kristoff@GENBANK.BIO.NET (Dave Kristofferson) (12/05/90)
REQUEST FOR APPLICATIONS
RFA: HL-91-01-H
P.T. 34, FC; K.W. 0715115, 0755030, 1002019, 1002004, 1002008,
1002030, 0785025
MECHANISMS OF HYPERTENSION IN BLACK MEN AND WOMEN
National Heart, Lung, and Blood Institute
Letter of Intent Receipt Date: March 6, 1991
Application Receipt Date: April 8, 1991
PURPOSE
The purpose of this Request for Applications (RFA) is to
stimulate studies to elucidate
specific mechanisms underlying the excessive prevalence of
hypertension in black men and women, and to delineate
mechanisms that direct the pathogenesis of hypertension in
blacks, including vascular sequelae such as nephropathy,
cerebral vascular disease, coronary artery disease, and
atherosclerosis in other vascular beds. This RFA also seeks
to encourage investigations that will examine gender-related
mechanisms associated with the development of hypertension in
blacks. Due to the multiple dimensions of the disease, a
variety of disciplines and approaches are encouraged, such as
genetic linkage analysis, molecular biology, biochemistry,
physiology, neurobiology, pharmacology, cell and structural
biology, cardiology, and nephrology.
BACKGROUND
In the United States, hypertension in blacks is a significant
clinical and public health problem. Not only are blacks more
likely to develop hypertension, but the disease develops
earlier, is often more severe, and is more likely to be fatal
at an earlier age. Mortality associated with hypertension in
blacks is substantially higher than in whites; there is a
six-fold greater incidence of hypertension-related deaths in
middle-aged blacks compared to middle-aged whites. Even
among blacks who do not die of hypertension, there is an
increased prevalence of the morbid consequences of this
disease: stroke is 50 percent higher in blacks compared to whites;
left ventricular hypertrophy or an enlarged heart as a
consequence of hypertension is 30 percent greater in blacks compared
to whites; and kidney failure or end-stage renal disease is 3
times higher in blacks compared to whites.
Abnormalities in glucose and insulin metabolism are common in
hypertensive patients, both white and black. Early
aberrations in insulin-stimulated glucose metabolism or
insulin resistance need to be detected and delineated by
race. There is a well-recognized association of
hyperinsulinemia with elevated cholesterol, elevated low-
density lipoprotein, and decreased high-density lipoprotein
that potentially contributes to cardiovascular disease
through progressive atherosclerosis. Little is known
regarding abnormalities in lipid metabolism in blacks,
independent of, or in association with, insulin resistance.
Recently, Williams et al. described a syndrome ("Familial
Dyslipidemic Hypertension"), that is present in 12 percent of
hypertensive whites. Multigenerational studies on familial
transmission may be able to detect distinctive phenotypes of
black hypertension in which metabolic pathways are linked to
hypertension.
Compared with whites, blacks have alterations in renal
function including blunted sodium excretion, blood pressure
sensitivity to sodium load, lower rate of renal blood flow,
higher vascular resistance, and reduced excretion of
kallikrein. Of particular interest in hypertensive
nephropathy is the observation that some hypertensive blacks
exhibit a reduction in renal function despite seemingly
adequate pharmacologic control of blood pressure. There is
also evidence of excess end-stage renal disease among
diabetic blacks. Blood pressure is generally higher in
diabetic blacks than diabetic whites. It is not known
whether the greater predisposition to hypertension among
blacks contributes to the increased rate of diabetic renal
failure. Alternatively, a single mechanism may be
determining both the hemodynamic and metabolic expressions of
a vascular disease more common in the black race.
Several reports have described racial differences in cellular
cation transport rates. Sodium-potassium cotransport is
lower in blacks, whereas the hypertension-associated increase
in sodium-lithium countertransport is greater in hypertensive
whites. Other transport mechanisms that may be related to
biochemical or metabolic variations among blacks include
sodium-hydrogen exchange, sodium-calcium exchange, and
sodium-potassium ATPase.
Sympathetic nervous system activity influences blood
pressure, arteriolar tone, glucose/insulin, and lipid
metabolism. Several studies have shown greater blood
pressure and vasoconstrictor responses to standardized
stimuli in blacks. The results of these investigations have
provided early evidence of augmented alpha receptor
sensitivity in blacks compared to whites. These data suggest
differences in peripheral vascular function or structure
resulting in greater vascular resistance in blacks. Another
possible avenue in the pathogenesis of hypertension and
vascular disease in blacks consists of abnormalities in
sympathetic activity that, in turn, lead to concurrent
derangements of metabolic regulation and blood pressure.
Alternatively, the chronic pressor effect of augmented
adrenergic activity could occur as a sequela to the metabolic
derangement via the mitogenic effects of insulin or related
growth factors on the vasculature.
