Full Text HD-94-006

HUMAN FETAL TISSUE CHARACTERIZATION FOR TRANSPLANTATION

NIH GUIDE, Volume 22, Number 28, August 6, 1993

RFA:  HD-94-006

P.T. 34

Keywords: 
  Fetus 
  Transplantation of Organs 
  Biological Resources 


National Institute of Child Health and Human Development
National Institute of Diabetes and Digestive and Kidney Diseases
National Institute of Neurological Disorders and Stroke

Letter of Intent Receipt Date:  October 1, 1993
Application Receipt Date:  November 19, 1993

PURPOSE

This Request for Applications (RFA) has been developed to encourage
research on the standards and methods for identifying and
characterizing optimal human fetal tissue for use in transplantation
therapy.  Joint funding by the National Institute of Child Health and
Human Development (NICHD), the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK), and the National Institute of
Neurological Disorders and Stroke (NINDS) reflects the extent of
interest in evaluating human fetal tissues and their biological
potentials.  Attention should be given to proper collection,
processing, culturing and preserving these tissues to ensure highest
quality control.  This research should consider addressing methods
for acquisition, handling, and processing, establishing morphologic
status, determining developmental age and viability, assessing
sterility and genetic normality, preserving by cryopreservation,
storing and establishing cell lines.  President Clinton's directive
of January 22 ended the moratorium on Federal funding for use of
fetal tissue from induced abortions in human transplantation
research.  Therefore, human fetal tissues studied under this
solicitation may be derived from spontaneous abortion, ectopic
pregnancy, or induced abortion.

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 Characterization for Transplantation, 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 or local governments.
Applications from investigators who are minority individuals and
women are encouraged.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) research
project grant (R01).  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 four years.  The
anticipated award date is July 1, 1994.

This RFA is a one time solicitation.  Future unsolicited competing
continuation applications will compete with all
investigator-initiated applications and be reviewed according to the
customary peer review procedures.

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 support
these awards, $1,000,000 has been set aside for the direct costs in
the first year.  The duration of these awards is to be four years and
the annual direct costs for the first year are not to exceed
$160,000.  This announcement is for a single competition with the
application receipt deadline of November 19, 1993.  Should there be a
sufficient continuing program need, this RFA may be reissued.

RESEARCH OBJECTIVES

Background

The use of human fetal tissue transplants has been advocated for
several years as a means of treating 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.

Childhood diseases such as inborn errors of metabolism, immune
deficiencies and other entities are being considered for very early
treatment using fetus-to-fetus transplants.  Diseases such as
insulin-dependent diabetes mellitus (IDDM) and Parkinson's Disease
are also prospective candidates for transplantation therapy.  The
results of the Diabetes Control and Complications Trial demonstrate
the profound importance of glucose control in the prevention of
diabetic complications.  Thus, transplantation therapy offers new
avenues for tighter glucose control in IDDM patients.  Initial
results of surgical transplantation in Parkinson's Disease for a
small number of cases hold considerable promise although more
definitive study and evaluation are required.

There is currently considerable interest in the therapeutic use of
fetal tissues for the treatment of incurable and chronic diseases,
both from the medical and the basic science community.  Methods
should be considered to optimize and standardize the handling and
processing of fetal tissues as well as their preservation and
storage.  It is evident that better characterization of these more
immature fetal tissues is required to assure optimal therapeutic
results.  Improved knowledge of the potential of these cells will
define their roles in normal developmental processes based on their
developmental age and biological potential, and will improve their
usefulness in replacement therapy.

Tissue Collection

Appropriate collaboration with clinicians will be required to obtain
necessary tissue in a timely fashion and collected in a manner
suitable for the scheduled tissue processing.  Accurate assessment of
developmental 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 be included.  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.

Data Collection

The data from these studies should be used to address the quality and
efficacy of the tissues under investigation for transplantation
therapy.  This information should be applicable to the establishment
of protocols and tissue processing innovations.

SPECIAL REQUIREMENTS

The fetal tissue acquisition and handling must comply with the
regulations for Federal Funding of Fetal Tissue Transplantation
Research as set forth in the NIH Guide for Grants and Contracts,
Volume 22, Number 11, March 19, 1993.

It is expected that at least two meetings per year in the Washington,
DC area of the awardees, NIH staff, and NIH 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
collaborative efforts 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

SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS

NIH policy is that applicants for NIH 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 provided.

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group.  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 Sections 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, 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
minorities.

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
policies.

LETTER OF INTENT

Prospective applicants are asked to submit, by October 1, 1993, 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, NIDDK, and NINDS 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 Dr. Delbert H. Dayton at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research and from the Office of
Grants Information, Division of Research Grants, National Institutes
of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892,
telephone (301) 435-0714.

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. The title can be abridged
to "Human Fetal Tissues."

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:

Susan Streufert, Ph.D.
Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5E03
Bethesda, MD  20892

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, NIDDK, and NINDS 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 and 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
appropriate National 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 the optimal methods of
tissue evaluation, processing, cryopreservation, maintenance,
storage, tissue/cell culturing and quality control for establishment
of viable, functional tissue/cells for transplantation

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

o  Adequacy of access to fetal tissue and 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  Quality of data analysis systems

AWARD CRITERIA

Responsiveness to the RFA, scientific merit, and technical
proficiency, as described in the application, will be the predominant
criteria for determining funding.

INQUIRIES

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

Direct inquiries regarding programmatic issues, and address the
letter of intent to:

Delbert H. Dayton, M.D.
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B01
Bethesda, MD  20892
Telephone:  (301) 496-5541

Joan T. Harmon, Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 622
Bethesda, MD  20892
Telephone:  (301) 594-7565

Eugene J. Oliver, Ph.D.
Division of Demyelinating, Atrophic, and Dementing Disorders
National Institute of Neurological Disorders and Stroke
Federal Building, Room 806
7550 Wisconsin Avenue
Bethesda, MD  20892
Telephone:  (301) 496-1431

Direct inquiries regarding fiscal matters to:

Ms. Mary Ellen Colvin
Office of Grants and Contracts
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17
Bethesda, MD  20892
Telephone:  (301) 496-1303

Ms. Betty E. Bailey
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 649
Bethesda, MD  20892
Telephone:  (301) 594-7543

Mr. George Tucker
Division of Extramural Activities
National Institute of Neurological Disorders and Stroke
Federal Building, Room 1004
7550 Wisconsin Avenue
Bethesda, MD  20892
Telephone:  (301) 496-9231

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance Nos. 93.847, 93.853, 93.854, and 93.865.  Awards are made
under authorization of the Public Health Service Act, Title IV, Part
A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and
285) and administered under PHS grants policies and Federal
Regulations 42 CFR 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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