INTERNATIONAL COLLABORATIONS IN INFECTIOUS DISEASE RESEARCH

Release Date:  May 8, 1998

RFA:  AI-98-009

P.T.

National Institute of Allergy and Infectious Diseases

Letter of Intent Receipt Date:  August 7, 1998
Application Receipt Date:  September 15, 1998

APPLICATIONS FOR MULTIPROJECT COOPERATIVE AGREEMENT (U19) AWARDS IN RESPONSE TO
THIS REQUEST FOR APPLICATIONS (RFA) MUST BE PREPARED USING SPECIFIC INSTRUCTIONS
IN AN NIAID BROCHURE ENTITLED "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT
AWARDS."

PURPOSE

International Collaborations in Infectious Diseases Research (ICIDR) is a
research program sponsored by the National Institute of Allergy and Infectious
Diseases (NIAID).  The ICIDR RFA is being jointly issued with the Actions for
Building Capacity (ABC) RFA (TW-98-004) a research training program sponsored by
the Fogarty International Center (FIC), NIH.

The research component, ICIDR, will be supported by the NIAID through funding of
applications in response to this RFA (AI-98-009).

The research training component, Actions for Building Capacity (ABC) will be
supported by FIC through funding applications in response to a companion RFA (TW-
98-004).  ABC awards will only be made to awardees of ICIDR Research grants.

NOTE:  Investigators may apply for:  (1) an ICIDR research grant only (in
response to this RFA) or (2) both an ICIDR research grant (in response to this
RFA) and an ABC grant (in response to RFA TW-98-004).  Independent applications
for research training (ABC) will NOT be accepted.

It is the NIAID's objective to develop a flexible tropical disease research
network that can be responsive to emerging scientific needs and challenges in the
field of tropical infectious diseases.  The purpose of the ICIDR RFA is to
stimulate high quality collaborative research that will lead to or result in
prevention, amelioration, and/or treatment of tropical infectious diseases and
thus improve the health and quality of life of individuals in endemic areas.

To facilitate this purpose NIAID and FIC have integrated training for foreign
investigators into the ICIDR program (see RFA-TW-98-004).  The purpose of the FIC
training program, Actions for Building Capacity, is to stimulate high quality
training and to support current and future collaborative research on infectious
diseases that are predominately endemic in or impact upon people living in
tropical countries.

ICIDR research must focus on protozoan and helminth infections, mycobacterial
diseases, bacterial and viral enteric infections, Hepatitis C and E, and
fulminant hepatitis of unknown etiology.  Applications in arboviral infections
and other tropical viral infections are specifically encouraged.  Studies focused
on the impact of human immunodeficiency virus (HIV) infection or nutrition on
tropical pathogens will be considered responsive to this RFA. Single and
multiproject programs will be accepted under this RFA, however, all applications
must be focused on a single pathogen or disease entity.

The intent of the ICIDR is to bring together relevant biomedical knowledge and
technology to develop new or improved methods for the prevention, detection, and
treatment of infectious diseases endemic in tropical countries that adversely
affect the health of individuals living in those and other parts of the world;
to increase relevant research experience for both the U.S. and foreign
investigators; to enhance opportunities for scientific linkages, interaction and
collaboration between U.S. and foreign investigators through regularly scheduled
communications, workshops, and meetings; and to provide opportunities for foreign
and U.S. cooperation on emerging research opportunities in tropical countries.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of  "Healthy People 2000," a PHS-led national
activity for setting priority areas.  This RFA, International Collaborations in
Infectious Disease Research, is related to the priority area(s) of immunization
and infectious diseases.  Potential applicants may obtain a copy of "Healthy
People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No.
017-001-00473-1) through the Superintendent of Documents, Government Printing
Office, Washington, DC 20402-9325 (telephone 202-512-1800).

ELIGIBILITY REQUIREMENTS

For applicants who apply for awards under both this ICIDR RFA (AI-98-009) and the
companion ICIDR ABC RFA (TW-98-004), both applications must have the same
principal investigator.

Applications may be submitted by domestic for-profit and non-profit
organizations; public and private institutions, such as universities, colleges,
hospitals, laboratories, etc.  Foreign institutions are not eligible. 
Racial/ethnic minority individuals and women are encouraged to apply as Principal
Investigators.  The U.S. grantee institution is responsible for developing
affiliation(s) with an established institution(s) (e.g. university, research
institute, federal or state health department, hospital) in the host country. 
Research activities on this project conducted at the foreign affiliate must be
supported under a consortium arrangement by the award made to the U.S. based
institution.  For the award to be considered, the domestic applicant institution
must include proof of having an off-site component as a foreign base of
operations and one or more specified employees of the foreign institution as co-
investigators.  The proposed research programs must be acceptable to the
collaborating overseas investigators and their institutions.  The application
will not be reviewed unless proof of such a foreign affiliation is included.

In addition, it will be necessary to establish a working agreement with the
government of the host country to expedite deputation of personnel, equipment and
supplies from the U.S. to the off-site facility.  The agreement may be developed
directly between the domestic applicant institution and the representatives of
the foreign government, or it may be more convenient for the domestic component
to arrange such an agreement through a regional organization such as the Pan
American Health Organization or the relevant office of the World Health
Organization.  Proof of such an agreement must be submitted no later than two
months after the application receipt date in order to assure its availability
prior to grant review.

