Part I Overview Information

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Department of Health and Human Services

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

Components of Participating Organizations
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)(http://www.nichd.nih.gov)

Title: Preterm Birth in Nulliparous Women: An Understudied Population at Great Risk (U10)

Announcement Type

New

Request for Applications (RFA) Number: RFA-HD-08-029

Catalog of Federal Domestic Assistance Number(s)
93.865

Key Dates
Release Date: June 24, 2008
Letters of Intent Receipt Date: February 18, 2009
Application Receipt Date: March 18, 2009
Peer Review Date(s): June/July 2009
Council Review Date: October 2009
Earliest Anticipated Start Date: December 1, 2009
Additional Information to Be Available Date (Url Activation Date): Not applicable
Expiration Date: March 19, 2009

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary  

• Purpose. The purpose of this solicitation is to create a network of clinical research sites with a Data Coordinating and Analysis Center (DCAC) to develop common research protocols to study nulliparous women. The goals of the network are to identify biomarkers and understand the mechanism and prediction of preterm birth in nulliparous women.
• Mechanism of Support. This FOA will utilize the U10 grant mechanism.
• Funds Available and Anticipated Number of Awards. The NICHD intends to commit approximately Total Costs [Direct plus Facilities and Administrative (F & A) costs] of 1.4 million in FY 2010, 3.9 million per year in FY2011-2013, and 4.4 million in FY2014 to fund six to eight new grants in response to this FOA, one of which will be the DCAC.  Although the financial plans of the NICHD provide support for this program, awards pursuant to this FOA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.
• Budget and Project Period.  An applicant may request a project period of up to five years.  An applicant for a clinical site may request a base budget (see Budget Preparation, below) for direct costs of up to $130,000 for the first year.  An applicant for the Data Coordinating and Analysis Center may request a budget (see Budget Preparation, below) for direct costs of up to $250,000 for the first year.  Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size of each award will also vary.
• Research Plan Page Limitations.  The Research Plan should not exceed 30 pages to include the 5 page sample protocol outline.
• Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
• Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
• Number of Applications. Applicants may submit more than one application, provided they are scientifically distinct.
• Resubmissions.  Resubmission applications are not permitted in response to this FOA.    
• Renewals.  Renewal applications are not permitted in response to this FOA.
• Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates
• Application Materials. See Section IV.1 for application materials.
• Hearing Impaired.  Telecommunications for the hearing impaired are available at: TTY 301-451-5936.

Table of Contents

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Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

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

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

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

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

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

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

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

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Section I. Funding Opportunity Description

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1. Research Objectives

Purpose

Women for whom the current pregnancy will lead to their first delivery (nulliparas) comprise about 40% of pregnant women in the United States. Because there is no information from previous pregnancy outcomes to guide assignment of risk or mitigating interventions, adverse pregnancy outcomes in nulliparas are especially unpredictable.  The underlying mechanisms of adverse pregnancy outcomes such as preterm birth, preeclampsia, fetal growth restriction, and stillbirth are interrelated and therefore should be studied as part of this FOA.  The objectives of the network are: (1) Determine maternal characteristics that influence and/or predict adverse pregnancy outcome  to include genetics, epigenetics, physiological response to pregnancy, and the interaction with environmental exposures (2) Identify specific aspects of placental development and function that lead to adverse pregnancy outcome (3) Characterize genetic, growth, and developmental parameters of the fetus that are associated with adverse pregnancy outcome (4) Determine whether assessments and potential interventions during pregnancy may provide useful information to reduce the incidence of adverse pregnancy outcome.

Background

Preterm birth affects 1 in 8 women in the U.S., with nearly half a million preterm births each year. Women for whom the current pregnancy will lead to their first delivery (nulliparas) comprise about 40% of pregnant women in the United States. A recent national registry study showed that the rate of preterm delivery among low risk primiparas increased 50% in the past decade.  Because there is no information from previous pregnancy outcomes to guide assignment of risk or mitigating interventions, adverse pregnancy outcomes in nulliparas are especially unpredictable.  At least 12% of nulliparous women will have a preterm delivery, with associated high rates of neonatal mortality and long term morbidity. In addition, complications during the first pregnancy impact subsequent pregnancies.  Because nulliparas are a large proportion of pregnant women, understanding the mechanism for future prevention of preterm birth and other related adverse pregnancy outcomes will have a significant public health impact.

