GENOMIC AND PROTEOMIC NETWORK FOR PREMATURE BIRTH RESEARCH

RELEASE DATE:  June 18, 2004

RFA NUMBER:  RFA-HD-04-002  

EXPIRATION DATE:  August 21, 2004

Department of Health and Human Services (DHHS)
 
PARTICIPATING ORGANIZATION:  
National Institutes of Health (NIH) 
 (http://www.nih.gov)
   
COMPONENT OF PARTICIPATING ORGANIZATION: 
National Institute of Child Health and Human Development (NICHD) 
 (http://www.nichd.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.865

LETTER OF INTENT RECEIPT DATE:  July 20, 2004
APPLICATION RECEIPT DATE:  August 20, 2004  

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

The purpose of this solicitation is to create a network for premature birth 
research. The aim of this network is to accelerate the pace of premature birth 
research by focusing on global genomic and proteomic strategies and the 
dissemination of genomic and proteomic data to the scientific community. 
Specifically, the network will:  1) design and implement hypothesis-driven, 
mechanistic studies based on large-scale, high-output genomic and proteomic 
approaches, and 2) provide a public, web-based, genomic and proteomic database 
for data mining and data deposition by the research community. It is 
anticipated that the creation of this network will hasten a deeper 
understanding of the pathophysiology of premature birth, discover novel target 
molecules and diagnostic biomarkers, and ultimately aid in formulating more 
effective interventions to prevent premature birth. 

RESEARCH OBJECTIVES

Background

Premature birth, which is defined as birth prior to 37 weeks of gestation, is 
a leading cause of infant morbidity and mortality. In the U.S. population, 
approximately 10 percent of all births are premature. This accounts for 
approximately 400,000 infants born annually. The incidence of premature birth, 
however, is not equally distributed among races and ethnic groups. For 
example, African-Americans have the highest rate of premature birth, followed 
by Mexican-Americans, Asians, and Caucasians. Strikingly, a substantial health 
disparity exists between African-Americans and Caucasians, with African-
Americans being 1.8 times more likely to deliver premature infants than 
Caucasians.

Most of the infant mortality and morbidity of premature birth is associated 
with the one to two percent of infants born very premature (birth at less than 
32 weeks of gestation). Excluding congenital malformations, premature birth 
accounts for approximately 70 percent of all neonatal deaths and nearly 50 
percent of long-term neurological problems. These long-term neurological 
problems include serious physical and mental disabilities, such as cerebral 
palsy, mental retardation, as well as vision and hearing loss. Despite decades 
of research, there has been little progress in developing effective 
interventions to prevent premature birth. In fact, the rate of premature birth 
has increased slightly over the last several decades. Although advances have 
been made in identifying some of the possible causes of premature birth, such 
as intrauterine infection, uterine bleeding, excessive uterine stretch, 
maternal psychosocial stress, and fetal physiological stress, a much deeper 
understanding at the molecular level is necessary to aid in formulating 
effective interventions. Thus, a new initiative is required to address this 
need as a means to accelerate knowledge in the mechanisms of premature birth.

Substantial strides have been made in the areas of genomics and proteomics, 
both of which have made major impacts in accelerating medical advances in many 
fields of medicine. However, the medical advances brought by these 
revolutionary technologies are generally due to coordinated, wide-scale, high-
output endeavors that are presently beyond the resources of investigators in 
the field of premature birth research. In addition, the research community 
lacks a centralized database for data mining and the deposition of genomic and 
proteomic data. The purpose of this solicitation is to create a collaborative 
research network to more effectively coordinate and apply the power of 
genomics and proteomics to the problem of premature birth. It is anticipated 
that the creation of this network will hasten a deeper understanding of the 
pathophysiology of premature birth, the discovery of novel target molecules 
and diagnostic biomarkers, and ultimately aid in formulating more effective 
interventional strategies to prevent premature birth.

Objectives and Scope

The main objective of the Network will be to use wide-scale, high-output 
genomic and proteomic strategies to accelerate knowledge in the mechanisms 
responsible for premature birth. Another objective of the network will be to 
act as a resource to the scientific community by providing genomic and 
proteomic data quickly for secondary analysis and creating, as well as 
maintaining, a public genomic and proteomic database dedicated to premature 
birth research. Specifically, the network will:  1) design and implement 
hypothesis-driven, mechanistic studies based on wide-scale, high-output 
genomic and proteomic strategies and 2) provide a public, web-based, genomic 
and proteomic database for data mining and data deposition by the research 
community. 