In the young, there are detectable racial differences in some
of these biochemical and physiologic parameters related to
hypertension in black adults. Black children have lower
rates of aldosterone excretion and lower urinary kallikrein.
Racial differences have been reported in cardiovascular
responses to sympathetic stimuli in childhood. The Bogalusa
Heart Study has demonstrated racial differences in
cardiovascular development in the young. Black adolescent
males have greater vascular resistance and there is
echocardiographic evidence of hypertensive changes in cardiac
structure at blood pressure levels in the upper quartiles of
the normal blood pressure distribution. Thus, another
question is whether or not a metabolic process is directing
early vascular changes, the rise in blood pressure occurring
concomitantly as a consequence of increased peripheral
vascular resistance.
It is also important to note that there are indications that
differences in the prevalence and effects of hypertension may
be associated with gender. Premenopausal women, at any
arterial pressure, have a total peripheral resistance that is
lower than men of the same chronological age. Furthermore,
clinical and epidemiological studies show essential
hypertension to result in lower mortality in women than in
men. To complicate these findings, black women show higher
prevalence of hypertension than white women, particularly as
age increases, and black women have a higher prevalence of
obesity - a risk factor for hypertension - than do black men.
Little attention has been paid to fundamental differences
between males and females regarding homeostatic mechanisms
that determine arterial blood pressure, vascular tone, and
resistance.
Finally, there is evidence that a significant component of
the hypertensive state is inherited. Molecular genetic
approaches utilizing family studies (genetic linkage) offer
new approaches for dissecting out the genetic components of
hypertension by providing DNA-based markers. These genetic
markers can lead to a cascade of important and illuminating
findings on the molecular and pathophysiological bases of
hypertension by providing direct access to the altered genes
in suitably configured American black families.
The choice of phenotype is central to the success of genetic
linkage analysis. The clearest possible results occur with
the use of a discrete, reproducibly measurable trait that can
distinguish affected individuals from non-affected
individuals. Blood pressure measurements are difficult to
use for phenotype characterization because blood pressure is
unimodally distributed throughout the population, varies in
its day-to-day levels, and is subject to other influences,
such as alterations with age. One way to minimize this
difficulty is to use "intermediate phenotypes" that are
commonly associated with the hypertensive state and have a
major gene effect. Some examples that may prove feasible
include cationic transport measurements, hormone levels, and
challenge-response tests.
Another way to minimize the problems associated with the use
of blood pressure as a phenotype is to do linkage studies
with sibling-pairs. This approach is advantageous for a
variety of reasons: there are no assumptions about the mode
of inheritance; it is possible to minimize some variability
effects (for example, the investigator could study siblings
who were all about the same age); there are a lot of
siblings, and they are easier to locate and recruit than
extended families. Although not as powerful as linkage in
extended families, this is a viable approach that operates
under the assumption that siblings have inherited the same
genetic predisposition.
OBJECTIVES AND SCOPE
Further research is needed to investigate the mechanisms
underlying the excessive prevalence, morbidity, and mortality
of hypertension in blacks, and to determine the mechanisms
that may underlie disparate findings between black women and
men. Recent data have identified racial differences in
biochemical, neural, endocrine, and hemodynamic function.
Further investigations are needed to fill the gaps in
understanding the pathways that link these biochemical,
neuroendocrine, or physiologic variations with progressive
hypertensive disease in blacks.
A number of examples of suitable research approaches are
given below. These are meant to be illustrative only, and
are not in any way meant to exclude other MECHANISTICALLY
oriented topics.
o elucidate pathophysiological mechanisms underlying
excessive prevalence, morbidity, and mortality in blacks
o examine gender-related mechanisms associated with the
development of hypertension in blacks
o build on observational data to develop and test
mechanistically oriented hypotheses, such as hypertension in
blacks is primarily:
a. a disorder of membrane transport systems with major
sequelae cascading from altered handling of calcium by
vascular smooth muscle cells
b. a renal disorder characterized by an impaired
ability to efficiently excrete a sodium load
c. a metabolic problem, such as insulin resistance and
hyperinsulinemia, that leads to increased peripheral
vascular resistance
d. a neurogenic abnormality, leading to altered
adrenergic sensitivity
e. an endocrine defect that diminishes vasodilation or
augments vasoconstriction
o initiate studies to determine specific gene
abnormalities responsible for this polygenic disorder in
black families and use this knowledge to elucidate
molecular, biochemical, and pathophysiological mechanisms.
This approach would include studies to select and identify
appropriate, black family configurations (for example,
sibling-pairs or pedigrees); to phenotypically characterize
their members, to collect, analyze, immortalize, and store
cell lines from these individuals; and to use the DNA to
identify markers and genes for hypertension.
