Full Text HD-92-06
RFA:  HD-92-06
P.T. 04

  Chemical Synthesis 
  Chemistry, Organic 
  Human Reproduction/Fertility 
  Biomedical Research, Multidiscipl 

National Institute of Child Health and Human Development
Letter of Intent Receipt Date:  January 31, 1992
Application Receipt Date:  April 24, 1992
The National Institute of Child Health and Human Development (NICHD)
invites applications from investigators willing to participate with
the NICHD, under a cooperative agreement, in establishing a Centers
program designed to conduct comprehensive research on the development
of new contraceptive products.  It is anticipated that ultimately
three Centers will participate in this program and that the award
period will be five years.  Two Centers were funded under a prior
Request for Applications (RFA) and one Center will be funded as the
result of the present RFA.  The aim of these Centers will be to
conduct a wide range of research activities that, with time, may
result in the development of clinically useful modalities.  The
Center should have, or should be able to develop, a broad range of
research activities that are classified as a research and development
(R&D) program.  It is understood that certain activities may have to
be conducted outside a specific Center via arrangements with other
Centers or other institutions.  By utilizing the framework of an
interdisciplinary approach, the Centers can conduct R&D activities
that are beyond the capabilities of individual investigators.
The Chief of the Contraceptive Development Branch (CDB) will serve as
the Research Coordinator for the Centers' program and will cooperate
with the Principal Investigator (PI) of the selected Center in the
identification of research priorities and the implementation of the
required steps in the overall process of product development.  The
Chief of the CDB may ask on occasion for participation of other CDB
staff members in the interactive process if and when their scientific
and managerial skills can contribute to effective program management.
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This RFA,
Cooperative Contraceptive Development Research Centers Program, is
related to the priority area of family planning.  Potential
applicants may obtain a copy of "Healthy People 2000" (Full Report:
Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report:
Stock No. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, DC  20402-9325 (telephone
The NICHD has supported contraceptive development research for the
past two decades.  The program focused on the development of methods
of fertility regulation that were reversible and acceptable to
various segments of the American public.  The retrenchment of the
American pharmaceutical industry in the area of contraceptive
development has had a negative effect on research and on the
availability of products for the American people.  A recent report
from the National Research Council/Institute of Medicine entitled
"Developing New Contraceptives - Obstacles and Opportunities"
identified several problems facing the overall area.  Among the
subjects discussed were the low funding levels for applied research
in contraceptive development and the scarcity of institutions
conducting research in this area.  Congressional committees have
directed NICHD to establish a Contraceptive Development Centers
program as a way of promoting research in this complex field.  The
Senate Appropriations Committee report stated:  "The Committee has
added $6,000,000 to create five new centers, two focused on
infertility research and three focused on contraceptive research.
The Committee considers this to be an adequate amount to initiate all
five of these centers and expects to provide additional funding for
these centers in subsequent years."  The Committee report went on to
say:  "Research and development problems within the complex field of
fertility cannot be solved by an individual investigator working
alone; to create a new contraceptive method or treatment for
infertility, the concerted efforts of highly skilled scientists from
a variety of disciplines are required.  Without specialized centers,
promising new leads may never be translated effectively into new
methods or ever made available to the public."  The Committee
concluded:  "By establishing these new research centers, the
Committee is taking an affirmative step to regain the United States'
rightful position while at the same time reaffirming its commitment
to those who are trying to plan their families."
Thus, the intent of the Congressional mandate and the needs of the
field support the concept that the Centers program should assume a
leadership role in contraceptive development.  Each Center will
coordinate the research conducted by the Center's investigators and
will attempt to interact with the pharmaceutical industry in order to
bring the newly developed technologies to the public.
The intent of the program is to develop an organizational
infrastructure that has the scientific and administrative
capabilities to address the broad issue of the development of methods
of contraception.  The proposed research should encompass ongoing and
new projects in contraceptive development.  Approaches to both male
and female fertility regulation are encouraged.  Innovative
approaches that show promise for effective fertility regulation, but
are in early developmental stages, will be considered for any of the
broad categories of family planning methods other than those related
to abortion.
