RESEARCH ON THE SCOPE AND CAUSES OF STILLBIRTH IN THE UNITED STATES
RELEASE DATE: October 3, 2002 (see amendment NOT-HD-03-008)
RFA: HD-02-025
National Institute of Child Health and Human Development (NICHD)
(http://www.nichd.nih.gov/)
LETTER OF INTENT RECEIPT DATE: February 13,2003
APPLICATION RECEIPT DATE: March 13,2003
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 of clinical research
sites with central data collection and analysis, which will develop and
implement common research protocols to study stillbirth (fetal death 20 weeks
or greater gestation). According to annual national vital statistics, the
number of fetal deaths at 20 weeks or greater gestation is similar in
magnitude to the total number of infant deaths in the U.S. Despite this
significant and persistent burden of stillbirths, they have remained largely
unstudied and, for at least half of all stillbirths, the cause is
undetermined. The objective of this RFA is to create a network of
multidisciplinary investigators to develop research diagnostic protocols as
well as a body of data on the scope and causes of stillbirths among varied
populations within the United States, while encouraging community involvement
to obtain an adequate sampling of rural and urban populations and a diverse
ethnic/racial makeup. The information that is obtained will aid in future
research to improve preventive and therapeutic interventions and to
understand the pathologic mechanisms leading to fetal death.
RESEARCH OBJECTIVES
Background
Stillbirths account for a large proportion of perinatal mortality. According
to annual national vital statistics, the number of fetal deaths, defined as
deaths at 20 weeks or more gestation, is similar in magnitude to the total
number of infant deaths in the U.S. In 1998, there were 28,371 infant deaths
and 26,702 fetal deaths. More than half of these fetal deaths are of 28
weeks or more gestation and 20 percent, or about 5000 cases, are term
gestation. In addition, the cause of about half of all stillbirths is
undetermined.
The stillbirth rate has been reduced dramatically since the 1950s with the
introduction of interventions for gestational diabetes, pre-eclampsia, and Rh
isoimmunization. However, while the infant mortality rate declined by about
32 percent between 1985 and 1998 from 10.6 to 7.2/1000 live births, the
stillbirth rate declined by only about 14 percent from 7.8 to 6.7 deaths/1000
live births. Despite this significant and persistent burden of stillbirths,
they have remained largely unstudied.
The National Institute of Child Health and Human Development (NICHD) convened
a workshop on March 26, 2001 with experts in the field to set a national
agenda for stillbirth research. Among the identified gaps in knowledge that
hamper progress in this field, were problems associated with current data on
stillbirths in the U.S. These include: (1) the fetal death report is
voluntary and under-reporting of stillbirths is as high as 10-15 percent; (2)
there is variability in the quality and completeness of the fetal death
certificates including certification of the cause of death; (3) there is no
standard protocol for postmortem investigation of stillbirths, including
serologic, toxicologic, and genetic tests; (4) while placental pathology is
common, fetal autopsy rates are low; and (5) there are few geographic
population-based, detailed investigations of reproductive and fetal risks
associated with stillbirth.
Some of the recent evidence points to the association of repeat fetal deaths
with the genetic predisposition for thrombophilias (Factor V Leiden mutation)
and genetic conditions (telomere mutations). Novel neuropathology findings
of CNS insults point to specific findings related to fetal death, involving
central nervous system insults. Other associations include maternal
complications (diabetes, hypertension, anemia) and umbilical cord accidents;
however, the limited ascertainment leads to a bias in the findings, as only a
small portion have autopsies or tests performed.
These deaths are devastating to the family. It is hoped that increased
knowledge regarding the causes of stillbirths will benefit families who have
experienced a loss, pregnant women, and their physicians, and may lead to the
development and evaluation of improved clinical and preventive interventions.
Objectives and Research Approach
Because procedures in case ascertainment and registration of fetal deaths
vary so widely across the U.S., we do not have a true picture of stillbirths.
This information is necessary for future studies to elucidate pathogenic
mechanisms and improve on current preventive and therapeutic strategies. The
objective of this RFA is to establish a network of clinical research sites
with central data collection and analysis to:
(1) develop a standard stillbirth postmortem protocol, to include review of
clinical history, protocols for autopsies and pathologic examinations of the
fetus and placenta, other postmortem tests to illuminate genetic, maternal,
and other environmental influences, and
(2) obtain a geographic population-based determination of the incidence of
fetal deaths at 20 weeks gestation or greater, their causes, and risk
factors. This will involve a geographic population-based study of
stillbirths enrolled at the time of demise, and a sub-cohort case-control
study.