MULTIDISCIPLINARY APPROACHES, STUDY DESIGN, AND INCLUSION OF
WOMEN
Due to the multifactorial nature of the disease, a
combination of disciplines would be appropriate. Relevant
disciplines may include, but are not limited to:
biochemistry, physiology, genetics, molecular biology,
cardiology, nephrology, endocrinology, neurology,
pharmacology, cellular and structural biology. Similarly,
multiple designs and groups (young, middle age, elderly) may
be appropriate. Studies, which may combine disciplines,
should incorporate into the investigative design controls for
age, body mass, and environmental factors.
Investigators should be aware that NIH requires applicants to
give added attention, where feasible and appropriate, to the
inclusion of women in study populations. Gender differences
must be noted and analyzed whenever possible. If women are
not included in a given study, a clear reason for their
exclusion must be provided. Merely including an arbitrary
number of women participants in a given study is insufficient
to guarantee generalization of results.
Collaborative work may involve individuals from within an
institution or it may be inter-institutional.
EXCLUSIONS
Although multidisciplinary approaches are encouraged, it is
not the intent of this announcement to solicit applications
for large studies that would encompass a variety of
independent projects, i.e., program projects. This program
will not support clinical trials or large epidemiological
studies. In general, funds will not be provided for the
purchase and installation of expensive, new equipment.
Awards under this announcement to foreign institutions will
be made only for research of very unusual merit, need and
promise, and in accordance with Public Health Service policy
governing such awards.
MECHANISM OF SUPPORT
The support mechanism for this program will be the
traditional, individual research grant. Although
approximately $1.5 million in total costs for this program is
included in the financial plans for fiscal year 1991, award
of grants pursuant to this RFA is contingent upon receipt of
funds for this purpose. It is anticipated that 4 to 6 grants
will be awarded under this program. The specific number to
be funded, however, will depend on the merit and scope of the
applications received and the availability of funds. Because a
variety of approaches would represent valid responses to this
announcement, it is anticipated that there will be a range of
costs among individual grants awarded.
Upon initiation of the program, the Division of Heart and
Vascular Diseases will sponsor periodic meetings to encourage
exchange of information among investigators who participate
in this program and to stimulate collaboration. Applicants
should request ADDITIONAL TRAVEL FUNDS for a one-day meeting
each year, most likely to be held in Bethesda, Maryland.
Applicants should also include a statement in their
applications indicating their willingness to participate in
these meetings.
Applicants, who will plan and execute their own research
programs, are requested to furnish their own estimates of the
time required to achieve the objectives of the proposed
research project. Up to FIVE YEARS of support may be
requested. At the end of the official award period, renewal
applications may be submitted for peer review and competition
for support through the regular grant program of the National
Institutes of Health (NIH). It is anticipated that support
for the present program will begin in September 1991.
Administrative adjustments in project period and/or amount of
support may be required at the time of the award.
If collaborative arrangements involve sub-contracts with
other institutions, the NHLBI Grants Operation Branch should
be consulted regarding procedures to be followed (Tel: 301-
496-7257).
All current policies and requirements that govern the
research grant programs of the NIH will apply to grants
awarded under this RFA.
REVIEW PROCEDURES AND CRITERIA
Review Method: All applications submitted in response to
this RFA will be evaluated for scientific and technical merit
by an initial review group, which will be convened for this
purpose by the Division of Extramural Affairs, NHLBI. Upon
receipt, applications will be reviewed for their
responsiveness to the objectives of this RFA. If an
application is judged unresponsive, the applicant will be
contacted and given the opportunity to withdraw the
application, or have it considered for the regular NIH grant
program.
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 that 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 which 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.
Review Criteria: The factors to be considered in the
evaluation of scientific merit of each application will be
similar to those used in the review of traditional research
project grant applications, including:
o the novelty, originality, and feasibility of the approach
and the adequacy of the experimental design, including the
suitability and composition of the study population
o the competence of the Principal Investigator and
collaborators to accomplish the proposed research, and the
commitment and time they will devote to the project
o the suitability of the facilities to perform the proposed
research, including laboratories, instrumentation, and data
management systems
o the appropriateness of the requested budget for the work
proposed
o adequate plans for interaction and communication of
information and concepts among investigators involved in
collaborative studies
METHOD OF APPLICATION
Letter of Intent: Prospective applicants are asked to submit
a letter of intent that
includes the names of participating institutions and all
investigators, together with a descriptive title. Such a
letter of intent is not binding and will not enter into
the review of any application subsequently submitted, nor is
it a necessary requirement for application. Letters of
intent are requested solely for planning purposes. The NHLBI
Staff will not provide responses to such letters. Letters of
intent should be received no later than
March 6, 1991, and be addressed to:
Dr. Charles L. Turbyfill
Review Branch
Division of Extramural Affairs
National Heart, Lung and Blood Institute
Westwood Building, Room 553
National Institutes of Health
Bethesda, MD 20892
Format for Applications: Submit applications on form PHS-398
(revised 10/88), the application form for the traditional NIH
research project grant. Copies of this form are available in
the applicant institution's office of sponsored research, or
may be obtained from:
Office of Grants Inquiries
Division of Research Grants
Westwood Building, Room 449
National Institutes of Health
Bethesda, MD 20892
Use the conventional format for research project grant
applications and ensure that the points identified in the
section above on "Review Procedures and Criteria" are
fulfilled. To identify the application as a response to this
RFA, CHECK "YES" on item 2 of page 1 of the application and
enter the title "Mechanisms of Hypertension in Black Men and
Women" and enter the RFA number HL-91-01-H in the space
provided.