For projects involving human subjects, NIH requires inclusion of women and
minority groups in study populations. If women or minorities are not included or
are inadequately represented in the study populations, a specific compelling
rationale and justification for this exclusion must be provided.  However, with
regard to the population of the foreign country, the definition of the minority
groups may be different than in the U.S.  If there is scientific rationale for
examining subpopulation group differences within the foreign population,
investigators should consider designing their studies to accommodate these
differences.

MECHANISM OF SUPPORT

The administrative and funding mechanism for the ICIDR will be the Cooperative
Agreement (single project U01 or multi-project U19), an "assistance" mechanism,
rather than an "acquisition" mechanism.  The cooperative agreement mechanism is
used when substantial NIH scientific and/or programmatic involvement with the
awardee is anticipated during the performance of the activity.  Under the
cooperative agreement, the NIH purpose is to support and/or stimulate the
recipient's activity by involvement in and otherwise working jointly with the
award recipient in a partner role, but it is not to assume direction, prime
responsibility, or a dominant role in the activity. Details of the
responsibilities, relationships, and governance of a study funded under
cooperative agreement(s) are discussed later in this document under the section
Terms and Conditions of Award.

The total project period for an application submitted in response to this RFA may
not exceed five years.  At this time, the NIAID has not determined whether and
how this solicitation will be continued beyond the present RFA.  If, by the end
of the third year of the award, NIAID has not announced its intent, due to budget
uncertainties, to reissue the RFA, incumbents should contact program staff before
preparing a recompeting application to seek advice on the most appropriate method
of application submission.

The cooperative agreement funding instrument can support ICIDR awards of either
a multiproject programs or single project programs, and both types of
applications will be considered by NIAID.  Single project applications are
encouraged and should focus on a hypothesis driven discrete, circumscribed
objective.  Multiproject programs consist of at least three interrelated research
projects.  Multiproject programs should be multidisciplinary and must have a
single pathogen or disease entity as the research focus.  Each related component
should make an essential contribution to a central research goal.  For the
purpose of this RFA, Principal investigators of multiproject programs and
Principal investigators for single project programs will be considered "ICIDR
Directors".

Multiproject cooperative agreement (U19) applications must include: (1) a minimum
of three interrelated individual research projects organized around a central
theme; (2) collaborative efforts and interaction among independent projects and
their investigators to achieve a common goal; (3) a single Program Director who
will be scientifically and administratively responsible for the group effort; (4)
a single applicant institution that will be legally and financially responsible
for the use and disposition of funds awarded; and (5) support provided, as
necessary, for "Core" resources or facilities, each of which is expected to be
utilized by at least two research projects in order to facilitate the research
effort.  Applications for multi-project programs should describe in detail their
organizational and administrative structure.  Whereas multi-project programs may
take advantage of the "core" mechanism to provide support for common resources
(e.g., laboratory or clinical facilities), it is understood that support for such
facilities will be included in the budget of a single project application as
required.

ICIDR research at the foreign affiliate institution will be supported by the U.S.
applicant institution through a consortium arrangement, and the programmatic,
fiscal and administrative agreements involved should be described within the
application.  The applicant organization's administrative support must provide
the necessary management for the transfer of funds and material to the off-site
component.  Indirect costs will not be paid on any expense incurred by the
foreign institution(s).  Travel, salaries, and fringe benefits will be subject
to the applicant institution's rules and regulations.

FUNDS AVAILABLE

The estimated total funds (direct and indirect costs) available for the first
year of support for all ICIDR Research awards made under this RFA will be $6.5
million. The number of awards will vary with the number of single project and
multi project applications, however, it is estimated that there will be twelve
to eighteen awards made.  This level of support is dependent on the receipt of
a sufficient number of applications of high scientific merit.

Because the nature and scope of the research proposed in response to the ICIDR
RFA may vary, it is anticipated that the size of the award will vary also. 
Applications for multi-project grants may not exceed $550,000 in direct costs in
the first year, while single component applications may not exceed $250,000 in
direct costs in the first year.  Exceptions to these budget limits must be
discussed with and approved by Dr. Higgs (see Inquiries below) before application
submission.  The usual PHS policies governing grants administration and
management will apply.  Although this program is provided for in the financial
plans of the NIAID, awards pursuant to this RFA are contingent upon the
availability of funds for this purpose and the receipt of a sufficient number of
applications of high scientific merit.  Funding beyond the first and subsequent
years of the grant will be contingent upon satisfactory progress during the
preceding years and availability of funds.

RESEARCH OBJECTIVES

Background

Tropical diseases constitute a global public health problem disproportionately
affecting populations residing in developing countries. Diseases caused by
protozoan and helminth parasites affect billions of people resulting in the death
and disability of millions annually.  According to a recent report of the World
Health Organization, at least 500 million people, the equivalent of one person
in ten worldwide, are estimated to be infected with one or more of the five major
tropical parasitic diseases malaria, schistosomiasis, filariasis,
trypanosomiasis, and leishmaniasis.  Children are disproportionately affected by
these infections due to their immature immune systems and overlapping
malnutrition. The impact of tropical infections is enormous, and is often cited
as a key impediment to further social and economic progress. No effective
vaccines have been identified for any human parasitic diseases.  Ninety percent
of the world's 30.1 million individuals living with HIV/AIDS reside outside the
western world in areas endemic for tropical infections.  The impact of HIV
infection on the incidence, clinical manifestations, treatment and infection of
tropical infections remains understudied.  Bacterial, viral and fungal infections
are also a major concern in tropical regions, resulting in such important health
problems as tuberculosis, diarrhea, hepatitis, and hemorrhagic fevers.