Objectives

This initiative addresses a critical group of at-risk women who are currently understudied and represent 40% of the population that will become pregnant in a given year. This initiative is for a prospective cohort study of a racially/ethnically/geographically diverse population of 10,000 nulliparous women with singleton gestations to undergo intensive research assessments during the course of their pregnancies to study the prediction and prevention of adverse pregnancy outcome.  The underlying mechanisms of adverse pregnancy outcomes such as preterm birth, preeclampsia, fetal growth restriction, and stillbirth are interrelated and therefore appropriate topics include but are not limited to those listed below.   

The specific aims of the study:

• Determine maternal characteristics that influence and/or predict adverse pregnancy outcome to include genetics, epigenetics, physiological response to pregnancy, and the interaction with environmental exposures
• Identify specific aspects of placental development and function that lead to adverse pregnancy outcome
• Characterize genetic, growth, and developmental parameters of the fetus that are associated with adverse pregnancy outcome
• Determine whether assessments and potential interventions during pregnancy may provide useful information to reduce the incidence of adverse pregnancy outcome 

Detailed epidemiologic data as well as intensive research assessments during the course of pregnancy to include serial ultrasounds, cervical length, and Doppler velocimetry (measurement of uterine and placental blood flow) will be collected. To examine the role of genetic and environmental exposures, biological samples will be obtained in each trimester and at delivery.  Recent technologic advances such as genomics, transcriptomics and proteomics will be applied to understand the interplay of genetic and environmental factors.  By identifying women at the highest risk for adverse pregnancy complications, individualized interventions may be developed to prevent the initial adverse pregnancy outcome.

Project Organization

This FOA solicits applications for clinical sites to study the mechanism and prediction of adverse pregnancy outcomes in nulliparous women. This FOA also solicits a Data Coordinating and Analysis Center.  The grantees will form a cooperative network in scientific partnership with NICHD to conduct a prospective study of adverse pregnancy outcomes such as preterm birth, fetal growth restriction, preeclampsia and stillbirth in a racially/ethnically diverse population

Clinical Sites

To obtain a study population of 10,000 nulliparous women with ethnic and racial diversity will require the participation of five to seven clinical centers over a three-year period, anticipating a total population pool of 70,000 deliveries.  The Clinical sites will be responsible for recruitment of human subjects, collection of relevant clinical information, and collection and temporary storage of biological specimens. The centers will be expected to be multidisciplinary with appropriate scientific expertise in clinical obstetrics, fetal imaging, genomics and proteomics, placental pathology, and epidemiology.

Data Coordinating and Analysis Center

The Data Coordinating and Analysis Center (DCAC) will be responsible for central data collection, quality control, management and analysis.  The analytic plan will be developed by the Steering Committee.

Steering Committee

A Steering Committee will be assembled and will consist of the Principal Investigators and Co-Principal Investigators of all awarded grants, and NICHD staff.  Each site and NICHD will have one vote on the Steering Committee.  The Steering Committee will be charged with the task of combining multiple perspectives and research agendas across sites into a coherent plan of action, to include the development of study protocols and the analytic plan.

It is anticipated that protocol development and piloting will take place in year one, study implementation and data collection in years two through four, and data analysis in years three through five.

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

Section II. Award Information

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1. Mechanism of Support

This funding opportunity will use the U10 award mechanism(s).

The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.  

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

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

2. Funds Available  

The estimated amount of funds available for support of 6-8 projects awarded as a result of this announcement is $1.4 million for fiscal year 2010, 3.9 million per year in FY2011-2013, and 4.4 million in FY2014. Future year amounts will depend on annual appropriations.  An applicant may request a project period of up to five years. An applicant for a clinical site may request a base budget (see Budget Preparation, below) for direct costs of up to $130,000 for the first year.  An applicant for the Data Coordinating and Analysis Center may request a budget (see Budget Preparation, below) for direct costs of up to $250,000 for the first 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.

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

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

Section III. Eligibility Information

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1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

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

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.

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

Resubmission applications are not permitted in response to this FOA.    

Renewal applications are not permitted in response to this FOA.

Institutions applying to be a Clinical Site are not barred from applying to be the Data Coordinating and Analysis Center provided that independence of functions is demonstrated. Therefore, a separate application is required for the Data Coordinating and Analysis Center. An institution may apply to be the Data Coordinating and Analysis Center only.

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

Section IV. Application and Submission Information

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1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected].

