Subject: RFA HD-91-05 2/l/9l NIH Guide
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Wed, 06 Feb 91 07:42 EST

Hi Paul,
   #2 in the string.   Please post as: RFAHD-91-05.910201
Thanks.  Dottie
 ---------------------------- Text of forwarded message -----------------------
 
ANIMAL MODELS FOR SUDDEN INFANT DEATH SYNDROME
 
RFA AVAILABLE:  HD-91-05
 
P.T. 34; K.W. 0755020, 0715205
 
National Institute of Child Health and Human Development
 
Application Receipt Date:  May 15, 1991
 
PURPOSE
 
The National Institute of Child Health and Human Development
(NICHD) is interested in expanding the scope of research
conducted into the causes and pathologic mechanisms of
Sudden Infant Death Syndrome (SIDS).  In this solicitation,
the NICHD invites applications for studies using fetal
and/or young developing animals to elucidate environmental
factors and developmental mechanisms during pregnancy and
early postnatal life that may result in a
SIDS-like event (i.e., sudden death during a sleep period),
or the inability to recover from hypoxic or other life-
threatening stresses.
 
Information derived from these animal studies is expected to
elucidate potential mechanisms of SIDS under experimental
conditions unavailable in human infants and lead to the
development of diagnostic and preventive strategies.
 
BACKGROUND INFORMATION
 
SIDS is the leading cause of mortality in infants between the
ages of one to twelve months in the United States.  It is
defined as "the sudden death of an infant under one year of
age which remains unexplained after a thorough case
investigation, including performance of a complete autopsy,
examination of the death scene, and review of the clinical
history" (1).  Despite decreases in the rate of infant
mortality overall, the incidence of SIDS remains unchanged
at 1-2 deaths per 1,000 live births in the United States.
 
In 1974, in response to the concerns of families and the
medical and scientific community, Congress passed the Sudden
Infant Death Syndrome Act (P.L. 93-270).  This legislation
gave NICHD responsibility for promoting research into the
etiologies and prevention of SIDS.  The NICHD is in the
process of implementing a five-year research plan that was
presented to the United States Senate in Fiscal Year 1989.
One of the goals of the plan is to increase basic research
in fields holding promise to understand what conditions may
place an infant at risk for a SIDS event and the potential
pathways for sudden death.
 
The pathogenic mechanisms and events leading to SIDS are
poorly understood; indeed, the absence of a detectable
causative factor of death is one of the criteria for the
diagnosis.  Research conducted over the past decade has led
to the realization that infants who succumb to SIDS
generally are not completely healthy at birth (2).  Results
from physiologic and pathologic investigations suggest that
infants who succumb to SIDS have subtle abnormalities in
cardiorespiratory function during sleep (3) and in the nervous
system prior to death (4).  Large-scale epidemiologic studies
reveal particular maternal risk factors that suggest a fetal
origin for vulnerability to a SIDS event:  young age at first
pregnancy, short inter-pregnancy interval, and smoking (5,6).
Triggers such as hypoxic insult, infection, environmental
temperature, or stress may start a susceptible infant on the
path to SIDS.  Although the precise cause of death is
obscure, certain factors are observed with a high frequency
in SIDS victims:  the deaths are unexpected in seemingly
healthy infants, they usually occur during a nighttime sleep
period, the peak age of occurrence is between two and four
months (5), and, at autopsy, intrathoracic petechiae (pinpoint
hemorrhages) are present (7).  Despite the lack of a unifying
hypothesis for pathogenic mechanisms, several fertile areas
of scientific research are apparent:  the control of
cardiorespiratory function during sleep, the developing
nervous system and behavioral repertoire of the infant, the
developing immune system, and the role of inherited
metabolic diseases.
 
To facilitate the conduct of research into the causes and
pathologic mechanisms of SIDS, NICHD invites applications
for studies using fetal and/or young developing animals to
elucidate environmental factors and developmental
mechanisms during pregnancy and early postnatal life that
predispose the young animal to a SIDS-like event or to the
inability to recover from hypoxic or other life-threatening
stresses.
 