It is anticipated that the Network will consist of the following:

o A Clinical Core, comprising up to three clinical sites, responsible for 
subject recruitment and specimen collection;

o An Analytical Core responsible for genomic and proteomic analyses;

o A Data Management, Statistics, and Informatics Core responsible for central 
data collection, analysis, and management; information technology; and 
coordination of the administrative activities of the Network.

The Clinical Core will consist of up to three separately awarded clinical 
research sites that will work cooperatively with one another. The Clinical 
Core will be responsible for recruitment of human subjects, collection of 
relevant clinical information, and collection and temporary storage of 
biological specimens. The Clinical Core will also be responsible for data 
entry into the Data Management, Statistics, and Informatics Core databases.

The Analytical Core will be responsible for "state-of-the-art", high-
throughput DNA, RNA, and protein analyses, as well as entry of data into the 
Data Management, Statistics and Informatics Core databases. This core will 
also be responsible for the receipt and storage of the biological specimens 
collected from the various clinical sites. In addition, the Analytical Core 
will be responsible for the computational analysis of genomic and proteomic 
data and synergistically interacting with the Data Management, Statistics, and 
Informatics Core in performing genomic and proteomic statistical analyses.

The Data Management, Statistics, and Informatics Core will be responsible for 
central data collection, analysis, and management. It will integrate clinical 
data with genomic and proteomic data. It will be responsible for the 
statistical analysis of data aided, in part, by the Analytical Core. It will 
also be responsible for creating and maintaining an internal and a public web-
based database. In addition, it will act as an administrative coordinating 
center for the Network.

Guidance and Management Structure

A Steering Committee will be assembled consisting of the Principal 
Investigators, participating NICHD staff, and other appropriate members. This 
committee will be responsible for the formulation of new projects, review of 
proposed projects, prioritization of workload, consideration of long-term 
strategic issues, policy and budgetary matters, and development of guidelines 
for operation of the Network. An outside advisory panel will also be formed to 
provide general oversight of the Network, as well as to provide technical and 
operational advice. 

MECHANISM OF SUPPORT

This RFA will use the NIH Cooperative Research Project Grant (U01) award 
mechanism. As an applicant you will be solely responsible for planning, 
directing, and executing the proposed project.  This RFA is a one-time 
solicitation. The anticipated award date is April 01, 2005.

The NIH U01 is a cooperative agreement award mechanism in which 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 "Cooperative Agreement Terms and Conditions of 
Award."  

FUNDS AVAILABLE

The NICHD intends to commit approximately $2.5 million in Total Costs [Direct 
plus Facilities and Administrative (F & A) costs] in FY 2005 to fund up to 
three clinical sites comprising the Clinical Core, one site comprising the 
Analytical Core, and one site comprising the Data Management, Statistics and 
Informatics Core.  An applicant may request a project period of up to five 
years.  An applicant for a clinical site in the Clinical Core or an applicant 
for the Analytical Core may request a base budget for direct costs of up to 
$125,000 for the first year (see SUBMITTING AN APPLICATION/SUPPLEMENTARY 
INSTRUCTIONS section under Budget Preparation).  An applicant for the Data 
Management, Statistics and Informatics Core may request a budget for direct 
costs of up to $250,000 for the first year (see SUBMITTING AN 
APPLICATION/SUPPLEMENTARY INSTRUCTIONS section under Budget Preparation). 
Subsequent budgets will be negotiated and consist of a base budget plus 
protocol-specific expenses. 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.  Although the financial plans of the NICHD 
provide support for this program, awards pursuant to this RFA are contingent 
upon the availability of funds and the receipt of a sufficient number of 
meritorious applications.

