kristoff@NET.BIO.NET (Dave Kristofferson) (11/10/89)
Vol. 18, No. 40, November 10, 1989 - Page 10
FULL TEXT OF RFAs FOR ONLINE ACCESS
INTERNATIONAL COLLABORATION IN
ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) RESEARCH (ICAR)
RFA-NIH-NIAID-89-AI-21
P.T. 34; K.W. 0715008, 0785055, 0710030
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
(NIAID)
Letter of Intent Date: December 15, 1989
Application Receipt Date: March 30, 1990
The NIAID invites applications for the expansion of the ICAR
program to link U.S. institutions to research units in
foreign countries with significant numbers of persons with
HIV infection but which may lack important features of the
research infrastructure or expertise necessary to conduct
epidemiologic research of HIV infection and disease,
including HIV-relevant opportunistic infections. Authority
for this international program is provided by Public Law 86-
610, the International Health Research Act of 1960. The
program focuses on infectious diseases and the immunology of
these diseases.
LETTER OF INTENT
Prospective applicants are encouraged to submit a
letter of intent by December 15, 1989, that includes a brief
description of the thrust of the research activities and the
names of the principal investigator and other key
investigators, if known, the U.S. institution, and the
foreign institution. The Institute requests such letters in
order to provide an indication of the number and scope of
applications to be received, permit early communication
between staff and the prospective applicant, and indicate
the research areas to be covered to allow early preparations
for expedited review. The letter of intent is not
binding, will not enter into the review of any application
subsequently submitted, and is not a requirement for
application. The letter of intent should be sent to:
Ms. Amy R. Sheon
Epidemiology Branch
Division of AIDS
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 240P
Bethesda, MD 20892
Telephone number: (301) 496-6177
Correspondence sent to Ms. Sheon by overnight or courier
service should use Rockville, MD 20852 for the city, state,
and zip code.
I. Background
HIV infection is a major health problem in many developing
countries. Risk factors of infected persons may be
represented in quite different proportions than comparable
data suggest for industrialized nations. As much as 80
percent of HIV infection in Africa may be acquired through
heterosexual transmission, where risk factors include
multiple sex partners, contact with prostitutes, and history
of sexually transmitted diseases (Johnson and Laga, 1988).
Intravenous drug use, prostitution, and receipt of blood
products are major risk factors in Asian countries (Des
Jarlais and Friedman, 1988). Given the nearly 1:1 male-to-
female ratio of infection, transmission from mothers to
infants is particularly common in developing countries (Chin
and Mann, 1988). By contrast, 63 percent of adult male AIDS
cases reported in the United States in 1988 were in non IV
drug-using homosexuals or bisexuals. Of all adult AIDS
cases reported to the U.S. Centers for Disease Control (CDC)
through the end of 1988, only 9 percent have been in
females; children under 13 years account for about 2 percent
of cases reported to date in the U.S. (CDC, 1989).
Little is known about perinatally-acquired HIV infection.
In utero transmission has been documented from the presence
of virus in cord blood and from necropsies of aborted
fetuses. Intra-partum transmission is plausible due to the
newborn's exposure to maternal blood during both vaginal and
caesarian deliveries, although confirmation of such
transmission has been difficult. Post-natal transmission to
infants through breastmilk is probably rare but has been
documented (Ryder and Hassig, 1988).
AIDS in developing countries exhibits virologic and clinical
manifestations infrequently seen in the US. HIV-2 has been
reported from nearly a dozen West African and Caribbean
countries but is rare elsewhere. This virus, first
identified in 1985, has biological and epidemiological
characteristics similar to HIV-1, although there are
striking differences in its antigenic components and nucleic
acid composition (Clavel, 1987). While Kaposi's Sarcoma is
extremely rare in children with AIDS in the United States,
cases have been reported in African children (Rolfe and
Wels, 1987). Pneumocystis carinii pneumonia is among the
most common serious opportunistic infections faced by
persons with AIDS in the U.S. but is rare in Africa (Lucas, et
al, 1989).
In 1988, five ICARS were awarded to set up collaborative
research centers in countries with significant levels of HIV
prevalence but with some limitations in their research
infrastructures, including Brazil, Malawi, Mexico, Uganda,
and Zaire. The present initiative would locate 1-2
additional ICARS in developing countries not already
participating in the ICAR Program where available
information suggests that HIV infection is currently or soon
will be an important public health problem.
II. Research Objectives and Scope
The mission of the Division of AIDS (DAIDS) is to find ways
to prevent, treat, and cure HIV infection and AIDS.
DAIDS has a broad interest in the virology, immunology,
pathogenesis, epidemiology, diagnosis, treatment, control
and prevention of HIV infection. Of special programmatic
interest is perinatal and pediatric infection and
heterosexual transmission; variability in HIV isolates in
different geographic areas and correlation with clinical and
epidemiologic factors; potential role of co-factors in
transmission or natural history; and similarities and
differences in clinical and epidemiologic presentation of
disease in different geographical areas.