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

2. Content and Form of Application Submission

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

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

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: February 18, 2009
Application Receipt Date: March 18, 2009
Peer Review Date(s): June/July 2009
Council Review Date: October 2009
Earliest Anticipated Start Date: December 1, 2009

3.A.1. Letter of Intent

A letter of intent is not required for the funding opportunity.

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

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

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

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

The letter of intent should be sent to:

Uma M. Reddy, M.D., M.P.H.
Pregnancy and Perinatology Branch
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Boulevard, Room 4B03, MSC 7510
Bethesda, MD 20892
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 496- 1074
Fax: (301) 496-3790
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:

Robert Stretch, Ph.D.
Director, Division of Scientific Review
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Boulevard, Room 5B01D, MSC 7510
Bethesda, MD 20892
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 496-1485
Fax: (301) 402-4104
Email: [email protected]

3.C. Application Processing

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

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

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

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

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

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

6. Other Submission Requirements and Information

Supplemental Instructions

Clinical Sites

Please provide the following in the research plan section of your application:

Patient population

• Documentation of > 4,500 deliveries per year (The total deliveries may be from 1 or 2 hospitals.  If 2 hospitals are used for the study population, documentation of prior research collaboration between the institutions and the PI position at both hospitals should be noted.)
• Documentation of number of pregnant women that can be enrolled in the first trimester at the clinical site per year for 2006-2007 (i.e. receiving prenatal care within the clinical site’s hospitals/prenatal care clinics) stratified by race/ethnicity and parity
• Documentation of number of deliveries at or later than 20 weeks stratified by gestational age (20-23 weeks, 24-27 weeks, 28-31 weeks, 32-36 weeks, 37 plus weeks).

Staffing and Procedures

• Descriptions of the staff and programs in place for the identification and enrollment of pregnant women in the first trimester and ability to perform follow-up study visits in the second and third trimesters
• Description of ultrasound/fetal assessment units, total number of ultrasounds performed, number of first trimester screens/nuchal translucency exams, number of second trimester fetal anatomic surveys (Level II sonograms), number of uterine artery Doppler exams for 2007.  The number, model and location of ultrasound machines as well as the number of faculty and sonographers (obstetrics, radiology and other) who perform fetal imaging and their level of training should be described.
• Description of perinatal pathology expertise with particular emphasis on placental pathology.  The number of placental histology examinations performed and proportion of deliveries undergoing placental exams should be described.  A description of participation of studies involving examination of the placenta should be provided.
• A screening and enrollment plan to include procedures for the identification and enrollment of potentially eligible pregnant women  in order to optimize enrollment, a sample consent form, and procedures for the collection and storage of biologic specimens for genomic and proteomic analyses.
• Descriptions of recent research productivity by the applicant clinical site in previous or present clinical studies, including cooperative multicenter studies, if possible.  Specifically, contributions in key areas such as protocol design, patient recruitment, data analysis and interpretation, and publication are important.
• Descriptions of research involving obstetric ultrasound or serial collection of longitudinal biologic specimens from pregnant women.
• A description of special areas of expertise among your applicant team that would benefit this multi-center cooperative study of adverse pregnancy outcomes in nulliparous women.  Such strengths would represent state-of-the-art scientific capabilities that might be shared or made available to the Network, to expand the scientific productivity of the research beyond what it might be otherwise.  Capabilities in areas such as genetics, genomics and proteomics, placental function, or perinatal pathology are examples of relevant strengths that could be included.
• Letters of collaboration from prenatal clinics, community hospitals, and medical centers within the clinical site documenting a commitment for timely notification of eligible women for enrollment into study, timely collection of biospecimens, and availability of maternal and neonatal records for abstraction.

Sample Study

Provide a description of a sample multi-center study of adverse pregnancy outcomes in nulliparous women that meets the objectives of the FOA.  The description should be focused on using a cohort of 10,000 nulliparous women enrolled in the first trimester, describing the serial biospecimen collection, screening and diagnostic testing, and information to be collected to answer a hypothesis focused on a significant adverse pregnancy outcome such as preterm birth.  It should not be a complete protocol and should not exceed five pages. 

The sample research study will serve as a starting point for deliberations within the Steering Committee and will enable reviewers to evaluate the applicant's ability to identify the critical issues to be addressed in a multicenter investigation of adverse pregnancy outcomes in the population of nulliparous women.   Investigators will not be expected to perform these studies at their site.   

Intent to Participate

• There must be a clearly expressed intent to participate in a cooperative manner with other Clinical Sites, the NICHD, and the data center, in all aspects of Network research as outlined in this FOA.

