Expired RFA-AI-04-017: INTERNATIONAL COLLABORATIONS IN INFECTIOUS DISEASE RESEARCH (ICIDR)

Department of Health
and Human Services (HHS)

NIH... Turning Discovery Into Health^®

This notice has expired. Check the NIH Guide for active opportunities and notices.

EXPIRED

INTERNATIONAL COLLABORATIONS IN INFECTIOUS DISEASE RESEARCH (ICIDR)

RELEASE DATE: April 23, 2004

RFA: RFA-AI-04-017 (This RFA has been reissued as RFA-AI-09-010. Also see amendment NOT-AI-04-030)

EXPIRATION DATE: October 14, 2004

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
(http://www.nih.gov/)

COMPONENT OF PARTICIPATING ORGANIZATION:
National Institute of Allergy and Infectious Diseases (NIAID)
(http://www.niaid.nih.gov)

CATALOGUE OF FEDERAL DOMESTIC ASSISTANCE NUMBERS:
No. 93.856, Microbiology and Infectious Diseases Research
No. 93.855, Immunology, Allergy, and Transplantation Research

LETTER OF INTENT RECEIPT DATE: September 13, 2004
APPLICATION RECEIPT DATE: October 13, 2004

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

Diseases caused by tropical parasites are a global health problem
disproportionately affecting populations residing in less developed
countries. The tropical infectious diseases research program of the National
Institute of Allergy and Infectious Diseases (NIAID) is predicated on the
view that we live in a global community and, therefore, the health problems
of the United States cannot be separated from those of the rest of the world.
NIAID’s ultimate goal in this research area is attainment of the highest
standard of health for a greater proportion of the global health community
through the development of new and improved vaccines, diagnostics, and
treatments. Fulfillment of NIAID’s commitment to tropical infectious
diseases requires the capacity to carry out research in endemic areas.

The goals of the NIAID International Collaborations in Infectious Disease
Research (ICIDR) program are to: support high-quality, collaborative research
that will lead to or result in prevention, amelioration, and/or improved
treatment of tropical infectious diseases caused by protozoa and helminth
parasites; increase relevant research experience for both U.S. and foreign
investigators; and facilitate and enhance scientific linkages between U.S.
and foreign investigators to enhance the independent research capacity of the
collaborating foreign institutions and strengthen their scientific
infrastructure for further international collaborative arrangements. NIAID
seeks to support research that will result in scientifically sound
information that can guide relevant clinical and public health policy in
endemic countries.

RESEARCH OBJECTIVES

Background

Diseases caused by protozoan and helminth parasites affect billions of people
and result in the death and disability of millions annually. One out of ten
persons worldwide is 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 parasitic diseases is often cited as a key impediment to
further social and economic progress. No effective vaccines have been
identified for any human parasitic diseases and many existing therapeutics
for parasitic diseases are toxic and only partially effective. Very few new
therapeutics have been developed in recent years for parasitic infections.
Therefore, the challenges of parasitic infections continue to outpace
solutions. Previous methods of control and treatment of malaria are no
longer effective due, in part, to the emergence and spread of drug
resistance. As a result, mortality for malaria is over one million deaths
per year. Furthermore, it is estimated that more than 300 million people
suffer from severe disease associated with schistosomiasis and soil-
transmitted helminth infections.

To confront the challenges in international health more effectively, NIAID
established the International Centers for Tropical Disease Research (ICTDR)
network in 1991. Since 1991, all ICIDRs have been part of the NIAID ICTDR
network. This network incorporates Institute-supported intramural and
extramural tropical disease research centers into a cooperative research
program on tropical infectious disease problems. The ICTDR network stresses
an interactive approach, emphasizing the development of partnerships between
domestic and foreign scientists in order to enhance transfer of modern
technology to institutions in endemic areas and increase opportunities for
U.S. scientists to work in endemic areas; between NIAID and other U.S.
government, private, and international agencies with interests in tropical
disease research in order to most effectively utilize available resources;
and between individual investigators, funding organizations, and industry in
order to encourage the relevant application of recent scientific advances
toward critical issues of international health.

Objective and Scope

This RFA invites applications for collaborative research focused on parasitic
infectious diseases in endemic areas that disproportionately affect the
health of people living in the tropics. The ICIDR program is intended to
support research requiring access to populations of infected human and other
mammalian hosts, parasites, and vectors that are limited or unavailable in
the U.S. and other developed countries. Therefore, the majority of research
supported under the ICIDR program must be conducted at endemic foreign sites
with an emphasis on field and clinical studies. A non-U.S. co-investigator
at the foreign site will serve as a Major Foreign Collaborator (MFC). The
MFC should have an appointment at the foreign institution. The U.S. Principal
Investigator must collaborate with the MFC in the design, implementation,
monitoring, and administrative management of the research projects. The
research should not be limited to sample collection for detailed sample
evaluation in developed countries. In addition, support will not be provided
for research that can be conducted in the U.S. or in U.S.-based laboratories.

All applications must be focused on a single pathogen or disease entity.
Both single and multi-project research programs will be supported under this
RFA. Multi-project applications must propose at least two interrelated
projects focused around a central theme. Multi-project applications
submitted in response to this RFA must include an interventional component
which is defined as experimental studies in clinical or field situations to
investigate the safety and/or efficacy of a drug, vaccine, or vector control
strategy. Multi-project applications must have at least two cores: an
administrative core and a data management/biostatistical core. In addition,
multi-project applications may propose one or more scientific cores to serve
as a central resource for two or more of the proposed research projects.
Additional information on multi-project cores is provided under Special
Requirements below.