THE RFA LABEL FOUND IN THE FORM PHS-398 APPLICATION KIT MUST
BE AFFIXED TO THE BOTTOM OF THE FACE PAGE OF THE ORIGINAL
COMPLETED APPLICATION FORM PHS-398. 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.
Application Procedure: Send or deliver the completed, signed
application and four (4) complete photocopies of it to the
following, making sure that the original application with the
RFA label attached is on top:
Division of Research Grants
Westwood Building, Room 240
National Institutes of Health
Bethesda, MD 20892**
SEND TWO ADDITIONAL COPIES OF THE APPLICATION TO DR. CHARLES
TURBYFILL AT THE ADDRESS LISTED UNDER "LETTER OF INTENT". IT
IS IMPORTANT TO SEND THESE TWO COPIES AT THE SAME TIME AS THE
ORIGINAL AND FOUR COPIES ARE SENT TO THE DIVISION OF RESEARCH
GRANTS, OR THE NHLBI CANNOT GUARANTEE THAT THE
APPLICATION WILL BE REVIEWED IN COMPETITION FOR THIS RFA.
Applications must be received by April 8, 1991.
An application not received by this date will be considered
ineligible.
Timetable:
Letter of Intent March 6, 1991
Application Receipt Date April 8, 1991
Review by National Heart, Lung,
and Blood Advisory Council September 12-13, 1991
Anticipated Award Date September 30, 1991
Inquiries: Inquiries regarding this announcement may be
directed to:
Dr. Stephen C. Mockrin
Chief
Hypertension and Kidney Diseases Branch
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
Federal Building, Room 4C10
National Institutes of Health
Bethesda, MD 20892
Telephone: (301) 496-1857
Fax: (301) 496-9882
*This program is described in the Catalog of Federal Domestic
Assistance number 93.837, Heart and Vascular Diseases.
Awards will be made under the authority of the Public Health
Service Act, Section 301 (42 USC 241) and administered under
PHS grant policies and Federal regulations, most specifically
42 CFR part 52 and 45 CFR part 74. This program is not
subject to the intergovernmental review requirements of
Executive Order 12372 or to review by a Health Systems Agency.
ANIMAL RESOURCES PROGRAM
INFORMATION FOR APPLICANTS
RFA: RR-91-01
P.T. 34; K.W. 1002002, 1014006
DEVELOPING AND IMPROVING INSTITUTIONAL ANIMAL RESOURCES
An Administrative Document Issued By:
Animal Resources Program
National Center for Research Resources
National Institutes of Health
Department of Health and Human Services
This is a reissuance of the Request for Applications (RFA)
RR-90-02, which was
originally
published in the NIH Guide for Grants and Contracts (Volume 19,
Number 18, May 4, 1990, and clarified in Volume 19, Number 21,
June 8, 1990).
A related RFA, "Animal Facility Improvements for Small Research
Programs," RR-90-03 was published in the NIH Guide for Grants
and Contracts on August 14, 1990, Vol. 19, No. 31.
INTRODUCTION
The Animal Resources Program (ARP) of the National Center for
Research Resources (NCRR), National Institutes of Health (NIH),
assists institutions in developing and improving animal
resources for biomedical research and research training through
the award of research and resource grants. For the purpose of
this program, animal resources are defined as all animals and
the associated animal facilities and staff that support biomedical
research activities. This document relates to institutional
animal resource improvement projects that will be supported
with funds anticipated to be made available to the Department
of Health and Human Services (DHHS) in Fiscal Year 1991 for
this activity. Other types of projects supported by ARP
include developing and defining animal models, animal resource
laboratories, and research and training related to laboratory
animal science and medicine. Additional information on these
latter grant programs may be requested from the Animal
Resources Program, NCRR (see address at end of this document).