The scope of the proposed program must involve the concurrent
development of at least three projects.  The investigators should
have a clear understanding of the complexities of the R&D process.
However, a single institution need not be capable of conducting all
of the necessary phases of product development.  Consortium
arrangements that utilize the capabilities of other research
organizations may be proposed.  The proposed investigational
approaches may represent different phases of R&D.  Thus the overall
program can present a variety of approaches representing the early
phases of R&D, such as synthesis of new compounds, and the more
advanced stages, such as clinical studies.
Although the initial funding is limited and can support only a part
of the projected activities of each Center, each application must
provide sufficient detail with respect to the research activities
that will be implemented when additional funding becomes available
from NICHD (see Budget section).  The new or expanded projects that
are proposed must be fully described since they will be subjected to
the initial peer review.  Projects funded by other sources may be
incorporated into the overall concept of the Center if they are
related to the projects for which NICHD funding is requested.
Projects able to attract industrial cosponsorship are encouraged.
Provision of financial assistance from the NICHD, together with other
funding sources, should permit these new Centers to assume a
leadership role in contraceptive development.
The NICHD invites applications from investigators based in
institutions that can provide a scientific and administrative
framework conducive to research directed toward development of new
technologies for fertility regulation.  The minimum requirements for
a Center application will be:
o  Commitment of a PI with experience in the area of contraceptive
development.  This experience may be in research conducted at the
different stages of the overall R&D process.  Consequently, the PI
may be either a clinician experienced in the development of fertility
regulation methods or a non-clinician who is familiar with the
preclinical aspects of contraceptive research.
o  Availability of other staff who will be responsible for both the
research and administrative aspects of the Center.
o  Evidence of ongoing applied contraceptive research projects that,
together with new initiatives, represents a minimum of three distinct
fundable projects (see below for project description).  This research
may be represented by any one of several R&D phases.  Projects
involving clinical studies must provide assurance of implementation
of NIH policies concerning inclusion of women and minorities in study
o  Ability to attract and train other investigators for a
comprehensive contraceptive development program.
o  Availability of facilities to conduct research leading to product
o  Institutional commitment to the project and flexibility for
implementation of interactions within the organization and with
outside resources.
Each Center must focus on a mix of research activities that are
classified as applied R&D, as distinguished from basic research.  The
proposed program must involve research endeavors that represent a
minimum of three distinct fundable projects.  With respect to the
Centers program, a project is defined as an activity involving, for
o  Research dealing with the pharmacology of a single drug.  Even if
this pharmacological assessment involves animal and clinical studies,
it would still be classified as a single project.
o  Research dealing with the development of a new spermicide based on
a compound would be construed as a single project.
o  Development of a transdermal patch or a vaginal ring to deliver
contraceptive drugs would be considered a single project.
These examples of research activities should not be construed as
indicating a preference on the part of NICHD in these areas of
research.  Investigators are invited to propose development of
methods, other than abortion, that can be made available to the
American public.  A Center application can build its research
strategy primarily on one broad approach to fertility regulation
within which the three projects are embedded.  For example, a Center
could devote its energies to the development of barrier methods of
contraception.  Under these circumstances the three Center projects
could be comprised of:
o  New spermicide development
o  Development of devices to block the cervix and deliver the new
o  Development of formulations for more effective delivery of
Alternatively, a Center application may be structured to represent
research from different approaches to fertility regulation.  There
could be a project involving drug development and two projects
dealing with barrier methods.  The overall Center plan must stress
internal priorities and be focussed on opportunities for progress.
