Number of deliveries
Number of C-sections
Number of multiple pregnancies delivered
Number of patients with diabetes (include gestational diabetes as well as patients with diabetes prior to pregnancy)
Number of patients with pregnancy induced hypertension or chronic Hypertension
Number of deliveries that are low birth weight (Number of antenatal consults performed by neonatalogy service (may include inpatient and outpatient consults)
Number of deliveries that are low birth weight: Number of antenatal consults performed by neonatalogy service (may include inpatient and outpatient consults).

Follow Up Program

An established neonatal follow up program with experience in tracking and retaining patients must be in place at the clinical site. The Neonatal Research Network strives for an 80 percent follow up rate at 18-22 months corrected gestational age. The number of clinic visits in 2001 and 2002 need to be included in the application, as well as criteria for follow up (e.g. LBW, ELBW, neurological issue, ECMO, etc.) and post conceptual age at which the children are seen in clinic visits. A designated facility for follow up must be in place at the clinical center. Applicants should describe in detail mechanisms in place to insure compliance and assistance with neonatal follow up including procedures for maintaining contact with families, scheduling appointments, actions taken for missed appointments, home visit appointments including staff participating in home visits, and creative measures instituted at the site to insure excellence in follow up rates and compliance with clinical research study protocols. There must be a follow up investigator (can be the PI) designated in the application with an included biosketch. The follow up portion of the clinical capabilities must include expertise in performing Bayley Developmental assessments, neurological examinations, and hearing and vision assessments. The current system of follow up assessment including data collection, population demographics, compliance rates, schedule of follow up visits, funding sources, policies and procedures for conducting research in the follow up setting and appropriate specialist involvement in the follow up program should be delineated in the application.

Perinatal Data System

An established electronic perinatal data system must be in place to collect and analyze patient information. A detailed description of variables collected, quality control, and management of the data system must be provided. An illustration of the use of the system for a recent clinical research application should be included in the application. All successful applications must provide complete, accurate and timely transmission of data to the Neonatal Research Network Data Coordinating Center.

Research Staff

A full time research nurse coordinator must be designated for the coordinator position. Additional research staff should be available, as many protocols require patient recruitment at night and on weekends. The individual staff training, experience, qualifications, and prior involvement in clinical research should be described in the application.

Intent to Participate

There must be a clearly expressed intent to participate in a cooperative manner with other NRN clinical centers, the NICHD and the data coordinating center in all aspect of research as outlined in this RFA. NRN projects are given priority at awarded clinical sites. Sites are expected to participate in all trials unless they describe trials that currently conflict with ongoing network trials as part of their application for this RFA.

Departmental and Institutional Commitment

The departmental and institutional commitments to participate in MFMU research should be clearly documented with letters of support from appropriate individuals. Evidence of past support can also be cited. Support in areas of grants management, personnel management; space allocation, procurement, equipment as well as general support of the research should be described as well as evidence of past research support.

Acceptance of the Budgetary Mechanism (see also budget preparation below)

Assurance of cooperation with the policy for capitation of research costs for each individual protocol, in addition to a base budget, should be provided from the departmental and institutional offices of sponsored research programs. The appropriate Federal cost policies and regulations governing NIH grant programs will be applied (see NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/index.htm).

If the institution submits applications in response to both the Neonatal Research Network RFA and the Maternal Fetal Medicine Unit RFA (HD-04-023), the applicant must describe how the two research programs will be integrated.

Section IV. Application and Submission Information

1. Address to Request Application Information

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

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

2. Content and Form of Application Submission

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

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

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(s): June 22, 2005
Application Receipt Date(s): July 22, 2005
Peer Review Date(s): October/November 2005
Council Review Date(s): January 2006
Earliest Anticipated Start Date: April 1, 2006

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 at the beginning of this document.

The letter of intent should be sent to:

Rosemary D. Higgins, MD
Pregnancy and Perinatology Branch
National Institute of Child Health And Human Development
6100 Executive Boulevard, Room 4B03B, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service, non-USPS service)
Telephone: (301) 435-7909
FAX: (301) 496-3790
Email: higginsr@mail.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the PHS 398 research grant application instructions and forms as described above. 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)

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

Robert Stretch, Ph.D.
Director, Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5B01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service, non-USPS service)
Telephone: (301) 496-1485
FAX: (301) 402-4104
Email: stretchr@mail.nih.gov

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf. Personal deliveries of applications are no longer permitted.

3.C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the NICHD. Incomplete and 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.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

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 http://grants.nih.gov/grants/policy/policy.htm (see also Section VI.3. Reporting).