The Public Health Service is committed to achieving the
health promotion and disease prevention objectives of
Healthy People 2000, a PHS-led national activity.
This Request for Applications (RFA), "Animal Models
for SIDS", is
related to the priority area of "Maternal and Infant
Health".
 
Literature Cited:
 
1.  Zylke JW.  JAMA 262: 1565-1566, 1989.
2.  Willinger M.  J NIH Res 1: 73-80, 1989.
3.  Kluge KA, Harper RM, Schechtman VL, Wilson AJ, Hoffman
    HJ, Southall DP.  Pediatr Res 24: 677-682, 1988.
4.  Kinney H, and Filiano JJ.  Pediatrician 15: 240-250, 1988.
5.  Hoffman HJ, Damus K, Hillman L, Krongrad E.  Annals NY
    Acad Sci 533: 13-30, 1988.
6.  Kraus JF, Greenland S, Bulterys M.  Int. J. Epidemiol.
    18: 113-120, 1989.
7.  Krous HF, and Jordan J. In: "Sudden Infant Death
    Syndrome, Risk Factors and Basic Mechanisms", (Harper
    RM, Hoffman HJ, Eds.), PMA Publishing Corp., New York,
    pp 91-100, 1988.
 
Research Goals
 
In order to develop strategies to identify an infant at risk
for SIDS and prevent death it is necessary to:
 
o  improve our understanding of the pathogenic mechanisms
   that may result in a SIDS death;
 
o  improve our knowledge of the development, function, and
   integration of life-sustaining systems in the fetus and
   infant; and
 
o  define acceptable boundaries over time for the range of
   maturational and  functional variability of these
   systems, particularly in response to intrinsic and
   extrinsic factors that may predispose an infant to sudden
   death.
 
Research Scope
 
Multidisciplinary investigations in animal systems
can help us to achieve the stated
research goals.  In this solicitation, the NICHD encourages
investigations in animal systems (intact and reduced
preparations) within the following research
areas/approaches:
 
1.  The effects of prenatal insults, such as hypoxia,
substance abuse (including smoking), and thermal and
metabolic stress, on the development and function of:
 
o  cardiorespiratory integration and control;
 
o  sleep states and circadian rhythmicity;
 
o  recruitment and pacemaking of cardiac and upper airway
   muscles; and
 
o  protective responses to postnatal stressors such as
   hypoxia, infection, changing thermal and metabolic
   demands.  Examples of protective responses are arousal,
   autoresuscitation, adrenomedullary and/or immune
   activation.  These may be investigated as they relate to
   what is known about the SIDS phenotype (see 3. below).
 
2.  The effects of postnatal insults, such as hypoxia or
infection, or of new stimuli associated with life ex-
utero, such as changing light, thermal, or metabolic
conditions, on the development and function of:
 
o  cardiorespiratory integration and control;
 
o  sleep states and circadian rhythmicity;
 
o  recruitment and pacemaking of cardiac and upper airway
   muscles; and
 
o  protective responses to postnatal stressors such as
   hypoxia, infection, changing thermal and metabolic
   demands.
 
3.  Investigations of developmental disorders/
susceptibilities that are naturally occurring or induced
and mimic some aspect(s) of the SIDS phenotype as
characterized by the physiology, age, risk factors, and
pathology of SIDS victims, and the association of the SIDS
event with sleep.  These may include proposals that further
define known animal model systems, or search for new
species or genetic variants that resemble some aspects of
SIDS.
 
In the context of these investigations parallel studies of
unperturbed development and function may be proposed.  The
extent of the normative studies should depend on the
existing knowledge base.  Developmental studies that span
the fetal and early postnatal period are encouraged.  All
studies proposed must address their potential or true
relationship to SIDS.
 
MECHANISM OF SUPPORT
 
Applications in response to this RFA will be funded through
the traditional individual research grant award program of the
NICHD.  Generally, future unsolicited competing renewal
applications will compete with all investigator-initiated
applications and be reviewed by a standing DRG study
section.
 