ELIGIBLE INSTITUTIONS

You may submit an application if your institution has any of the following 
characteristics: 

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments 
o Eligible agencies of the Federal government  
o Domestic or foreign institutions/organizations  

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

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

SPECIAL REQUIREMENTS

Minimum Application Requirements

Applicants may submit applications for one or more cores described in this 
RFA. If applying to be more than one core, applicants must submit separate 
applications, each focusing on a particular core. Only one award, however, 
will be made to a single institution. Due to the scope of this solicitation, 
it is anticipated that applicants may have to form consortiums with other 
entities, since a single entity may not have the sufficient catchment study 
population, expertise or facilities to carry out all aspects expected of each 
of the cores as described. 

Minimum requirements for applicants are listed below. Detailed application 
instructions can be found in the SUBMITTING AN APPLICATION section under 
SUPPLEMENTARY INSTRUCTIONS. 

All Applicants:

o All applicants should be prepared to work collectively and in a cooperative 
manner with each other and the NICHD to achieve the goals of this 
solicitation. 

o Departmental and institutional commitments to collaborative research should 
be clearly documented by providing letters to the Principal Investigator that 
should accompany the application. 

o All applicant Principal Investigators, or their appropriate representatives, 
should be prepared to meet as a Steering Committee to develop the necessary 
infrastructure and study protocols. It is anticipated that the Steering 
Committee will meet about six times in the first year and three times per year 
afterwards. Expenses related to these meeting should be included in the 
application budget request (see Budget Preparation section under SUBMITTING AN 
APPLICATION/SUPPLEMENTARY INSTRUCTIONS, below). 

o The applicant must exhibit a preparedness to pursue capitation of particular 
operational costs of the protocol (see Budget Preparation section under 
SUBMITTING AN APPLICATION/SUPPLEMENTARY INSTRUCTIONS, below). 

o The applicant must agree to the conditions of data and resource sharing as 
described below. 

Clinical Core Applicants: 

o Each of the clinical sites must have a catchment population of at least 2500 
deliveries per year. 

o The Principal Investigator for each site must have expertise in obstetrics. 

o Clinical sites must have a research team with expertise in obstetrics with 
special interest in premature birth research. 

o The assembled research team must have sufficient familiarity in genomics and 
proteomics to effectively participate in the formulation of study protocols. 

o Each clinical site must have an established perinatal data system, 
preferably computerized, to collect and tabulate perinatal statistics, as well 
as the ability to easily extract data for export. 

o Each clinical site must have a research nurse designated as the Nurse 
Coordinator. 

Analytical Core Applicants: 

o The applicant must have the ability to appropriately store biological 
specimens. 

o The applicant must have the ability to perform genetic analyses at high-
throughput and/or genome-wide capacity, such as sequencing, genotyping, 
haplotyping, and gene expression analysis. 

o The applicant must have the ability to perform proteomic profiling of 
complex mixtures such as tissue and biological fluids, using high-throughput 
platforms such as mass spectrometry analysis (e.g., coupled to liquid 
chromatography-MS, SELDI-TOF-MS, etc.) and protein microarray. 

o The applicant must demonstrate the ability to perform genomic and proteomic 
computational and statistical analyses. 

o The applicant must demonstrate the potential of incorporating other types of 
existing and evolving genomic and proteomic technologies. 

o The applicant must have most of the infrastructure necessary (e.g., 
instrumentation, computer hardware and software, etc.) to carry out the 
objectives of the Analytical Core. 

Data Management, Statistics and Informatics Core Applicants: 

o The Data Management, Statistics and Informatics Core must have the ability 
to develop and disseminate protocol materials (e.g., data collection 
instruments, procedural manuals, etc.), train study site personnel for 
centralized data entry, monitor data quality, and carry out data analysis and 
reporting. 

o Applicants must have the ability to coordinate the activities of the Network 
by scheduling and coordinating, as well as documenting Network meeting 
activities, including the dissemination of meeting documents. 

o The core must have the ability to electronically collect and store data 
generated by the Clinical and Analytical Cores and provide an interactive user 
interface for all components of the Network. 

o The core must have the ability to devise methods for integrating clinical 
data with genomic and proteomic data into a database. 

o The core must have the ability to perform biostatistics, including the 
statistical analysis of genomic and proteomic data.

o The core must have the ability to incorporate the proper informatics and 
bioinformatics tools to facilitate analysis, extraction, and efficient 
dissemination of information from these databases to the Network members. 

o The core must have the ability to create and maintain a public, web-
accessible database for secondary analysis of the data generated by the 
Network and to provide the necessary bioinformatic tools to mine this 
database. 

o The core must have the ability to disseminate data generated by the Network 
to the National Center for Biotechnology databases; act as a conduit for the 
deposition of genomic and proteomic data eventually submitted to the core by 
researchers, outside of the Network, investigating premature birth; and to 
integrate this data into the public, web-accessible database described above. 