The ICAR seeks to establish collaborative research
initiatives between U.S. and collaborating country (host)
investigators to conduct research of recognized relevance to
the health of people in both countries. It is intended that
the effort give priority to the development of self-
direction and self-sufficiency of the collaborating foreign
laboratory and clinical investigators. The present
initiative will permit a wide range of investigations
including, but not limited to the following:
A. study of the natural history of HIV infection
B. identification of risk groups and risk behaviors
associated with transmission
C. establishment of seroprevalence and
seroincidence rates among selected populations
D. evaluation of the immunological parameters that
affect either the susceptibility to infection
among the uninfected or the infectivity among
the infected
E. assessment of the efficacy of prevention
strategies
F. investigation of the routes of transmission in
perinatally acquired infection
G. identification of early biological or clinical
markers of HIV infection and HIV disease in
adult and pediatric cases
Safeguarding the rights and welfare of individuals who
participate as subjects in research activities supported by
the U.S. Department of Health and Human Services is of
paramount importance. Applicants are urged to pay
particular attention to the instructions for
compliance with regulations concerning the protection of
human subjects contained in the Instructions for PHS 398 (rev. 10/88),
including convening an Institutional Review Board (IRB) in
the host country and developing appropriate consent forms in
compliance with DHHS regulations.
MINORITIES AND WOMEN
The NIH in general, and the NIAID in particular, place
special emphasis on the need for inclusion of individuals
belonging to those ethnic groups that are considered to be
disenfranchised or underprivileged in studies of diseases
which disproportionately affect them. Applicants are urged
to give special attention, where feasible and appropriate,
to the inclusion of these groups in these studies. It is
understood that the majority of the study population in the
ICARS will, by definition, be comprised of populations which
are in a minority in the U.S., which NIAID considers as
supportive of an important objective of the Institute. In
addition, NIAID urges the applicants to make a special
effort to recruit women into study populations, and to
devote ICAR resources to studying gender-related issues in
HIV infection and disease.
III. Additional Information
A. Definition of Program Project Grant
A program project grant is a mechanism to support a
broadly based multidisciplinary research program that
has a well-defined central research focus or
objective. A principal investigator (PI) representing
a U.S. institution is responsible for leadership of the
overall program. The application must document the
scientific and administrative competence of the PI
and provide evidence that the PI has had professional
experience in the host country. The program project
grant consists of three or more interrelated sub-
projects that contribute to the program objective.
Each of these scientifically meritorious sub-projects
usually is under the leadership of a co-investigator,
referred to as a project leader, who usually will be
on site in the host country.
B. Site of Research
Most of the research should be conducted in the
foreign country, and the funds should be allocated
between the U.S. and host country accordingly. At
least 70 percent of all direct costs should be spent
in the host country. Any application with below 50
percent of the funds spent in the host country will be
returned to the applicant without further review. Any
application with between 51 and 69 percent of funds
spent in the host country should include strong
justification for the reduced foreign allocation and
will be considered for acceptance on a case-by-case
basis. The U.S. Grantee institution is responsible for
developing a mutually acceptable affiliation with an
established university, research institute, federal or
state health department, hospital, laboratory, etc.,
in the host country. For an award to be considered,
the domestic applicant institution must include proof
of affiliation with a host country institution
offering to provide a base for project operations and
one or more host country collaborators specified as
co-investigators. The grant application will not be
reviewed unless proof of an acceptable foreign
affiliation is included; a letter of agreement signed
by a sanctioned representative of the host country
institution shall be accepted as proof of affiliation.
In addition, it will be necessary to provide
documentation that the government of the host country
approves of the affiliation and research plans and
will facilitate the duty-free importation of equipment
and supplies from the U.S. to the host country. Also,
it is essential that a plan for release of research
findings generated by the collaboration be included
with the application. It is anticipated that
publications resulting from such collaborative
research efforts will be co-authored by foreign and US
scientists and that the data will be available to
scientists both in the host country and in the U.S.
collaborating institution. The plan should
demonstrate that host country researchers will take
key roles in preparing, authoring, and presenting
scientific findings in national, U.S., and/or
international refereed journals and scientific
meetings.
The investigators should demonstrate awareness of
other pertinent bilateral or multilaterally-funded
research activities in the host country in order to
avoid duplication of effort or to take advantage of
biomedically-related research or program interventions
already underway.
C. Off-Site Facilities
The grant can provide support for common resources
(e.g. laboratory or clinical facilities) that are
utilized by two or more projects within the program
when such sharing facilitates the total research
effort in a cost-effective manner. Since this program
is covered by Public Law 86-610, existing facilities
may be renovated but new structures may not be
constructed.
