kristoff@GENBANK.BIO.NET (Dave Kristofferson) (03/02/90)
NIH GUIDE - Vol. 19, No. 9, March 2, 1990 - Page 12
FULL TEXT OF RFAs FOR ONLINE ACCESS
REQUEST FOR COOPERATIVE AGREEMENT APPLICATIONS:
RFA: 90-AI-04
AIDS CLINICAL TRIAL INFRASTRUCTURE COOPERATIVE AGREEMENT FOR
MINORITY INSTITUTIONS
P.T. 34, FF; K.W. 0715008, 0755015, 0404000, 0403004
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Letter of Intent: March 23,
1990
Application Receipt Date:
April 26, 1990
The Division of AIDS, National Institute of Allergy and
Infectious Diseases (NIAID), invites minority institutions
to submit applications for cooperative agreements to support
the establishment of an AIDS Clinical Trial infrastructure
for the purpose of increasing the participation of
underrepresented minority populations in AIDS Clinical
Trials Group (ACTG) studies.
There are no plans to reissue this Request for Applications (RFA)
at any future time.
I. BACKGROUND INFORMATION
Infection with human immunodeficiency virus (HIV) and
the Acquired Immunodeficiency Syndrome (AIDS)
constitute a profound and increasing
health problem for minority populations. Recent
epidemiologic data indicate that minorities suffer
disproportionately from AIDS. Blacks account for 27%
of all adult cases of AIDS and 52% of pediatric cases,
while Hispanics account for 15% of all adult cases and
23% of the pediatric cases, yet these groups comprise
only 12 and 8%, respectively, of the population in the
United States. Overall, the relative risk of AIDS for
Black and Hispanic men is between two and ten times
greater than for white men. The vast majority of these
individuals are HIV-infected intravenous drug users
(IVDUs) and more than 50% of their female sex partners
are HIV seropositive. Of the adult cases of AIDS
reported among females, 52% are Black, 11% are
Hispanic and 29% are white, suggesting that AIDS is
becoming a serious health problem for minority women
as well. (Racial designation was not available for 8%
of patients.)
Since the initial recognition of AIDS in the early
1980s,
NIAID has been fully committed
to the struggle against this disease. This commitment
has been characterized by the evolution of a
multicenter network of institutions designated as the
ACTG which is opening new
avenues in evaluating therapies and methods to restore
immune function and to treat opportunistic infections
associated with AIDS. Although considerable progress
has been made in bringing ACTG research to many
individuals with HIV infection, there has been
insufficient progress in bringing these studies to
minorities. Despite the fact that several clinical
trial sites are located in geographical areas with
substantial minority populations, minorities with HIV
infection are markedly underrepresented in ACTG
research. Of 8,288 patients enrolled in ACTG studies
as of November 13, 1989, 77.6% are white, 9.6% are
Black, and 11.7% are Hispanic. Of the total number
reported, 592 (7.6%) are women. These statistics are
disturbing in that they do not accurately reflect the
demographics of HIV infection in the overall
population; moreover, they may suggest significant
gaps in scientific knowledge about HIV infection in
minority patients. To date, most ACTG studies
evaluating treatment therapies have been conducted in
homosexual and bisexual men and on a whole have
involved relative small numbers of minorities with HIV
infection, thus making the results of the studies of
uncertain applicability as far as nationwide disease
trends are concerned.
While disparity in incidence and survival between
majority and minority populations may be a reflection
of our health care delivery system,
underrepresentation of minorities in ACTG research may
also reflect structural gaps in the existing system
that limit participation in clinical trials and
access to experimental therapeutic resources. One way
to overcome these imbalances is to encourage greater
participation of minority institutions and minority
investigators in ACTG research. Currently, the ACTG is
comprised of scientists and clinical researchers at 47
main AIDS Clinical Trials Units (ACTUs) and patients
are enrolled in clinical research at 109 affiliated
sites throughout the United States. These ACTUs were
funded by the NIAID based on criteria relevant to
institutional clinical trials research capabilities
and availability of HIV-infected patients. Access and
participation by minorities were not primary
considerations for funding, particularly during the
early years when the urgency to mobilize against this
devastating disease was being felt. Now that the
magnitude of HIV infection in minority populations has
been fully realized, the NIAID is committed to
improving access and participation among these groups
and has given high priority to increased involvement
in clinical trials for both minority patients with HIV
infection and minority health professionals in AIDS
research.
NIAID realizes that while many minority institutions
have access to the desired underrepresented minority
populations and are in unique positions to address
issues related to HIV infection in minorities, many of
these institutions, for a myriad of reasons,
experience difficulties in competing for research
grants to conduct AIDS Clinical Trials. In this
regard, NIAID plans to offer cooperative agreement
grants to enable minority institutions to develop the
capability and expertise necessary to establish and
implement an AIDS Clinical Trial infrastructure and to
participate more fully for competitive AIDS Clinical
Trials research grants.
II PURPOSE
The purpose of this RFA is to provide a period of
support of 3 years for minority institutions to
establish an ACTU infrastructure
and to acquire sufficient expertise in clinical trials
for successful submission of a cooperative agreement
to participate in ACTG research.