Data and Resource Sharing

The NICHD expects that the Network investigators benefit from the first and 
continuing use, but not from prolonged exclusive use of data and resources. 
One of the major intents of this initiative is to make the data quickly 
available to the research community for secondary analyses. In order to 
accomplish this goal, the RFA sets a limit to the exclusive use of final data 
sets generated by the Network. This is defined as the following:  The final 
data set for a particular protocol generated by the Network will be made 
publicly available after the date of acceptance of publication or no longer 
than one year after the final collection and analysis of a data set for a 
particular protocol, whichever occurs first. 

Another purpose of this RFA is to allow investigators, outside the Network, 
access to Network resources. Thus, research studies proposed by investigators 
outside the Network will be accepted and reviewed by the Network for possible 
execution of the study using the Network's infrastructure, according to the 
guidelines established by the Network's Steering Committee. In addition, 
excess or archival specimens biological specimens or derivatives thereof, 
which are not anticipated to be used or no longer required for analyses by the 
Network, will be made available to outside investigators, also according to 
the guidelines established by the Network's Steering Committee.

Cooperative Agreement Terms and Conditions of Award

The following Terms and Conditions will be incorporated into the award 
statement.  They are to be followed in addition to, and not in lieu of, 
otherwise applicable OMB administrative guidelines, HHS grant administration 
regulations at 45 CFR Parts 74 and 92, and other HHS and NIH grant 
administration policies.

The administrative and funding instrument used for this program will be the 
U01, an "assistance" mechanism (rather than an "acquisition" mechanism), in 
which substantial NIH scientific and/or programmatic involvement with the PI 
is anticipated during performance of the activities. Under the cooperative 
agreement, the NIH purpose is to support and/or stimulate the PI's activities 
by involvement in and otherwise working jointly with the PI 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 PI for the project as a whole, although 
specific tasks and activities may be shared between the awardee and the NICHD 
Project Scientist.  Business management aspects of these awards will be 
administered by the NICHD Grants Management Branch in accordance with HHS and 
NIH grant administrative requirements.

1.  Awardee Rights and Responsibilities

All awardees will agree to accept the participatory and cooperative nature of 
the group process. All awardees are required to submit annual progress reports 
to NICHD, as appropriate, and to provide study and site performance 
information as stipulated by NICHD. 

The responsibilities and rights of the awardees will be as follows: 

o Identification of priority issues for research 

o Development and implementation of protocols 

o Collection and transmission of accurate data in a timely manner 

o Analysis of data and publication of results

o Sharing of data and resources, following the procedures developed by the 
Network Steering Committee according to the guidelines specified in RFA-HD-04-
002.

Awardees will retain custody of 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.

2. NIH Responsibilities

NICHD Project Scientists: 

Two Project Scientists will be appointed by the NICHD. Their roles will be to 
aid the awardees and the Steering Committee in the following ways:

o Assistance in the identification of important areas of study

o Assistance in the development of study protocols

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

o 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

o 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

o Participation on the Steering Committee and all active subcommittees

o Recommend consultants for appointment to the Steering Committee on an as-
needed basis

NICHD Project Officer:

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

o Carry out continuous review of all activities to ensure that the objectives 
are being met and that all regulatory, fiscal, and administrative matters are 
handled according to NIH guidelines.

o Have the option to withhold support to a participating institution if 
technical performance requirements are not met.

o Perform other duties required for normal program stewardship of grants.

3. Collaborative Responsibilities

The guidance and management structure of the Network will include the 
following: 

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 the Principal Investigators (voting members), two designated NICHD 
Project Scientists from the Pregnancy and Perinatology Branch (who will share 
one vote), and other non-voting and non-NIH members who are deemed necessary 
for the conduct of the Network. All members of the Steering Committee are 
expected to play an active role in Steering Committee activities. An outside 
chairperson, who is not participating as a Principal Investigator, will be 
selected by the NICHD. The chairperson will act as a voting member only in 
case of a tie vote. 

