Full Text HD-94-015

IDIOPATHIC MALE INFERTILITY

NIH GUIDE, Volume 23, Number 8, February 25, 1994

RFA:  HD-94-015

P.T. 34

Keywords: 
  Human Reproduction/Fertility 
  Urogenital System 


National Institute of Child Health and Human Development

Letter of Intent Receipt Date:  April 8, 1994
Application Receipt Date:  May 18, 1994

PURPOSE

The National Institute of Child Health and Human Development (NICHD)
invites research grant applications for the support of investigations
comprising basic and clinical research on the etiology and
pathophysiology of infertility in the otherwise normal male.  Report
language accompanying the House of Representatives 1994
appropriations bill encouraged NICHD to expand research activities in
male infertility.

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 Request
for Applications (RFA), Idiopathic Male Infertility, 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 202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.
Foreign institutions are not eligible for the First Independent
Research Support and Transition (FIRST) (R29) award.  Applications
from minority individuals, persons with disabilities, and women are
encouraged.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) individual
research project grant (R01) and FIRST (R29) award.  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
five years.  The earliest expected award date is December 1, 1994.
Because the nature and scope of the research proposed in response to
this RFA may vary, it is anticipated that the size of an award will
vary also.

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 expected that up to four new awards will be funded, within the
total direct cost limit of $800,000 available for the first year.
This level of support is dependent of the receipt of a sufficient
number of applications of high scientific merit.  Although this
program is provided for in the financial plan of the NICHD, awards
pursuant to this RFA are contingent upon the availability of funds
for this purpose.

RESEARCH OBJECTIVES

Background

Infertility affects millions of United States couples, and the female
partner is apparently normal in some 60 percent of those couples
affected.  Where infertility is attributed to a male factor, it is
unusual to make a clear diagnosis of an explanatory condition, such
as hypogonadism or obstruction within the male genital tract.  Thus,
it is rare that treatment can be directed at an established cause in
the male.  More often, the male is well virilized and clinically
normal, but has a gross or subtle abnormality in sperm function.
Infertility treatment in these cases is typically in the form of
ovulation induction and/or assisted reproductive technology.  In
cases where ovulation induction is successful, it could be deduced,
retrospectively, that a subtle ovulation defect had been, in fact,
treated.  Usually, however, these techniques are applied empirically
in hopes of maximizing chances to conceive.  Thus, there is a need
for basic and clinical research on the causes of infertility in the
apparently normal male.  The anticipated benefits of this research
are development of a sound scientific basis for treatment choices, as
well as prospects of new treatments for male infertility.

Objectives

The overall objective of this RFA is to support and encourage
research on the etiology and pathophysiology of infertility in men
who are otherwise clinically normal, that is, have no evidence of a
treatable cause for their infertility such as hypogonadism or
obstruction.  The long term goals of such research would be to
delineate diagnostic subcategories within this group of men that
would provide meaningful guidance for choice of treatment, and also
provide research leads for the development of new treatments for male
infertility.

Laboratory research using human cells and tissues, and clinical
research in human subjects, are invited under this RFA.  Animal
models will also be considered relevant if they can be justified as
being applicable to human infertility.

There is controversy in the field regarding the relationship of
varicocele to infertility, and specifically regarding the potential
benefits of varicocelectomy.  For purposes of this RFA, men who
remain infertile following correction of varicocele(s) may be
considered among the idiopathic group if they are otherwise eligible.

Examples of topics appropriate for this RFA might include, but not be
limited to:

o  Subtle sperm function defects not being detected with existing
methods;

o  Effects on fertility of immune sequelae following transient
insult, e.g., postinfectious, postinflammatory, posttraumatic;

o  Physiological insult resulting in testicular dysfunction and
subsequent impaired spermatogenesis;

o  Defective sperm-egg interaction;

o  Genetic abnormality manifested as early embryo loss.

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 are 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 must 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 must 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 must be addressed in developing a research
design and sample size appropriate for the scientific objectives of
the study.  This information must be included in the form PHS 398
(rev. 9/91) 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 is defined as 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 reflected
in assigning the priority score to the application.