These cooperative agreements are intended to provide a
reasonable opportunity to demonstrate creativity and
productivity and to assist in the preparation for
competition for regular cooperative agreement support
for conduct of ACTG research.
III. DEFINITIONS
MINORITY INSTITUTION - An institution that has more
than 50% minority student enrollment, awards an M.D.,
D.D.S., D.V.M or other doctoral degree in the
health professions.
COOPERATIVE AGREEMENT - An assistance mechanism in
which substantial NIH staff involvement with the
recipient during the performance of the planned
activity is anticipated.
AIDS CLINICAL TRIALS GROUP (ACTG) - A network of
institutions, investigators, NIAID personnel, and a
Statistical and Data Analysis Center (SDAC), organized
for the purpose of evaluating potential therapies for
HIV infection and its sequelae.
AIDS CLINICAL TRIALS UNIT - An institution that has
been awarded an NIAID cooperative agreement to
participate in ACTG clinical trials.
PRINCIPAL INVESTIGATOR - The licensed physician who
submits the single application in response to this RFA
and who is responsible both scientifically and
administratively for the performance of the
participants as a whole.
NIAID SCIENTIFIC COORDINATOR - A member of the NIAID
extramural staff who assists and facilitates the
partnership relationship between NIAID, the individual
award recipients, and the ACTG as a whole.
ARBITRATION PANEL - A group composed of an individual
designated by the Principal Investigator of an
individual minority institution cooperative agreement,
one NIAID designee, and a third designee with
expertise in the relevant area and chosen by the other
two. Such panels may help resolve both scientific and
programmatic issues that develop during the course of
the work and restrict progress. The interaction of
this panel is detailed in section VI, part D under
"TERMS OF AWARD: NATURE OF PARTICIPATION OF NIAID
STAFF".
IV. MECHANISM OF SUPPORT
Awards will be made as Cooperative Agreements.
Assistance by Cooperative Agreement differs from the
research grant in that the Government component
(NIAID) awarding the Cooperative Agreement anticipates
substantial involvement during the performance of the
award. The nature of NIAID staff participation is
described in section VI under "TERMS OF AWARD: NATURE
OF PARTICIPATION OF NIAID STAFF." There is no intent,
real or implied, for NIAID staff to direct an
awardee's activities. The interaction of NIAID staff
with the investigators is expected to assist and
facilitate planning and development of an AIDS
Clinical Trial capability.
NIAID has set aside $3,632,000 in total costs for the
initial year's funding to minority institutions. The
NIAID plans to fund between 4 and 5 awards from this
announcement. The starting date for the initial annual
period will be on or before September 1990. Awards
will be made for a period of 3 years with yearly
evaluation involving competent consultants. Awardees
are expected to develop an infrastructure and
capabilities for AIDS Clinical Trials research and to
submit a competitive grant application by the
thirtieth month of operations under the award
mechanism for conduct of AIDS Clinical Trials
research.
All policies and requirements that govern the grant
program, Public Health Service, and the National
Institutes of Health apply.
Although this program is provided for in the financial
plans of NIAID, the award of Cooperative Agreements
pursuant to this RFA is also contingent upon the
scientific merit of the applications received and the
continuing availability of funds for this purpose.
V. RESEARCH GOALS AND SCOPE
The long-term objective of this RFA is to increase the
involvement of underrepresented minority populations
in AIDS Clinical Trials. The immediate goal is to
provide funding to:
o Plan and develop an AIDS Clinical Trial
Unit infrastructure.
o Acquire the necessary expertise in
clinical trials needed for the successful
submission of a cooperative agreement to
participate in the ACTG.
o Acquire the administrative and scientific
training and skills
to
participate in AIDS Clinical Trials research.
o Recruit professional and support staff.
(See the fifth statement under section VI,
Part B, "Participation of NIAID Staff in
Cooperative Agreement Activities".)
o Renovate existing structures or rental of
space, at a cost not to exceed $85,000,
for provision of suitable facilities for
conduct of AIDS Clinical Trials research.
NOTE: Funds will not be provided to
establish new facilities (e.g., new
virology or immunology laboratories).
o Purchase of equipment, at a cost not to
exceed $40,000, for conduct of AIDS
Clinical Trials research.
o Support travel and training activities
related to AIDS Clinical Trials research.
Long-term goals are to:
o Encourage the participation of minority
institutions and minority investigators in
ACTG research and provide a basis for
involving underrepresented populations in
AIDS Clinical Trials studies.
o Increase the scientific base of
understanding the unique social and
medical issues related to AIDS in minority
populations.
o Increase the understanding of the
potential for adverse drug reactions in
minority intravenous drug-using patient
populations.
The culmination of this effort will be the submission
of a grant application for conduct of AIDS Clinical
Trials. The Division of AIDS, NIAID, intends to support
this planning initiative by awarding cooperative
agreements to minority institutions. The institutions
should be capable of developing a process to improve
research capability and to begin protocol studies
under the leadership of a qualified Principal
Investigator sensitive to the needs and concerns of
minority populations infected with HIV.