Perinatal Data System

• A perinatal data system, preferably computerized, to identify potentially eligible women for participation and to collect and tabulate perinatal statistics is desirable.  Applicants must provide a detailed description of the variables collected, and the data quality and management activities. 

The applicant must also illustrate how the system has been used recently to plan and perform clinical research. All successful applicants must be willing to provide complete, accurate, and timely data to the study.

Acceptance of Budgetary Mechanism (see also Budget Preparation below)

• Assurance of willingness and ability to cooperate with the policy of capitation of research costs for each individual protocol, in addition to a base budget, should be provided from the department and from the institutional office of sponsored research programs.

Data Coordinating and Analysis Center

Please provide the following in the research plan section your application:

Research Experience

• Description of previous experience in managing multi-center clinical research studies.
• Description of previous experience in obstetrical studies.
• Description of epidemiology expertise, including perinatal epidemiology if possible
• Description of genetic epidemiology expertise, specifically knowledge of application of the latest technology developments such as genomic and proteomic analyses
• Description of applicant's perception of their role in the study.

Staffing and Procedures

• Description of staff and computing, data processing, and analytic capability.
• A plan detailing methods of data receipt, quality control, analysis and reporting, including communication with clinical and administrative personnel. This plan should be based on the assumption that there will be a patient tracking system and a database that will include information from medical records and specialized laboratory studies (genetics, pathology, and maternal interview).

Intent to Participate

• There must be a clearly expressed intent to participate in a cooperative manner with the Clinical Sites and the NICHD in all aspects of Network research as outlined in this FOA.

Budget Preparation

Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information". The instructions for budget requests provided with the research grant application form PHS 398 (rev 5/01) 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 the application, each applicant should submit budget estimates for all years.

Clinical Sites

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

• Principal Investigator/Co-Principal Investigator(s):  up to a total of 30 percent effort for the first year and then up to a total of 20 percent effort for years 2-5.
• Research Nurse Coordinator/outreach worker:  50 percent effort for the first year and then 100 percent effort for years 2-5.
• Supplies and Small Equipment (itemized and justified):  Not to Exceed $4,500
• Travel (a total of 18 person trips to Bethesda):  as appropriate
• Other costs (itemized and individually justified):  Not to Exceed $2,500

Each Clinical Site will be given base costs (listed above) in addition to a flat fee per subject. When protocol development is near completion, a final per-subject rate will be determined, that will include costs, which cannot be estimated at this time, such as pathology, imaging and laboratory tests.

After protocol development, the individual member sites will be required to project subject enrollment during a specified time frame.  Taking this information into account, NICHD will determine the capitation level and make an award. Continuation and level of funding for future years will be based on the number of subjects successfully enrolled and completed. 

Future years' budget requests should be limited to base budget costs, with an annual increment of base salary not to exceed three percent.  The travel should be reduced to 12 person trips per year after the first year, with an annual increment not to exceed three percent.  The maximum amount available for equipment, supplies, and other costs will not increase.  Federal agencies shall use negotiated rates for F&A costs in effect at the time of the initial award throughout each competitive segment of the project.  Award levels for sponsored agreements may not be adjusted in future years as a result of changes in negotiated rates.

Data Coordinating and Analysis Center

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

• Principal Investigator/Biostatistician team:  up to 100 percent effort
• Programmer/Systems Analyst:  50 percent effort
• Study Coordinator/Administrative Assistant:  50 percent effort
• Travel (a total of 12 person trips to Bethesda):  as appropriate
• Consultants for protocol development and one meeting of the ASMB:  $10,000
• Supplies and small equipment:  $10,000

When an application has been reviewed and is being considered for funding, the applicant will be required to complete a budget based on operational costs. The data center will be given base costs (listed above) in addition to operational costs. When protocol development is near completion, operational costs will be determined, that will include costs, which cannot be estimated at this time, such as data entry and management, quality control costs, software, printing and duplication of forms, distribution and storage of forms, and service contracts, logistic support to the study, report generation, and data analysis. Taking subject enrollment estimates into account, NICHD will determine the level of operational costs and make an award.  Continuation and level of funding for future years will be based on the number of subjects successfully enrolled and completed. 

Future years' budgets may include annual increment of base salary and travel costs not to exceed three percent. The maximum amount available for supplies and other costs not increase.  Federal agencies shall use negotiated rates for F&A costs in effect at the time of the initial award throughout each competitive segment of the project. Award levels for sponsored agreements may not be adjusted in future years as a result of changes in negotiated rates.