In structuring the Center application, investigators must take into
account two important aspects of the program:
o  Projects that require funding from the proposed Center grant
o  Projects that are part of the program but do not require funding
from the proposed grant since it is available from other sources
It must also be kept in mind that the NICHD is currently involved in
funding research in the following areas:
o  Synthesis and biological evaluation of antagonists of
gonadotrophic releasing hormone
o  Condom development and clinical evaluation
o  Isolation of peptides that can influence reproductive processes
o  Development of contraceptive vaccines
It is not the intent of the NICHD that the Centers should allocate
fiscal resources to duplicate research areas listed above.  On the
other hand, fiscal resources may be allocated to research that
represents a programmatic progression from what is currently being
supported by the NICHD.  For example, if funding is already provided
for synthesis and biological evaluation, funds may be requested for
toxicology or clinical evaluation.  Because phase III multicenter
clinical trials require a substantial investment of funds, they
should not be proposed for funding during initial phases of the
Center program.
Each research project that is proposed for inclusion in the Center
must be described independently using the PHS 398 application format.
The page limitations stated in PHS 398 instructions must be followed
for each individual sub-project.  The overall Center application must
also use the PHS 398 format to summarize the Center's organization
and cumulative budgeting for the various budget categories.  All
essential information necessary for the evaluation of the Center
application must appear in the body of the application rather than as
appendixes.  In view of the fact that the overall Center evaluation
process will not include site visits, investigators must provide
sufficient details for the assessment of scientific and technical
The application must include the following information:
1.  Center Staffing
Provide a complete description of the qualifications of the PI and
the research staff who will be responsible for the Center's
activities.  Specify past and current involvement of the staff in
applied research directed toward the development of new fertility
regulation technology. Specify the extent of the commitment that each
investigator can make to the Center's program.  Indicate possible
staff additions in the event of program expansion.  If actual
individuals cannot be specified, indicate the nature of expertise
that is needed.
2.  Center Research Activities
Provide information concerning the details of the proposed Center
program.  Provide a five-year research plan for activities that may
result in the development of new contraceptive products.  The plan
must include:
o  Information concerning current projects or, in their absence,
information on projects that will become part of the Center
o  Evidence of understanding of the research that must be in place
for successful implementation of a goal oriented program
o  Phasing of new studies based on an increase in fiscal resources to
be provided by NICHD (Consideration must be given to budgetary
expansion in succeeding years (see Budget Section)
o  Provision for activities for young investigators interested in
contraceptive development
3.  Facilities
Describe the nature of facilities that will be made available to the
Center.  Describe availability of essential core facilities and
indicate major equipment needs.
4.  Departmental and Institutional Commitment
Provide letters of commitment from all individuals and departments
that are not currently directly affiliated with the PI. Provide
letters of commitment from the institution to the Center.
5.  Collaboration
Describe past and current collaborative studies that have been
conducted by the PI and the proposed Center staff.  Indicate which
projects may require collaboration with other departments or
6.  Center Management
Provide information concerning the scientific and administrative
management of the Center.  Indicate what decision-making processes
will be utilized in order to optimize successful progression of
The funding mechanism to be used will be the Specialized Center
Cooperative Agreement (U54) between the Center and the NICHD.  It is
expected that one application will be funded for a five-year period,
contingent upon the receipt of a sufficient number of meritorious
applications, within the total cost limit of $750,000 available for
the first year of this award.  The major difference between a
Cooperative Agreement and a research grant is that there will be a
substantial programmatic involvement of NICHD Research Coordinator
(Chief of CDB or designee) above and beyond the levels required for
traditional program management of grants.  Specifically, the awardee
will proceed with peer reviewed and approved projects that result
from discussions and subsequent agreement between the awardee and
NICHD.  Recognizing that the available funding may be below the level
needed to support all of the peer reviewed and approved projects,
research priorities will be established after in-depth discussions
between the awardee and the NICHD.  Outside consultants/experts may
be asked to participate in these discussions.  Once priorities have
been agreed upon, the awardee will assume the responsibility for
implementation of research activities.  It is anticipated that the
awardee and NICHD Research Coordinator (Chief of CDB or designee)
will interact throughout the duration of the award in order to
facilitate progress and resolve any problems that may arise.