Minimum Requirements for Applicants:
Applicant institutions seeking funding must meet the
following requirements:
A. Have a student enrollment which is more than 50%
minority and awards an M.D., D.D.S., D.V.M
or other doctoral degree in the health
professions.
B. Demonstrate access, as evidenced by written
documentation, to at least 100 minority
individuals with HIV infection as proven by
standard serologic methodologies such as ELISA,
Western Blot, or p24 antigen determination.
C. Provide written documentation of institutional
commitment to participate fully in planning and
developing the capability and expertise to
conduct ACTG research and to submit a
competitive application for conduct of AIDS
Clinical Trials.
D. Provide written documentation of the scientific,
administrative/management, and organizational
capabilities of the Principal Investigator and
the existing, or to be recruited, professional
and support personnel necessary to carry out the
objectives of this grant.
Applicant institutions should provide letters of
commitment from qualified individuals who will
be recruited.
E. Provide evidence of an institutional plan and
commitment to recruit and hire necessary and
competent professional and paraprofessional
staff to establish an ACTU and to conduct AIDS
Clinical Trials research.
F. Provide evidence of an institutional plan to
provide adequate facilities and equipment to
establish an ACTU and to conduct AIDS Clinical
Trials research.
G. Provide evidence of provision of health care for
HIV-infected IVDUs.
H. Provide a reasonable timetable for implementing
plans related to organization, training (in
conjunction with NIAID), personnel, facilities,
and equipment for establishment of the necessary
ACTU infrastructure.
VI. TERMS OF THE AWARD: NATURE OF PARTICIPATION OF NIAID
STAFF
A. Responsibilities of the Awardees
Assistance via Cooperative Agreement differs
from the traditional research grant in that, in
addition to the normal programmatic and
administrative stewardship responsibilities, the
component awarding the Cooperative Agreement
anticipates substantial involvement during
performance of the project. However, the
awardee must define its objectives in accord
with its own interests and perceptions of novel
and exploitable approaches and develop the
details of the project following the guidance
given in this RFA. It is the primary
responsibility of the awardee to appoint a
Principal Investigator who is: a staff member of
the awardee institution, available to devote at
least 50% effort per year to the development of
an ACTU, and ensure the
development of the ACTU in a timely fashion.
o Awardees will accept NIAID site visits and
scientific and technical advice in all
relevant areas to develop an effective and
efficient system for conduct of AIDS
Clinical Trials research.
o Awardees will accept relevant training,
when provided, for key personnel in the
areas of data management, quality
assurance/quality control, protocol
development, etc., and regular interaction
with ACTG investigators.
o Awardees will accept input and advice
regarding the selection of key personnel
to fill positions which were not filled
prior to this application.
B. Participation of NIAID Staff in Cooperative
Group Activities
Through the NIAID Scientific Coordinator, the
following support can be anticipated from the
Treatment Research Program, Division of AIDS.
o NIAID will maintain a close ongoing
cooperation with cooperative agreement
recipients. In this regard, NIAID staff
will participate in site visits to
facilitate this development activity.
o NIAID will provide scientific and
technical advice to awardee institution(s)
in all areas relevant to the establishment
and operation of an ACTU.
o NIAID contractors will provide relevant
training to key personnel for development
of the expertise necessary for conduct of
AIDS Clinical Trials in the areas of data
management, quality assurance/quality
control, intercommunication among
participating institutions, protocol
development, investigational drug
management and distribution, and grant
writing.
o NIAID will provide linkage between awardee
institutions and ongoing clinical trials
efforts and epidemiologic and
natural history studies by serving a
referral function and providing baseline
data when needed.
o NIAID will provide logistical support for
frequent and regular interaction among
ACTG investigators and minority
institutions.
o NIAID will provide input and advice
regarding the selection of key
professional and support personnel to
fill positions which were not filled prior
to the review of application.
C. The special "TERMS OF AWARD: NATURE OF
PARTICIPATION OF NIAID STAFF" described in this
section are in addition to, and not in lieu of,
otherwise applicable OMB administrative
guidelines, HHS Grant Administration Regulations
at 45 CFR Part 74, and other HHS, PHS, and NIH
grant administration policy statements.
D. Inasmuch as certain of the activities described
herein require approval by NIAID staff during
performance of this Cooperative Agreement (e.g.,
training), NIAID will establish an arbitration
process to resolve any differences of opinion.
An arbitration panel, composed of one minority
institution awardee designee, one NIAID
designee, and a third designee with expertise in
the relevant area and chosen by the other two,
will be formed to review any scientific or
administrative issue that is significantly
restricting progress. This arbitration process
in no way affects the right of an award
recipient 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.
VII. REVIEW PROCEDURES AND CRITERIA
Applications that are incomplete or
nonresponsive to this RFA will be withdrawn by the
National Institute of Health (NIH) staff upon receipt
and returned to the applicants without further
consideration.
Applications that are judged responsive will be reviewed in
accordance with the usual NIH peer review procedures. They
will first be reviewed for scientific and technical merit by
the AIDS Research Review Committee of the Extramural
Activities Program, organized by NIAID for this purpose.
Following the initial review, the applications will be
considered by the NIAID Advisory Council.