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 competing continuation award if such costs: are necessary to conduct the project, and 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 competing continuation 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

In addition to the information under Section III. Eligibility Information 3. “Other Special Eligibility Criteria,” applicants must include the following in their application:

Clinical Capabilities

The applicant clinical center is expected to have a full range of perinatal subspecialists, clinical capabilities and support staff including an active research coordinator. A detailed description of the clinical attributes of the NRN must be provided. This should include antenatal fetal testing, intrapartum diagnosis, laboratory testing, and perinatal pathology. Other institutional components related to the NRN must also be described. In particular, the ambulatory facilities for prenatal and postpartum care must be presented, including the established policies and procedures for conducting clinical research in these facilities, in both low risk and complicated pregnancies. Also, the availability of an institutional pharmacy capable of supporting clinical research must be documented. A description of whether, and how, policies and procedures may have been modified to support perinatal clinical research in the past must be provided.

A clinical research coordinator must be designated for a full time position.

Capabilities for patient recruitment on nights and weekends should be outlined in the application

Concept Proposal

To provide peer reviewers and the NICHD an idea of capabilities of investigators, a concept proposal for a project for the Neonatal Research Network submission should be described briefly (two to three pages maximum). A proposal including hypothesis, specific aim(s), background, methods, and data analysis (including a consideration of power) for potential conduct in the NRN must be provided in the application. The proposed "concept" will serve as an indicator of the applicant's ability to participate in the development and design of cooperative protocols in the network. The "concept" needs to be appropriate for the NRN in that it requires a multicenter design. The "concept" or another design on the same topic may or may not actually be performed in the network. It is anticipated that funded NRN centers will be invited to submit the "concepts" included in their application to the Steering Committee.

The "concept" should also demonstrate use of the applicant's perinatal data system to estimate numbers of available patients eligible for the protocol at the institution. In addition, the protocol should address relevant ethical issues and the appropriate inclusion of minorities as subjects.

Special Strengths of the PI or Institution

Applications are encouraged to describe special or unique strengths that may be relevant to NRN research. This can include state-of-the art scientific capabilities such as modern imaging techniques, proteomics, genomics, micro analysis, genetics, placental function, clinical pharmacology and so forth, which may be shared or may be available to develop and expand the scientific productivity of the NRN.

In addition special administrative strengths or experience as well as participation in administrative aspects of clinical research (institutional review board, data safety monitoring committee, advisory board for clinical research, clinical research committees and so forth) should be highlighted. Level and support of clinical trials can be described.

Applications from institutions that have a General Clinical research Center (GCRC) funded by NIH or other funded perinatal research centers as resources for conducting the proposed research should provide a letter of agreement that identifies the level of support from the PI or the GCRC program director.

Budget Preparation

The instructions for the budget requests provided with the research grant application (PHS 398) should be followed. F&A costs will be awarded in the same manner as for research project grants. Budgets will be reviewed on the basis of appropriateness for the work proposed. Allowable costs and policies governing the research grants programs of the NIH will prevail. In planning the budget section of your application, each applicant should submit the base budget estimates for all years.

The first year budget at the time of application will be limited to a BASE BUDGET with maximum allowances as follows:

The base budget direct costs are limited to $180,000 for the first year.

When an application has been favorably recommended and is being considered for funding, the applicant will be required to complete protocol budgets for those studies underway in the network. These budgets will consist of specific protocol related allowances and will be capitated on the anticipated number of subjects to be enrolled in the study at the applicant NRN center.

Ongoing annual budgets of the NRN centers will be based on individual protocols that will be funded through a capitation system. Each NRN center will be given base costs (listed above), in addition to a flat fee for a patient successfully enrolled and completed for individual studies. For centers with GCRC funding, applicable capitation funds can be reduced relative to the amount of GCRC support. The Principal Investigator will be required to project patient enrollment for a specific protocol during a specified time frame; continuation and the level of funding will be based on actual enrollment. Each year, capitation budgets are rectified based on actual enrollment. Future years' base budgets should be limited to the first year base budget costs, with an annual increment of base salary and travel costs not to exceed 3 percent (the maximum amount available for equipment, supplies, and other costs will not increase). Federal agencies shall use the negotiated rates for F&A costs in effect at the time of the initial award throughout each competitive cycle of the project. Award levels for sponsored agreements may not be adjusted in future years as a result of changes in negotiated rates.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

The data sharing plan should be in accordance with current NRN Policies.

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The reasonableness of the data sharing plan or the rationale for not sharing research data 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.

Section V. Application Review Information

1. Criteria

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

Applications recommended by the National Advisory Child Health and Human Development Council will be considered for award based primarily on scientific and technical merit, as determined by peer review. Program balance, that is, the scope and variety of research strengths to enable a successful collaborative program, will be considered. Final selection of Clinical Centers for funding may be partly based on the need for diversity including geography and special populations in the study population. Availability of funds may also determine the awards made.

The following will be considered in making funding decisions:

2. Review and Selection Process

Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the NICHD. Incomplete and/or non-responsive applications will not be reviewed.

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NICHD in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

The following review criteria will be applied:

Applications will be reviewed based on their ability to meet overall requirements of the RFA and to cooperatively participate as an NRN site. Review of the concept proposal is one component and is used to demonstrate the site's ability to formulate appropriate and timely scientific questions applicable to the network.