Project Organization
This RFA solicits applications for clinical sites to form a network to obtain
an accurate ascertainment of the stillbirths and understanding of causes.
This RFA also solicits a Data Coordinating and Analysis Center. The grantees
will form a cooperative network in scientific partnership with NICHD to
conduct a geographic population-based study of stillbirths, which will
require a highly effective surveillance system and at least 90 percent
ascertainment. The catchment for the study will include a diversity of
populations (urban/rural/different social and racial groups). The sites will
employ a standardized protocol for evaluation of the cases.
Clinical Sites:
With a stillbirth rate estimated at five per 1000, we anticipate a sample
size of 500 would be an adequate initial sampling. This would require four
to seven clinical centers over a five-year period, anticipating the total
geographic population pool has 100,000 deliveries. Importantly, the centers
will be multidisciplinary and have significant community involvement to
obtain an adequate sampling of rural and urban populations and a diverse
ethnic/racial makeup.
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 vote may be divided into shares at the discretion of the participating
sites and the NICHD. 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.
MECHANISM OF SUPPORT
This RFA will use the National Institutes of Health (NIH) Cooperative
Clinical Research (U10) award mechanism. This RFA is a one-time
solicitation. The anticipated award date is September 26, 2003.
The NIH U10 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 $3 million in Total Costs [Direct
plus Facilities and Administrative (F & A) costs] in FY 2003 to fund five to
eight new grants in response to this RFA, one of which will be the DCAC. 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 $120,000 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. 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 Domestic
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.
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 their institution to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH programs.
SPECIAL REQUIREMENTS
Clinical Sites
o Minimum Catchment Populations: Clinical Sites with urban populations
should have a catchment population with at least 8,000 deliveries per year,
and those with rural populations at least 3,000 deliveries per year in order
to apply. Applicants may propose urban only, rural only, or urban and rural
geographic areas for case ascertainment. The applicant must demonstrate that
a large majority of the population receives prenatal care within the
catchment.
o Clinical Sites should have experience in multi-center research
investigations.
o Some, but not necessarily all, of the following expertise should be part of
the research team: obstetrics, maternal-fetal medicine/perinatology,
neonatology, perinatal pathology, genetics, infectious disease/immunology,
epidemiology, and neuropathology.
o There also should be a dedicated research nurse and a community outreach
worker.
o The site should have experience in community outreach to pregnant women and
in working with community clinics, hospitals, and other organizations that
provide support to pregnant women.
o The site must have an established perinatal data system, preferably
computerized, to collect and tabulate perinatal data statistics.
o The investigators should be prepared to meet as a Steering Committee about
six times in the first year to develop protocols and three times per year
thereafter.
o The investigators should be prepared to work collaboratively with the NICHD
and the DCAC to achieve the goals of this solicitation.
o Departmental and institutional commitments to collaborative research
(including departments of obstetrics, pediatrics, genetics, pathology, etc.)
should be clearly documented by providing letters to the Principal
Investigator that should accompany the application.
o The applicant must exhibit a preparedness to pursue capitation of
particular operational costs of the protocol (see Budget Preparation).
Data Analysis and Coordinating Center
o The applicant must have demonstrated prior experience as a coordinating and
statistical center in multi-center clinical studies.
o The Principal Investigator, with other staff, must have appropriate
biostatistical, computational, data management, and coordination expertise
and capability. The applicant must have the ability to assist in designing
protocols, study manuals, and data collection systems, including distributed
data entry.
o The applicant must have experience in developing and maintaining a quality
control system, and should demonstrate experience in monitoring quality
assurance of data.
o The applicant must have experience in data monitoring, patient tracking
systems, and coordination.
o The DCAC will report quarterly to the NICHD, and to the Steering Committee
prior to/at each meeting regarding accumulated data and clinical unit
performance. The applicant should document the ability to meet such
reporting deadlines.
o The investigators should be prepared to meet as a Steering Committee about
six times in the first year to develop protocols and three times per year
thereafter.
o The applicant must be prepared to cooperate with the Clinical Sites and
NICHD in all design, collection, and analysis functions.
o The applicant must be prepared to assist the NICHD in securing services of
research sub-specialties to supplement the expertise of members of the
Steering Committee.