Peer Review Criteria for Applicants:
Acceptable applications for evaluation must be
directed toward the attainment of programmatic goals
as stated in Section V, "RESEARCH GOALS AND SCOPE."
Listed below are the criteria that will be used by the
AIDS Research Review Committee and the Advisory
Council when reviewing the applications.
A. Rationale
Availability of patient population
o Access to at least 100 minority persons
with HIV infection as evidenced by the
ELISA, Western Blot, or p24 antigen
determination.
o Proof of access to these numbers must be
made available to the NIAID upon
submission of the cooperative agreement application.
o Clearly stated institutional plans for
recruitment, follow up, and retainment of
patients.
B. Procedures and Plans for Organization
Quality of a plan to develop the
capabilities of the minority institution
to establish an infrastructure for the
conduct of AIDS Clinical Trials research
and to integrate that unit within the
existing ACTG structure. The plan should
indicate how the following capabilities
will be developed:
o Clinical Activities;
o Data Management;
o Quality Assurance/Quality
Control of data;
o Investigational Drug
Management;
o Pharmacy support;
o Immunologic Monitoring and
Evaluation; *
o Virologic Monitoring and
Evaluation; *
o Clinical Pharmacokinetics
(optional);
o Outreach and recruitment;
o Social services support for
infants born to women who
are HIV infected; and,
o Social, legal, and economic
problems and other issues
that will bear directly on
the ability to conduct
clinical trials in minority
populations.
*NOTE: The NIAID suggests that
applicant institutions plan to
have these tests performed by a
certified ACTG laboratory.
C. Plans for Training
Merit of a plan for coordinating the
training of key staff
in areas of data management, quality
assurance, protocol development, IND
management, grant writing, and other
training relevant to the development of
a clinical trial unit.
o Clearly stated training needs.
o Suitability in terms of requests
for the necessary training.
o Practicability, especially with
reference to the stated time-
frame to acquire proficiency.
D. Plans for Facilities and Major
Equipment
Adequacy of a plan to improve
facilities and equipment for the
development of the proposed AIDS
Clinical Trials infrastructure.
o An applicant institution should
assess its existing
infrastructure and provide a plan
for modification or expansion, if
necessary, in order to provide an
appropriate environment for
developing an ACTU.
o Renovations or alterations of
facilities, rental of space, and
purchase of large equipment are
justifiable when a description of
their use or existing unmet needs
are included in the plan.
E. Investigators and Key Personnel
Demonstrated qualifications,
availability, competence, experience
and an adequate mix of key professional
and support personnel to develop this
project as evidenced by:
o Scientific and technical
expertise of the Principal
Investigator in the area of HIV
infection.
o Administrative/management
competence of the Principal
Investigator to develop an AIDS
Clinical Trials infrastructure.
o Expertise and time commitment of
the Principal Investigator to
assemble, coordinate, and manage
a comprehensive planning and
development team.
NOTE: At the end of the funding period,
awardees wishing to recompete for funds
to conduct clinical trials will be
required to submit an application
detailing a relevant concept to the
conduct of ACTG research. Applicants
are advised to allow approximately 6-9
months for the development of a
proposal.
VIII. METHOD OF APPLYING
A. Letter of Intent
Prospective applicants are asked to submit,
by March 23, 1990, a short letter of intent
that includes a descriptive title(s) of the
proposed research, and if possible, names of
key members of the proposed group. The
letter of intent is requested in order to
provide an indication of the number and scope
of applications to be reviewed. The letter
of intent does not commit the sender to
submit an application, nor is it a
requirement for submission of an application.
The letter of intent should be sent to:
George W. Counts, M.D.
Chief, Clinical Research
Management Branch
Treatment Research Program
Division of AIDS Research
National Institute for Allergy
and Infectious Diseases
6003 Executive Blvd., Room 207P
Bethesda, Maryland 20892
Telephone: (301) 496-8214
B. Receipt Date
The deadline for receipt of application is
April 26, 1990. In light of accelerated
receipt to award processing requirements
mandated by Section 2302 of the Title II
(AIDS Amendment of 1988), there must be
strict adherence to the receipt date
announced in this RFA. No exceptions will be
made. All applications received past the
receipt date will be returned to the
investigator.
C. General
1. The regular research grant application
form PHS-398 (rev. 10/88) must be used
in applying. These forms are available
at most institutional business offices
or from the Division of Research
Grants, National Institutes of Health,
Bethesda, Maryland 20892.
Submit a signed, typewritten original
of the application, including the
Checklist and four signed, exact,
single-sided photocopies, in one
package to:
Division of Research Grants, NIH
Westwood Building, Room 240
Bethesda, MD 20892**
In addition, submit 19 exact, single-sided, photocopies of
the application plus six copies of the appendices to:
Sally Mulhern, Ph.D.
AIDS Research Review Section
Program and Project Review Branch
National Institute of Allergy and
Infectious Diseases
National Institutes of Health
Westwood Building, Room 3A-14
Bethesda, MD 20892
2. TO ASSURE PROPER IDENTIFICATION OF YOUR
APPLICATION WITH THIS RFA, the applica-
tion form should have "AIDS MINORITY
INFRASTRUCTURE (RFA 90-AI-04)" typed on
line 2 of the face page of the
application form.