The most successful international collaborations
incorporate a thorough integration of host and U.S.-
based researchers. It is expected that a core of
scientists from the U.S. institution would spend
six months to two years or more at the host
institution, collaborating with host country scientists
in working toward solutions to local health problems
associated with HIV infection. Senior scientists with
major institutional responsibilities in the U.S. would
be expected to spend shorter periods of time, e.g.,
one or two months at a time several times during the
course of the grant. Also, it is permissible to
support the travel of foreign professionals and
selected technical staff for short visits to the US
institution to obtain additional training.
D. Guest Scientists
To increase the exchange of scientific ideas and
expertise, it may be desirable to include one position
in the overall personnel projection for a guest
scientist from another domestic institution to spend
6-12 months of a sabbatical leave at a host country
institution. The nominated individual must have the
joint approval of the applicant organization, the host
country organization, the nominee, and the nominee's
home institution, and must have prior approval by the
NIAID.
IV. Administration
Limited support for administrative activities and
research endeavors at the U.S. institution are permitted
as long as at least 70 percent of the grant funds
(direct costs) are expended in the host country, as
discussed above. Recovery of indirect costs will be
based on the percentage effort expended by the grantee
personnel. Indirect costs will not be paid on any
expense incurred by the host country institutions.
Coach class travel, or the equivalent thereof, on U.S.
flag carriers must be used for international travel.
Travel, salary and fringe benefits, and allowances for
housing of U.S. personnel based in the host country will
be subject to the applicant organization's rules and
regulations.
Official approvals must be obtained as follows:
A. Staff of U.S.-based institutions who visit the
host country in connection with ICAR activities
must have the concurrence of the U.S. Embassy in
the host country prior to the visit.
B. Persons coming from other countries to visit the
host country on behalf of the applicant
institution also must have the concurrence of
the U.S. Embassy in the host country prior to
the visit.
C. A mechanism for approval by officials of the
host country for receiving visitors must be
developed and must be described in the proposal.
Requests for concurrence by the U.S. Embassy
must be requested no later than four (4) weeks
prior to commencement of travel.
Plans should be made for an orderly rotation of
domestic investigators visiting the host country base
that would not be disruptive to the ongoing research
program. For persons planning a prolonged residence
at the host country base, opportunities should be made
for periodic return visits to the parent or related
domestic institutions for training, program planning,
or data analysis and to attend relevant scientific
meetings. Consequently, domestic investigators based
overseas should have the opportunity to participate in
scientific forums inside and outside the host country.
A. Support Mechanism
Approved grants will be funded for up to five (5)
years. Long-term support is considered essential for
the development of projects that will fully utilize
the international medical experience of the individual
scientist and that develop effective linkages between
domestic and foreign investigators. However,
continued support will be based on the satisfactory
performance of the grantee as judged by progress
described in annual reports (including copies of
abstracts and papers submitted for presentation at
scientific meetings or for publication) and by
periodic site visits by NIAID program personnel.
The total cost per grant should be between $300,000
and $500,000 per year (including direct and indirect
costs). One (1) to two (2) awards shall be made
contingent upon the availability of funds and receipt
of a sufficient number of high quality applications.
This grant is anticipated to supply seed money for
attracting additional funding from other sources. It
is expected that the foreign investigators will be
encouraged, and assistance will be provided if
requested, in preparing grant applications to request
such outside support. Grantee institutions which have
demonstrated good progress during the project period
will be encouraged to reapply for a competing renewal
grant application.
V. REVIEW PROCEDURES
Before preparing an application, the prospective
applicant should carefully read the NIAID Information
Brochure on Program Project and Center Grants that
accompanies copies of this Request for Applications (RFA).
The Information Brochure contains special instructions
for preparing multi-project applications, review
procedures, review criteria and other important
information. It is important to follow the
instructions for
preparing the application as outlined in the
Information Brochure. Failure to do so may result in
an application with insufficient information for
appropriate scientific review.
Applications will be reviewed by NIAID staff to
determine administrative and programmatic
responsiveness to this RFA; those judged to be non-
responsive will be returned to the applicant without
review.
Those applications that are complete and responsive
may be subjected to a triage by an NIAID peer review
group to determine their scientific merit relative to
the other applications received in response to this
RFA. NIH reserves the right to withdraw from
competition those applications judged as non-
competitive and to so notify the applicants.
Those applications judged to be competitive for award
will be further reviewed for scientific and technical
merit by the AIDS Research Review Committee convened
by the Division of Extramural Activities, NIAID, during
July, 1990. The final level of review will be
provided by the National Advisory Allergy and
Infectious Diseases Council.
REVIEW CRITERIA
The application must be directed towards the
attainment of the stated programmatic goals (see
Section II, "Research Objectives and Scope").
