Full Text HD-92-10

HUMAN FETAL TISSUE BANKS

NIH GUIDE, Volume 21, Number 22, June 12, 1992

RFA:  HD-92-10

P.T. 0780020, 0705035, 0780030


Keywords: 


National Institute of Child Health and Human Development

Letter of Intent Receipt Date:  June 26, 1992
Application Receipt Date:  August 3, 1992

PURPOSE

The purpose of this Request for Applications (RFA) is to support the
initial research necessary to provide and assess the quality and
quantity of human fetal tissues available solely from spontaneous
abortions and ectopic pregnancies to serve as sources for
transplantation therapy; to develop and test effective methods for
human fetal tissue banks to use in obtaining, testing, culturing, and
preserving those tissues and transporting them for transplantation; and
to gain information on the epidemiology and mechanisms of early
pregnancy loss.  Transplantation therapy requires viable, sterile,
well-characterized tissue that is obtained, maintained, and distributed
to investigators under conditions of highest quality control.  Data
generated from the studies supported under this RFA to develop the
initial stages of human fetal tissue banks will be evaluated and
utilized in the establishment of a national network of human fetal
tissue banks entirely dependent on tissue from spontaneous abortions
and ectopic pregnancies.

HEALTHY PEOPLE 2000

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,
Human Fetal Tissue Banks, is related to the priority areas of maternal
and infant health, and diabetes and chronic disabling conditions.
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 202-783- 3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and non-profit
organizations, public and private, such as universities, colleges,
hospitals, laboratories and units of state and local governments.
Applications from minority and women investigators are encouraged.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH)
Resource-Related Research Project Grant (R24).  Responsibility for the
planning, direction, and execution of the proposed project will be
solely that of the applicant.  The total project period for
applications submitted in response to the present RFA may not exceed
two years for Phase I of this study.  The anticipated award date is
September 28, 1992.

This announcement is for a single competition with the application
receipt deadline of August 3, 1992.  After the NICHD establishes that
there are sufficient data from these Phase I studies to support
development of a network of defined human fetal tissue banks,
additional applications will be solicited and competed.  Future awards
based on a new competition will be made as cooperative agreements
(U01), which create an assistance relationship with substantial
involvement of NICHD staff during the performance of the projects, as
will be outlined in the Phase II request for applications (RFA).

FUNDS AVAILABLE

It is anticipated that up to six grants will be awarded under this
program, contingent upon receipt of a sufficient number of meritorious
applications and the availability of funds.  To fund these awards,
$3,000,000 has been set aside for the total costs in the first year.

RESEARCH OBJECTIVES

Background

The use of human fetal tissue transplants has been advocated for
several years as a means of alleviating symptoms of a number of
devastating diseases.  Fetal tissue transplants may allow replacement
of tissues and cell products that have been damaged, destroyed, or that
never developed properly due to disease or a genetic disorder.  These
maladies are life threatening unless intervention is instituted.

Inborn errors of metabolism are being considered for very early
treatment using fetus to fetus transplants.  But diseases confined to
the fetus are not the only disorders under consideration.  Adult
diseases such as diabetes mellitus and Parkinson's Disease are also
candidates for transplantation therapy.  Initial results of surgical
transplantation in Parkinson's Disease for a small number of cases hold
considerable promise although more definitive study and evaluation is
required.

Using fetal tissues from spontaneous abortions and ectopic pregnancies
only, tissue banks are to be developed to determine the ability of such
facilities to provide adequate amounts of the biological materials
required to further this research and to establish protocols, tissue
processing innovations, logistical systems, and a data base appropriate
to the need.

Tissue Collection

There are many factors that must be considered in the evaluation of
such fetal tissue banks and accessioned fetal tissues.  First among
these is an assessment of the quantity and quality of the tissues
derived entirely from spontaneous abortions and ectopic pregnancies.
An urban setting for such a bank is considered essential to assure
maximum numbers of specimens for study and logistical efficiency.  It
is estimated that no fewer than 100 fetuses/year of 8-16 weeks
gestational age will be needed from each of these sources of tissue
(spontaneous abortions and ectopic pregnancies) for each grantee site.
Consideration should be given to a collection system to provide the
maximum accession of these tissues.  Accurate assessment of gestational
age, gross examination of tissues, and grading of tissues for viability
will also require a pathology/teratology assessment.  In obtaining
medical histories and serological screening of contributors of the
products of conception for this research, appropriate informed consent
must be obtained.