THE RFA LABEL PROVIDED WITH THE
INSTRUCTIONS MUST BE AFFIXED TO THE
BOTTOM OF THE FACE PAGE. FAILURE TO USE
THIS LABEL COULD RESULT IN DELAYED
PROCESSING OF YOUR APPLICATION SUCH
THAT IT MAY NOT REACH THE REVIEW
COMMITTEE IN TIME FOR REVIEW.
IX. SUMMARY OF TARGET DATES
LETTER OF INTENT: March 23, 1990
APPLICATION RECEIPT DATE: April 26, 1990
REVIEW DATE: July 1990
COUNCIL DATE: September 1990
AWARD DATE: September 30, 1990
X. INQUIRIES
Inquires of a Programmatic nature should be
addressed to:
George W. Counts, M.D.
Chief, Clinical Research
Management Branch
Treatment Research Program
Division of AIDS Research
National Institute for Allergy
and Infectious Diseases
6003 Executive Blvd., Room 207P
Bethesda, Maryland 20892
Telephone: (301) 496-8214
B. Receipt Date
Inquiries of the review process should be addressed
to :
Sally Mulhern, Ph.D.
AIDS Research Review Section
Program and Project Review Branch
National Institute of Allergy and
Infectious Diseases
National Institutes of Health
Westwood Building, Room 3A-14
Bethesda, Maryland 20892
Telephone: (301) 496-2550
Inquiries of a fiscal nature should be addressed to:
Ms. Mary Kirker
Grants Management Branch
National Institute of Allergy and
Infectious Diseases
National Institutes of Health
Westwood Building, Room 710
Bethesda, Maryland, 20892
Telephone: (301) 496-7075
Prospective applicants should request the brochure
"Guidelines for Program Projects" from Dr. Mulhern
before preparing an application.
XI. PROGRAM DESCRIPTION
This program is described in the Catalog of Federal
Domestic Assistance 13.856-Microbiology and
Infectious Diseases Research and 13.855-Immunology,
Allergic and Immunologic Diseases Research.
Cooperative agreements are awarded under the
authority of the Public Health Service Act, Section
301 (42 USC 241) and administered under PHS grant
policies and Federal Regulations 42 CFR Part 52 and
45 CFR part 74. This program is not subject to the
intergovernmental review requirements of Executive
Order 12372 or Health Systems Agency review.
Request for Cooperative Agreement Applications: RFA-90-HD-04
COOPERATIVE MULTICENTER NETWORK OF MATERNAL-FETAL MEDICINE UNITS
P.T. 34, FF, II; K.W. 0785135, 0775020, 0775025, 0785035, 0745020
National Institute of Child Health and Human Development
Application Receipt Date: May 22, 1990
PURPOSE
The National Institute of Child Health and Human Development
(NICHD) invites applications from investigators to
participate with the NICHD under a Cooperative Agreement in
an ongoing multicenter clinical study designed to
investigate problems in clinical obstetrics, particularly
those related to prevention of low birth weight. The
objective of this study is to facilitate resolution of these
problems by establishing a network of centers that, by
vigorous patient evaluation using common protocols, can
study the required numbers of patients and can provide
answers more rapidly than individual centers acting alone.
The NICHD program staff will assist the principal
investigators of the Maternal-Fetal Medicine Units (MFMUs)
and the Advisory Board in identifying research topics of
high priority, and in designing protocols appropriate to the
evaluation of optimum management in these areas.
It is anticipated that approximately 8 to 10 clinical
centers will be involved in the program.
The deadline for receipt of applications is May 22, 1990.
Applications received after this date will not be
considered. Only institutions in the United States will be
eligible for participation.
ADMINISTRATIVE BACKGROUND
Modern obstetrical management, especially the management of
high-risk pregnancies, has in some instances adopted
principles of care, and at times employed pharmaceuticals
and methodologies without rigorous use of the controlled
observation necessary for their objective evaluation. Often
the development of this medical specialty (and others as
well) has been marked by the enthusiastic adoption of
concepts and procedures followed by their modification or
replacement, sometimes decades later, after extensive
experience has failed to support their usefulness or shown
unexpected consequences. Costs involved in instrument
purchase and employment often have been large, and
uncertainties embedded in such obstetrical practices have
contributed at least partly to the rising incidence of
cesarean delivery. Regional differences in practice have
complicated the field.
In an attempt to respond to the need for well-designed
clinical trials in maternal-fetal medicine, NICHD
established a Network of MFMUs in 1986. Seven university
units were selected among respondents to a Request for
Applications (RFA). The Network Steering Committee, which
consists of representatives from each clinical center, NICHD
staff, and data coordinating center staff, evaluated several
controversial issues for study. It then selected certain
priority areas on which to develop protocols for randomized
clinical trials. Trials have actually been initiated on
questions of postterm pregnancy, management of preterm
labor, and prevention of preeclampsia. A Data Monitoring
and Safety Committee also advises NICHD on research design
issues, data quality and analysis, and ethical and human
subject aspects of protocols.