Awardees will retain custody and rights to the data developed under
these awards subject only to the Government rights of access
consistent with current HHS, PHS, and NIH policies.
The awardees will be responsible for:
o   Defining the research objectives
o   Designing the necessary research protocols
o   Conducting specific studies
o   Analyzing and interpreting research data
o   Modifying protocols as required
o   Interacting with the Food and Drug Administration (FDA)
concerning clinical investigations
o   Providing information to the NICHD Research Coordinator
concerning progress
The involvement of the NICHD Research Coordinator will be:
o  Assistance in setting research priorities and in avoiding
unwarranted duplication of effort
o  Review and comment on critical stages in the R&D program before
subsequent stages are implemented
o  Assistance in the interaction between the awardee and the FDA
o  Assistance in the interaction between the awardee and
investigators of other institutions and between the awardee and
potential commercial sponsors
o  Retains the option to recommend termination of studies if
technical performance falls below acceptable standards or when
specific lines of research cannot be effectively pursued in a timely
o  Retains the option to recommend additional research endeavors
The specific terms and conditions of the award and details of
arbitration procedures pertaining to the scope and nature of the
interactions between the NICHD and the participating sites will be
incorporated into the Notice of Grant Award.  These procedures will
be in addition to the customary programmatic and financial
negotiations that occur in the administration of grants.  Arbitration
procedures will be invoked only when agreement cannot be reached on
programmatic issues that may arise between (an) awardee(s) and the
NICHD after the award has been made.  In that event, an arbitration
panel will be formed consisting of one person selected by the PI of
each of the three Centers and one person selected by the NICHD.  The
decision of the arbitration panel, by majority vote, will be binding.
The process to resolve programmatic differences described above in no
way affects the right of a recipient of a cooperative agreement
assistance grant to appeal adverse determination in accordance with
PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at
45 CFR Part 16.
The above Terms of Award are in addition to, and not in lieu of,
otherwise applicable Office of Management and Budget administrative
guidelines, HHS grants administration regulations at 45 CFR Part 74,
and other HHS, PHS, and NIH grants administration policies.
Cooperative agreements are subject to the administrative requirements
outlined in pertinent OMB, HHS, PHS, and NIH guidelines, with
particular note of HHS regulations at 42 CFR Part 52 and 45 CFR Part
74.  The indirect cost award procedures will apply to cooperative
agreement awards in the same manner as for grants.
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required to
include minorities and women in study populations so that research
findings can be of benefit to all persons at risk of the disease,
disorder or condition under study; special emphasis should be placed
on the need for inclusion of minorities and women in studies of
diseases, disorders and conditions which disproportionately affect
them.  This policy is intended to apply to males and females of all
ages.  If women or minorities are excluded or inadequately
represented in clinical research, particularly in proposed
population-based studies, a clear compelling rationale should be
The composition of the proposed study population must be described in
terms of gender and racial/ethnic group, together with a rationale
for its choice.  In addition, gender and racial/ethnic issues should
be addressed in developing a research design and sample size
appropriate for the scientific objectives of the study.  This
information should be included in the form PHS 398 in Section 2, A-D
of the Research Plan AND summarized in Section 2, E, Human Subjects.
Applicants/offerors are urged to assess carefully the feasibility of
including the broadest possible representation of minority groups.
However, NIH recognize that it may not be feasible or appropriate in
all research projects to include representation of the full array of
United States racial/ethnic minority populations (i.e., Native
Americans (including American Indians or Alaskan Natives),
Asian/Pacific Islanders, Blacks, Hispanics). The rationale for
studies on single minority population groups should be provided.
For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology,
prevention (and preventive strategies), diagnosis, or treatment of
diseases, disorders or conditions, including but not limited to
clinical trials.