Research Plan Page Limitations

The Research Plan should not exceed 30 pages to include the 5 page sample protocol outline.

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CD 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)

The following resource sharing policies do not apply to this FOA:

• Data Sharing Plan. Not Applicable
• Sharing Model Organisms. Not Applicable
• Genome Wide Association Studies (GWAS). Not Applicable

Section V. Application Review Information

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

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

2. Review and Selection Process

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

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

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

The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by peer review
• Availability of funds
• Relevance of the proposed project to program priorities
• Applications recommended by the National Advisory Child Health and Human Development Council (NACHHD) will be considered for award based primarily on scientific and technical merit as determined by peer review, of the relevant capabilities and experience to be used in executing the responsibilities of the clinical site as well as, although to a lesser extent, the evaluation of the concept proposal.  Program balance, that is, the scope and variety of research strengths to enable a successful collaborative program, will be considered.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a meritorious priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

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

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

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

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

In addition to the above review criteria, the following criteria will be applied to applications in the determination of scientific merit.

For the Clinical Sites specific review criteria for this announcement are as follows:

Qualifications, Experience, and Commitment of Key Personnel

• Scientific, clinical, and administrative abilities and academic productivity of the Principal Investigator, co-investigator and other team members;
• Knowledge and experience in areas relevant to the conduct of collaborative clinical research, especially in maternal-fetal medicine.  This should include specific experience in research design; fetal imaging; genomics and proteomics;
• Commitment of staff time for the satisfactory conduct of the study;
• Experience and qualifications of team members who would be responsible for data quality and management activities.

Documentation and Procedures

• Adequacy of documentation of access to patient population of interest as outlined in supplemental instructions;
• Quality of the site's participation in collaborative clinical research;
• Adequacy of surveillance procedures and enrollment plan and ability to carryout the surveillance, enrollment and diagnostic procedures;
• Willingness to work and cooperate with other sites, the DCAC, and the NICHD in the manner summarized in this FOA;
• Additional research strengths, as presented.

Description of sample study

• Quality and relevance of proposed hypotheses, background and significance, objectives, study design and data analysis (including considerations of sample size and power);
• Adequacy of the conceptual framework and design to meet the objectives of the FOA;
• Potential of the proposed study elements to advance knowledge, methodology, and/or concepts relating to the mechanism and prediction of adverse pregnancy outcomes such as preterm birth.

Facilities and Management

• Adequacy of administrative, clinical, and data organizational management facilities as described in supplemental instructions;
• Institutional commitment to provide support to the study in such areas as fiscal administration, personnel management, space allocation, procurement, planning, and budgeting.

For the Data Coordinating and Analysis Center specific review criteria for this announcement are as follows:

• Experience and ability in multi-center, collaborative clinical studies:  Documentation of expertise in protocol development, staff training, research instrument development, data management, biostatistical expertise as applied to study design, data administration and coordination.
• Qualifications, Experience, and Commitment of Key Personnel: Scientific and administrative abilities of the Principal Investigator and other team members; experience of the Principal Investigator and other key personnel in study design, statistical data management, quality control, study coordination, and administrative aspects.
• Protocols and Procedures:  Quality of past performance and proposed plans for study coordination, data collection, analysis, and monitoring.
• Facilities and Management:  Evidence of satisfactory facilities and supporting environment, including space and equipment for work proposed (any new equipment requested under this award must be adequately justified); evidence of institutional support for participation in a long-term collaborative project.
• Willingness to work cooperatively with other awardees and NICHD in the manner summarized in the Cooperative Agreement Terms and Conditions of Award.
  

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the rating:

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

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

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

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

2.B. Additional Review Considerations

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

2.C. Resource Sharing Plan(s)   

The following resource sharing policies do not apply to this FOA:

• Data Sharing Plan. Not Applicable
• Sharing Model Organisms. Not Applicable
• Genome Wide Association Studies (GWAS). Not Applicable

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information

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1. Award Notices

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

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

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 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:

• Identification of priority issues for research.
• Development and implementation of protocols.
• Collection and transmission of accurate data in a timely manner.
• Analysis of data and publication of results.

The DCAC will be responsible for central data collection, quality control, management, and analysis.  The DCAC will also be responsible for contracting with consultants to the Steering Committee on an as-needed basis.