Data Collection and Sharing
o There will be central data collection, management, and analysis for this
study. The Data Coordinating and Analysis Center, in collaboration with the
Steering Committee, will develop and implement plans to create a database
that is accessible to the public within a year of study completion.
o Because the data elements and study design will be developed after award,
the data-sharing plan will not be reviewed at the time of application. It
will be reviewed after award by the Advisory Board (see below) and the NICHD,
before implementation.
Cooperative Agreement Terms and Conditions of Award
Cooperative agreements are assistance mechanisms and are subject to the same
administrative requirements as grants. The special Terms and Conditions of
Award are in addition to, not in lieu of, otherwise applicable OMB
administrative guidelines, HHS, PHS, and NIH grant regulations, policies, and
procedures, with particular emphasis on HHS regulations at 42 CFR Part 74 and
92. Facilities and Administrative cost (indirect cost) award procedures will
apply to cooperative agreement awards in the same manner as for grants.
Business management aspects of these awards will be administered by the NICHD
Grants Management Branch in accordance with HHS and NIH grant administration
requirements.
The cooperative agreement funding mechanism will require collaboration among
the NICHD Project Scientists and the Principal Investigators of the Clinical
Sites and the Data Coordinating and Analysis Center. The NICHD Project
Scientists will coordinate the activities of the Stillbirth Research
Collaboration, and will facilitate communication and the exchange of
information as described below.
1. The Primary Rights and Responsibilities of the Awardees
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.
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.
All parties will agree to accept the coordinating role of the group and the
participatory and cooperative nature of the group process.
Awardees will retain custody of, and primary rights to, their data developed
under the award, subject to Government rights of access consistent with
current HHS and NIH policies.
2. NICHD Staff Responsibilities
NICHD Project Scientists:
The role of the NICHD Stillbirth Project Scientists 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 reporting results in the community of investigators and
health care recipients.
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 Program Official:
The NICHD will appoint a Stillbirth Program Official, apart from the
Stillbirth Project Scientist, who will:
o 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.
o Initiate a decision to modify or terminate a study based on the advice of
the Data Safety and Monitoring Committee and the Advisory Board with the
mutual consent of the Steering Committee.
o Perform other duties required for normal program stewardship of grants.
3. Collaborative Responsibilities
The guidance and management of the Stillbirth Research 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 Stillbirth Project Scientists. There will
be only one vote for NICHD staff, which will be shared by the Stillbirth
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.
The responsibilities of the Steering Committee are as follows:
o Develop the study protocols to include postmortem protocols for diagnosis,
protocols for surveillance and case enrollment, and protocols sub-cohort
case-control study.
o Develop a data management plan, with primary input from the DCAC, to
include plans for quality assurance and plans for public access to the
database.
o Monitor surveillance and enrollment upon study initiation.
o Establish Policies and Procedures that govern its operations, including
publications.
o Develop an analytic plan in collaboration with the Data Coordinating and
Analysis Center.
Advisory Board:
An Advisory Board will advise the Steering Committee in the development of
research protocols. The Advisory Board, chosen by the NICHD with the advice
of the Steering Committee, will comprise individuals with expertise in
obstetrics, perinatal pathology, biostatistics, epidemiology, perinatology,
neonatology, and genetics. The Chairperson of the Steering Committee, the
Principal Investigator of the Data Coordinating and Analysis Center, and the
Stillbirth Project Scientists may attend Advisory Board meetings to provide
information as needed. Additional members will participate based on the need
for specific expertise.
Data Safety and Monitoring Committee:
A Data Safety and Monitoring Committee (DSMC) will monitor the safety of
ongoing study protocols. This committee will be established by NICHD and
will represent expertise in ethics, clinical trials/epidemiology,
perinatology, neonatology, genetics, and pathology.
4. Arbitration Procedures
When agreement between an awardee and NICHD staff cannot be reached on
programmatic and scientific-technical issues that may arise after the award,
an arbitration panel will be formed. The panel will consist of one person
selected by the Principal Investigators, one person selected by the NICHD
staff, and a third person selected by these two members. The decision of the
arbitration panel, by majority vote, will be binding. These special
arbitration procedures in no way affect the awardees right to appeal an
adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart
D, and HHS regulations at 45 CFR Part 16.