Research areas relevant to this RFA include studies of epidemiology, natural
history, pathogenesis, interventional studies including Phase I, II and III
preventive and therapeutic clinical trials, and vector control.
Multidisciplinary collaborations are encouraged to ensure the appropriate
breadth of scientific expertise in contributing fields, including but not
limited to infectious diseases, biochemistry, immunology, genetics,
pharmacology, molecular biology, microbiology, zoology, nutrition, and
medical entomology. Studies focused solely on HIV or the impact of HIV
infection on other tropical diseases, as well as studies of non-parasitic
infections in developing countries are supported by other NIAID activities
and will not be considered responsive to this solicitation.

MECHANISM OF SUPPORT

This RFA will use the NIH multi-project cooperative agreement (U19) and
single project cooperative agreement (U01), "assistance" mechanisms, rather
than "acquisition" mechanisms in which substantial NIH scientific and/or
programmatic involvement with the awardee is anticipated during the
performance of the activity. This RFA is a one-time solicitation. Future
unsolicited, competing-continuation applications based on this program will
compete with all investigator-initiated applications and will be reviewed
according to the customary peer review procedures. The anticipated award date
is July, 2005. Applications that are not funded in the competition described
in this RFA may be resubmitted as NEW investigator-initiated applications
using the standard receipt dates for NEW applications described in the
instructions to the PHS 398 application
(http://grants.nih.gov/grants/funding/phs398/phs398.html).

The NIH U19 and U01 are cooperative agreement award mechanisms in which the
Principal Investigator retains the primary responsibility and dominant role
for planning, directing, and executing the proposed project, with NIH staff
being substantially involved as a partner with the Principal Investigator, as
described under the section "Cooperative Agreement Terms and Conditions of
Award".

The total project period for applications submitted in response to this RFA
may not exceed five years.

This RFA uses just-in-time concepts.

FUNDS AVAILABLE

NIAID intends to commit approximately $7.5 million in FY 2005 to fund 8 to 12
new and/or competitive continuation grants in response to this RFA. An
applicant may request a project period of up to five years and a budget for
direct costs of up to $400,000 per year for single component applications and
up to $800,000 per year for multi-project applications. Because the nature
and scope of the proposed research will vary from application to application,
it is anticipated that the size and duration of each award will also vary.
Although the financial plans of NIAID provide support for this program,
awards pursuant to this RFA are contingent upon the availability of funds and
the receipt of a sufficient number of meritorious applications.

At this time, the NIAID has not determined whether or how this solicitation
will be continued beyond the present RFA.

ELIGIBLE INSTITUTIONS

The following may submit an application:

o Domestic for-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals,
and laboratories
o Faith-based or community-based organizations

Foreign institutions are not eligible to apply as the primary awardee
institution.

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any U.S.-based individual with the skills, knowledge, and resources necessary
to carry out the proposed research is invited to work with their institution
to develop an application for support. Individuals from underrepresented
racial and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH programs.

SPECIAL REQUIREMENTS

1. Overall Research Goals and Objectives, and Strategic Plan

The application must identify and describe overall goals and objectives of
the ICIDR, the potential importance of the proposed research to the health
and well being of the population in the endemic country, the ICIDR
organization, the participating institutions, and the role of all consortium
members. The application should include a strategic plan for strengthening
research capacity at the endemic site and disseminating research findings to
host country health leaders. The strategic plan should include an outcome
evaluation plan for capacity building and research and training objectives.
The following areas should be included in the strategic plan:

o Strengths - Identify and describe the strengths of the proposed consortium
including a brief summary of the research and development experience and
expertise of ICIDR participants, as well as the current facilities and other
research resources available. Identify and evaluate the potential
opportunities to establish high quality research, and the capacity of the
host country research team to function independently through the ICIDR
collaboration. Discuss how collaborations with endemic institutions will be
further developed and target opportunities that will address the goals of the
NIAID tropical disease research program and how the specific project(s) will
enhance clinical research capacity at the host site e.g. laboratory and/or
clinical infrastructure.

o Research Focus - The intent of the ICIDR Program is to support research
with potential to significantly improve the health and well being of
individuals living in tropical countries. Describe how the proposed research
might translate into improved disease control, vaccines, therapeutics and/or
diagnostics. The application should state how the research may potentially
impact on future public health policy.

o Structure - Provide a detailed plan for the organizational structure, lines
of authority and communications, and staffing of the proposed ICIDR. This
includes: (1) an organizational diagram showing the various ICIDR
participating institutions, projects, and proposed staffing for scientific,
technical and administrative functions; (2) a narrative description of the
roles and responsibilities of all scientific and administrative staff and
their level of effort; and (3) a narrative description of plans and
procedures for ensuring adequate coordination among participating
institutions and personnel, with special emphasis on data sharing,
publication agreements and publication goals.

2. Research Plan

Applicants must provide a detailed description of the proposed research
project(s), including: (1) the pathogen or disease entity proposed for
study; (2) the research question(s) to be addressed and a description of the
facilities available as needed for the proposed research projects; (3) the
proposed methodology; (4) where appropriate, the study population,
documentation of access to necessary patients and/or samples, and plans for
the recruitment and retention of study participants; (5) quality control and
analysis plans; and (6) training as required by investigators and field staff
to conduct research. The Research Plan must also include the proposed
timelines for the planning, implementation, conduct and completion of
research projects.

