Subject: RFA HD-90-l2.081090
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Thu, 09 Aug 90 09:32 EST

Again,
   This is the fourth item coming to you for the NIHLISTERVER.
Please post to the listserver as: RFAHD-90-12.081090
   Thanks.
          Dottie
 ---------------------------- Text of forwarded message -----------------------
 
REQUEST FOR COOPERATIVE AGREEMENT APPLICATIONS:
 
RFA:  HD-90-12
 
NATIONAL COOPERATIVE PROGRAM ON CULTURE CONDITIONS FOR
NON-HUMAN IN VITRO FERTILIZATION AND PREIMPLANTATION
DEVELOPMENT
 
P.T. 34; K.W. 0413002, 1002017, 0780000
 
NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
 
Application Receipt Date:  November 20, 1990
 
OVERVIEW
 
The National Institute of Child Health and Human Development
(NICHD) invites applications from investigators willing to
participate, with the assistance of the NICHD under  cooperative
agreements, in an ongoing multisite Cooperative Program designed
to establish improved culture conditions for non-human in vitro
fertilization and preimplantation embryo development.  It is
anticipated that a multi-species approach will be continued
as a central feature of the Program.  New findings obtained
from research on one species could be rapidly tested in
other species owing to the lines of communication between
cooperating sites.
 
The Institute staff Research Coordinator will cooperate with
the Principal Investigators of the selected sites in the
determination of approaches and protocol designs, planning,
evaluation, and publication of the research, and serve as
coordinator, facilitator, and partner in the research.  It is
expected that protocols will change as new information is
gathered and shared.
 
A general overview of Program phases follows.  These phases
are not necessarily sequential since the Program will
evolve, but can serve as a guide for applicants:
 
PHASE I (one month) - Determination, by consensus, of
experimental approaches, design of protocol(s), methods of
standardization of experiments between sites, determinations
of experimental end points and methods of evaluation;
methods of standardization of reagents and other culture
conditions; determination of statistical methods;
 
PHASE II (47 months) - Testing of culture media
formulations, gas phases and culture vessels for non-human
in vitro fertilization and preimplantation development;
 
PHASE III (12 months) - Analysis and dissemination of
results to be done as various segments of the research are
completed.
 
These Phases are intended to be flexible, recognizing that
the Program is likely to undergo continuous evolution.
Applicants should provide an in-depth justification and
description of how they might approach and conduct the
study, including their own capabilities and any special
considerations peculiar to their organism(s) of choice.
 
The deadline for applications is November 20, 1990.
Applications received after this date will not be
considered.  Only applicant institutions in the United
States will be eligible.
 
BACKGROUND
 
The goal of this Cooperative Program is to improve the
culture conditions for non-human in vitro fertilization and
preimplantation development that are necessary for basic and
applied reproductive research on mammalian gametes and
preimplantation development.  This basic and applied
research has implications for several critical problems that
lie at the center of mammalian reproductive biology.
Included among these problems are:
 
1  The mechanisms of fertilization and implantation, the
prevention of polyspermy, contraception, the causes and
alleviation of infertility, and genetic assessment;
 
2  The genetic and epigenetic regulation of the program of
preimplantation development, the initiation of placenta
formation (i.e., trophectoderm formation) that is the
critical prerequisite for successful embryo transfer,
implantation, and the establishment of pregnancy; and
 
3  The initiation and maintenance of normal mammalian embryo
development, as well as the production of healthy oocytes
and eggs that are capable of fertilization and development.
 
Because of the development of new technology and a
broadening interest, there exists an
opportunity for rapid progress on these critical problems of
mammalian reproductive biology.  This progress will depend
upon the use of more efficient in vitro techniques for the
study of mammalian gametes and preimplantation embryos.
This is the case for many gene transfer experiments,
twinning experiments, and a multitude of experiments on the
genetic assessment, morphology, physiology, biochemistry, and
molecular biology of oocytes and eggs and on embryo
development from fertilization through implantation.  In
applied science, in vitro procedures are widely
used in commercial endeavors, such as producing twins of
valuable animals and improving the commercial qualities of
livestock for food production.  Knowledge gained from the
animal studies may also relate to human in vitro
fertilization, preimplantation development, and embryo
transfer.
 
Those who use in vitro fertilization, oocyte and
preimplantation development and implantation as model
systems for reproductive toxicology studies also need in
vitro systems that produce high quality oocytes, eggs, and
embryos.  Sensitivity of these systems to drugs and
radiation may be much different in culture media that
support growth better than the previously and currently used
media.  A far-reaching benefit of this Cooperative Program
will be the improvement of conditions for the production and
genetic assessment of transgenic embryos and animals that
could be used in many biomedical experiments.
 