Evaluation of pathogenic contaminants, cytogenetic studies, and
assessment of genetic mutations in at-risk specimens are research areas
to consider.  Applicants should be able to demonstrate immunologic and
transplantation expertise and have available established tissue culture
facilities with the expertise for growing, characterizing,
cryopreserving and maintaining suitable fetal cell lines.  The research
team should include obstetric clinical professionals and fetal tissue
bank staff.

These research projects to develop human fetal tissue resources should
address acquisition, maintenance, storage (including cryopreservation),
ability to grow in tissue culture, assessment of cell lineages and cell
products, suitability for research applications, and the ability to
distribute widely.  Documentation of specimens lost to the study would
provide needed epidemiological data and should be part of the design.

Data Collection

It is desirable to have epidemiologic input to assess the incidence of
spontaneous abortions and ectopic pregnancies in the hospital-based
population to provide a denominator for this sample, to consider
subsamples based on ethnic groups and socio-economic class, and to make
comparisons of ectopic and spontaneously aborted tissue characteristics
and quality.  In addition, the establishment of a fetal tissue bank
provides an opportunity to conduct research on pregnancy loss and
causes of embryonal and fetal demise.  A computerized data base is
necessary for storing this information.

SPECIAL REQUIREMENTS

Data obtained from the Phase I study of fetal tissue banks, dependent
on tissue entirely from spontaneous abortions and ectopic pregnancies,
will be evaluated at the end of the first year by a panel of outside
experts convened by, and advisory to, the NICHD.  Based on the
recommendations of the advisory panel, plans for Phase II will be
developed.  During this period of data evaluation, the second year of
the Phase I study will be carried out to ensure continuity and further
refinement of the design and data.  During this second year, an RFA for
cooperative agreements would be published and competed for the Phase II
full study.

It is expected that at least two meetings of the awardees, NICHD staff,
and the advisory panel consultants, during both the first and
subsequent years, will be required to assess progress and workscope.
These meetings will be of benefit to the grantees and will allow them
to address unforeseen difficulties, establish networking of fetal
tissue banks, and assess the schedule of progress.  The grantees will
retain primary authority and responsibility for the work.  Funds for
this travel should be requested in the application.

STUDY POPULATIONS

Applicants are requested to collect and study tissues from all
spontaneous abortions and ectopic pregnancies derived from women
admitted to the participating hospitals for treatment of these
conditions during the duration of the study.  Tissues that are lost
from the study should be accounted for to provide accurate
epidemiologic data.

The composition of the proposed study population must be described in
terms of racial/ethnic group.  NIH and ADAMHA policy is that applicants
for NIH/ADAMHA clinical research grants and cooperative agreements are
required to include minorities 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 in studies of diseases, disorders
and conditions that disproportionately affect them.  If minorities are
excluded or inadequately represented in clinical research, particularly
in proposed population-based studies, a clear compelling rationale
should be provided.

This information should be included in the form PHS 398 in Section 2,
1-4 of the Research Plan and summarized in Section 5, Human Subjects.
Applicants are urged to assess carefully the feasibility of including
the broadest possible representation of minority groups.  However, NIH
recognizes 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,
and Hispanics.

The usual NIH policies concerning research on human subjects also
apply.

Peer reviewers will address specifically whether or not the research
plan in the application conforms to these policies.  If the
representation of 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 policies.

LETTER OF INTENT

Prospective applicants are asked to submit, by June 26, 1992, a letter
of intent that includes a descriptive title of the proposed research;
the name, address, and telephone number of the Principal Investigator;
the identities of other key personnel and participating institutions;
and the number and title of the RFA in response to which the
application may be submitted.