The NICHD expects that ongoing clinical trials dealing with
preterm labor and preeclampsia prevention will continue into
the continuation grant period for existing centers. Centers
that might join the Network in the next award period
(beginning April 1, 1991) would be expected to participate
in the protocols ongoing at that time.
NICHD intends to enable the Network to initiate new
protocols within the first year of the next award period.
The topics of these protocols will be decided cooperatively
by the Steering Committee. Some areas of interest include:
Doppler velocimetry; Cesarean birth; chronic (essential)
hypertension during pregnancy; home uterine monitoring and
other techniques in reducing the risk of preterm labor and
birth.
RESEARCH SCOPE
NICHD invites applications both from current members of the
MFMU Network (competitive continuation applications), as
well as from prospective members (new applications). The
minimum requirements for applicant investigators and their
maternal-fetal research units, are as follows:
1. Professional staffing of the MFMU should include at
least three maternal-fetal medicine subspecialists, each of
whom would be available to take primary responsibility for
one or more of the network protocols at the unit.
2. The application should identify one or more
neonatologists at the center who would be designated to
participate in protocol development and implementation.
Such an individual(s) must have documented interest and
experience with clinical trial research, and be willing to
participate in the MFMU Network.
3. The applicant unit must demonstrate the existence of an
established perinatal data system, preferably computerized,
providing documentation of previous performance, e.g., in
defining and quantitating patient populations for clinical
studies. All successful applicants must be willing to
provide complete, accurate, and timely data to the MFMU
generic data base.
4. Applicant maternal-fetal units should have at least
2,500 births per year, with a minimum of 30 percent
high-risk pregnancies. There must be evidence that a large
majority of patients with obstetric complications use the
prenatal, delivery, and postpartum care system affiliated
with the hospital in which the unit is located. There
should also be documentation of the proportion of various
subgroups of the obstetric population that have been
eligible for, and have been randomized, in previous, or
ongoing, clinical trials.
5. Applicants should document the clinical capabilities of
the unit, including antenatal fetal testing, intrapartum
diagnosis, laboratory testing, and perinatal pathology, and
indicate how these clinical services have been modified, if
necessary, to support clinical research in the past. Also,
the existence of a pharmacy capable of supporting clinical
research should be documented.
6. The application should describe the neonatal intensive
care unit in the same hospital, and document current
collaborative relationships with the unit, in terms of
patient care, teaching, and research. Specifically, the
infant follow-up arrangements for NICU "graduates," and
their rate of follow up for both clinical care and research
should be described.
7. There should be a clearly expressed intent to
participate in a cooperative manner with other units, the
NICHD, and the data coordinating center, in all aspects of
randomized clinical trials in obstetrics, within the context
of this MFMU Network, as outlined in this RFA.
8. The departmental and institutional commitment to
collaborative maternal-fetal research should be clearly
documented by evidence of its research productivity
(recruitment performance, publications, etc.) in past or
present clinical trials.
9. The application must exhibit a preparedness to pursue
capitation of operational costs for each protocol in the
Network. (See Budget Section.)
10. The NICHD also funds clinical trials in a Neonatal
Network whose applications will be due on May 22, 1990.
NICHD encourages applications from institutions which
propose participation in both the Maternal-Fetal and
Neonatal Networks.
DIRECTION AND MANAGEMENT OF THE NETWORK
The management of the MFMU Network includes three committees
whose functions are as follows:
1. A Steering Committee will be responsible for protocol
development, assisted by the Advisory Board and the Data
Safety and Monitoring Committee. The Steering Committee
will have primary responsibility for the conduct of
protocols and the preparation of publications. The Steering
Committee will be composed of each principal investigator,
one representative from the Data Center, and three NICHD
staff. NICHD staff will comprise the Director of the Center
for Research for Mothers and Children (CRMC), an
obstetrician from the Pregnancy and Perinatology Branch, and
a representative from the Epidemiology and Biometry Research
Program. The MFMU program officer will be the only voting
NICHD staff member of the Steering Committee. An outside
chairman, who is not participating as a principal
investigator, will be selected by the NICHD.
2. An Advisory Board will advise the Steering Committee in
the identification and prioritization of topics for network
research. The Advisory Board, chosen by the NICHD with the
advice of the Steering Committee, will be composed of
individuals with expertise in clinical trials,
biostatistics, epidemiology, perinatology, and neonatology;
the Chairman of the Steering Committee; and the Director of
the CRMC and the MFMU program officer. Additional members
will participate based on the need for specific expertise.
3. A Data Safety and Monitoring Committee will monitor the
safety of ongoing clinical trials and advise on their
conduct. It will be established by NICHD and will represent
expertise in ethics, clinical trial design, perinatology,
neonatology, and basic science.
CONTENT OF APPLICATION
The following information should be included in the
application:
1. MFMU Staffing. Provide complete descriptions of the
training and qualifications of the maternal-fetal medicine
subspecialists (see minimum requirements under RESEARCH
SCOPE). Specify their past and current involvement in
clinical and basic research and their availability to take
primary responsibility for one or more of the Network
protocols at the unit. Detail the current pattern of
research nurse staffing of clinical trials in the unit,
including arrangements for recruitment into protocols during
evening, nighttime, and weekend hours.