In addition, all projects proposing clinical studies must include a brief
concept proposal for each clinical study, detailing the following aspects of
the proposed clinical research:

Study Title
Hypothesis to be tested
Study objectives
Population
Clinical sites
Intervention and comparators (if any)
Regimen (if any)
Study design (not all parts may be relevant)
Eligibility/exclusion criteria
Randomization/stratification plan
Number of subjects
Anticipated duration of recruitment phase
Total study duration
Interim study progress and safety monitoring plan, if applicable
Primary endpoints/outcomes
Secondary endpoints/outcomes
Study visit schedule and primary evaluations (including laboratory
evaluations)
Sample size justification
Any proposed sub-studies
Data analyses planned

3. Collaborative Arrangements and Capacity Building

The domestic applicant institution is responsible for developing an
affiliation(s) with an established institution(s) (e.g., university, research
institute, federal or state health department, hospital) in the tropical host
country. ICIDR research activities conducted at the foreign affiliate must
be supported under a consortium agreement made with the U.S.-based
institution. The U.S. Principal Investigator must designate one MFC from the
foreign institution(s) to serve as the co-investigator and provide
documentation of an off-site component as the foreign base of operations.
Proposed research projects must be acceptable to the collaborating foreign
investigators and their institutions. A countersigned letter of intent from
the foreign institution documenting off-site components and investigators
must be included in the application. Applications that do not provide such
documentation will be considered unresponsive and will not be reviewed.

In addition, it may be necessary to establish a working agreement with the
government of the host country to expedite exchange of personnel, equipment
and supplies from the U.S. to the off-site facility, and to provide assurance
that study data can be exported for public use. 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 institution 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.

4. Percent Effort of ICIDR Personnel

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. It is anticipated that the Principal Investigator will spend up
to 2 months per year at the foreign site. Other U.S. ICIDR investigators are
expected to spend longer periods of time at the foreign site. The Principal
Investigator for single-project ICIDRs must expend at least 20% effort on the
ICIDR program. It is anticipated that the demands of multi-project ICIDR
programs will require even greater effort on the part of the Principal
Investigator. The MFC must be substantially involved in the project,
committing at least 40% effort for single projects and a higher level of
effort for multi-project programs. Each ICIDR must have a designated
biostatistician and data manager; multi-project programs must have a core
designated for these functions. The biostatistician must expend no less than
5% effort for single projects and 10% effort for multi-project programs. A
full-time data manager is required at the endemic site for both U01s and
U19s.

5. Administration/Administrative Core

It is expected that there will be both a domestic and a foreign
administrative structure with intentional transfer of administrative capacity
to the foreign site. The Principal Investigator and the MFC are responsible
for administration of the ICIDR program. A well-developed administrative
plan is integral to the ICIDR success, and must be clearly defined in the
application. The plan should include discussion of the structure and roles
of administrative staff including: the training and experience of proposed
staff; the functions to be performed; the plans for the transfer of
administrative capacity to the foreign site; and the time frame within which
such responsibilities will be transferred to the foreign site. For multi-
project U19 applications, an administrative core must be included. This
administrative core is responsible for managing, coordinating, and
supervising the entire range of ICIDR activities, monitoring progress, and
ensuring the strategic plan is implemented effectively and within proposed
timelines. This administrative core should clearly identify personnel and
resources needed to oversee the overall program. The description must
provide a clear and explicit discussion of how fiscal and other resources
will be allocated and prioritized, how communications throughout the ICIDR
will be facilitated, and how research- related travel will be organized and
budgeted.

In the proposed budget, both single-project (U01) and multi-project (U19)
applications must include funding for overall administrative staff and
services, expenses for publications for collaborative efforts, communication
expenses, travel, as well as administrative capacity building at the foreign
institution to meet reporting and oversight requirements of the program.

6. Data Management and Biostatistical Component/Core

A data management system, managed by the MFC, and a full-time data manager
must be present at the foreign site. Applications must provide a detailed
description of the existing or planned data management system. The data
management system should ideally include: security features for controlled
access to project data; a tracking system for data forms and activities;
double data entry of data forms; date and time of stamping of all data
records with electronic signatures; and audit trails to track all changes
made to data records. In addition, it is expected that U.S. and foreign
staff will collaborate on the design, development and testing of databases
and data management software, training of data management and field personnel
on data collection activities, maintenance of the database and software
systems, documentation of changes, and preparation of standard operating
procedures for all aspects of data management. Applications must also
address how such a collaborative onsite approach will be planned and
implemented, as well as the time frame within which all design, development,
testing and training activities will take place to achieve a fully
operational data management system and appropriately trained staff.
Applicants with inadequate data systems and data management support currently
in place should budget at least $50,000 each year in the first two years of
the program to ensure development of robust and comprehensive data management
systems and for related training needs. It is recommended that data
management systems for clinical trials be developed using FDA guidelines on
electronic records issued in 21 CFR part 11
(http://www.biotechnicalservices.com/downloads/21CFRpart11.pdf).