Despite advances in molecular biology, immunology, biology, chemotherapeutic
agents, immunotherapy, vaccinology, genetics, and other scientific fields, the
challenges of tropical infections outpace solutions. Tuberculosis and malaria are
examples where previous methods of control and treatment are no longer effective.
Thus, mortality has risen to approximately 3 million/year for TB and between 1.5-
2.7 million/year for malaria. The co-endemnicity of the HIV with some tropical
diseases has rendered large populations more susceptible to various tropical
infections such as TB, leishmaniasis, and cryptosporidiosis.

As the challenges of tropical diseases increase so does their relevance to the
entire population of the world. Environmental and ecological changes, combined
with increases in global travel have brought individuals from industrialized
countries into contact with traditionally tropical pathogens. Pathogens formerly
viewed as tropical or restricted geographically to the Southern Hemisphere have
been "emerging" globally. For all these reasons, NIH has expanded its commitment
and mission to research on prevention, control, and treatment of tropical and
emerging pathogens.

Fulfillment of this mission requires the capacity to carry out research on
tropical infectious diseases in endemic areas.  The integration of the Fogarty
Actions for Building Capacity (ABC) program into the ICIDR is intended to train
foreign scientists in the context of ICIDR research and thus facilitate
sustainable collaborative research between the US and foreign tropical countries.
The improvement of scientific linkages between U.S. and foreign investigators
stimulates self-sufficiency of the collaborating foreign institution and
strengthens the scientific infrastructure for further international collaborative
arrangements.  The linkage of the ICIDR research and the ABC training programs
is responsive to the recommendations of the Committee on International Science,
Engineering and Technology Working Group on Emerging and Re-emerging Infectious
Diseases which specifically recommends the following actions by the U.S.
government; "Encouraging and assisting other countries to make infectious
diseases detection and control a national priority; and Preserving existing U.S.
Government activities that enhance other countries abilities to prevent and
control emerging and re-emerging health threats."(1)

Scope of Research

The purpose of this RFA is to stimulate high quality collaborative research that
will lead to or result in prevention, amelioration, and/or treatment of tropical
infectious diseases and thus improve the health and quality of life of
individuals in endemic areas.

The research solicited by this RFA will focus on those infectious diseases
primarily endemic in or disproportionately impacting the health of people living
in the tropics, including but not limited to protozoan and helminth infections,
mycobacterial diseases, bacterial and viral enteric infections, Hepatitis C and
E, and fulminant hepatitis of unknown etiology.  Applications on arboviral
infections and other tropical viral infections are specifically encouraged. 
Studies of focused on the impact of human immunodeficiency virus (HIV) on
tropical pathogens are encouraged.  Studies, however, solely focused on HIV or
on the impact of other tropical diseases on HIV infection, as well as studies of
sexually transmitted diseases, hepatitis A, B, and D, influenza, HSV 1 & 2, RSV,
and rotavirus in developing countries are supported by other NIAID activities and
will not be considered in response to this solicitation.  Each ICIDR application,
whether single or multicomponent, must focus on studies related to a single
pathogen or group of pathogens presenting as a single disease entity.

This RFA is intended to support research which requires access to populations and
is not meant to support the conduct of research which can be done in U.S. based
labs. Thus, an emphasis on field based and clinical studies would be appropriate. 
Therefore the kinds of research that are appropriate to this RFA would include
but are not limited to studies of: epidemiology, natural history, pathogenesis,
immunopathogenesis, phase I, II, III preventive and therapeutic clinical trials,
and vector biology control. Likewise relevant disciplines include, but are not
limited to, infectious diseases, pathology, epidemiology or other medical or
public health specialties which contribute to a greater understanding of the
interaction between a specific tropical pathogen and the host.  Contributing
fields could also include: biochemistry, immunology, genetics, pharmacology,
molecular biology, microbiology, zoology, nutrition, and medical entomology.

U.S. applicant institutions will make their own arrangements for a mutually
acceptable affiliation with one or more collaborating foreign institutions
located in or near regions where tropical diseases are endemic.  The majority of
the research effort must take place in the endemic area.  The major foreign
collaborator must be substantially involved (with at least 40% effort for a
single project award and no less than 60% for a multiproject award), inasmuch as
it is intended that there be active collaboration between U.S. personnel and
scientists of the foreign affiliate(s).

Special Requirements

Travel:  It is expected that ICIDR scientists from the U.S. institution will
travel to the foreign affiliate for long-term collaborations with the resident
scientists in research directly related to the objectives of the ICIDR award
(involving periods of at least six months each).  Senior scientists with major
institutional responsibilities in the U.S. may spend shorter periods of time,
e.g. one to two months several times a year, working at the foreign site with
their associates.