Provide specific information on research nurses who would be
available for Network assignment.
2. NICU Staffing. Document current collaborative
relationships with neonatologists for patient care, teaching
and research. Identify one or more neonatologists who would
collaborate actively in protocol development and
implementation for the MFMU Network.
3. Perinatal Data System. Describe the perinatal data
system used by the maternal-fetal unit, and document how it
has been used, and is being used, to plan and carry out
clinical research. Include the data form as an appendix.
4. Available Population of Clinical Research Subjects.
Applicants are encouraged to include minorities among study
populations. If minorities are not included, a clear
rationale for their exclusion should be provided.
Characterize the patients served by the maternal-fetal
medicine unit (see minimum requirements). Specify the
proportions of various subgroups (by payment status, race,
age, parity, etc.) that have been eligible for, and have
actually been randomized, in previous or current clinical
trials.
5. Clinical Strengths and Weaknesses of the MFMU. Describe
in detail the clinical attributes of the MFMU, with special
attention to ambulatory services, antenatal fetal testing,
intrapartum diagnosis, laboratory testing, and perinatal
pathology. Indicate how these clinical services have been
modified, if necessary, to support clinical research in the
past. Also, document the availability of an institutional
pharmacy capable of supporting clinical research. Finally,
discuss any perceived weaknesses in the MFMU clinical care
system and review planned solutions.
6. Neonatal Intensive Care Unit. Describe the organization
and service load of the neonatal intensive care unit (NICU)
in the same hospital as the MFMU, including the existing
follow-up program.
7. Intent to Participate. Based on your understanding of
the MFMU Network's structure and function, indicate specific
ways in which MFMU policies and procedures could be modified
to allow effective participation in randomized, multi-center
clinical trials. Specifically, indicate your preparedness
to participate in network clinical trials according to the
terms and conditions of this RFA.
8. Departmental and Institutional Commitment and
Experience. Provide letters of commitment from all involved
departments to ensure optimal cooperation for network
protocols. Provide evidence of research productivity by the
applicant unit in previous or present clinical trials,
especially of a cooperative, multicentric nature. Describe
allocations of office space, equipment, and faculty time to
previous or present clinical trial research. Specifically,
summarize your experience with a non-network clinical
protocol, including preparation for the trial (retrospective
studies, identification of the study population, funding
applications, budget preparation), conduct of the trial
(recruitment of patients, integration with other clinical
research, assignment of costs to research versus clinical
care), resolution of problems encountered, results, and
their implications. (The actual protocol and IRB approval
for the described trial should be appended.)
Applicants who are current MFMU Network members and are
reapplying should provide a description of their
participation in the Network protocols to date. Include in
this description numbers of patients enrolled and completed,
percent enrollment of available patients, and the nature and
extent of staff involvement as it affected performance.
Also, current MFMU Network members should summarize how they
have met the terms of award that accompanied the Notice of
Award for their initial grant period.
9. Acceptance of Budgetary Mechanism. Provide a statement
from the department and institutional office of sponsored
programs assuring cooperation with the proposed plan to
capitate operational costs for each protocol. Also, discuss
innovative ideas for making the conduct of clinical trials
within the MFMU Network more efficient and cost-effective.
MECHANISM OF SUPPORT - Terms of Agreement
The funding mechanism to be used to assist the scientific
community in undertaking this system of clinical
investigation will be a Cooperative Agreement between the
participating units and NICHD. The major difference between
a Cooperative Agreement and a research grant is that there
will be substantial programmatic involvement of NICHD staff
above and beyond the levels required for traditional program
management of grants. Specifically, the role of the NICHD
MFMU program officer 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 to the community of
investigators and health care recipients.
Programmatic responsibility for review and oversight of
these Cooperative Agreements will reside with the MFMU
program officer. This role will include the following:
o Assurance of the scientific merit of the trials, including
the option to withhold support of a participating center if
technical performance requirements such as protocol
compliance, enrollment targets, or randomization of subjects
are not met.
o Assistance in the efficient conduct of the trials,
including ongoing review of progress; possible redirection
of activities to improve performance and cooperation; and
frequent communication with other members of the Steering
Committee.
o Initiation of a decision to modify or terminate a study
based on the advice of the Data Center, Data Safety and
Monitoring Committee, and Advisory Committee with the mutual
consent of the Steering Committee.
The responsibilities and authorities 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 of the MFMU
trials.
All parties will agree to accept the coordinating role of
the group and the participatory and cooperative nature of
the group process.
The support of awards pursuant to this RFA is contingent
upon ultimate receipt of appropriated funds for this
purpose. The number of awards will be influenced by the
overall merit of the applying centers and by the amount of
funds available to the Institute. It is anticipated that
eight to ten meritorious applications will be funded.
The specific terms, conditions, and details of arbitration
procedures pertaining to the scope and nature of the
interaction between NICHD and the participating MFMUs will
be incorporated into the Notice of Grant Award. These
procedures will be in addition to the customary programmatic
and financial negotiations which occur in the administration
of grants; they will be invoked only when agreement cannot
be reached on issues that may arise after the award between
the awardee and the MFMU program officer. In that event, an
arbitration panel will be formed consisting of one person
selected by the principal investigators, one person selected
by Chief of the Pregnancy and Perinatology Branch, and a
third person selected by these two members. The decision of
the arbitration panel will be binding.