Biostatistical support is required for assisting with protocol design,
development and analysis. This support should provide for activities such as
developing randomization procedures, developing stopping rules, monitoring
study progress, and analyzing interim and final study results. For clinical
trials that require Data Safety and Monitoring Board (DSMB) oversight,
biostatistical support will include analytical plans, DSMB reports, and the
preparation of responses to DSMB requests. A designated biostatistician must
expend no less than 5% effort for single projects and 10% effort for multi-
project programs.

U19 multi-project applications must include the data management and
biostatistical support requirements in a separate core.

7. Meetings

An ICIDR Executive Committee (IEC), comprised of the ICIDR Principal
Investigators and the NIAID Program Officers, will be formed to address the
need for communication, collaboration, and flexibility to meet emerging
research challenges within the ICIDR and the ICTDR programs, as well as
within the tropical medicine research community. The IEC will have primary
responsibility for identification of emerging research projects for support
from the ICIDR Opportunity Pool (see below) and assisting with the planning
of an annual ICTDR meeting.

The initial meeting of the IEC, to be convened by NIAID, will be held within
six (6) months of award. The IEC will meet twice annually thereafter, once
at the annual ICTDR meeting and one additional meeting that may be scheduled
around the American Society of Tropical Medicine and Hygiene annual meeting.
Meeting budget requests should include funds for travel by the ICIDR
Principal Investigator to two IEC meetings per year including the ICTDR
meeting; and travel for the MFC, and one or two additional ICIDR staff, if
needed, to the annual ICTDR meetings.

8. Opportunity Pool

The NIAID has established an ICIDR Opportunity Pool
(http://www.niaid.nih.gov/ictdr/op-pool.htm) to respond to unanticipated
scientific needs and opportunities in tropical medicine in order to enhance
translation from basic research to field research and site-to-site
collaboration. Scientific needs and opportunities eligible for support by
the ICIDR Opportunity Pool include, but are not limited to, research-oriented
investigations of anticipated or unanticipated outbreaks of infectious
diseases, evaluation of new diagnostics or therapeutics, and pilot studies.
It is anticipated that the research supported under this Opportunity Pool
would produce scientific advances as a result of multi-site cooperation and
collaboration. ICIDR Opportunity Pool proposals are not part of the ICIDR
application. Therefore, budgets for Opportunity Pool funds should not be
included in the ICIDR application. At the initial IEC meeting, one of the
awardees will be selected by the IEC to manage the Opportunity Pool funds.
The IEC will be responsible for the administration and scientific review of
Opportunity Pool proposals once the ICIDR awards are made.

9. Pathogen Study Groups

Pathogen Study Groups (PSGs) focused on a specific pathogen or disease entity
and Interest Groups (IG) focused on research approaches will be established
or continued by ICIDR investigators and the NIAID Program staff.
Responsibilities of these groups will include: facilitation of information
exchange including research advances; fostering collaboration and
translational research; coordination of activities to minimize duplication;
and identification of emerging research opportunities. The PSGs may be
comprised of ICIDR investigators, other investigators participating in the
ICTDR network, other members of the NIAID-supported research community,
international organizations such as WHO, trainees supported by the NIH
Fogarty International Center, and other interested participants. Each PSG or
IG will be responsible for electing a chairperson who will work with NIAID
Program Staff to organize communication and activities. Each applicant must
budget $15,000 per year for PSG or IG activities such as conference calls,
internet connectivity, attending special training courses or workshops, and
organizing interest group meetings. Support for this activity should be
included in the administrative budget.

COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF AWARD

The following terms and conditions will be incorporated into the award
statement and provided to the Principal Investigator as well as the
institutional official at the time of award.

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 instruments used for this program are the
single project (U01) and multiproject (U19) cooperative agreements,
"assistance", rather than "acquisition", mechanisms, 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 a
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 Program
Staff.

1. Monitoring Clinical Studies

When clinical studies or trials are a component of the research proposed,
NIAID policy requires that studies be monitored commensurate with the degree
of potential risk to study subjects and the complexity of the study. An
Updated NIAID policy was published in the NIH Guide on July 8, 2002 and is
available at
http://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html.
The full policy, including terms and conditions of award, is
available at http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf; Guidance for
Compliance with NIAID Clinical Terms of Award at
http://www.niaid.nih.gov/ncn/pdf/clintermguidance.pdf; and the DMID Policies
and Guidance for Data and Safety Monitoring at
http://www.niaid.nih.gov/dmid/clinresearch/.

Award of a cooperative agreement does not constitute approval for initiation
of human subjects research. ICIDR investigators will be required to develop
and conduct all studies involving human subjects using Good Clinical Practice
Standards as defined and published by the International Conference on
Harmonization (ICH) and adopted by the FDA (Federal Register Vol.62 No. 90
(5/9/97) (http://www.fda.gov/oc/gcp/guidance.html).

Prior to study initiation, NIAID staff will review all studies involving
human subjects at two stages. The first stage will be a review of the
research concept and the second review will be during protocol development.
Both stages will be reviewed for scientific content, design, safety,
feasibility, statistical, and regulatory compliance. Use of the NIAID
protocol template, found at the International Clinical Studies Support Center
website (http://icssc.org/rel_links.htm#templates), is encouraged.

All ICIDR protocol documents for interventional studies should include the
ICH protocol requirements outlined in part 6 of the ICH Harmonized Tripartite
Guideline for Good Clinical Practice website http://www.ich.org or at
http://www.mch.com/doctors_caregivers/research/Forms/ICH%20Guidlines%20
for%20Research%20Protocols.pdf.