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:
Marian Willinger, Ph.D.
Pregnancy and Perinatology Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B03, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 435-6896
FAX: (301) 496-3790
E-mail: mw75q@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
Rockville MD 20852 (for express/courier service)
Telephone: (301) 496-1485
FAX: (301) 402-4104
E-mail: stretchr@mail.nih.gov
o Direct your questions about financial or grants management matters to:
Christopher P. Myers
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17H, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 435-6996
FAX: (301) 402-0915
E-mail: cm143g@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:
Marian Willinger, Ph.D.
Pregnancy and Perinatology Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B03, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 435-6896
FAX: (301) 496-3790
E-mail: mw75q@nih.gov
SUBMITTING AN APPLICATION
Applications must be prepared using the PHS 398 research grant application
instructions and forms (rev. 5/2001). The PHS 398 is available at
https://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.
SUPPLEMENTAL INSTRUCTIONS:
Clinical Sites
Please provide the following in your application:
(1) Patient population
o Geographic definition of the catchment area proposed for a population-based
assessment of stillbirths by the applicant organization.
o Documentation of number of deliveries at or later than 20 weeks within the
catchment geographic population from 1995-1999 to include: (a) each pregnancy
outcome (fetal death, live birth,) stratified by race/ethnicity; (b) each
pregnancy outcome stratified by gestational age (20-23 weeks, 24-27 weeks,
28-31 weeks, 32-36 weeks, 37 plus weeks); (c) proportion receiving prenatal
care within the catchment stratified by trimester.
o Estimated rates of fetal deaths at or later than 20 weeks per 1000 live
births plus stillbirths, and rates of fetal autopsy and placental pathology
from 1995-1999.
o Distribution of causes of fetal deaths at or later than 20 weeks from 1995-
1999.
(2) Staffing and Procedures
o Descriptions of the staff and programs in place for surveillance of
deliveries in the catchment area to identify all eligible fetal deaths at or
later than 20 weeks, and proposals for expansion of services if needed. This
includes creative proposals for partnering with community-based organizations
including health departments.
o Descriptions of staff and subspecialty services, support services and
laboratories necessary for evaluating and investigating the cause of death.
Provision should be made for a dedicated research nurse and a community
outreach worker.
o An enrollment plan to include procedures for approaching the families to
optimize enrollment, a sample consent form, and procedures for supplying
grief support to the families.
o Descriptions of recent research productivity by the applicant clinical site
in previous or present cooperative multicenter studies. Specifically,
contributions in key areas such as protocol design, patient recruitment, data
analysis and interpretation, and publication are important.
o A description of special areas of expertise among your applicant team that
would benefit this multi-center cooperative study of stillbirth. 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, placental function, or perinatal pathology are
examples of relevant strengths that could be included.
o Letters of collaboration from prenatal clinics, community hospitals, and
medical centers within the catchment area to participate in a geographic
population-based study of stillbirth. This includes a commitment for timely
notification of eligible stillbirths for enrollment into study, utilization
of a standard postmortem protocol, and availability of medical records for
abstraction.
(3) Sample Study
Provide a description of a sample multi-center, geographic population based
study of stillbirth that meets the objectives of the RFA. The description
should include elements of the surveillance system, diagnostic procedures,
and information to be collected. 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
geographic population-based assessment of stillbirth, and to conceptualize a
multi-center investigation of fetal deaths. Investigators will not be
expected to perform these studies at their site.
(4) Intent to Participate
o 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 RFA.
(4) Perinatal Data System
o A perinatal data system, preferably computerized, 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.
(5) Acceptance of Budgetary Mechanism (see also Budget Preparation below)
o 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 your application:
(1) Research Experience
o Description of previous experience in managing multi-center clinical
research studies.
o Description of applicant's perception of their role in the study.
(2) Staffing and Procedures
o Description of staff and computing, data processing, and analytic
capability.
o 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.
(3) Intent to Participate
o 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 RFA.