Percent Effort: U.S. Principal Investigators must expend at least 30% effort on
the ICIDR award.  It is anticipated that the demands of the multiproject program
awards will require even greater effort on the part of the ICIDR Director.  The
Major Foreign Collaborator (MFC) of single project awards will be expected to
expend 40% effort on the ICIDR award. The Major Foreign Collaborator for
multiproject awards will be expected to expend 60% effort on the ICIDR.

ICIDR Structure: The ICIDR has grown along with the increasing awareness of the
incidence, prevalence, and geographic distribution of tropical diseases. Since
1991 all ICIDR centers have been part of the NIAID International Centers for
Tropical Disease Research (ICTDR) network. Applicants must include within their
application travel costs for the ICIDR Director and MFC to attend the annual
ICTDR meeting in Bethesda.  With this renewal there will be new structure within
the ICIDR program in the form of an Executive Committee, Pathogen Study Groups,
and (in conjunction with the FIC ABC training awards) a Training Advisory Group
(see RFA TW-98-003). These groups will address the need for communication,
collaboration, and flexibility within the ICIDR, ICTDR, and the tropical medicine
research community.  (See TERMS AND CONDITIONS OF ICIDR AWARD for more details
on special requirements of these groups.)

Studies involving human subjects.  Population-based research and clinical trials
are encouraged.  For such trials involving human subjects the following special
requirements apply:

ICIDR investigators will be required to develop all studies involving human
subjects in accordance to U.S. government guidelines.  Clinical trials will be
reviewed by DMID's Clinical Trial Review Committee (CTRC).  The CTRC will is
comprised of NIAID program staff and outside expertise when needed. Clinical
protocols involving human subjects will be reviewed at two stages of development;
early (during the concept stage) and later close to protocol completion, for;
scientific content, design, safety, feasibility, statistical and regulatory
issues such as adverse experience reporting mechanisms and informed consent. The
appropriate scientific coordinator (see NIAID Extramural Staff Responsibilities)
will be responsible for presentation of the clinical research protocols.

All ICIDR protocol documents for clinical trials should at minimum include the
following sections: an introduction, including background and rationale; a
statement of the study objectives; criteria for selection of subjects, and
enrollment procedures; clinical and laboratory evaluations to be performed; plans
for data management, collection, and monitoring, and for reporting of adverse
events; a complete description of the study treatment; and statistical
considerations, including general design issues, endpoints, sample size, accrual
and power, monitoring and analysis, and stopping rules.

C. All Phase III ICIDR clinical trials will be monitored by a Data Safety and
Monitoring Board to be selected and overseen by NIAID.  All phase I and II
clinical trails will be monitored by interim monitoring boards that will be
established jointly by NIAID program staff, the ICIDR Executive Committee, and
the Principal Investigator.

TERMS AND CONDITIONS OF ICIDR AWARD

AWARDEE RIGHTS AND RESPONSIBILITIES

These special Terms of Award are in addition to, and not in lieu of, otherwise
applicable OMB administrative guidelines, HHS Grant Administration Regulations
at 45 CFR part 74 and 92, and other HHS, PHS, and NIH Grant Administration policy
statements.

The administrative and funding instrument used for this program is the
cooperative agreement (U01 or U19), an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH scientific and/or programmatic
involvement with the awardee is anticipated during the performance of the
activity.  Under the cooperative agreement, the NIH purpose is to support and/or
stimulate the recipient's activity by involvement in and otherwise working
jointly with the award recipient in a partner role, but it is not to assume
direction, prime responsibility, or the dominant role in the activity.

Consistent with this concept, the dominant role and prime responsibility for the
activity resides with the awardees for the project as a whole, although specific
tasks and activities in carrying out the research will be shared among the
awardees and the NIAID, DMID Program Staff.

Awardees will have primary responsibility for defining the research objectives,
approaches and details of the projects within the guidelines of the RFA and for
performing the scientific activity.  Specifically the awardee is responsible for:

Clearly stating the rational, objectives and methods for proposed research
projects. Research design and protocol development, for example; definition of
objectives and approaches, planning, implementation, participant recruitment and
follow-up, data collection, quality control, interim data and safety monitoring,
final data analysis and interpretation, and publication of results.

Maintaining a mutually acceptable arrangement with the foreign affiliate
institution and host country.

Establishing, with other ICIDR Principal Investigators/Program Directors and the
NIAID Program Officer, an ICIDR Executive Committee (IEC). (See Section C
"Collaborative Responsibilities" TERMS AND CONDITIONS OF AWARDS.)

Establishing with the other ICIDR investigators, a Pathogen Study Group (PSG)
centered on a specific pathogen or disease entity (See Section C "Collaborative
Responsibilities" under TERMS AND CONDITIONS OF AWARDS.).

Establishing a Training Advisory Group (TAG) to oversee training activities. (See
Section C "Collaborative Responsibilities" under TERMS AND CONDITIONS OF AWARDS.)

Preparing when relevant detailed protocols, consent forms, etc. for submission
to the Program Officer and Institutional Review Boards at relevant U.S. and
foreign institutions for approval.  All studies involving human subjects will be
required to be filed with the FDA.  Decisions regarding who will hold the IND
will be made by NIAID.  When NIAID holds the IND the ICIDR Director will be
required to provide to NIAID all the necessary information and documentation for
filing the IND with the FDA and to amend as necessary after comments by the
Program Officer, local IRB, and regulatory authorities. Additionally, individual
investigators/sites must demonstrate the ability to implement the strategy
specifically designed for their individual study population. For clinical
studies, when relevant, present and carry out plans for a data coordination
center and preparation of statistical reports for DSMBs.