Unfortunately, the culture conditions in current use bear
little resemblance  to in vivo conditions; our understanding
of nutritional requirements and basic principles of
nutrition is practically nonexistent, and oocytes, eggs, and
embryos raised under these conditions are inferior.  This
inferior development may be responsible for defects that
interfere either with fertilization, the implantation
process, or with early post-implantation development
resulting in limited success of embryo transfer experiments.
 
Despite the fact that numerous successful pregnancies have
followed from in vitro procedures, the efficiency and,
therefore, the cost-effectiveness could be greatly improved
by increased basic knowledge expected from the results of
this Cooperative Program.  This would be especially true in
the case of domestic livestock and of non-human primates,
but also for small laboratory animals.
 
Thus, there are both basic and applied science needs for
improvement of culture conditions for successful in vitro
reproductive procedures for a variety of mammalian species.
It is expected that the results of the Cooperative Program
will provide a better understanding of the general
principles of nutrition, particularly with regard to the
interaction of the preimplantation embryo with the maternal
environment.
 
The ongoing Cooperative Program with seven research sites
was established by NICHD more than three years ago.  During
that time, significant improvements have been made in the
culture conditions for the production of higher quality
mammalian oocytes and eggs that are capable of fertilization
and subsequent development.  Significant progress has also
been made in solving the problem of in vitro "blocks" for
preimplantation development for several mammalian species.
It is clear that further improvements in oocyte and embryo
quality will be critical for successful, cost-effective in
vitro fertilization and subsequent development in vitro and
in vivo.
 
STUDY ORGANIZATION AND RESEARCH SCOPE
 
Requirements for Applicants:
 
NICHD invites applications both from current members of the
Cooperative Program (competitive continuation applications),
and from prospective members (new applications).  The
minimal requirements for applicants are as follows (See also
Review Criteria and Procedures below):
 
o  Competent, experienced principal investigators who are
committed to this problem;
 
o  Access to properly managed animal colonies with breeding
capabilities;
 
o  Demonstration of the capability of producing and
evaluating sufficient numbers of oocytes, eggs, or embryos
for sound statistical analysis;
 
o  Experience with in vitro fertilization and/or
preimplantation development followed by embryo transfer;
 
o  Excellent technical resources necessary for conduct of
the experiments; and
 
o  Evidence of departmental and institutional support and
commitment.
 
Direction and Management:  The Steering Committee:
 
Planning and implementation of the study will be done by a
Steering Committee consisting of the Principal Investigators
from each of the participating sites, one NICHD staff member
from the Reproductive Sciences Branch who will serve as
Research Coordinator, and an independent chairperson.  To
ensure impartiality, the independent chairperson will be a
scientist of national stature who is not participating as a
Principal Investigator and who is mutually acceptable to the
participants.
 
General Scope of the Study:
 
The protocols will be approved, developed and/or modified by
the Steering Committee through a consensus process.  The Program
is expected to have the following features:
 
o  Different sites that emphasize the study of different
aspects of the culture environment and utilize different
species; some sites may emphasize micronutrients, some may
emphasize macronutrients, and some will study other aspects
of the environment.  This underscores the need for
coordination and communication;
 
o  The determination and prioritization of approaches to be
taken;
 
o  Principles obtained from research on one species can be
rapidly tested in other species;
 
o  Establishment of significant endpoints, including
initiation of pregnancy and birth; methods for evaluation of
endpoints;
 
o  Some sites will place more emphasis on oocyte
development, others on preimplantation development, but the
goals of improved quality of embryos will be a necessary
feature;
 
o  Establishment of detailed experimental design, in order
to maximize  chances of success and to facilitate
statistical analysis;
 
o  Transmission of progress reports to the cooperating sites
and NICHD;
 
o  Analysis and dissemination of results; and
 
o  Meeting at least three times each year to discuss
progress and future plans.
 
In general, the Program will be conducted in the three
phases given in the OVERVIEW section.  However, since
extensive evolution of the Program is expected, the Phases
are expected to overlap.
 