The usual NIH policies concerning research on human subjects also
apply.  Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded.  However,
every effort should be made to include human tissues from women and
racial/ethnic minorities when it is important to apply the results of
the study broadly, and this should be addressed by applicants.
For foreign awards, the policy on inclusion of women applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including
If the required information is not contained within the application,
the application will be returned.
Peer reviewers will address specifically whether the research plan in
the application conforms to these policies.  If the representation of
women or minorities in a study design is inadequate to answer the
scientific question(s) addressed AND the justification for the
selected study population is inadequate, it will be considered a
scientific weakness or deficiency in the study design and will be
reflected in assigning the priority score to the application.
All applications for clinical research submitted to NIH are required
to address these policies.  NIH funding components will not award
grants or cooperative agreements that do not comply with these
Review Procedure
A preliminary review will be conducted by NICHD staff upon receipt of
the application.  Any application that does not meet the minimum
requirements (see ORGANIZATION AND SCOPE, above) of this RFA will be
returned to the applicant without technical review.  Applications
meeting the minimum requirements will be reviewed as a group on a
competitive basis with each other and in accordance with the usual
NIH peer review procedures for research grants.
Projects proposing clinical studies must ensure that adequate
representation of minorities and women are included in the study
population in accord with NIH policy.  Failure to comply with this
policy may result in the application being returned without review
(see above).
Responsive applications may be subjected to a triage by a peer-review
group to determine their scientific merit relative to the other
applications received in response to this RFA.  NIH will withdraw
from competition those applications judged to be non-competitive, and
notify the Principal Investigator and institutional official.
The review will be conducted for scientific and technical merit by a
special review committee convened specifically for this purpose by
the Division of Scientific Review, NICHD.  This will be followed by a
second-level review by the National Advisory Child Health and Human
Development Council.
Criteria for Review of Applications
Applications meeting the minimum requirements will be evaluated on
scientific and technical merit according to the criteria listed
1.  Scientific, Technical and Programmatic Merit of the Proposed
o  Clear understanding of the relationship of the proposed research
to the future of fertility regulation
o  Description of the experimental plan, including phasing, that may
maximize progress
o  Appreciation of potential problems that may be encountered in the
conduct of research and how they may be resolved
2.  Qualifications, Experience, and Commitment of Key Personnel
o  Scientific, clinical, and administrative abilities of the PI and
other team members
o  Knowledge and experience in areas relevant to the conduct of
potential studies in contraceptive development
o  Commitment of staff time for the satisfactory conduct of the study
o  Experience and qualifications of team members who would be
responsible for internal coordination of activities
3.  Adequacy of Facilities and Availability of Equipment and
volunteer population
o  Present facilities
o  Facilities necessary to meet future needs
o  Availability of suitable volunteer population for clinical
4. Nature of Departmental and Institutional Commitment
Institutional assurance to provide support for the study in such
areas as fiscal administration, personnel management, space
allocation, procurement, planning, and budgeting
5. Nature of Potential Arrangements Outside of Center
o  Willingness to work with other organizations in the conduct of
contraceptive research
o  Information on the implementation of these arrangements
6. Appropriateness of budget
Letter of Intent
Prospective applicants are asked to submit a letter of intent that
includes the names of the Principal and Co-Investigators, identify
the cooperating institutions, and indicate whether the application
will be for a Field Center, Coordinating Center, or both.  The NICHD
requests such letters only for the purpose of providing an indication
of the number and scope of applications to be received and, usually
does not acknowledge their receipt.  A letter of intent is not
binding, it will not enter into the review of any application
subsequently submitted, nor is it a necessary requirement for
applications.  This letter of intent is to be received no later than
January 31, 1992, and is to be sent to:
Application Procedures
Applications must be submitted on form PHS 398 (revised 10/88,
reprinted 9/89), that is available in most institutional business
offices and from:
Division of Research Grants
Office of Administrative Management
Office of Grants Inquiries
National Institutes of Health
Westwood Building, Room 449
Bethesda, MD  20892
Telephone:  (301) 496-7441
Applications must be identified by checking the "yes" box in Item
Number 2 on the face page of the application, and typing in the
words, "Cooperative Contraceptive Development Research Centers
Program RFA HD-92-06."  In addition, the RFA label available in the
10/88 revision of application form PHS 398 must be affixed to the
bottom of the face page and placed on top of the entire package.