Establishing mechanisms for internal quality control and monitoring.  Awardees
are responsible for ensuring the accurate and timely assessment of the progress
of research, including development of procedures to ensure that data collection
and management are:  (a) adequate for quality control and analysis; (b) for
clinical trials, as simple as appropriate in order to encourage maximum
participation of clinicians and other providers and study subjects and to avoid
unnecessary expense; and (c) sufficiently staffed across the participating
institutions.

Establishing procedures, where applicable, for all participating institutions in
coordinated awards to comply with FDA regulations for studies involving
investigational agents or devices and to comply with the requirements of 45 CFR
Part 46 for the protection of human subjects.

Where relevant, as in malaria, work with NIAID staff to facilitate the
development of repositories of research reagents.  This may involve the
collection and transportation of pathogen specimens, vectors, and/or human
material.

Cooperating in the reporting of the study findings. It is specifically intended
that publications resulting from collaborative research will be co-authored by
the involved foreign scientists(s) and that the data will be made readily
available to the government of the host country.  The NIAID will have access to
and may periodically review all data generated under an award.  Where warranted
by appropriate participation, plans for joint publication with NIAID of pooled
data and conclusions are to be developed by the Principal Investigator or
Executive Committee, as applicable.  NIH policies governing possible
co-authorship of publications with NIAID staff will apply in all cases.

B.  NIAID EXTRAMURAL STAFF RESPONSIBILITIES

It is expected that the dominant role and prime responsibility for the activity
will reside with the awardee(s) for the project as a whole.  However, specific
tasks and activities will be shared among the awardee(s) and the NIAID Program
Officer and/or Scientific Coordinator(s).  As required for the coordination of
activities and to expedite progress, the NIAID Program Officer may designate
additional scientific coordinator(s) to provide advice or assistance to the
awardee on specific scientific, technical or management issues.  The NIAID
Program Officer shall retain overall programmatic responsibility for the award(s)
and will clearly specify to the awardee(s) the name(s) and role(s) of any such
additional individuals and the lines of reporting authority.

Dr. Elizabeth S. Higgs is the Program Officer who will be responsible for the
overall program. The following NIAID staff will serve as Scientific Coordinators
for specific diseases or pathogens: Dr. Lee Hall- malaria, Dr. Stephanie James-
schistosomiasis, Dr. Michael Gottlieb- leishmaniasis and trypanosomiasis, Dr. Ann
Ginsberg- tuberculosis and Mycobacteria, Dr. Leslie Johnson- hepatitis, Dr. James
Meegan- arboviruses and tropical viral infections, Dr. Dennis M. Dixon- tropical
mycoses, Dr. Dennis Lang- enteric diseases, Dr. Elizabeth Higgs- geohelminths and
amebiasis.  Other program staff will be assigned when needed. The NIAID
Scientific Coordinator will have substantial scientific/programmatic involvement
during the conduct of this activity through technical assistance, advice and
coordination above and beyond normal program stewardship for grants, as described
below.  NIAID staff responsibilities are enumerated below:

The Program Officer, and when scientifically appropriate the Scientific
Coordinator, will interact with the Principal Investigator(s) on a regular basis
to monitor study progress.  Monitoring may include:  (a) regular communications
with the Principal Investigator and staff, (b) periodic site visits for
discussions with awardee research teams, (c) observation of field data collection
and management techniques, quality control, fiscal review, and other relevant
matters.  The NIAID retains, as an option, periodic external review of progress.

The Scientific Coordinator will work with the Chair of the appropriate PSG(s) to
meet the objectives of the PSG(s). (See Section C "Collaborative
Responsibilities" under TERMS AND CONDITIONS OF AWARDS.)

The NIAID Program Officer or designee will be a full participant and voting
member of the ICIDR Executive Committee. (See Section C "Collaborative
Responsibilities" under TERMS AND CONDITIONS OF AWARDS.)

NIAID staff through interaction on the PSGs will serve as a resource with respect
to ongoing NIAID activities that may be relevant to the research to facilitate
compatibility and avoid unnecessary duplication.

Program staff, both Scientific Coordinators and the Program Officer, will provide
substantial assistance in the design and coordination of research activities for
awardees including:

Assisting by providing advice on the management and technical performance of the
investigations.

Providing access to and use of, when appropriate, reagents and assays, and other
resources available through NIAID contractors and awardees.

Provision of technical advice and assistance with meeting FDA requirements for
investigational agents (with the assistance of DMID's Clinical and Regulatory
Affairs Branch).

For clinical protocols the NIAID Scientific Coordinator will assist in the
design, development, and coordination of a clinical protocol and statistical
evaluations of data.