RESEARCH GOALS AND SCOPE
Animal resource improvement grants are awarded to assist
biomedical research and educational institutions in upgrading
their animal facilities and in developing administratively
centralized programs of animal care. Another major objective
is to enable institutions to comply with the USDA Animal
Welfare Act and DHHS policies related to the care and use of
laboratory animals. Requests should describe a discrete
project, the total cost of which is no greater than
approximately twice the PHS request. If this project is part
of a larger renovation plan, the larger plan can be described
in the body of the grant. Requests are limited to alterations
and renovations (A&R) to improve laboratory animal facilities
and major resource equipment related to the improvement, such
as animal cage systems and cage washers. Large pieces of basic
equipment for centralized surgeries or diagnostic laboratories
are allowable if well justified. This improvement grant is not
intended to provide general operational support for the
resource (e.g., funding for personnel, consumable supplies for
routine animal care, or small equipment items) or to provide
specialized research equipment or facilities for use by only a
few investigators. To gain approval and support, both the need
for resource improvements and a sound plan to bring the entire
animal resource up to required standards must be demonstrated
and well-described in the context of the biomedical research
programs of the institution.
ELIGIBILITY AND SUPPORT
NCRR anticipates that $9.4 million may be available to support
animal resource improvement grants in Fiscal Year 1991. It is
anticipated that approximately 40 grant awards will be made.
The number and specific amounts of these awards will depend on
the merit and scope of the applications received and the
availability of funds. Awards will be made for a project
period of one year. All policies and requirements which govern
PHS grant programs will apply.
Any domestic public or private institution, organization, or
association with one or more research projects supported by the
Public Health Service (PHS) that involve the use of laboratory
animals is eligible to apply. For the purposes of this
program, an institution is defined as the organizational
component covered under a single Biomedical Research Support
Grant code. Separate applications may be submitted from
different colleges or schools on the same campus of a
university within the same fiscal year. However, if this is
done, documentation from an appropriate institutional official,
stating that the applications are part of a coordinated,
campus-wide plan to improve the animal facilities must be
provided. The applicant institution is strongly encouraged to
develop a single proposal for a campus-wide program with a
single, centralized animal care program whenever possible.
The total request for PHS support and the award are limited to
$700,000. Within this limit, the equipment request may be of
any size, but the A&R portion cannot exceed $500,000. Matching
funds from non-Federal sources, and equal to the total award,
are required. These matching funds must be applied to the
specific project described in the application and cannot be met
by citing other expenditures. A letter of assurance of
matching funds and the projected source of these funds, signed
by the responsible institutional official, must be included in
the body of the application. Support for construction is not
authorized.
REVIEW PROCEDURES AND CRITERIA
Applications will be received by the Division of Research
Grants (DRG). There will be a single receipt date of February
12, 1991. Applications received after this deadline will be
returned without further processing. All applications
submitted in response to this RFA will be reviewed for
scientific merit by an appropriate review committee managed by
the Office of Review, NCRR, and by the National Advisory
Research Resources Council for program considerations. Final
funding decisions will be made during the summer of 1991.
Review of animal resource improvement projects will be based on
the request itself, as well as on the entire animal resource
program of the submitting institution. Factors entering into
the appraisal of an animal resource improvement project
include:
A The Improvement Request
1 Need - Evidence of the need of resource grant support for
improvements for the institution to meet or maintain
the standards of the Animal Welfare Act and DHHS policies on
the care and use of animals should be demonstrated. The amount
and source(s) of funding for animal-related biomedical research
utilizing the resource will also be evaluated.
2 Procedural Plans - Evidence of institution-wide planning to
assure a comprehensive and acceptable research animal program
will be evaluated. The specific methods proposed will be
judged for scientific and technical soundness and their ability
to meet the applicable standards.
3 Budget - The budget will be evaluated in relationship to the
responsiveness to the RFA, justification provided for each of
the requested items, cost effectiveness and institutional
commitment.
4 Animal Welfare - The extent to which the project will
enhance the welfare of animals maintained in the facility to be
served by the resource will be an important part of the
evaluation. An assessment of the benefit of the improvements
to the welfare of animals in the facility, including advances
in the humane treatment of the animals due to husbandry changes
allowed by the improvements, should be described. Increases
above the minimum space recommendations for laboratory animals
(as set forth in the Guide for the Care and Use of Laboratory
Animals, (Guide), HHS, NIH Publication No. 85-23, 1985 edition
or succeeding revised editions), may be requested by the
applicant from the ARP, NCRR office noted later in this
document. The overall application will be evaluated for its
scientific merit, technical soundness, and cost effectiveness.
B The Animal Resources Program
The scope of coverage of the animal resources program to be
enhanced by this facility improvement request should be
carefully defined. Normally, it should cover the applicant
institution.
1 Animal Care - The quality of the animal husbandry program
will be assessed, including training of the animal technical
staff, housing, caging, feeding, record keeping, sanitation,
and other animal care practices. Consideration of the animal
health program will include clinical services, laboratory
support, preventive medicine programs, and any relevant
specialized procedures.