Review criteria outlined in the NIAID Information
Brochure for Program Project and Center Grants will be
used by the scientific review group to evaluate
proposals. The following ADDITIONAL factors will be
considered in the scientific and technical review of
the application:
A. Relevance of applicant's objectives to
objectives of the RFA;
B. Documented commitment of collaborating
institutions and availability of host country
personnel;
C. Administrative experience and competence of
Principal Investigator in the development,
implementation, and management of comprehensive
research programs and documented capability of
Principal Investigator's institution to
coordinate the collaboration;
D. Familiarity of the principal investigator with
the investigators and facilities of the host
country institution, and the study populations;
E. Adequacy of existing physical facilities and
resources of the domestic and host country
institutions;
F. Applicant awareness of the NIH desire to include
women and minorities in study populations, and
sensitivity to the host country's culture and to
the protection of human subjects.
VI. METHOD OF APPLYING
The deadline for receipt of applications is March 30,
1990. Applications received after this date will be
considered as not responsive to this RFA and will be
returned without review.
APPLICATIONS THAT ARE NOT RECEIVED AS A SINGLE
PACKAGE FROM THE PRINCIPAL INVESTIGATOR AND THAT DO
NOT CONFORM TO THE INSTRUCTIONS CONTAINED IN THE PHS
398 (rev. 10/88) APPLICATION KIT WILL BE JUDGED NON-
RESPONSIVE AND WILL BE RETURNED TO THE APPLICANT.
The regular research grant application form PHS-398
(rev. 10/88) should be used and is available at most
institutional business offices or from:
Office of Grants Inquiry
Room 449 Westwood Building
Division of Research Grants
National Institutes of Health
9000 Rockville Pike
Bethesda, Maryland 20892
Submit a signed, typewritten original of the
application, including the Checklist, and six signed,
exact, single-sided photocopies, in one package to:
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, Maryland 20892**
If sending the application by overnight mail or
courier service, send the application to the above
address, but using 20816 as the Zip Code.
The RFA label available in the form PHS-398 (rev.
10/88) must be affixed to the bottom of the face page
of the original signed application. Failure to use
this label could result in delayed processing of the
application such that it may not reach the committee
in time for review.
TO ASSURE THE IDENTIFICATION OF YOUR APPLICATION WITH
THIS RFA:
The application form must have "International
Collaboration in AIDS Research (ICAR)" (RFA 89-
AI-21) typed on item 2 of the face page of the
application form; and
SUBMIT 17 EXACT COPIES OF YOUR APPLICATION DIRECTLY
TO:
Dr. Manuel J. Torres-Anjel
Executive Secretary
Epidemiology and Technology Transfer
Sub-Committee
AIDS Research Review Committee, AIDS
Section
Program Project and Review Branch
National Institute of Allergy
and Infectious Diseases
Westwood Building, Room 3A10
Bethesda, MD 20892
(301) 496-0818
If sending the application by overnight mail or
courier service, send the application to the above
address, but using 20816 as the Zip Code.
Inquiries regarding matters pertaining to the review
of this application or instructions in the brochure
should be directed to Dr. Torres-Anjel. Inquiries
regarding fiscal matters may be addressed to Ms. Mary
Kirker. Questions regarding responsiveness to the RFA
should be directed to Ms. Amy R. Sheon.
Ms. Mary Kirker
Grants Management Branch
International Health Section
Westwood Building, Room 710
Division of AIDS, NIAID, NIH
Bethesda, Maryland 20892
Telephone: (301) 496-7075
Ms. Amy R. Shoen
Epidemiology Branch
NIAID, NIH
6003 Executive Boulevard
Bethesda, Maryland 20892
Telephone: (301) 496-6177
REFERENCES
Centers for Disease Control: AIDS and human immunodeficiency
virus infection in the United States: 1988 update. MMWR
1989; 38 (4), May 12.
Chin J, Mann JM: The global patterns and prevalence of AIDS
and HIV infection. AIDS 1988; 2: S247-252.
Clavel F: Editorial review: HIV-2, the west African AIDS
virus. AIDS 1987; 1: 135-140.
Des Jarlais DC, Friedman SR: HIV and intravenous drug use.
AIDS 1988; 2: S65-S69.
Johnson AM, Laga M: Heterosexual transmission of HIV. AIDS
1988; 2: S49-S56.
Lucas S, Goodgame R, Kocjan G, Serwadda D: Letter: Absence
of pneumocystosis in Ugandan AIDS patients. AIDS 1989: 3:
47.
Rolfe M, Wels KHG: Letter: Kaposi's sarcoma in Zambian
children. AIDS 1987; 1: 259-260.
Ryder RW, Hassig SE: The epidemiology of perinatal
transmission of HIV. AIDS 1988; 2: S83-S89.