The special terms of Award of Cooperative Agreement are in
addition to, and not in lieu of, otherwise applicable OMB
administrative guidelines, DHHS grant administration
regulations at 45 CFR Part 74 and other DHHS, PHS, and NIH
grant administration policies. The NICHD review procedure
in no way affects the right of a recipient of a cooperative
agreement to appeal an adverse determination under the terms
of PHS regulations at 42 CFR Part 50, Subpart D, and DHHS
regulations at 45 CFR Part 16. Business management aspects
of these awards will be administered by the NICHD Grants
Management Section in accordance with DHHS, PHS, and NIH
grant administration requirements.
Program staff intend that the ongoing Cooperative Agreements
will be recompeted every five years, depending on available
funds.
REVIEW CRITERIA AND PROCEDURES
A. Review Procedures
Applications that are incomplete or nonresponsive to this
RFA will be withdrawn by the Division of Research Grants and
NICHD staff upon receipt, and returned to the applicants
without further consideration. Applications that are
complete and responsive may be subjected to a preliminary
evaluation by an NICHD peer review group to determine their
scientific merit relative to the other applications received
in response to this RFA (triage); the NICHD will withdraw
from further consideration applications judged to be
noncompetitive for award and promptly notify the principal
investigator/program director and the official signing for
the applicant organization. Those applications judged to be
competitive will be further evaluated for
scientific/technical merit by a special review committee
convened specifically for this purpose by the Scientific
Review Program, NICHD. This review will include an
evaluation of past performance in the MFMU Network for
current members followed by a second-level review by the
National Advisory Child Health and Human Development
Council. Final selection of clinical centers for funding
may also be based on the need for diversity in the study
population.
B. Criteria for Review. Strengths and weaknesses will be
considered in the following areas specified in the Content
section:
1. Personnel - (Content items #1 and #2)
2. Facilities - (Content items #3, #4, #5, and #6)
3. Management Intent, Commitment, and Experience - (Content
items #7 and #8)
4. Budget - (Content item #9) (See Appendix I)
METHOD OF APPLYING
Applications should be submitted on form PHS-398 (revised
10/88). The conventional presentation format for regular
research grant applications should be used, with care taken
to address the points identified under review criteria and
eligibility for participation.
The title "MFMU COOPERATIVE AGREEMENT APPLICATIONS, RFA
90-HD-04" should be typed in item 2 of the face page of the
application. The RFA label included in the PHS 398 (rev.
10/88) application kit must be affixed to the bottom of the
face page. Failure to use this label could result in
delayed processing of your application such that it may not
reach the review committee in time for review. The original
and four copies of the application should be sent or
delivered to:
Application Receipt Office
Division of Research Grants
National Institutes of Health
Room 240, Westwood Building
Bethesda, MD 20892
Also send two copies to:
Laurance S. Johnston, Ph.D.
Scientific Review Program
National Institute of Child Health and Human Development
Executive Plaza North, Room 520
Bethesda, MD 20892
Applications must be received by May 22, 1990.
Late applications will not be accepted.
TIMETABLE
Application Receipt Date: May 22, 1990
Initial Review Date: June-July, 1990
Review by Advisory Council: January 1991
Anticipated Award Date: April 1, 1991
Inquiries regarding this announcement may be directed to:
Donald McNellis, M.D.
Special Assistant for Obstetrics
Pregnancy and Perinatology Branch
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
Executive Plaza North, Room 643
Bethesda, MD 20892
Telephone: (301) 496-5575
This program is described in the catalog of Federal Domestic
Assistance No. 13.865, Research for Mothers and Children.
Awards will be made under the authority of the Public Health
Service Act, Section 301 (42 USC241), and administered under
PHS grant policies and Federal Regulations 42 CFR Part 52
and 45 CFR Part 74. This program is not subject to the
intergovernmental review requirements of Executive Order
12372 or Health Systems Agency Review.
APPENDIX I
BUDGET
The budget at the time of application will be limited to a
BASE BUDGET with maximum allowances as follows:
Principal/Co-Investigator component 10% effort
Coordinator 100% effort
Data Entry Clerk 50% effort
Supplies and Small Equipment (itemized and justified) NTE $4,500
Travel (a total of 10 trips to Bethesda per Network team) as appropriate
Other costs (itemized and individually justified) NTE $2,500
At such time as an application has been approved and is
being considered for funding, the applicant will be required
to complete protocol budgets for those studies underway
within the network. These budgets will consist of specific
protocol-related allowances and will be capitated on the
anticipated number of subjects to be enrolled in the study
at the applicant MFMU.
Ongoing annual budgets of MFMU Network members will be based
on individual protocols which will be funded through a
capitation system. Each MFMU Network member will be given
base costs (listed above), in addition to a flat fee per
patient successfully enrolled and completed. The individual
members will be required to project patient enrollment for a
specific protocol during a specified time frame;
continuation and level of funding will be based on actual
recruitment.