NIAD Scientific Coordinator and the ICIDR Program Officer will participate in the
DMID Clinical Trial Review Committee (CTRC). The CTRC will review and approve
all, clinical trial concepts and protocols involving human subjects to insure
that they are within the scope of peer review and for adequacy of safety, human
subjects, and representation of women and minorities, as required by Federal
regulations. The NIAID Program Officer/Scientific Coordinator will monitor
protocol progress, and may request that a protocol be closed to accrual for
reasons including:  (1) accrual rate insufficient to complete study in a timely
fashion; (2) accrual goals met early; (3) poor protocol performance; (4) patient
safety, human subjects, and women/minority recruitment concerns; (5) study
results that are already conclusive; and (6) emergence of new information that
diminishes the scientific importance of the study.

If applicable, reviewing and providing advice regarding the establishment of
mechanisms for quality control and study monitoring for any clinical trials.

The Program Officer will have primary responsibility to make recommendations for
continued funding based on: (a) overall progress, including study subject and/or
data accrual; (b) cooperation in carrying out the research (e.g., participation
in PSG activities described above, implementation of group decisions, compliance
with terms of award and reporting requirements); and/or (c) maintenance of a high
quality of research.

NIAID will retain the option to cross-file or independently file an application
for investigational clinical trial: i.e. an Investigational New Drug Application
(IND) to the United States Food and Drug Administration.  All clinical trails
will adhere to DMID policies on holding INDs.  NIAID may decide at any time to
add a NIAID medical officer to any clinical ICIDR protocol.

C.  COLLABORATIVE RESPONSIBILITIES

In addition to the interactions defined above, awardees and NIAID staff shall
share responsibilities for the scientific coordination and communication.  With
the growth of the ICIDR program there is an increasing need for communication,
collaboration and flexibility to meet emerging research challenges. These needs
will be met through the establishment of three administrative groups: The ICIDR
Executive Committee (IEC), the Pathogen Study Groups (PSGs) and the Training
Advisory Group (TAG).  The awardees will have primary responsibility for the
organization and activities of these groups.

Specifically:

The ICIDR Executive Committee (IEC) will be established by ICIDR Directors with
the assistance of the NIAID Program Officer. Membership will include ICIDR
directors, the NIAID Program Officer and the FIC Program officer.  The IEC will
have primary responsibility for information exchange across pathogens and
diseases, identification of emerging research opportunities, review of research
concepts and protocols for emerging research opportunities, oversight of the TAG
and PSGs, and planning of the ICTDR meeting.

An initial meeting of the Executive Committee will be convened early in the award
period (within the first six months). A Chairperson, other than the NIAID staff,
will be selected by vote of the members at the initial meeting.  The Chairperson
is responsible for coordinating the Committee activities, for preparing meeting
agendas, and for scheduling and chairing meetings. The NIAID Program Officer or
designee will have voting membership on the Executive Committee and, as
appropriate, its subcommittees.  The IEC will communicate regularly.  ICIDR
Directors should budget for 2 domestic meetings per year one of which could be
the ICTDR meeting.

In the event that opportunities arise and funds become available for emerging
research opportunities or multicenter clinical trials, the IEC will work with the
relevant PSG to develop (through appropriate designees) common protocols and
manuals, questionnaires and other data recording forms, establish and maintain
quality control among awardees, review progress, monitor patient/subject accrual,
coordinate and standardize data management and cooperate on the publication of
results. Major scientific decisions regarding the core data of multicenter
clinical trials will be determined by the Executive Committee.  The Executive
Committee will document progress in written reports to the NIAID Program Officer
and will provide periodic supplementary reports upon NIAID request.

The Pathogen Study Groups (PSGs) centered on a specific pathogen or disease
entity will be established by ICIDR investigators and the NIAID Scientific
Coordinator. Responsibilities will include facilitation of information exchange
including research advances; fostering collaboration and translational research;
coordination of activities to minimize duplication; identification of emerging
research opportunities; development of facilitate information exchange including
research advances; foster collaboration and translational research; coordinate
activities to minimize duplication; identify emerging research opportunities;
develop research proposals and where appropriate, multicenter studies; and
participate in planning of the annual ICTDR meeting.

Multidisciplinary PSG communication can take place through conference calls, work
shops, and meetings and may result in research proposals, new collaborations,
position papers, etc.  It is NIAID's expectation that such scientific exchange
will result in new collaborations and research proposals. Thus, a PSG may also
coordinate multicenter clinical trial protocols if such research strategies
evolve over the award period.  Examples of such coordination would be definition
of core data collection strategies, methods and cross-study analyses.

The PSG may be comprised of ICIDR investigators, other investigators
participating in the ICTDR network, other interested scientists from the R01
community, international organizations such as WHO, ABC trainees supported by the
Fogarty International Center, and other interested participants. Each PSG will
be responsible for electing a chairperson who will work with the NIAID Scientific
Coordinator to organize PSG communication and activities.  It is expected that
$15,000 to $30,000/year be set aside for PSG activities.  Internet connectivity
is encouraged as a means of PSG participation.  ICIDR Directors are encouraged
to work with NIH if Internet connectivity is to be established.