The responsibilities of the Steering Committee are as follows: 

o Development of guidelines and procedures for the operation of the Network 

o Formulation of new projects 

o Review of proposed projects 

o Prioritization of workload 

o Consideration of long-term strategic issues 

o Policy and budgetary matters 

Advisory Board 

An Advisory Board will be formed to provide general oversight of the Network, 
as well as to provide technical and operational advice to the Steering 
Committee, as needed. This board, chosen by the NICHD with the advice of the 
Steering Committee, will be composed of individuals not associated with the 
Network or its members. The board will include members with expertise in 
premature birth, genomics, proteomics, molecular epidemiology, bioinformatics, 
and bioethics. The Chairperson of the Steering Committee and the NICHD Project 
Scientist may attend Advisory Board meetings to provide information as needed. 
Additional members will participate based on the need for specific expertise.

4.  Arbitration Process

Any disagreements that may arise in scientific or programmatic matters within 
the scope of the award between grantees and the NIH may be brought to 
arbitration.  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 regulation 
at 45 CFR Part 16.  An Arbitration Panel will help resolve both scientific and 
programmatic issues that develop during the course of work that restrict 
progress.  The Arbitration Panel will be composed of three members:  a member 
selected by the Steering Committee without NIH staff voting, a member selected 
by NICHD, and a member with expertise in the relevant area selected by the 
other two members.

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA 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:  

o Direct your questions about scientific/research issues to:  

John V. Ilekis, Ph.D.
Pregnancy and Perinatology Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, 4B03, MSC 7510
Bethesda, MD  20892-7510
Telephone: (301) 435-6895
FAX: (301) 496-3760
Email:  ilekisj@mail.nih.gov 

o Direct your questions about peer review issues 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
Telephone: (301) 496-1485
FAX: (301) 402-4104
Email:  stretchr@mail.nih.gov 

o Direct your questions about financial or grants management matters to:  

John  Chris  Robey
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, 8A17, MSC 7510
Bethesda, MD  20892-7510
Telephone: (301) 435-6996
FAX: (301) 480-4783
Email:  robeyj@mail.nih.gov 

LETTER OF INTENT

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

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

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 NICHD 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:  

John V. Ilekis, Ph.D.
Pregnancy and Perinatology Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, 4B03, MSC 7510
Bethesda, MD  20892-7510
Telephone: (301) 435-6895
FAX: (301) 496-3760
Email:  ilekisj@mail.nih.gov 

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001). Applications must have a Dun and 
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the 
Universal Identifier when applying for Federal grants or cooperative 
agreements. The DUNS number can be obtained by calling (866) 705-5711 or 
through the web site at http://www.dunandbradstreet.com/. The DUNS number 
should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 
document is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 710-0267, 
Email: GrantsInfo@nih.gov.
 
SUPPLEMENTARY INSTRUCTIONS:  All applications should be prepared according to 
the instructions accompanying PHS 398, with the following specific information 
provided.  Please see Minimum Application Requirements, above, in addition to 
the following.

Clinical Core applicants, please provide the following descriptions in your 
application:

o The facilities and clinical services available

o The quality of the facilities and services provided 

o The qualifications, experience, and commitment of the personnel 

o Prior experience related to performing clinical research such as protocol 
design, data analysis and interpretation (include relevant publications)

o The number of births and the percentage of spontaneous and induced preterm 
births, stratified by gestational age (20-23 weeks, 24-27 weeks, 28-31 weeks, 
32-36 weeks, 37 plus weeks), race, and ethnicity

o The proportion of women who give birth at the site who also receive prenatal 
care within the site. Include the definition of prenatal care as well as the 
number of visits that constitutes prenatal care

o The perinatal data system available to collect and tabulate perinatal 
statistics, including the variables collected, and the data quality and 
management activities

o Procedures for subject enrollment and recruitment 

o The success rate for subject enrollment and maintaining subject 
participation in an ongoing or recently completed study

o The cost associated with recruiting and maintaining subject participation

o Description of special talents or resources pertinent to the objective of 
this RFA