2. Awardee Rights and Responsibilities

Awardees will have primary responsibility for collaborating with the foreign
sites; for defining the research objectives, approaches and details of the
projects within the guidelines of the RFA; and for performing the scientific
activity. Specifically, awardees have primary responsibility to:

o Develop affiliations with one or more established institutions in the
tropical host country (e.g., university, research institute, federal or state
health department, hospital). ICIDR research activities conducted at foreign
sites must be supported under a consortium agreement between the tropical
host country/institution(s) and the U.S. institution
(http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600251).
Signed copies of the consortium agreements should be submitted to
NIAID Grants Management Staff and Program Staff within 60 days after the
issue date of the Notice of Grant Award.

o Maintain a mutually acceptable arrangement with the host country affiliate
institution(s) and any relevant governmental agencies. This includes
communicating with and seeking required approvals, and complying with all
requirements of regulatory and health governmental agencies in the host
country. Where applicable, procedures must be established for all
participating institutions to comply with FDA regulations for studies
involving investigational agents, and to comply with the requirements of 45
CFR Part 46 for the protection of human subjects.

o Develop protocols that clearly state the rationale, objectives and methods
for proposed research projects. This includes the 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. Study
protocols should be reviewed and endorsed by all participating investigators
prior to submission to NIAID.

o Submit for approval final protocols, informed consent documents, relevant
procedure manuals and all required amendments to the NIAID Program Officer,
Institutional Review Boards (IRBs) at all participating institutions as per
the Office of Human Research Protection (OHRP) guidelines, and all relevant
regulatory agencies.

o Provide for quality assurance/quality control, data management, drug
distribution and drug accountability (pharmacy plans), and appropriate
laboratory procedures and standards. The Principal Investigator will provide
and document necessary training for clinical research staff in protection of
human subjects training as required by NIH policy
http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part5.htm#_Toc54600083
, Good Clinical Practices, regulatory adherence, protocol specific
procedures, and other training as needed, e.g., for trial-related medical
management issues prior to initiation of the study.

o Establish a statistical and data management capacity, and when required,
prepare statistical reports for DSMBs. The requirements, criteria, and
procedures for serious adverse events (SAE) reporting and any other types of
study safety monitoring reporting as determined by NIAID must be followed for
each study.

o Cooperate with the NIAID Division of Microbiology and Infectious Diseases
(DMID) clinical site monitoring contractor and other federally supported site
monitoring staff or regulatory auditors who will inspect records to ensure
compliance with all federal regulations, Good Clinical Practice, accurate
protocol implementation, internal quality management, NIH policies on patient
safety, and quality management and data completeness and accuracy. Typical
visits will consist of the monitoring of protocol adherence, review of the
regulatory file, review of case report forms and source documents, review of
internal quality management plans, and audit pharmacies for care and
accountability of investigational products. The Principal Investigator will
be responsible for the response to monitor findings.

o Ensure the accurate and timely assessment of the progress of research.
This includes, but is not limited to, the development of adequate internal
Quality Assurance/Quality Control (QA/QC) procedures for data collection and
management and laboratory performance, ensuring adequate supervision at all
field sites, laboratories, and data facilities, and generation of periodic
reports addressing study conduct quality and progress.

o Cooperate in the reporting of the study findings. It is specifically
intended that publications resulting from collaborative research will be
primary authored and/or co-authored by 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. NIH policies governing possible co-authorship of
publications with NIAID staff will apply in all cases. Publications or oral
presentation of work done under this award will require appropriate
acknowledgement of NIAID/DHHS support.

o Domestic and Foreign Opportunity Pool Funds. The manager of the ICIDR
Opportunity Pool must include in his/her annual progress report a listing of
the recipients of the pool funds, the awarded amount, the time period, and a
brief statement of progress submitted to NIAID Grants Management and Program
Staff. Recipients of ICIDR Opportunity Pool funds should also include a
statement detailing the progress in their annual report submitted to NIAID
Grants Management Staff and Program Staff.

o Foreign Opportunity Pool Funds. For Foreign Opportunity Pool Funds
(approved by the IEC) involving international studies, the awardee
institution must submit a copy of the application to NIAID Grants Management
and Program Staff prior to obtaining support. No funds may be provided for
projects involving foreign sites unless specifically indicated on a revised
Notice of Grant Award.

o Provide NIAID with all the necessary information and documentation for
filing the IND application with the FDA when NIAID holds the IND, amend after
comments are provided by the Program Officer, local IRB, and regulatory
authorities, and submit safety reports and annual IND reports.

3. NIAID Program Responsibilities

NIAID staff assistance will be provided by a Program Officer who will serve
as NIAID's Scientific Coordinator. 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.