BUDGET PREPARATION:
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:
o Principal Investigator/Co-Principal Investigator(s): up to a total of 30
percent effort
o Research Nurse Coordinator/outreach worker: 50 percent effort
o Data Entry Clerk: 50 percent effort
o Supplies and Small Equipment (itemized and justified): Not to Exceed
$4,500
o Travel (a total of 18 person trips to Bethesda): as appropriate
o Other costs (itemized and individually justified): Not to Exceed $2,500
When an application has been reviewed and is being considered for funding,
the applicant will be required to complete the budgets based on capitation
funding. 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 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:
o Principal Investigator/Biostatistician team: up to 100 percent effort
o Programmer/Systems Analyst: 50 percent effort
o Study Coordinator/Administrative Assistant: 50 percent effort
o Travel (a total of 12 person trips to Bethesda): as appropriate
o Consultants for protocol development and one meeting of the DSMC: $10,000
o 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' budget requests should be limited to base budget costs, with an
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.
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:
https://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 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 by 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.
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. The
CSR will not accept any application that is essentially the same as one
already reviewed. This does not preclude the submission of substantial
revisions of applications already reviewed, but such applications must
include an Introduction addressing the previous critique.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR and
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 Receive a written critique
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 second level review by the National Advisory Child Health and
Human Development Council
REVIEW CRITERIA
Clinical Sites:
(1) Qualifications, Experience, and Commitment of Key Personnel
o Scientific, clinical, and administrative abilities and academic
productivity of the Principal Investigator and other team members;
o 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;
o Commitment of staff time for the satisfactory conduct of the study;
o Experience and qualifications of team members who would be responsible for
data quality and management activities.
(2) Documentation and Procedures
o Adequacy of documentation of the patient population as outlined in
supplemental instructions;
o Quality of the site's participation in collaborative clinical research;
o Adequacy of surveillance procedures and enrollment plan and ability to
carryout the surveillance, enrollment and diagnostic procedures.
o Willingness to work and cooperate with other sites, the DCAC, and the
NICHD in the manner summarized in this RFA;
o Additional research strengths, as presented.
(3) Description of sample study
o Adequacy of the conceptual framework and design to meet the objectives of
the RFA.
o Potential of the proposed study elements to advance knowledge,
methodology, and/or concepts relating to the scope and causes of fetal death
in the United States.
(4)Facilities and Management
o Adequacy of administrative, clinical, and data organizational management
facilities as described in supplemental instructions; this includes
documentation of collaborative arrangements to ensure geographic population-
based surveillance and enrollment within the catchment area;
o Institutional commitment to provide support to the study in such areas as
fiscal administration, personnel management, space allocation, procurement,
planning, and budgeting;
Data Coordinating and Analysis Center:
(1) 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
statistical data management, quality control, study coordination, and
administrative aspects.
(2) Protocols and Procedures: Quality of past performance and proposed
plans for study coordination, data collection, analysis, and monitoring.
(3) 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.
(4) Willingness to work cooperatively with other awardees and NICHD in the
manner summarized in the Cooperative Agreement Terms and Conditions of Award.
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your
application will also be reviewed with respect to the following:
o PROTECTIONS: The adequacy of the proposed protection for humans, animals,
or the environment, to the extent they may be adversely affected by the
project proposed in the application.
o INCLUSION: 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. Plans for the recruitment and
retention of subjects will also be evaluated. (See Inclusion Criteria
included in the section on Federal Citations, below.)
o BUDGET: The reasonableness of the proposed budget in light of the budget
guidelines listed under "Budget Preparation" and the requested period of
support in relation to the proposed research.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: February 13, 2003
Application Receipt Date: March 13, 2003
Peer Review Date: June/July 2003
Council Review: September 2003
Earliest Anticipated Start Date: September 2003
AWARD CRITERIA
Criteria that will be used to make award decisions include:
o Scientific merit (as determined by peer review). The combined expertise of
all sites will play a role in the selection of grants for award. These
include but are not limited to community outreach, perinatal pathology, and
epidemiology.
o Availability of funds
o Programmatic priorities to include geographic and subpopulation diversity.
REQUIRED FEDERAL CITATIONS
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 AMENDMENT "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
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete
copy of the updated Guidelines is available at
https://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. This policy applies to all initial (Type 1) applications submitted for
receipt dates after October 1, 1998.
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
https://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
https://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
https://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.
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 No. 93.865 and is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review. Awards are made under authorization of Sections 301
and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and
administered under NIH grants policies described at
https://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations
42 CFR 52 and 45 CFR Parts 74 and 92.
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.