Analytical Core and Data Management, Statistics and Informatics Core 
applicants, please provide the following descriptions in your application:

o The quality of the facilities or services provided by the core (including 
procedures, techniques, and quality control)

o The qualifications, experience, and commitment of the personnel involved in 
the core

o Prior experience related to the objectives and functions of the core 
(include relevant publications)

o Description of special talents or resources pertinent to the objective of 
the RFA

o The cost associated with performing various analyses based on volume 
(Analytical Core only)

o The cost associated with data integration, data analysis, database 
development, and database maintenance (Data Management, Statistics and 
Informatics Core only)

Concept Protocol

In addition to the items listed above, all applicants must submit a "concept 
protocol." This should be included at the end of the Research Plan section of 
the application. The concept protocol is a three- to six-page narrative to 
provide peer reviewers and the NICHD an idea of the capabilities of the 
investigators described as follows:

o Applicants for a clinical site within the Clinical Core must submit a 
concept protocol that describes two separate research projects, one that 
focuses on a genomic approach and the other on a proteomic approach consistent 
with the intent of the RFA. These projects must be hypothesis driven and may 
address the same or different clinically relevant questions regarding 
elucidating mechanisms involved in premature birth. Although the description 
for one project may be longer or shorter than the other, the concept protocol 
in total should not exceed six pages in length.

o Applicants for the Analytical Core must submit a concept protocol that 
describes the overall scheme for specimen handling and storage, genomic and 
proteomic analyses, and genomic and proteomic computational and statistical 
capabilities to meet the objectives of the Analytical Core as stated above in 
Objectives and Scope.

o Applicants for the Data Management, Statistics and Informatics Core must 
submit a concept protocol that describes the overall scheme for coordinating 
Network activities, central data collection, data integration, statistical 
analysis, database development and maintenance, bioinformatics, and 
informatics to meet the objectives of this core as stated in the Objectives 
and Scope section. 

Budget Preparation

The instructions for budget requests provided with the research grant 
application form PHS 398 (rev 5/2001) should be followed. F&A costs will be 
awarded in the same manner as for research project grants (R01). 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 based on a Base Budget. The base budget 
consists of the expenses to create and/or maintain a basic infrastructure 
until a particular protocol is introduced. First year base budgets in direct 
costs are limited to $125,000 per clinical site in the Clinical Core, $125,000 
for the Analytical Core, and $250,000 for the Data Management, Statistics and 
Informatics Core. This should include such expenses as personnel, supplies and 
equipment, and travel to Bethesda for Steering Committee meetings (estimated 
to be six trips in the first year and three trips per year afterwards). All 
requests for supplies and equipment have to be itemized and justified. Travel 
for each site in the Clinical Core will be limited to the Principal 
Investigator and Research Nurse Coordinator. Travel for the Analytical Core 
and Data Management, Statistics and Informatics Core will be limited to two 
individuals each, one of which will include the Principle Investigator. The 
first-year budget for each of the Clinical Core sites, the Analytical Core and 
Data Management, Statistics and Informatics Core at the time of application 
will be limited to a BASE BUDGET with the maximum allowances as follows:

o Principal Investigator: up to a total of 25 percent effort

o Research Nurse Coordinator: up to a total of 100 percent effort (Clinical 
Core sites only)

o Data Entry Clerk: up to a total of 25 percent effort (Clinical Core sites 
only)

o Office Supplies and Office Equipment (itemized and justified): Not to Exceed 
$5,000

o Travel expenses: Not to exceed $12,000

o Other costs (itemized and individually justified)

Once the Network has initiated a protocol, subsequent budgets will consist of 
a base budget plus protocol specific expenses, and funding will be based on a 
capitation system as follows:

The Principal Investigator of each of the clinical sites in the Clinical Core 
will be given base budget costs, in addition to the expenses associated with a 
particular protocol. The Principal Investigator of each of the clinical sites 
in the Clinical Core will be required to project subject enrollment for a 
specific protocol during a specified time frame. Continuation and the level of 
funding will be based on actual recruitment with a flat fee paid per subject 
recruited and successfully carried on the protocol. 