2 Personnel - The adequacy of the staff will be evaluated.
There should be a sufficient number of professional staff with
appropriate qualifications to operate the animal resource in a
competent manner. Provisions should be made for an adequate
number of appropriately trained non-professional staff and
supporting services. An appropriate preventive health program
should be in place.
3 Administrative Arrangements - An evaluation will be made of
the administrative arrangements for planning and day-by-day
management of the animal resource. There should be a sound
plan for financial support of the resource, through a recharge
system, per diems, institutional support, or other means. Previous
expenditures by the institution for capital improvements of the
animal resource program should be described.
4 Resources and Environment - The suitability of the
institutional setting for achieving the goals of the program
will be considered. This will include an appraisal of the
academic environment and the support for the animal resource by
the administration and faculty. The adequacy of the physical
environment, buildings, and equipment for the animal resource
will be evaluated.
APPLICATION PROCEDURES
There will be a single receipt date of February 12, 1991.
Applications received after this date will be returned to the
applicant. Applications must be submitted on Form PHS 398
(Rev. 10/88), the application form used for research grants.
Application kits can be obtained from most institutional
business offices, or from the Division of Research Grants, NIH
(see address below). The RFA label included in 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 format and details
applicable to regular research grant applications should be
followed, except for the following:
SECTION 1
A Face Page of the Application - Item 2 - Check the box marked
"yes" and type in the number and title of this RFA (RFA RR-91-
01, "Developing and Improving Institutional Animal Resources").
Item 5 - Check the box marked "No" at Item 5a. Item 5b - Not
applicable. Item 7 - This figure refers to the direct costs
requested from the PHS only and should not include the required
matching dollars.
B Key Personnel - Application Page 2 - Only key personnel
should be listed here. This must include the chief or
attending veterinarian, and may include the principal
investigator, additional veterinarians, director of the animal
facility, or chief animal technician, as appropriate.
Biographical sketches must be provided for all people listed.
C Table of Contents - Indicate page numbers for all major
headings outlined under Section 1 and Section 2, Research Plan.
This is an important aid in the review process for the
application.
D Detailed Budget - Application Page 4 - The total request for
PHS support may not exceed $700,000. Of this, the request for
A&R may not exceed $500,000. Matching funds, equal to the
total award and from non-Federal sources, are required.
Personnel Category - List only those individuals who will spend
time on the execution of the facility improvement project and
the time needed for this project. Salary support should not be
requested.
The requested budget should be limited to items of major
equipment for animal care, or other aspects of facility
function, and A&R. Equipment should be classified as movable
or fixed using the institution's classification guidelines as
provided by the institution's Business Office. Fixed equipment
is considered as part of the A&R request. Small equipment
items costing less than $1,000 per manufacturer's unit should
not be requested. This includes multiple polycarbonate rodent
cages for replacement or change-out purposes. However, as an
exception to this, microisolator cages are acceptable if an
appropriate change station is also purchased or already
available. To avoid deletion, requests for items that may
require the purchase of small component parts, e.g., a rack and
cages, should be priced as a single item, but a description of
the individual components must be provided (see below).
Large pieces of basic surgical equipment, such as tables,
lights, and gas anesthesia machines may be requested if the
operating room is an integral part of the animal facility and
is available to all investigators. Such a request must be
justified by listing the number of investigators, case load,
and types of surgeries involved. Similarly, basic diagnostic
equipment to be used in support of the animal facility, but not
for research, will be allowed if adequate justification is
given. Office equipment (including data processing items), and
research equipment should not be requested. Physical security
systems are not allowable, but systems for environmental
monitoring are acceptable.
Each major equipment item must be fully described. The
manufacturer, model number, size, capacity, or design criteria,
total unit cost and facility where it will be used must be
given. This information should be provided on a separate page
immediately following the budget. It should not be in an
appendix.
On the budget page the total cost of the equipment and A&R
needed for the discrete project described should be given in
the rectangular space under the appropriate headings on the
left. The right hand column should reflect only the PHS
request. The Total Direct Costs (bottom right hand column
total) should be the total application request to the PHS, not
including the required matching funds. These data should be
summarized in tabular form. (Contact the Animal Resources
Program at address below for suggested format.)
E Budget for Entire Proposed Project Period - Application,
Page 5 - Not applicable (do not complete this section).
F Justification - Application, Page 5 - Justification should
be provided in this section for all equipment items requested
in terms of the proposed improvement program. Failure to
adequately justify why each requested item is needed will
likely result in its deletion from the recommended budget.
More extensive justification may be provided in the body of the
narrative (SECTION 2, D.2.f.). As part of the justification,
information such as the species and number of animals, cages,
tests or surgeries involved, should be provided as
appropriate. The location and use of each piece of equipment
should be clearly described. The failure to adequately justify
equipment items has been a major weakness of applications in
the past.