Content of Applications:
 
A response to this Request for Applications (RFA) should consist
of a proposal that includes:
 
o  A description of the capabilities of the site to meet or
exceed the minimal requirements (see STUDY ORGANIZATION AND
RESEARCH SCOPE above);
 
o  A proposed five-year research plan that should be the
applicant's perception of the study and of his/her
cooperative role.  This plan should demonstrate the
applicant's knowledge, ingenuity, practicality, and
commitment to improve the culture conditions for non-human
in vitro oocyte development, fertilization and/or in vitro
preimplantation development followed by embryo transfer.
 
o  All essential information in the body of the proposal
rather than in the Appendix.
 
o  Current members who wish to submit competitive
continuation applications should prepare a renewal proposal,
and are required to list significant progress they have made
in this Program and indicate how they have met any special
cooperative agreement terms and conditions of their awards.
In order to respond to these requirements, current members
may use up to five additional pages in the Progress Report
section of their proposals.
 
MECHANISM OF SUPPORT
 
The funding mechanism to be used to assist the scientific
community in undertaking this program of basic and applied
science will be cooperative agreements between participating
sites and NICHD.  The major difference between a cooperative
agreement and a research grant is that there will be
substantial programmatic involvement of the NICHD staff
Research Coordinator above and beyond the levels required
for traditional program management of grants.  Specifically,
an NICHD staff member will cooperate with the Principal
Investigators as a partner in the research and serve as
Research Coordinator.  All parties will agree to accept the
participatory and cooperative nature of the group process.
 
It is anticipated that up to seven (7) awards will be made with an
award period of five (5) years.
 
The primary responsibilities of the awardees are:
 
o  Determine experimental approaches
o  Design protocols
o  Conduct experiments
o  Analyze and interpret the results
o  Present results and plans to Steering Committee
o  Publication of results
o  Modify, delete, or add protocols
 
The degree of programmatic assistance by the NICHD staff
Research Coordinator includes:
 
o  Participation in the development of optimal approaches
and protocol designs (and adjustments of protocols and
approaches when needed).  The Research Coordinator will
assist and facilitate the process, rather than directing it;
 
o  Assistance and review of all phases of the study to
assure consistency of protocol compliance, to improve and
strengthen cooperation between the sites, and to help
redirect efforts, if necessary.  In the event of
disagreement among participants, NICHD staff will assist in
forming an arbitration panel acceptable to participants (see
below);
 
o  Participation in data analyses, interpretation, and
publication of study results; and
 
o  To determine jointly with awardees, the need to add
additional sites, or to phase out a site when performance
requirements are not met.
 
The specific terms, conditions, and details of arbitration
procedures pertaining to the scope and nature of the
interaction between 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 Research Coordinator after the award
has been made.  In that event, an arbitration panel will be
formed consisting of one person selected by the Principal
Investigators, one person selected by the Research
Coordinator, and a third person selected by these
two members.  The decision of the arbitration panel, by
majority vote, will be binding.
 
The above Terms of Award 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 policies.
 
Cooperative agreements are subject to the administrative
requirements outlined in OMB circulars A-102 and A-110; and
all pertinent HHS, PHS, and NIH grant regulations, policies
and procedures, with particular emphasis on HHS regulations
at 42 CFR Part 52 and 45 CFR Part 74, are applicable.  The
NIH Information for Management and Planning Analysis and
Coordination (IMPAC) system and indirect cost award
procedures will apply to cooperative agreement awards in the
same manner as for grants.  The special arbitration
procedures described above in no way affect the right of a
recipient of a cooperative agreement assistance grant to
appeal an adverse determination in accordance with PHS
regulations at 42 CFR Part 50, Subpart D, and HHS
regulations at 45 CFR Part 16 and 75.  Business management
aspects of these awards will be  administered by the NICHD
Grants Management Office in accordance with HHS, PHS, and
NIH grant administration requirements.
 
REVIEW CRITERIA AND PROCEDURES
 
Review Procedure:
 
A preliminary review will be done by NICHD staff upon
receipt of the  application.  Any application that does not
meet the minimal requirements (see STUDY ORGANIZATION AND
RESEARCH SCOPE above) of this RFA will be judged to be
unresponsive to this RFA and will be returned to the
applicant without technical review.  Applications that are
complete and responsive may be subjected to a triage
procedure by a peer review group to determine their
scientific merit relative to the other applications received
in response to this RFA.  Applications judged to be competitive
for awards will be reviewed in detail in accordance
with established NIH peer review procedures for research
grants.  The review will be conducted first for scientific
and technical merit by a special review committee convened
specifically for this purpose by the Scientific Review
Program, NICHD.  This will be followed by a second-level
review by the National Advisory Child Health and Human
Development (NACHHD) Council in June 1991.
 
Criteria for Review:
 
Applications will be evaluated on scientific and technical
merit according to the criteria listed below.  During the
review of applications, ethical and animal welfare issues
will be addressed.  If reviewers identify concerns and
problems with respect to animal welfare, this will be
brought to the attention of appropriate NIH officials as
well as the applicant institution.
 