SPECIALIZED CENTERS OF RESEARCH FOR CHRONIC DISEASES OF THE
AIRWAYS, OCCUPATIONAL AND IMMUNOLOGIC LUNG DISEASES, AND
LUNG BIOLOGY AND DISEASE IN INFANTS AND CHILDREN
RFA 90-HL-01-L
P.T. 04, AA; K.W. 0715165, 0705065, 0785055, 1002004, 1003002, 1002034
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
Application Receipt Date: July 16, 1990
GENERAL INFORMATION
The Division of Lung Diseases (DLD) is announcing its Specialized
Centers of Research (SCOR) programs for new and renewal
applications in the following categories:
o Chronic Diseases of the Airways
o Occupational and Immunologic Lung Diseases
o Lung Biology and Disease in Infants and Children
These SCOR programs represent a concerted effort that
involves both clinical and basic research relative to the
etiology, diagnosis, pathogenesis and treatment of these
disorders.
The special features of SCOR grants include:
o They provide opportunities for investigators with mutual
or complementary interests to engage in multidisciplinary
research focusing on a specific respiratory disorder.
o Inherent in the SCOR program is a special interaction
between the SCOR director, the grantee institution and the
DLD. Funds specifically allocated in a
SCOR grant make it possible for investigators from different
SCORs to meet and discuss problems of mutual interest and to
participate in workshops addressing common research areas.
o The DLD's overall SCOR program and each SCOR grant
undergo periodic evaluation. The resulting reports of
progress are prepared for the information of the Pulmonary
Diseases Advisory Committee, the National Heart, Lung, and
Blood Advisory Council, and DLD
staff.
The requirements of SCOR grants include:
o Research efforts of the individual centers must emphasize
both basic science and clinical research, to assure that
advances in the basic sciences are translated rapidly into
clinical applications and that clinical needs will provide a
direction for the basic sciences. Therefore, applications
must include one or more research projects involving human
subjects, human materials, or both. Applications must also
include basic research projects which clearly relate to the
disease focus and which contribute to elucidation of
mechanisms underlying the disease, or to improved diagnosis
or management of the disease.
o Each SCOR must have a well-delineated organizational
structure and administrative mechanism to ensure a productive
research effort.
Because of the size and complexity of a SCOR, prospective
applicants are urged to take advantage of the opportunity to
consult with DLD staff early
in the preparation of the application (See Method of
Applying). To provide opportunity for such interactions, the
time frame for implementation of this program includes an
ample interval between the release of this announcement
(11/89) and the receipt date for applications (07/16/90).
BACKGROUND AND HISTORY OF THE SCOR PROGRAM
The SCOR program was initiated within the Division of Lung
Diseases in 1971 as a "Pulmonary SCOR". Since then, several
modifications and changes in program direction have been made
based on advice and recommendations from the Pulmonary
Diseases Advisory Committee. In the 1975 and 1980
competitions, the DLD SCOR program was announced in four
disease categories: chronic airways diseases, fibrotic and
immunologic lung diseases, pediatrics, and pulmonary vascular
diseases; in the 1985 competition the disease categories
were: chronic diseases of the airways, occupational and
immunologic lung diseases, respiratory diseases of neonates
and children and pulmonary vascular diseases. The program
expanded in 1977 with the solicitation for applications for
adult respiratory failure SCOR grants. Awards were made in
two new SCOR disease categories, cystic fibrosis and
cardiopulmonary disorders of sleep, following a national
competition in 1988. Therefore, new applications entirely
devoted to cystic fibrosis or cardiopulmonary disorders of
sleep will not be considered responsive to this solicitation
as these two topics are the subject of recent SCOR programs.
However, individual projects on these topics, if they fit
the theme of the center application, may be included in
response to this solicitation.
In preparation for the current competition, the DLD
conducted a series of workshops which included members of the
Pulmonary Diseases Advisory Committee, participants in SCOR
programs, and ad hoc advisors. Several recommendations made
during the workshops have been incorporated into this
announcement. For example, the change in the name of the
program "Respiratory Diseases of Neonates and Children" to
"Lung Biology and Disease in Infants and Children" was a
specific recommendation of the workshop participants.
Likewise, the scientific program examples under Objectives,
Research Goals and Scope of this announcement were
recommendations from these meetings.
One of the major recommendations from the workshops was to
combine the "Pulmonary Vascular Diseases" and "Adult
Respiratory Failure" SCOR programs into a single program.
This will not be possible as part of this solicitation as the
two programs are not in phase, therefore, the DLD will
invite the two current pulmonary vascular diseases centers to
submit two year renewal applications in response to this
announcement; they will compete for available funds (see
Mechanism of Support) with all new and renewal applications
that are submitted in the three disease categories included
in this announcement.