During performance of the award, the NIAID Scientific Coordinator, with
assistance from other scientific program staff who are designated based on
the research topic and their relevant expertise, may provide appropriate
assistance, advice, and guidance by participating in the design of the
activities; by advising in the selection of sources or resources (e.g.,
determining where a particular reagent can be found); by coordinating or
participating in the collection and/or analysis of data; by advising in
management and technical performance; or by participating in the preparation
of publications. The NIAID Scientific Coordinator will serve as a
liaison/facilitator between the awardee, pharmaceutical and biotech
industries, and other government agencies (e.g., FDA, USDA, CDC) and will
serve as a resource of scientific and policy information related to the goals
of the awardee's research. However, the role of NIAID will be to facilitate
and not to direct the activities. It is anticipated that decisions in all
activities will be reached by consensus and the NIAID staff will be given the
opportunity to offer input into this process. The manner of reaching this
consensus and the final decision-making authority will rest with the
Principal Investigator.

o Provide substantial assistance in the design and conduct of research
activities, including advice on the design, development, and technical
performance of clinical protocols and statistical evaluations of data; and
access to and use of reagents, assays, and other resources available through
NIAID contractors and awardees, as appropriate. For interventional studies,
NIAID Program Staff are responsible for coordinating with DMID’s Office of
Regulatory Affairs (ORA) for advice and assistance in meeting FDA
requirements for investigational agents.

o Coordinate protocol review and consent review using standard NIAID
procedures. The NIAID Program Officer will return comments and
recommendations to the Principal Investigators in a timely manner.

o Make decisions regarding the need for a U.S. FDA IND, and who would hold
the IND when needed.

o Receive and review all reports of adverse events and serious adverse
events.

o Review progress and make recommendations for continued funding based on a
review of annual and periodic reports on progress, findings, and future
plans; periodic site visits for discussions with research teams; observation
of field data collection and management, quality control, fiscal review, and
other relevant matters; publications; study subject and/or data accrual;
cooperation in carrying out the research; and/or maintenance of a high
quality of research.

o Provide for clinical site monitoring contractors or regulatory auditors to
make site visits and assessments at endemic sites when deemed necessary, to
ensure site capacity and evaluate progress of the proposed research.

o Determine whether it is necessary to terminate an ongoing study for any of
a number of reasons which include, but are not limited to, risk to subject
safety; the scientific question is no longer relevant or the objectives will
not be met; failure to comply with Good Clinical Practices, applicable
federal regulations, or Terms of Award; occurrence of unforeseen drug safety
issues or data from preclinical studies indicate a presence of unanticipated
toxicity; risks that cannot be adequately quantified; ethical concerns raised
by the local community or local medical care/health care authorities; failure
to remedy deficiencies identified by site monitoring teams; substandard data;
inadequate progress in fulfilling the research plan; or successful completion
of study not feasible with prevailing accrual rates.

o Assist, where warranted, in data analyses and interpretation, and the
dissemination of study findings to the research community and health care
recipients, including co-authorship of the publication of results of studies
conducted by the ICIDRs, subject to NIH publication policies.

o Phase III and selected Phase II interventional studies will be monitored by
a DSMB, to be selected and overseen by NIAID staff (see DMID Policies and
Guidance for Data and Safety Monitoring
http://www.niaid.nih.gov/dmid/clinresearch/). All Phase I and II
interventional studies will be monitored by interim monitoring boards that
will be established jointly by NIAID program staff, the ICIDR Executive
Committee, and the Principal Investigator.

4. Collaborative Responsibilities

In addition to the interactions defined above, awardees and NIAID staff shall
share responsibilities for the scientific coordination and communication of
the ICIDR network through the IEC, PSGs, and IGs. In the event that
opportunities arise and funds become available for multi-center research
studies, the IEC will work with the relevant PSG to develop common protocol,
manuals, questionnaires, data sharing, analysis, and publications.

5. Arbitration

Any disagreement that may arise on scientific/programmatic matters (within
the scope of the award) between award recipients and NIAID may be brought to
arbitration. An arbitration panel will be composed of three members one
chosen by the awardee, a second member selected by NIAID, and the third
member selected by the two prior selected members. This special arbitration
procedure in no way affects the awardee's right to appeal an adverse action
that is otherwise appealable in accordance with the PHS regulations at 42 CFR
Part 50, Subpart D and HHS regulation at 45 CFR Part 16.

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 Parts 74 and 92, and other HHS, PHS, and NIH Grant
Administration policy statements

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity to
answer questions from potential applicants. Inquiries may fall into three
areas: scientific/research, peer review, and financial or grants management
issues:

o Direct questions about scientific/research issues to:

Elizabeth S. Higgs, MD, DTMH, MIA
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room 5067, MSC-6604
6610 Rockledge Drive
Bethesda, MD 20892-6603
Telephone: 301-402-8372
FAX: 301-402-0659
Email: [email protected]

Malla R. Rao, DrPH, M.Eng
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases, DHHS
Room 5095, MSC-6604
6610 Rockledge Drive
Bethesda, MD 20892
Telephone: 301- 451-3749
FAX: 301-402-0659
Email: [email protected]

o Direct questions about peer review issues to:

Gary Madonna
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3135, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: 301-496-3528
FAX: 301-402-2638
Email: [email protected]

o Direct questions about financial or grants management matters to:

Donna R. Sullivan
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room Number 2232, MSC-7614
6700-B Rockledge Drive
Bethesda, MD 20892-7614
Telephone: 301-594-6361
FAX: 301-480-3780
Email: [email protected]

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o Number and title of this RFA

Although a letter of intent is not required, is not binding, and does not
enter into the review of a subsequent application, the information that it
contains allows IC staff to estimate the potential review workload and plan
the review.

The letter of intent is to be sent by the date listed at the beginning of
this document. The letter of intent should be sent to:

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application
instructions and forms (rev. 5/2001). Applications must have a DUN and
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the
Universal Identifier when applying for Federal grants or cooperative
agreements. The DUNS number can be obtained by calling (866) 705-5711 or
through the web site at http://www.dunandbradstreet.com/. The DUNS number
should be entered on line 11 of the face page of the PHS 398 form. The PHS
398 document is available at
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive
format. For further assistance contact GrantsInfo, Telephone (301) 710-0267,
Email: [email protected].