Evaluation of the proposals will be based upon the
following:
 
1  Qualifications, Experience, and Commitment of Key
Personnel
 
o  Scientific and administrative abilities of the Principal
Investigator and other team members, as evidenced by
pertinent publications
 
o  Knowledge and experience in areas relevant to the conduct
of the experiments proposed
 
o  Commitment of time for the proposed study and stated
willingness to work and collaborate with other sites
and the NIH in the manner summarized in this RFA
 
2  Protocols and Procedures
 
o  Responsiveness of the application to the objectives of
the study as outlined in this RFA
 
o  Scientific merit of the proposal
 
o  Demonstration of cost-effectiveness through improved
oocyte and/or embryo quality
 
3  Facilities and Management
 
o  Adequacy of administrative and technical capabilities
 
o  Adequacy of animal facilities and appropriateness of
animal care management
 
o  Institutional assurance to provide support to the study
in such areas as fiscal administration, personnel
management, space allocation, procurement, planning,
and budgeting
 
4  Budgeting
 
o  Appropriateness of budget
 
METHOD OF APPLYING
 
Application Procedures:
 
Applications must be submitted on form PHS-398 (Revised
10/88), that is available in most institutional business
offices or from the Division of Research Grants, NIH
(301/496-7441).  The conventional presentation format for
regular research grant applications should be used, with
care taken to address the eligibility requirements (see
STUDY ORGANIZATION AND RESEARCH SCOPE) and review criteria
requirements (see REVIEW CRITERIA AND PROCEDURES).
Applications should be identified by checking the
"yes" box in Item Number 2 on the face page of the
application, and typing in the RFA number and the RFA Title.
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.  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 (4) copies should be received by the Division of
Research Grants no later than November 20, 1990.
 
Applications should be sent or delivered to:
 
Application Receipt Office
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
5333 Westbard Avenue
Bethesda, Maryland  20892**
 
In addition to those applications mailed to the Division of
Research Grants, two (2) copies of the application should be
sent or delivered to:
 
Laurance Johnston, Ph.D.
Scientific Review Program
National Institute of Child Health and Human Development
National Institutes of Health
Executive Plaza North, Suite EPN-520
Rockville, Maryland  20892
 
Deadline for Submission:
 
The deadline for receipt of applications by the NIH Division
of Research Grants is November 20, 1990.  Late applications
will not be accepted.
 
Budget:
 
The format/forms/instructions for budget estimates provided
with research grant application kits (PHS 398) should be
followed.  Indirect costs will be awarded in the same manner
as for research grants.  Budgets will be reviewed on the
basis of appropriateness for the work proposed.  Allowable
costs and policies governing the research grant programs of
the NIH will prevail.  The requested budget should not be in
excess of the amount generally requested for a regular
research grant.  Include estimates for staffing needs,
although it is expected that some modification will be
needed once the final research protocol(s) has been
developed.
 
Since the final protocol(s) for this study will not be
exactly known at the time of submission of the application,
the budget request should be based on the plan proposed by
the applicant and should reflect the scope of the project.
The budget should also include estimates of travel expenses
for three meetings of two days each of the Steering
Committee per year.  The first meeting will be a Phase I
meeting held in Bethesda, Maryland, in September 1991.
 
The application should include a detailed summary of all
sources of actual and pending
support for each key investigator participating in the study
with grant or other award number identification and percent
effort committed.
 
Additional Information:
 
Timetable
 
Application Receipt Date:   November 20, 1990
Initial Review Date:        February/March 1991
Review by NACHHD Council:   June 1991
Earliest Award Date:        September 1, 1991
 
It is expected that up to seven (7) applications will be
funded, contingent upon the receipt of meritorious
proposals.  For further information, please contact:
 
Program/Scientific Matters:
Richard J. Tasca, Ph.D.
Reproductive Sciences Branch
Center for Population Research
National Institute of Child Health and Human Development
National Institutes of Health
Executive Plaza North, Room 603
Bethesda, Maryland  20892
Telephone:  301/496-6515
 
Administrative Policy:
Robin Bissell
Office of Grants and Contracts
National Institute of Child Health and Human Development
National Institutes of Health
Executive Plaza North, Room 505
Bethesda, Maryland  20892
Telephone:  301/496-5001
 
This program is described in the Catalog of Federal Domestic
Assistance No. 13.864, 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 Grant Policies and Federal Regulations 42 CFR Part 52
and 45 CFR Part 74.  This program is not subject to A-95 or
Health Systems Agency review.