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.  The original and four copies must be received by the
Division of Research Grants no later than April 24, 1992.
Applications must be sent or delivered to:
Application Receipt Office
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**
In addition, two copies of the application must be simultaneously
sent to:
Laurance Johnston, Ph.D.
Division of Scientific Review
National Institute of Child Health and Human Development
National Institutes of Health
Executive Plaza North, Room 520
Bethesda, MD  20892
Applicants from institutions must have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the GCRC as a resource for conducting
the proposed clinical research.  In such a case, a letter of
agreement from either the GCRC program director or PI must be
included with the application.
The instructions for budget estimates provided with the research
grant application form (PHS 398) must be followed.  Indirect costs
will be awarded in the same manner as for research project grants
(R01).  Budgets will be reviewed on the basis of appropriateness for
the work proposed.  Allowable costs and policies governing the
research grants programs of the NIH will prevail. In planning the
budget section of the application investigators should submit
detailed budget estimates for each project.  It should be kept in
mind that the requested budget for the first year may far exceed the
total funds ($750,000) made available for this award.  Consequently,
the peer-reviewed and approved projects will be subject to
negotiations between the Center and the NICHD to bring the overall
funding level in line with allocated funds.  The NICHD may be in
position to negotiate the second year budget at a higher level,
two-fold, but this will depend on appropriations for this program.
For subsequent years (3, 4, and 5) budgetary increases of up to 20
percent may be negotiated, but these will also depend on
appropriations for the Center's program.  All budgetary negotiations
between the Center and the NICHD will be based strictly upon projects
that have been peer reviewed.  A summary of sources of actual and
pending support for each investigator participating in the study,
with grant or other award number identification and percent effort,
must be in the application.
The intent of the Contraceptive Development Centers program is to
establish scientific/administrative organizations capable of
undertaking the various phases of the R&D process leading to the
development of improved methods of fertility regulation for men and
women.  It is not the intent of this program to enable the awardee to
merely shift the funding currently available from a variety of
sources to other projects and to reallocate the Center's funds to the
ongoing projects.  The Center's funds may be used to supplement
ongoing projects if such supplementation is programmatically
justifiable.  Funds may be used in any one of the accepted budget
categories.  With respect to travel, the budget must include funds
for at least one trip to Bethesda per year and a cost estimate for a
yearly meeting of Center PIs.  It is anticipated that no more than
three individuals from any one of the Centers will participate in
these meetings.
Deadline for Submission
The deadline for receipt of applications by the NIH Division of
Research Grants is April 24, 1992.  Applications received after this
date will be returned to the applicant.
Application Receipt Date:           April 24, 1992
Review by Initial Review Group:     June 1992
Review by NICHD Advisory Council:   September 1992
Earliest Award Date:                September 1992
Additional Information
For further information, investigators are encouraged to contact the
NICHD staff members listed below.
Program/Scientific Matters:
Gabriel Bialy, Ph.D.
Contraceptive Development Branch
National Institute of Child Health and Human Development
Executive Plaza North, Room 600
Bethesda, MD  20892
Telephone:  (301) 496-1661
Administrative Policy:
Ms. Melinda Nelson
Office of Grants and Contracts
National Institute of Child Health and Human Development
Executive Plaza North, Room 505
Bethesda, MD  20892
Telephone:  (301) 496-5481
This program is described in the Catalog of Federal Domestic
Assistance NO. 93,864, Population Research.  Awards will be made
under the authority of the Public Health Service Act 301 (42 USC 241)
and 441 (USC 289d) and administered under PHS Grants 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.

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