G Summary Sheets - (Contact the Animal Resources Program at
address below for suggested format.) These sheets have been
developed to assist investigators in the preparation of the
application as well as to assist the reviewers in their review
of the application. They should be completed and placed
between the Budget Justification and the Biographical Sketches
section of the application.
H Letter of Assurance - Provide assurance of matching funds
for the total PHS award and the projected source(s) and amount
of these funds in a separate letter or memorandum signed by a
responsible institutional official. This letter should be
placed before the start of SECTION 2.
SECTION 2 Research Plan
The points identified under Review Procedures and Criteria
should be considered when this section is prepared. All
information critical to the review should be in SECTION 2, and
not in an appendix. Please note the instructions on Page 20 of
Form PHS 398 concerning the limitation of 20 pages for Sections
A-D of the Research Plan.
A Specific Aims - (Limit to 1 page) Clearly present the aims
of the animal resource improvement project and relate them to
the short- and long-term goals of the institution's animal
resource program.
B Background and Significance - (Limit to 2-3 pages) This
section should demonstrate the institution's overall
involvement in animal related research. In addition, the
following current information should be provided as shown on
the sample Data Sheet (contact the Animal Resources Program at
the address below for sample Data Sheet): 1) the institution's
total annual research budget that involves the use of animals;
2) the annual dollar level of support (direct costs) from PHS
vs. non-PHS sources that make up this budget; and 3) the
institution's total number of projects using laboratory
animals. Failure to provide these data will weaken the
application.
This section should also be used to relate the significance of
the proposed resource improvement project to the institution's
overall biomedical research programs as well as to the
individual research projects that will be affected. If the
resource will be used by a relatively small number of research
projects, a brief description of those projects, including the
source and amount of funding on an annual basis for each, must
be indicated.
C Progress Report/Preliminary Studies - Not applicable.
D Experimental Design and Methods - This section should
provide an overall description of the institution's animal care
and use program. It should also demonstrate how the proposed
facility improvement program will enhance the resource and how
it fits into the institution's overall plan to meet or maintain
PHS standards for animal care and use. The equipment items
requested may be justified further in the context of the
overall animal care program as part of this narrative. The A&R
request should be described/justified as indicated in Paragraph
2.g. below.
1 Introduction - Provide relevant background information and a
description of the current status of the institution's animal
resource facilities and program as they relate to biomedical
research and research training. Include relevant information
regarding current deficiencies in the animal care program as
cited by the American Association for Accreditation of
Laboratory Animal Care (AAALAC), the Institutional Animal Care
and Use Committee (IACUC) facility review reports, and the
institution's PHS Animal Welfare Assurance Statement. Any
problems in meeting the provisions of the Animal Welfare Act
should also be addressed. This information is important for
documenting the need for facility improvement support.
2 Project Plan - This section should describe how the
requested improvements will accomplish the Specific Aims
presented in Item A. It is important to describe how the
requested improvements will correct the deficiencies and
problems documented above. If the project is part of an
overall larger facility improvement plan, the larger plan and
how the project fits into it should be described. This section
should also include a description of the following aspects of
the animal resource:
a Administrative arrangements and structure of the animal
resource. The lines of authority and responsibility for
administering the institution's program for the care and use of
animals should be clearly presented. The role and composition
of the IACUC and how compliance with relevant laws, policies,
and guidelines is achieved should be included. If this
proposal encompasses several institutions in a campus-wide
program, the planning process that resulted in this proposal
should be described.
b Animal care procedures and the animal health program. This
section should include information concerning veterinary
oversight, vendor surveillance, conditioning programs, colony
and environmental monitoring, and diagnostic capabilities in
anatomic pathology, clinical chemistry, hematology, and
microbiology. The general description of the animal care
program should be supported by data that characterize various
activities, such as numbers of laboratory procedures for
monitoring and disease diagnosis, veterinary inspections for
animal health, etc. If specialized equipment, such as
microisolators, are requested, they should be part of an overall
system, and the husbandry program to utilize this equipment
should be carefully outlined. Failure to carefully describe
the basic program of animal care, including veterinary care,
has been a major weakness of many applications.
c Outline the total staff and functional organization of the
animal resource, both current and planned, following the
requested improvements. Outline the qualifications of the
animal care staff and the training opportunities available to
them.
d List all financial support for the animal resource,
including sources and amounts (e.g., recharge, core funding
from the institution, etc.) and the operating budget (listed by
major categories). Provide a copy of per diem and service
charge schedules and indicate their method of determination.