Although a letter of intent is not required, is not binding, and does
not enter into the review of subsequent applications, the information
that it contains is helpful in planning for the review of applications.
It allows NICHD staff to estimate the potential review workload and to
avoid conflict of interest in the review.

The letter of intent is to be sent to:

Delbert H. Dayton, M.D.
Genetics and Teratology Branch
National Institute of Child Health and Human Development
Executive Plaza North, Room 643
9000 Rockville Pike
Bethesda, MD  20892
Telephone:  (301) 496-5541
FAX:  (301) 402-2085

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) must be used in
applying for these grants.  These forms are available at appropriate
institutional offices and from the Office of Grants Inquiries, Division
of Research Grants, National Institutes of Health, 5333 Westbard
Avenue, Room 449, Bethesda, MD  20892, telephone (301) 496-7441.

The RFA label available in the PHS 398 application form must be affixed
to the bottom of the face page. Failure to use this label could result
in delayed processing of an application such that it may not reach the
review committee in time for review.  In addition, the RFA title and
number must be typed on line 2a of the face page of the application
form and the YES box checked.

Submit a signed, typewritten original of the application, including the
Checklist, and three signed, exact photocopies, in one package to:

DIVISION OF RESEARCH GRANTS
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

At the time of submission, two additional copies of the application
must also be sent to:

Laurance Johnston, Ph.D.
Acting Director, Division of Scientific Review
National Institute of Child Health and Human Development
Executive Plaza North Building, Room 520
9000 Rockville Pike
Bethesda, MD  20892

Applications must be received by August 3, 1992.  Applicants should
call Dr. Dayton regarding additional specific submission guidance or
instruction.

REVIEW CONSIDERATIONS

Applications will be received by the NIH Division of Research Grants
and reviewed for completeness.  Incomplete applications will be
returned to the applicant.  NICHD staff will review the applications
for responsiveness to the RFA.  Applications judged to be nonresponsive
will be returned.  Responsive applications may be subjected to a triage
by a peer-review group to determine the scientific merit relative to
the other applications received in response to this RFA.  NICHD will
withdraw from competition those applications judged to be
noncompetitive and will notify the applicant and institutional
official.  Those applications judged to be competitive will be further
evaluated for scientific/technical merit by a review group convened
solely for this purpose by the Division of Scientific Review, NICHD.
Following review by the Initial Review Group, applications will be
evaluated by the NICHD Advisory Council for program relevance and
policy issues before awards for meritorious applications are made.

Review Criteria

Applications must contain sufficient information for scientific review
based on the following criteria:

o  Quality of proposed research to determine optimal methods for:
tissue evaluation and processing; tissue cryopreservation, maintenance,
and storage; tissue culturing; quality control

o  Demonstrated experience of the principal investigator and proposed
staff relevant to this RFA, especially in the areas of
pathology/teratology and tissue preparation techniques

o  Adequacy of access to fetal tissue from spontaneous abortions and
ectopic pregnancies

o  Confirmed cooperation of the professional clinical obstetric
community

o  Plans for tissue collection to assure a broad population base,
maximum access and ascertainment, rapid transport, and support of
cooperating institutions

o  Adequacy of physical facilities for proposed studies

o  Methods for establishing a tissue distribution plan

o  Quality of data storage, retrieval, and analysis systems

AWARD CRITERIA

Applications must be of sufficiently high merit, based on the review
criteria, to warrant funding.  Geographic location of approved projects
will also be a consideration.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged to
clarify any issues or questions from potential applicants.

Direct inquiries regarding programmatic issues to:

Delbert H. Dayton, M.D.
Chief, Genetics and Teratology 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) 496-5541

Direct inquiries regarding fiscal matters to:

Ms. Mary Ellen Colvin
Office of Grants and Contracts
National Institute of Child Health and Human Development
Executive Plaza North, Room 501
Bethesda, MD  20892
Telephone:  (301) 496-1303

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance
No. 93.865, Research for Mothers and Children.  Awards will be made
under the authority of the Public Health Service Act, Section 301 (42
USC 241), 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 review by a Health Systems Agency.

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