For the purpose of this RFA, these requirements must be addressed
even if the nature of the research is such that only male subjects
are involved.  An explanation that the condition under investigation
only affects males will be acceptable regarding the policy on
inclusion of women.  An estimate of the number or percentage of
minority subjects participating or providing samples in the proposed
research, with a justification if these numbers are low relative to
the general population, is generally sufficient to comply with the
requirements on inclusion of minorities.

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 April 8, 1994, 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 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 Dr. Donna L. Vogel 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 Westward Avenue, Room 449, Bethesda, MD 20892,
telephone 301/435-0714.

The RFA label available in the PHS 398 (rev. 9/91) application form
must be affixed to the bottom of the face page of the application.
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.  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 must
be marked.

Applicants from institutions that 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 research, if appropriate.  If so, a letter of agreement
from either the GCRC program director or Principal Investigator could
be included with the application.

Applications for the FIRST Award (R29) must include at least three
sealed letters of reference attached to the face page of the original
application.  FIRST Award (R29) applications submitted without the
required number of reference letters will be considered incomplete
and will be returned without review.

Submit a signed, typewritten original of the application, including
the Checklist, and three signed 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
Building 61E, Room 5E03
Bethesda, MD  20892

Applications must be received by May 18, 1994.  If an application is
received after that date, it will be returned to the applicant
without review.  The Division of Research Grants (DRG) will not
accept any application in response to this announcement that is
essentially the same as one currently pending initial review, unless
the applicant withdraws the pending application.  The DRG will not
accept any application that is essentially the same as one already
reviewed.  This does not preclude the submission of substantial
revisions of applications already reviewed, but such applications
must include an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed by DRG staff for
completeness and by NICHD staff for responsiveness.  Incomplete
applications will be returned to the applicant without further
consideration.  If the application is not responsive to the RFA, it
will be returned to the applicant, who may then submit it for review
in competition with unsolicited applications at the next available
review cycle.

Responsive applications may be triaged by a peer review group to
determine their relative competitiveness.  The NIH will withdraw from
further competition those applications judged to be noncompetitive
for award and notify the applicant Principal Investigator and
institutional official.  Those applications judged to be competitive
will undergo further evaluation for scientific merit.  Those
applications that are complete and responsive will be evaluated in
accordance with the criteria stated below for scientific/technical
merit by an appropriate peer review group convened by the NICHD.  The
second level of review will be provided by the National Advisory
Child Health and Human Development (NACHHD) Council.

Review criteria for RFAs are generally the same as those for
unsolicited research grant applications.

o  Scientific, technical, or medical significance and originality of
proposed research;
o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;
o  qualifications and research experience of the Principal
Investigator and staff, and of collaborators, if applicable;
o  adequacy of time and effort dedicated to the project;
o  availability of the resources necessary to perform the research;
o  appropriateness of the proposed budget and duration in relation to
the proposed research.

AWARD CRITERIA

The earliest anticipated date of award is December 1, 1994.  Funding
decisions will be based on peer review and NACHHD Council
recommendations, program relevance, and availability of funds.

In some cases, if the proposed research has relevance to the research
program of another NIH Institute as well as that of the NICHD, the
application may be dually assigned to and considered for funding by
that Institute.  Any such assignment will be made according to
existing DRG referral guidelines and independently of peer review
procedures.

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Donna L. Vogel, M.D., Ph.D.
Center for Population Research
National Institute of Child Health and Human Development
Building 61E, Room 8B01
Bethesda, MD  20892
Telephone:  (301) 496-6515
FAX:  (301) 496-0962

Direct inquiries regarding fiscal matters to:

Ms. Melinda Nelson
Office of Grants and Contracts
National Institute of Child Health and Human Development
Building 61E, Room 8B17
Bethesda, MD  20892
Telephone:  (301) 496-5481
FAX:  (301) 402-0915

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.864, Population Research.  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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