The latter information may be included in an appendix.
e Expenditures for capital improvements (facilities and
equipment) during the past five years and future plans for such
needs should be described. Any previous support for
improvement of the institution's animal facilities from the
ARP, NCRR should be noted. How the support was utilized and
the effect on the animal care program should be described
briefly.
f Provide a brief description of all campus and off-campus
animal facilities, including sites where experimental surgery
is performed. Indicate the person responsible for the
direction and day-to-day management of each animal facility.
In this section, the need for specific items of equipment, in
relation to the various facilities where they will be located,
should be justified (See D.2.g. below for A&R). The reason for
the need, the facility that will benefit, and the ultimate
improvement of the overall animal care program should be
clearly evident. As shown on the sample Data Sheet (contact
the Animal Resources Program at address below for sample Data
Sheet), indicate the number of animals (by species) used or
produced per year, and the average daily census for each major
component of the animal resource. If equipment is requested
for surgical or diagnostic facilities, the case load, species,
and types and numbers of surgeries or diagnostic tests must be
documented on the Data Sheet. These data are important to the
evaluation of the application, as well as for the justification
of need.
g For any proposed A&R, a narrative summary (as outlined
below), line drawings, and cost estimates must be included.
(Contact the Animal Resources Program at address below for
sample format.) If multiple sites are involved, the A&R,
including cost estimates proposed for each site, should be
described separately for each site. The following narrative
format should be followed:
Narrative Summary
(1) Relate the proposed renovation to projected animal
populations by the species and research projects that will
utilize the facility. Daily and annual census data (by
species) must be provided. The animal care and use program for
the animal facility that is to be renovated must be well
described in D.2.b., Animal care procedures and animal health
plan.
(2) List the functional components, size, and square footage
of each component (room, alcove, cubicle, etc.) that will be
directly affected by the renovation project.
(3) List engineering criteria applicable to each component
(mechanical, electrical, and utilities). Include information
such as the number of air changes per hour, electrical power,
light levels, hot and cold water, and steam.
(4) List appropriate architectural criteria, such as width of
corridors and doors, and surface finishes.
(5) List all fixed equipment requested for the renovated area.
(6) List all movable equipment requested for the renovated
area.
Line Drawings (On 8-1/2" x 11" paper only, DO NOT SUBMIT
BLUEPRINTS). These drawings will not be considered within the
20 page limit for Section 2.
All floor plans must be legible, with the scale clearly
indicated.
(1) The plot plan should indicate the location of the proposed
renovation area in the building.
(2) Include the as-built drawings of the proposed renovation
area and indicate any demolition.
(3) Provide the architectural plan(s) of the proposed
renovation. The plans should indicate size (dimensions),
function, and net and gross square feet of space for each room.
The total net and gross square feet of space to be renovated
should also be given.
(4) Changes or additions to existing mechanical and electrical
systems should be clearly narrated in notes made directly on
the plan or attached to the plan.
(5) A Finish Schedule which indicates the type of new finishes
to be applied to room surfaces should be included in the plan.
SECTION 3 Appendix Material
All information critical to the review must be included in
Sections 1 and 2 of the application. Be very selective and
include only relevant supplementary information in the
appendix. Do not include standard references or other
generally available information. Six collated sets of the
appendix material must be included in the application package.
All appendix material must be identified with the name of the
Principal Investigator and the institution. Do not mail this
appendix material separately, but include it with the original
grant application.
SUBMISSION PROCEDURE
1 The completed original application and four copies including
appendix material should be mailed or delivered to:
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892**
2 An additional two copies of the application and appendix
material should be mailed to:
Dr. Arthur Schaerdel, Executive Secretary
Office of Review
National Center for Research Resources
National Institutes of Health
Westwood Building, Room 10A16
5333 Westbard Avenue
Bethesda, MD 20892**
3 Inquiries about specific instructions for application and
other aspects of the program should be directed to:
Animal Resources Program
National Center for Research Resources
National Institutes of Health
Westwood Building, Room 857
5333 Westbard Avenue
Bethesda, MD 20892
Telephone: (301) 496-5175
4 Application forms (PHS 398) may be obtained from grantee
business or sponsored projects offices or from:
Office of Grants Inquiries
Division of Research Grants
National Institutes of Health
Westwood Building, Room 440
5333 Westbard Avenue
Bethesda, MD 20892
Telephone: (301) 496-7441
** The mailing address given for sending applications to the
Division of Research Grants or contacting program staff in the
Westwood Building is the central mailing address for the NIH.
Applicants who use express mail or a courier service are
advised to follow the carrier's requirements for showing a
street address. The address for the Westwood Building is: 5333
Westbard Avenue, Bethesda, Maryland 20816.
This program is described in the Catalog of Federal Domestic
Assistance No. 93.306, Laboratory Animal Sciences and Primate
Research. Awards will be made under the authority of the
Public Health Service Act, Title III, Section 301 (Public Law
78.410, as amended; 42 USC 241) and administered under PHS
grant 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 Health Systems Agency review.