It is anticipated that eight (8) applications will be
funded, contingent on the receipt of a sufficient number of
meritorious applications and the availability of funds.
The earliest possible start date for grants will be
September 30, 1991.
 
REVIEW PROCEDURES AND CRITERIA
 
REVIEW PROCEDURE
 
Applications will be reviewed by NICHD staff for
completeness and responsiveness to the RFA.  Incomplete
applications will be returned to the applicant without
further consideration.  An application is considered
nonresponsive if (1) the investigations proposed are not
within the research scope outlined above, or (2) the
application is considered identical to one already submitted
to NIH for review.
If the application submitted in response to this RFA is
substantially similar to a research grant application already
submitted to the NIH for review, but has not yet been reviewed,
the applicant will be asked to withdraw either the pending
application or the new one.  Simultaneous submission of identical
applications will not be allowed, nor will essentially identical
applications be reviewed by different review committees.
Therefore, an application cannot be submitted in response to this
RFA that is essentially identical to one that has already been
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.
 
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
committee convened solely for this purpose by the Division
of Scientific Review, NICHD.
 
The complete and responsive applications may be subjected to
triage by a peer review group to determine their scientific
merit relative to other applications received in response to
this RFA.  The review criteria to be used are identified
below.  The NIH will administratively withdraw from
competition those applications judged to be noncompetitive,
and notify the applicant and institutional business
official.  Those applications judged to competitive will
undergo further scientific merit review.  The second level
of review will be provided by the National Advisory Child
Health and Human Development Council.
 
REVIEW CRITERIA
 
Criteria for the initial review of applications include:
 
o  scientific significance and originality of research goals
   and approaches;
 
o  medical significance as it relates to the causes and
   pathogenesis of SIDS and/or infants at risk for SIDS;
 
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, particularly, but not exclusively,
   in the area of the proposed research;
 
o  availability of resources necessary to perform the
   research;
 
o  appropriateness of the proposed budget and duration in
   relation to the proposed research; and
 
o  adequacy to protect against or minimize adverse effects
   on animals.
 
METHOD OF APPLYING
 
o  Application Procedure
 
Applications must be submitted on form PHS-398 (revised
10/88) that includes appropriate documentation regarding
the protection of animal subjects.  The conventional
presentation format for research grant applications
should be used with care taken to address the points
identified under review criteria and eligibility for
participation.
 
The RFA label available in the 10/88 revision of Application
Form 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 phrase "ANIMAL MODELS
SIDS APPLICATIONS, RFA HD-91-05" must be typed in item 2
of the face page of the application.
 
The original and four copies of the application must be
sent or delivered to:
 
Application Receipt Office
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**
 
Also send two copies to:
 
Laurance S. Johnston, Ph.D.
Division of Scientific Review
National Institute of Child Health and Human Development
Executive Plaza North, Room 520
Bethesda, MD  20892
 
o  Application Deadline - Applications including copies must
   be received by May 15, 1991.  Late applications will not
   be accepted.
 
o  Timetable
 
Application Receipt Date:  May 15, 1991
Initial Review Date:  July 1991
Review by Advisory Council:  September 1991
Anticipated Award Date:  September 30, 1991
 
o  Additional Information - Inquiries regarding scientific
   or programmatic issues may be directed to:
 
Marian Willinger, Ph.D.
Health Scientist Administrator
Pregnancy and Perinatology 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) 496-5575
 
Inquiries regarding grants management and administrative
policy may directed to:
 
Douglas Shawver
Supervisory Grants Management Specialist
Grants Management Branch
Office of Grants and Contracts
National Institute of Child Health and Human Development
Executive Plaza North, Room 505
Bethesda, MD  20892
Telephone:  (301) 496-1303
 
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 USC241), and administered under
PHS grant policies and Federal Regulations 42 CFR Part 52
and 45 CFR Part 74.  This program is not subject to review
under the intergovernmental review requirements of Executive
Order 12372 or Health Systems Agency review.