The Analytical Core will be given base budget costs, in addition to the 
expenses associated with a particular protocol. The Principal Investigator 
will be required to project expenses associated with specimen handling and the 
type(s) of analyses associated with a specific protocol during a specified 
time frame. Continuation and the level of funding will be based on the actual 
number of specimens handled and analyzed.

The Data Management, Statistics and Informatics Core will be given base budget 
costs, in addition to expenses associated with a particular protocol. The 
Principal Investigator will be required to project expenses for a particular 
protocol during a specified time frame.

USING THE RFA LABEL:  The RFA label available in the PHS 398 (rev. 5/2001) 
application form 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/label-bk.pdf.

SENDING AN APPLICATION TO THE NIH:  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
Bethesda, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application and all 
appendix materials 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)

APPLICATION PROCESSING:  Applications must be received on or before the 
application receipt date listed in the heading of this RFA.  If an application 
is received after that date, it will be returned to the applicant without 
review.

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

The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA 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 an RFA, 
it is to be prepared as a NEW application.  That is, the application for the 
RFA 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.  

PEER REVIEW PROCESS

Upon receipt, applications will be reviewed for completeness by the CSR and 
for responsiveness by the NICHD.  Incomplete and/or non-responsive 
applications will be returned to the applicant without further consideration.  

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 
the NICHD in accordance with the review criteria stated below.  As part of the 
initial merit review, all applications will: 

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

REVIEW CRITERIA

Review Criteria for all Applicants

(1) Qualifications, Experience, and Commitment of Key Personnel

o Scientific, administrative, and/or clinical abilities of the Principal 
Investigator and other key personnel

o Experience of the Principal Investigator and other key personnel relevant to 
the objectives of the respective core 

o Commitment of personnel time for the satisfactory conduct of the study

(2) Protocols and/or Procedures

o Adequacy of protocols and/or procedures

o Cost effectiveness and quality control

o Quality of past performance

(3) Facilities and Management

o Adequacy of administrative, clinical, and/or data management facilities

o 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)

o Evidence of institutional support for participation in a long-term 
collaborative project

o Institutional commitment to provide support to the study in such areas as 
fiscal administration, personnel management, space allocation, procurement, 
planning, and budgeting

(4) Concept Protocol

o Adequacy of the conceptual framework and design

o Innovation in terms of approaches, methods, and/or analyses

Specialized Review Criteria for Particular Core Applicants

Clinical Core Sites:

o Adequacy of the study population

O Ability to recruit and retain study subjects

o Adequacy of surveillance procedures and enrollment plan and ability to 
carryout the surveillance, enrollment and diagnostic procedures

o Quality of the site's participation in collaborative clinical research

o Significance of the concept protocol in terms of addressing the problem of 
premature birth using genomic and proteomic strategies

Analytical Core:

o Adequacy of the facilities and procedures for receipt and storage of 
biological specimens for analysis

o Proficiency in performing "state of the art" high-throughput DNA, RNA and 
protein analyses

o Proficiency in genomic and proteomic computational and statistical analyses.

Data Management, Statistics and Informatics Core:

o Capability to act as an administrative coordinating center for the Network

o Adequacy of the facilities and procedures for central data collection, 
statistical analysis and management

o Proficiency in biostatistics, including the statistical analysis of genomic 
and proteomic data 

o Proficiency in bioinformatics and informatics, including creating and 
maintaining web-accessible, interactive databases

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following 
items will 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 criteria included in the section 
on Federal Citations, below.)

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 Inclusion Criteria in the sections on 
Federal Citations, below.)

ADDITIONAL CONSIDERATIONS 

BUDGET:  The reasonableness of the proposed budget and the requested period of 
support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:  July 20, 2004
Application Receipt Date:  August 20, 2004
Peer Review Date:  October/November 2004
Council Review:  January 2005
Earliest Anticipated Start Date:  April 01, 2005

AWARD CRITERIA

Criteria that will be used to make award decisions include: 

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities

In addition, final selection of sites for the Clinical Core will also be based 
on plans for maintaining satisfactory racial and ethnic representation in the 
overall study population.

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).

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 - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts 
on October 9, 2001 
(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 RESEARCH INVOLVING HUMAN SUBJECTS:  
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects 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 that is available at 
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 proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, 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 RFA 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 
RFA 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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