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001)
application form must be affixed to the bottom of the face page of the
application. Type the RFA number on the label. Failure to use this label
could result in delayed processing of the application such that it may not
reach the review committee in time for review. In addition, the RFA title
and number must be typed on line 2 of the face page of the application form
and the YES box must be marked. The RFA label is also available at:
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.

SENDING AN APPLICATION TO THE NIH : Submit a signed, typewritten original of
the application, including the Checklist, and three signed, 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:

Applications that are not received as a single package on or before the
October 13, 2004 or that do not conform to the instructions contained in PHS
398 (rev. 5/01) Application Kit (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.

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 contact under INQUIRIES).

SPECIAL INSTRUCTIONS FOR COMPLETION OF APPLICATIONS IN RESPONSE TO THIS RFA:

(See also the SPECIAL REQUIREMENTS section above for additional application
instructions and requirements.)

Applicants for U19 grants must follow special application guidelines in the
NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT
AWARDS; this brochure is available via the WWW at
http://www.niaid.nih.gov/ncn/grants/multibron.htm. This brochure presents
specific instructions for sections of the PHS 398 (rev. 5/01) application
form that should be completed differently than usual. For all other items in
the application, follow the usual instructions in the PHS 398.

U01 Single Project Applications

For this initiative, the overall page limit for Sections a-d of the Research
Plan is increased from the normal 25 page limit of the PHS 398 to a total of
35 pages to accommodate the special requirements listed below:

a. Specific Aims
b. Background and Significance
o Overall Research Goals and Objectives, and Strategic Plan
o Collaborative Arrangements and Capacity Building
o Administrative requirements
c. Preliminary Studies/Progress Report
d. Research Design and Methods
o Research Plan
o Concept Proposal for Clinical Studies (5 pages recommended)
o Data Management and Biostatistical support requirements

U19 Multi-Project Applications

The Overall Research Goals and Objectives, and Strategic Plan and the
Collaborative Arrangements and Capacity Building sections should be included
in the overview of the application.
Sections a-d of each individual project should not exceed 30 pages. This
increases the normal 25 page limit outlined in the NIAID Multiproject
Brochure to accommodate the special requirements listed below:
a. Specific Aims
b. Background and Significance
c. Preliminary Studies/Progress Report
d. Research Design and Methods
o Research Plan
o Concept Proposal for clinical studies (5 pages recommended)
e. Administrative Core 5 pages recommended
f. Data Management and Biostatistical Core 5 pages recommended
g. Scientific Cores, if proposed 5 pages recommended

APPLICATION PROCESSING: Applications must be received by the application
receipt date listed in the heading of this RFA. If an application is
received after that date, it will be returned to the applicant without
review.

The Center for Scientific Review (CSR) will not accept any application in
response to this RFA that is essentially the same as one currently pending
initial review, unless the applicant withdraws the pending application.
However, when a previously unfunded application, originally submitted as an
investigator-initiated application, is to be submitted in response to an RFA,
it is to be prepared as a NEW application. That is, the application for the
RFA must not include an Introduction describing the changes and improvements
made, and the text must not be marked to indicate the changes from the
previous unfunded version of the application.

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.

Although there is no immediate acknowledgement of the receipt of an
application, applicants are generally notified of the review and funding
assignment within 8 weeks.

PEER REVIEW PROCESS

Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the NIAID. Incomplete and/or nonresponsive applications
will be returned to the applicant without further consideration.
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, all applications will:

o Undergo a selection process in which only those applications deemed to have
the highest scientific merit, generally the top half of applications under
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the National Advisory Allergy and
Infectious Diseases Council

REVIEW CRITERIA

SINGLE PROJECT EVALUATION (U01)

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. In
the written comments, reviewers will be asked to evaluate the application in
order to judge the likelihood that the proposed research will have a
substantial impact on the pursuit of these goals. The scientific review group
will address and consider each of the following criteria in assigning the
application’s overall score, weighting them as appropriate for each
application. The application does not need to be strong in all categories to
be judged likely to have 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.

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?

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?

INNOVATION: Does the project employ novel concepts, approaches or methods?
Are the aims original and innovative? Does the project challenge existing
paradigms or develop new methodologies or technologies?

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 researchers (if any)?

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?

MULTI-PROJECT EVALUATION (U19)

The general review criteria for U19 multi-project cooperative agreement
applications are presented in the NIAID brochure entitled "INSTRUCTIONS FOR
APPLICATIONS FOR MULTI-PROJECT AWARDS at
http://www.niaid.nih.gov/ncn/grants/multibron.htm. Each scientific research
project proposed in a multi-project (U19) application will be reviewed
according to the criteria stated above for single project applications. In
addition, the following items will also be considered in the determination of
scientific merit and the priority score:

Overall Application:

The initial review group will judge the relationship and contributions of
each component research project and core to the overall theme of the
application. This evaluation is separate from the merit evaluation of
individual projects and cores. Reviewers assess the overall application after
rating individual research projects and cores according to the following
criteria:

o Scientific merit of the program as a whole as well as that of the
individual research projects and cores.

o Significance of the overall program goals.

o Scientific gain achieved by combining the component projects into a multi-
project program beyond that achievable if each project were pursued
independently.

o Cohesiveness and multi-disciplinary scope of the program and the
coordination and interrelationships-of individual projects and core or cores
to the common theme.

o Leadership and scientific ability of the principal investigator: ability to
develop a program of integrated research projects with a well-defined central
research focus, and commitment and ability to devote adequate time and effort
to the program.

o Qualifications, experience, and commitment of investigators responsible for
the individual research projects or core or cores and their contribution to
the program, including their ability to devote adequate time and effort to
the program.

o For competing renewal and supplement applications, accomplishments of the
program to date.