I.The Technical Advisory Group (TAG) will be a subcommittee of the IEC and be
primarily responsible for oversight of the ABC training program. The TAG
membership will include ABC PIs, the Major Foreign Collaborator for each ABC and
the Fogarty Program Officer and the NIAID ICIDR Program Officer. The TAG will
have responsibility for overseeing training plans, development of an annual short
course, and progress of trainees.
D.  Arbitration

Any disagreement that may arise on scientific or
programmatic matters (within the scope of the award) between award recipients and
the NIAID may be brought to arbitration.  An arbitration panel will be composed
of three members -- one selected by the Executive Committee (with the NIAID
member not voting) or by the individual awardee in the event of an individual
disagreement, a second member selected by the NIAID, and the third member with
expertise in the relevant area and selected by the two prior members will be
formed to review any scientific or programmatic issue that is significantly
restricting progress.  While the decisions of the Arbitration Panel are binding,
these special arbitration procedures will in no way affect the awardee's right
to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50,
subpart D, and HHS regulations at 45 CFR Part 16.

Cooperative agreements are subject to the administrative
requirements outlined in OMB circulars A-102 and A-110.  All pertinent HHS, PHS,
and NIH grant regulations, policies and procedures, with particular emphasis on
PHS regulations at 42 CFR Part 52 and HHS regulations at 45 CFR Part 74, are
applicable. These special terms and conditions pertaining to the scope and nature
of the interaction between the NIAID and the investigators will be incorporated
in the Notice of Grant Award.  However, these terms will be in addition to, not
in lieu of, the customary programmatic and financial negotiations that occur in
the administration of cooperative agreements.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and their
sub-populations must be included in all NIH supported biomedical and behavioral
research projects involving human subjects, unless a clear and compelling
rationale and justification are provided that inclusion is inappropriate with
respect to the health of the subjects of the purpose of the research.  This
policy results from the NIH Revitalization Act of 1993 (Section 492B of Public
Law 103-43).

All investigators proposing research involving human subjects should read the
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research", which have been published in the Federal Register of March 28, 1994
(FR 59 14508-14513) and the NIH Guide for Grants and Contracts, Vol. 23, No. 11,
March 18, 1994 and is available at the following URL address:
http://grants.nih.gov/grants/guide/notice-files/not94-100.html

Investigators may obtain copies from these sources or from Dr. Higgs (listed in
INQUIRIES below) who may also provide additional relevant information concerning
the policy.

LETTER OF INTENT

Prospective applicants are asked to submit, by August 7, 1998, a letter of intent
that includes a descriptive title of the overall proposed research; the name,
address and telephone number of the Principal Investigator; and the number and
title of this RFA.  Although the letter of intent is not required, is not
binding, does not commit the sender to submit an application, and does not enter
into the review of subsequent applications, the information that it contains
allows NIAID staff to estimate the potential review workload and to avoid
conflict of interest in the review.  The letter of intent is to be sent to Dr.
Hornbeak at the address listed under INQUIRIES.

APPLICATION PROCEDURES

Applications are to be submitted on the research grant application form PHS 398
(rev. 5/95).  Application kits are available at most institutional offices of
sponsored research and may be obtained from the Division of Extramural Outreach
and Information, National Institutes of Health, 6701 Rockledge Drive, MSC 7910,
Bethesda, MD 20892-7910, telephone (301) 435-0714, email: grantsinfo@nih.gov

Applicants for single project (U01) awards must follow the instructions in the
PHS 398 grant application kit.

Applicants for multi-project (U19) cooperative agreements must follow special
application guidelines in the NIAID Brochure entitled INSTRUCTIONS FOR
APPLICATIONS FOR MULTI-PROJECT AWARDS (September 1997); this brochure is
available via the WWW at:  http://www.niaid.nih.gov/ncn/grants/multibron.htm

For purposes of identification and processing, item 2 on the face page of the
application must be marked "YES" and the RFA number "AI-98-009" and the words
"ICIDR: RESEARCH" must be entered on the face page.

Applications must be received by September 15, 1998.  Applications that are not
received as a single package on the receipt date or that do not conform to the
instructions contained in PHS 398 (rev. 5/95) Application Kit (for multi-project
awards as modified in, and superseded by, the NIAID BROCHURE ENTITLED
"INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS"), will be judged non-
responsive and will be returned to the applicant.  The RFA label available in the
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 the application such that
it may not reach the review committee in time for review.

Concurrent submission of an R01 and a Component Project of a Multi-project
Application: Current NIH policy permits a component research project of a multi-
project grant application to be concurrently submitted as a traditional
individual research project (R01) application.  If, following review, both the
multi-project application and the R01 application are found to be in the fundable
range, the investigator must relinquish the R01 and will not have the option to
withdraw from the multi-project grant.  This is an NIH policy intended to
preserve the scientific integrity of a multi-project grant, which may be
seriously compromised if a strong component project(s) is removed from the
program.  Investigators wishing to participate in a multi-project grant must be
aware of this policy before making a commitment to the Principal Investigator and
awarding institution.

It is highly recommended that the appropriate NIAID program contact be consulted
before submitting the letter of intent and during the early stages of preparation
of the application.  (See program contacts under INQUIRIES).

Submit a signed, typewritten original of the application, including the
checklist, and three signed, exact, single-sided photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional exact copies of the grant application
and all five sets of any appendix material must be sent to Dr. Hornbeak at the
address listed under INQUIRIES.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the Center for
Scientific Review (CSR) and for responsiveness by NIAID staff; those judged to
be incomplete will be returned to the applicant without review.  Those considered
to be non-responsive will be returned without review.