OBJECTIVES, RESEARCH GOALS AND SCOPE
Applications must be addressed to only one of the three
disease categories identified below to be acceptable for this
competition. A SCOR grant is a five-year program, therefore,
an applicant should submit a five-year plan for all the
projects. If a project can be completed in less than five
years, it should not be included in the application.
Applications may include longitudinal studies or
epidemiologic surveys if they are based on populations
already under study. The grant will not provide funds for
selection of new populations but will support appropriate
expansion of populations already being examined under an
existing SCOR or under some other program. The maintenance
of an ongoing study population, however, is not in itself
justification for funding a center.
Women and minority individuals should be included in the
study population; otherwise, a clear rationale for their
exclusion must be provided in the application.
Examples of research topics of interest for each SCOR program
under competition are listed below. These research topics
are intended to provide a perspective of the scope of
research that would meet the objectives of this program. It
is not required that all or any of these topics be included;
investigators are encouraged to consider other topics that
are relevant to the goals of these programs.
1 Chronic Diseases of the Airways
Chronic bronchitis, emphysema, and the pulmonary aspects of
adult and pediatric asthma are the major diseases included in
this program area. Elucidation of the basic molecular,
cellular and pathophysiologic mechanisms underlying these
diseases, combined with strong clinical studies aimed at
prevention, improved diagnosis and treatment of these
disorders, remain the major goals of research. The research
topics identified below are offered only as examples of areas
of interest.
Better definition of the cellular, humoral and neural
mechanisms underlying airways inflammation and airways
obstruction is needed. A combination of biochemical,
cellular biology and physiologic approaches should help to
elucidate the relationship between inflammatory and repair
processes and airway obstruction. Further investigations to
examine the cellular and biochemical mechanisms of
parenchymal lung destruction in emphysema and the
relationship of parenchymal destruction to chronic airflow
obstruction are also needed.
The factors regulating normal airway tone are still not
understood. Also the mechanisms by which airways narrow
during bronchoconstriction require further definition. The
relationship between airway hyperreactivity and acquired
smooth muscle hypercontractility warrants further study.
Investigations are also needed to determine the role of the
bronchial circulation in airway injury and repair. Studies
of the effects of chronic obstructive lung disease on
respiratory muscle structure and function and on the
pulmonary circulation are encouraged. The production,
clearance and regulation of airway secretions in health and
airway diseases need to be addressed.
An important topic for study is the natural history of acute
and chronic airways disease, particularly in their early
phases, including the effect of respiratory diseases in
childhood on pulmonary health in later life. One approach
could be through population based studies with emphasis on
the identification of risk factors, host and environmental
determinants, disease markers and predictors. The genetic
basis of airway disease is also of interest. This topic
could be addressed using either animal models or existing
cohorts.
Critical assessment of therapeutic measures and development
of new therapeutic strategies remain important goals of this
program.
2 Occupational and Immunologic Lung Diseases
The Occupational and Immunologic Lung Diseases Program
includes basic and clinical research on diseases resulting
from exposure to inhaled organic and inorganic substances
that may be found in the ambient air of the home or the
workplace. Also included in this program are the fibrotic
and granulomatous lung diseases of unknown etiology. To be
considered responsive to this request, applications should be
directed primarily toward investigations of pulmonary
processes. Accordingly, proposed studies of systemic
responses to substances, even if delivered by the pulmonary
route, will not be considered responsive. The research
topics identified below are offered only as examples of areas
of interest.
Of continued interest to the Occupational and Immunologic
Lung Diseases SCOR Program is fundamental research on the
pulmonary immune system and the role of basic immunologic
mechanisms involved in the onset and progression of human
interstitial lung diseases. For pulmonary diseases of
unknown cause such as idiopathic pulmonary fibrosis and
sarcoidosis, determination of the etiology and mechanisms
leading to the development of fibrosis in the lung is of
particular interest. The pathogenesis of pulmonary fibrosis
associated with the pneumoconioses (silicosis and
asbestosis) is not well defined and requires continued
clinical and basic research efforts.
Little is known about the genetic factors that regulate the
host response that contributes to the fibrotic process in the
lung. Application of molecular genetic and molecular
biologic approaches to the study of interstitial lung
diseases constitutes a new and desirable direction for
future clinical application.
The mechanisms by which the human lung responds to
infections, whether bacterial, viral, or other microbial
agents, are poorly understood. Investigations are needed to
define the effects of infections on cellular responses such
as the production of cytokines, the induction of
inflammatory mediators and the evocation of immune responses
in the lung. These studies should be designed to elucidate
the events that take place during the reparative processes
which occur in the injured human lung, and ultimately the
development of chronic interstitial lung disease.