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 role of the NICHD Project Scientists will be to aid the awardees and the Steering Committee by providing:

• Assistance in the identification of important areas of study.
• Assistance in the development of study protocols.
• Assistance in the development and review of capitation-based budgets, including the identification of study costs and special institutional needs.
• 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.
• Assistance in reporting results in the community of investigators and health care recipients.
• Assistance in the efficient conduct of the study, including ongoing review of progress; possible redirection of activities to improve performance and cooperation; and frequent communication with other members of the Steering Committee.
• Participation on the Steering Committee and all active subcommittees.
• Recommend consultants for appointment to the Steering Committee on an as needed basis.

NICHD Program Official

The NICHD will appoint a Program Official, apart from the Project Scientist, who will:

• Assure the scientific merit of the study, including the option to withhold support of a participating center if technical performance requirements such as protocol compliance and enrollment targets are not met.
• Initiate a decision to modify or terminate a study based on the advice of the Advisory Safety and Monitoring Board with the mutual consent of the Steering Committee.
• Perform other duties required for normal program stewardship of grants.
• While providing a data sharing plan and GWAS data plan are not part of the initial application process, if as part of the network’s activities, data is generated,  the Program Official will assure that the Steering Committee will develop and implement a data sharing plan consistent with the NIH data sharing policy, See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html. 

Likewise, if generated, the Program Official will assure that the Steering committee will establish guidelines to make biologic samples available to outside investigators at the conclusion of analyses by the network.   Finally, if a GWAS study is executed through the network, the Program Official will assure that the Steering committee will develop a plan for submission of GWAS data to the NIH-designated GWAS data repository. 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/.

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.

2.A.3. Collaborative Responsibilities (optional)

The guidance and management of the Network will include, but not be limited to the following committees whose functions are as follows:

Steering Committee

A Steering Committee will be responsible for protocol development, assisted by the Advisory Board and, at times, consultants to the Steering Committee. The Steering Committee will have primary responsibility for the conduct of protocols and the preparation of publications.  The Steering Committee will comprise all Principal Investigators, one representative from the Data

Center, and two NICHD staff.  Participating NICHD staff will include the Pregnancy and Perinatology Branch Project Scientists. There will be only one vote for NICHD staff, which will be shared by the Project Scientists. A nonvoting member of the NICHD Grants Management Branch

will advise the Steering Committee on administrative and funding matters. An outside chairperson, who is not participating as a Principal Investigator, will be selected by 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.

The responsibilities of the Steering Committee are as follows:

• Develop the study protocols to target the understanding and prediction of adverse pregnancy outcomes in nulliparous women such as preterm birth, stillbirth, fetal growth restriction and preeclampsia.
• Develop a data and management plan, with primary input from the DCAC, to include plans for quality assurance and plans for public access to the database.
• Monitor surveillance and enrollment and biologic specimen collection upon study initiation.
• Establish Policies and Procedures that govern its operations, including publications.
• Develop an analytic plan in collaboration with the Data Coordinating and Analysis Center.

Advisory and Safety Monitoring Board

An Advisory and Safety Monitoring Board (ASMB) will advise the Steering Committee in the development of research protocols. The Advisory and Safety Monitoring Board, chosen by the NICHD with the advice of the Steering Committee, will comprise individuals with expertise in obstetrics, perinatology, genetics, perinatal pathology, biostatistics, epidemiology, and neonatology. The Chairperson of the Steering Committee, the Principal Investigator of the Data Coordinating and Analysis Center, and the NICHD Project Scientists may attend Advisory Board meetings to provide information as needed.  Additional members will participate based on the need for specific expertise.  In addition, the ASMB will monitor the safety of ongoing study protocols. 

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

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

1. Scientific/Research Contacts:

Uma M. Reddy, M.D., M.P.H.
Pregnancy and Perinatology Branch
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Boulevard, Room 4B03, MSC 7510
Bethesda, MD 20892
"Rockville, MD 20852 (for express/courier service)
Telephone: (301) 496-1074
Fax: (301) 496-3790
Email: [email protected]

2. Peer Review Contacts:

Robert Stretch, Ph.D.
Director, Division of Scientific Review
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Boulevard, Room 5B01D, MSC 7510
Bethesda, MD 20892
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 496-1485
Fax: (301) 402-4104
Email: [email protected]

3. Financial or Grants Management Contacts:

Bryan S. Clark, M.B.A.
Chief Grant Managements Officer
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Boulevard, Room 8A01A, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: (301) 435-6975
Fax: (301) 402-0915
Email: [email protected]

Section VIII. Other Information

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Required Federal Citations

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This 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 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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

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