Qualifications and Commitment of Key Personnel:

Protocols and Procedures

Facilities and Management

Scientific Review of Concept Proposal

Evaluation of the concept proposal for an interventional or observational study for potential implementation in the Neonatal Research Network in terms of the quality of proposed hypotheses, specific aim(s), background, methods, and data analysis (including a consideration of power).

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 priority score:

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 E on Human Subjects in the PHS Form 398).

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 E on Human Subjects in the PHS Form 398).

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.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data may 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. The funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing.

2.D. Sharing Research Resources
Not applicable

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 Principal Investigator will also receive a written critique called a Summary Statement.

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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

A formal notification in the form of a Notice of Grant Award (NGA) will be provided to the applicant organization. The NGA signed by the grants management officer is the authorizing document.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NGA 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.

Once all administrative and programmatic issues have been resolved, the Notice of Grant Award will be generated via e-mail notification from the awarding component to the grantee business official (designated in Item 14 on the Application Face Page). If a grantee is not e-mail enabled, a hard copy of the Notice of Grant Award will be mailed to the business official.

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 grant 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 (NIH Cooperative Clinical Research U10), 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 NICHD Program Scientist. Facilities and Administrative cost (indirect cost) award procedures apply to cooperative agreements in the same manner as for grants. Business management aspects of these awards will be administered by the NICHD Grants Management Branch in accordance with HHS and NIH grant administrative requirements.

2.A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for:

The Data Coordinating Center is funded through a separate solicitation as a cooperative agreement (U01).

All parties will agree to accept the coordinating role of the group and the participatory and cooperative nature of the group process.

The individual members will be required to project patient enrollment for a specific protocol during a specified time frame; continuation and level of funding will be based on actual recruitment.

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

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

NICHD Program Scientist

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

1. Assistance with the identification of important areas of study.

2. Assistance in the development of study protocols.

3. Assistance in the development and review of capitation-based budgets, including the identification of study costs and special institutional needs.

4. Assistance in the review and evaluation of each stage of the program before subsequent stages are started, in conjunction with the Steering Committee and the Advisory Board.

5. Assistance in reporting results in the community of investigators and health care recipients.

6. Assisting in the conduct of the trials, including ongoing review of progress; possible redirection of activities to improve performance and cooperation; and frequent communication with other members of the Steering Committee.

7. Participation on the Steering Committee and all active subcommittees.

NICHD Project Officer

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.

Traditional program management/stewardship responsibility for review and oversight of the cooperative agreement award will reside with the NRN Project Officer. This role is separate from the Program Scientist and will include the following:

2.A.3. Collaborative Responsibilities

The management of the Neonatal Research Network includes committees with the following functions:

Steering Committee

A Steering Committee will be responsible for protocol development, assisted by the Advisory Board and the Data Safety and Monitoring Committee. The Steering Committee will have primary responsibility for the conduct of protocols and the preparation of publications. The Steering Committee will be composed of all Principal Investigators, one representative from the data center, and two NICHD staff. The Data Coordinating Center is supported through a separate cooperative agreement solicited in a separate RFA. Participating NICHD staff will include the Pregnancy and Perinatology Branch NRN Program Scientist. The NRN Program Scientist will be the only voting NICHD staff member of the Steering Committee. A member of the NICHD Grants Management Branch advises the Steering Committee on funding matters. An outside chairperson, who is not participating as a Principal Investigator, will be selected by the NICHD.

Advisory Board

The Advisory Board assists the Steering Committee in the identification and prioritization of topics for perinatal research. The advisory board is selected by the NICHD and consists of individuals with expertise in clinical trials, biostatistics, epidemiology, perinatology, and neonatology, and the Chairperson of the Steering Committee. Additional members will participate based on the need for specific expertise.

Data Safety and Monitoring Committee

A Data Safety and Monitoring Committee (DSMC) monitors the safety of ongoing clinical trials. The DSMC is established by the NICHD and reports to the Director of NICHD. The DSMC is composed of individuals with expertise in clinical trial design and conduct, perinatology, neonatology, basic science, and ethics.

In addition, the NICHD Neonatal Research Network has established policies and procedures that govern its operations, including publications. These policies and procedures can be amended by the Steering Committee and the NICHD.

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 PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

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:

Rosemary D. Higgins, MD
Pregnancy and Perinatology Branch
National Institute of Child Health And Human Development
6100 Executive Boulevard, Room 4B03B, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service, non-USPS service)
Telephone: (301) 435-7909
FAX: (301) 496-3790
Email: higginsr@mail.nih.gov

2. Peer Review Contacts:

Robert Stretch, Ph.D.
Director, Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5B01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service, non-USPS service)
Telephone: (301) 496-1485
FAX: (301) 402-4104
Email: stretchr@mail.nih.gov

3. Financial or Grants Management Contacts:

Chris Robey
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service, non-USPS service)
Telephone: (301) 435-6996
FAX: (301) 402-0915
Email: robeyj@mail.nih.gov

Section VIII. Other Information

Required Federal Citations

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).

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.

Public 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 PA 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.

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. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to 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.


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