Applications that are complete and responsive to the RFA will be evaluated for
scientific and technical merit by an appropriate peer review group convened by
the NIAID in accordance with the review criteria stated below.  As part of the
initial merit review, a process may be used by the initial review group in which
applications will be determined to be competitive or non-competitive based on
their scientific merit relative to other applications received in response to the
RFA.  Applications judged to be competitive will be discussed and be assigned a
priority score.  Applications determined to be non-competitive will be withdrawn
from further consideration and the Principal Investigator and the official
signing for the applicant organization will be notified.  The second level of
review will be provided by the National Advisory Allergy and Infectious Diseases
Council.

Review Criteria

The general criteria for multi-project (U19) cooperative agreement applications
are presented in the NIAID BROCHURE.

The criteria to be used in the evaluation of single project applications are
listed below.  To put those criteria in context, the following information is
contained in instructions to the peer reviewers.

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.  The
reviewers will comment on the following aspects of the application in their
written critiques in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals.  Each of these
criteria will be addressed and considered by the reviewers in assigning the
overall score weighting them as appropriate for each application.  These criteria
are not listed in any order of priority. Note that the application does not need
to be strong in all categories to be judged likely to have a major scientific
impact and thus deserve a high priority score.  For example, an investigator may
propose to carry out important work that by its nature is not innovative but is
essential to move a field forward.

1.  Significance.  Does this study address an important problem? If the aims of
the application are achieved, how will scientific knowledge be advanced?  What
will be the effect of these studies on the concepts or methods that drive this
field?

2.  Approach.  Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project?  Does the applicant acknowledge potential problem areas and consider
alternative tactics?

3.  Innovation.  Does the project employ novel concepts, approaches or method? 
Are the aims original and innovative? Does the project challenge existing
paradigms or develop new methodologies or technologies?

4.  Investigator.  Is the investigator appropriately trained and well suited to
carry out this work?  Is the work proposed appropriate to the experience level
of the principal investigator and other researcher?

5.  Environment.  Does the scientific environment in which the work will be done
contribute to the probability of success?  Do the proposed experiments take
advantage of unique features of the scientific environment or employ useful
collaborative arrangements?  Is there evidence of institutional support?

In addition, the following RFA-specific criteria will be used in the evaluation
of all (U01 and U19)applications:

1. Scientific appropriateness and administrative adequacy of the proposed
affiliation with the foreign institution(s) and host country.

2. Adequacy of the time (effort) which the Principal Investigator(s), foreign
investigators and staff would devote to the proposed studies.  Are the scientists
from the host country appropriately integrated into the research plan?

Adequacy of facilities, both at the domestic and foreign institutions, including,
if relevant to the proposed research, adequacy of the clinical facilities and
patient availability for clinical studies.

Responsiveness to the RFA's specific intention to support research which requires
access to field based populations and not to support the conduct of research
which can be done in U.S. based labs.

The initial review group will also examine: the appropriateness of proposed
project budget and duration; the adequacy of plans to include both genders and
minorities and their subgroups as appropriate for the scientific goals of the
research and plans for the recruitment and retention of subjects; the provisions
for the protection of human and animal subjects; and the safety of the research
environment.

AWARD CRITERIA

Funding decisions will be made on the basis of scientific and technical merit as
determined by peer review, program balance with regard to diversity of diseases
addressed and host country, and the availability of funds. The earliest
anticipated date of award is June 1999.

INQUIRIES

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

Direct inquiries regarding ICIDR programmatic (research scope and eligibility)
issues to:

Dr. Elizabeth S. Higgs
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 3A34
Bethesda, MD  20892-7630
Telephone:  (301) 496-2544
FAX:  (301) 402-0659
Email:  eh63a@nih.gov

Direct inquiries regarding review issues and special instructions for application
preparation; address the letter of intent to; and mail two copies of the
application and all five sets of appendices to:

Dr. Hortencia Hornbeak
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4C16
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-7291
FAX:  (301) 402-2638
Email:  hh7q@nih.gov

Direct inquiries regarding fiscal matters to:

Todd Ball
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4B35
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 402-5512
FAX:  (301) 480-3780
Email:  tb22j@nih.gov

Schedule

Letter of Intent Receipt Date:  August 7, 1998
Application Receipt Date:       September 15, 1998
Scientific Review Date:         February 1999
Advisory Council Date:          May 25, 1999
Earliest Award Date:            June 1, 1999

AUTHORITY AND REGULATIONS

This program is supported under authorization of the Public Health Service Act,
Sec. 301 (c), Public Law 78-410, as amended.  The Catalogue of Federal Domestic
Assistance Citation Sec. 93.856, Microbiology and Infectious Diseases Research. 
Awards will be administered under PHS grants 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
review.

The PHS strongly encourages all grant and contract recipients to provide a smoke-
free workplace and promote the non-use of all tobacco products.  In addition,
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain
facilities (or in some cases, any portion of a facility) in which regular or
routine education, library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS mission to
protect and advance the physical and mental health of the American people.

Reference

1.  Infectious DiseaseþA Global Health Threat, Report of the National Science and
Technology Council Committee on International Science, Engineering, and
Technology Working Group on Emerging and RE-emerging Infectious Diseases. 
September 1995.


Return to Volume Index

Return to NIH Guide Main Index


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.