Basic studies of the occupational lung diseases resulting
from exposure to a wide variety of industrial and other
workplace substances are needed. For example, immunochemical
studies designed to better characterize and purify antigens
from organic dusts may lead not only to improved
understanding of the immunologic mechanisms triggered by
antigens but also to development of more sensitive
and specific diagnostic tests. Application of molecular
biological and immunologic technology should help to develop
more effective techniques for screening individuals who are
at increased risk for development of occupational lung
disease.
3 Lung Biology and Disease in Infants and Children
The objective of this SCOR program is to expedite the
development and application of new knowledge essential for
improving the diagnosis, management and prevention of
respiratory disorders in neonates, infants and children.
Applications should include multidisciplinary approaches that
take advantage of the most current ideas and methods of
molecular and cellular biology, neurobiology, immunology,
developmental biology and physiology. An important goal of
this program is to attract basic scientists with expertise in
these disciplines, and clinical investigators with training
in areas other than neonatal lung diseases, to work with
pediatric pulmonary clinicians on problems that encompass the
breadth of pulmonary biology and disease in infants and
children. The research topics identified below are offered
only as examples of areas of interest.
Recent advances in molecular and cellular biology offer new
opportunities for significant progress in understanding the
factors that control growth and differentiation in the
developing lung, and that determine the response of the
developing lung to injury and repair. The cell biology of
developing airway epithelium and the changes in pulmonary
endothelial cell functions during development are areas that
need further exploration.
Developmental neurobiology, including the neuroanatomy,
physiology and pharmacology of the developing respiratory
networks, needs further investigation. Genetic expression of
putative neuromodulators, peptides and mediators during lung
development, and the relation of these events to the control
of breathing during the perinatal period is another area
requiring investigation. These approaches may provide new
insights and a better understanding of infant apnea and apnea
of prematurity.
Since the newborn period is a time of great vulnerability to
pulmonary infections, continued efforts are needed to enhance
understanding of lung host defense mechanisms. Little is
known about the development of pulmonary immune functions,
how prematurity affects lung defense functions or the
influence of environmental factors on lung defense functions
in neonates, infants and children. These issues are
important to the development of new approaches for the
prevention and treatment of diseases caused by respiratory
infections in pediatric populations.
Although surfactant replacement therapy holds great promise
for the prevention and amelioration of neonatal respiratory
distress syndrome (RDS) and bronchopulmonary dysplasia (BPD),
strategies for improving respiratory therapies to reduce or
minimize chronic lung disease are needed. Careful followup
of survivors of RDS and BPD to determine long-term sequelae
remains an important priority. The role of genetic factors
in determining susceptibility to RDS or chronic lung disease
is not known at this time. The efficacy of lung surfactant
in treatment or prevention of acute lung injury syndromes,
pneumonia, and perhaps other pediatric respiratory disorders
also should be explored.
EXCLUSIONS
Support will not be provided under SCOR grants for research
activities focused exclusively on clinical trials or
epidemiologic studies. Similarly, support will not be
provided for proposed programs containing only basic or only
clinical research. While the development of new
instrumentation may be a part of a SCOR, support cannot be
provided for instrument development alone. In general, funds
will not be made available for the purchase and installation
of expensive, new equipment that is not closely linked to
proposed research. Institute staff should be consulted
if there are questions regarding these exclusions.
MECHANISM OF SUPPORT
The support mechanism for the SCORs solicited in this
Request for Applications (RFA)
will be the research grant-in-aid (P50) for a period of five years
commencing December 1, 1991 (Fiscal Year 1992). Thus, all
policies and requirements which govern the grant programs of
the Public Health Service will prevail, including the
requirement for cost sharing. However, it will differ from
the traditional research grant in the degree of goal
orientation and in the degree of direct participation by the
National Heart, Lung, and Blood Institute (NHLBI). While it is
expected that the investigators of the individual centers
will plan, direct and execute their own research program, any
substantive modifications in the program must be mutually
agreed upon by the center director, the grantee institution
and the NHLBI. The
DLD will monitor the progress of each
center throughout the five-year period of support.
To foster cooperation among centers, the DLD may arrange
periodic meetings of the SCOR investigators. Applicants
should include a statement in the application indicating a
willingness to participate in such meetings.
The policy for SCOR grants establishes the following limits
to the requested budgets:
o Applications for new SCOR grants may request up to $1.0
million direct costs in the 01 year with a maximum of 4 percent annual
escalation thereafter.
o Competing renewal applications for SCOR grants may request
up to $1.0 million direct costs or 10 percent increase in
direct costs over the last noncompeting year, whichever is
greater, in the first year of renewal, with a maximum of 4 percent
annual escalation thereafter.
Applications which exceed these limits will be returned.
Requests for special equipment which cause the applications
to exceed these limits, however, will be permitted and
considered on an individual basis. Applicants should contact
DLD staff if they have
questions (see Method of Applying).
Although this solicitation is included in the plans for
Fiscal Year 1992, support of grants pursuant to this
announcement is contingent upon receipt of
appropriate funds. It is anticipated that 14-20 SCORs will
be funded at a total cost of approximately $24 million. The
funding of SCORs will be influenced by the amount of funds
available to NHLBI, by the overall scientific merit of
applications, and by their relevance to NHLBI program
objectives. A variety of approaches could be responsive to
this solicitation. Accordingly, it is anticipated that there
will be a range of requested costs among individual grant
applications submitted.
REVIEW PROCEDURES AND CRITERIA
Applications for SCOR grants will be reviewed and evaluated
for scientific, technical and programmatic merit by an
initial review group specifically convened for this purpose
by the Division of Extramural Affairs, NHLBI. Applications
deemed sufficiently meritorious will be site visited. A
second level review will be performed by the National Heart,
Lung, and Blood Advisory Council.
Applicants should submit the strongest application possible.
Revisions of
applications (additions and deletions of projects, cores or
studies) after submission will no longer be permitted. The
NHLBI has established a new policy that a SCOR grant
application may not be modified by the applicant during the
review process, which begins with the submission of the
application to the Division of Research Grants (DRG). All
projects reviewed at a site
visit will be included when the proposal is evaluated by the
parent review committee and also when it is considered by the
NHLBI Advisory Council.
During the review, individual projects will be disapproved by
the reviewers only if they are considered to have no
scientific merit and will be deleted only if they do not fit
into the overall programmatic theme of the application.
The major factors to be considered in the evaluation of
applications will be:
1 The scientific merit of each proposed project, including
the novelty, originality, feasibility and the adequacy of the
experimental design;
2 The justification of any core unit designed to support a
major component(s) of a SCOR;
3 The adequacy of resources and facilities to support the
proposed clinical and basic research;
4 The integration of the various components into an
effective center, and the adequacy of plans for interaction
and dissemination of information among investigators;
5 The competence of the investigators to accomplish the
proposed research goals, and the adequacy of their time
commitments to the SCOR program;
6 The qualifications, experience and commitment of the
center director and the director's ability to devote adequate
time and effort to provide effective scientific and
administrative leadership to the SCOR; and
7 The adequacy of internal and external procedures of
monitoring and evaluating the proposed research and for
providing ongoing quality control and scientific review.
Other factors that will be considered in the evaluation of
applications include:
1 The commitment of the grantee institution and any
cooperating institutions to the program, and the
appropriateness of its resources and policies for the
administration of a research program of the type proposed;
2 The appropriateness of the budget; and
3 The willingness to interact with other centers and with
the NHLBI.
METHOD OF APPLYING
Letter of Intent. Prospective applicants are requested to
submit a letter of intent by April 16, 1990. The letter
should include a descriptive title, investigators
who might be involved, and any participants outside the
applicant institution. The Institute requests such letters
only for the purpose of providing an indication of the number
and scope of applications to be received and, therefore,
usually does not acknowledge their receipt. A letter of
intent is not binding; it will not enter into the review of
any application subsequently submitted, nor is it a necessary
requirement.
The letter of intent should be sent to:
Charles L. Turbyfill, Ph.D.
Review Branch, Division of Extramural Affairs
National Heart, Lung, and Blood Institute, NIH
Westwood Building, Room 553
Bethesda, MD 20892
Format for Applications
Submit applications on PHS Form 398 (rev. 10/88), the same form used for
the traditional research-project grant. This form is
available in an applicant institution's office of sponsored
research (or business office) or from DRG. Specific instructions for
preparing a SCOR application are available and should be
requested from DLD.
Submission of Application
Send or deliver the completed application and four (4) signed
exact photocopies of it prior to July 16, 1990 to:
Division of Research Grants
Westwood Building, Room 240
National Institutes of Health
Bethesda, Maryland 20892**
In addition, two signed copies of the application should be
sent directly to Dr. Charles L. Turbyfill at the address
listed under Letter of Intent. Applications not received by
July 16, 1990, will be considered ineligible.
Timetable
RFA Release Date: -November 1989
Letter of Intent: -April 16, 1990
Application Receipt Date: -July 16, 1990
National Heart, Lung, and Blood
Advisory Council Review: -May 23-24, 1991
Program Initiation: -December 1, 1991
Inquiries
Prospective applicants are strongly advised to discuss
their potential programs or to seek clarification of this
announcement and the special instructions for preparation of
applications. Inquiries about preparation of applications
should be addressed to:
Suzanne S. Hurd, Ph.D.
Director
Division of Lung Diseases
National Heart, Lung, and Blood Institute
Westwood Building, Room 6A16
Bethesda, Maryland 20892
(301) 496-7208
The programs of the Division of Lung Diseases of the
National Heart, Lung, and Blood Institute are identified in
the Catalog of Federal Domestic Assistance, number 13.839.
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 Health Systems Agency Review.