Note: If peer reviewers deem that fewer than the required minimum number of
research projects (two) have substantial and significant scientific merit,
the application will not be recommended for further consideration. NIAID
will not award such applications or consider a strong project within a multi-
project application for a separate award. As stated above, you can submit
your application simultaneously as an independent R01.

ADDITIONAL REVIEW CRITERIA FOR ALL APPLICATIONS (U01/U19): In addition to
the above criteria, the following items will be considered in the
determination of scientific merit and the overall priority score:

o Strength of the proposed collaborative relationships and strategic plan
including scientific, administrative and organizational structures,
communications, defined scientific and administrative roles and
responsibilities and decision-making processes that facilitate attainment of
the objective or objectives of the program.

o Potential for the project to enhance the clinical research capacity at the
host site, including strengthening of administrative, laboratory, or clinical
infrastructure and strengthening capacity of the host country research team
to function independently on this and other research projects.

o Features and strengths of the existing field sites and/or scientific and
clinical facilities where the research will be conducted and abilities of the
key foreign staff to conduct the proposed study.

o Strengths of the proposed study design and conduct of the field or clinical
research described in the five-page concept proposal.

o Adequacy of the time and effort proposed by the Principal Investigator,
MFC, Data Manager, and Biostatistician.

o Adequacy of existing or planned data management systems and proposed plans
to enhance the capabilities and quality of the onsite data management system
and expertise.

o Importance of the proposed project to public health in the endemic country
and likelihood that the proposed project would have an impact on the health
of those in the host country.

o Adequacy of outcome evaluation plan to evaluate success of research,
collaboration, strengthening of research capacity, training, and impact of
research results.

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human
subjects and protections from research risk relating to their participation
in the proposed research will be assessed. (See criteria included in the
section on Federal Citations, below).

INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of
plans to include subjects from both genders, all racial and ethnic groups
(and subgroups), and children as appropriate for the scientific goals of the
research. Plans for the recruitment and retention of subjects will also be
evaluated. (See Inclusion Criteria in the sections on Federal Citations,
below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to
be used in the project, the five items described under Section f of the PHS
398 research grant application instructions (rev. 5/2001) will be assessed.

ADDITIONAL REVIEW CONSIDERATIONS

SHARING RESEARCH DATA: Applicants requesting more than $500,000 in direct
costs in any year of the proposed research are expected to include a data
sharing plan in their application. The reasonableness of the data sharing
plan or the rationale for not sharing research data will be assessed by the
reviewers. However, reviewers will not factor the proposed data-sharing plan
into the determination of scientific merit or priority score. (See
instructions and URL to policy in the Federal Citations, below.)

BUDGET: The reasonableness of the proposed budget and the requested period of
support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date: September 13, 2004
Application Receipt Date: October 13, 2004
Peer Review Date: February, 2005
Council Review: May, 2005
Earliest Anticipated Start Date: July, 2005

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit of the proposed project as determined by peer review
o Availability of funds
o Programmatic priorities.

REQUIRED FEDERAL CITATIONS

HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and
others, and the importance of the knowledge gained or to be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II), efficacy,
effectiveness and comparative trials (phase III). The establishment of data
and safety monitoring boards (DSMBs) is required for multi-site clinical
trials involving interventions that entail potential risk to the
participants. (NIH Policy for Data Safety and Monitoring, NIH Guide for
Grants and Contracts, June 12, 1998:
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

SHARING RESEARCH DATA: Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are expected to include a
plan for data sharing or state why this is not possible.
http://grants.nih.gov/grants/policy/data_sharing Investigators should seek
guidance from their institutions, on issues related to institutional
policies, local IRB rules, as well as local, state and Federal laws and
regulations, including the Privacy Rule. Reviewers will consider the data
sharing plan but will not factor the plan into the determination of the
scientific merit or the priority score.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: 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 clinical research projects unless a
clear and compelling justification is provided indicating that inclusion is
inappropriate with respect to the health of the subjects or 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 clinical research should read the AMENDMENT "NIH
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research - Amended, October, 2001," published in the NIH Guide for Grants and
Contracts on October 9, 2001
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the new PHS Form 398; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a)
all applications or proposals and/or protocols must provide a description of
plans to conduct analyses, as appropriate, to address differences by
sex/gender and/or racial/ethnic groups, including subgroups if applicable;
and b) investigators must report annual accrual and progress in conducting
analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:
The NIH maintains a policy that children (i.e., individuals under the age of
21) must be included in all human subjects research, conducted or supported
by the NIH, unless there are scientific and ethical reasons not to include
them.

All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines" on the inclusion of children as participants in
research involving human subjects that is available at
http://grants.nih.gov/grants/funding/children/children.htm

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH
policy requires education on the protection of human subject participants for
all investigators submitting NIH proposals for research involving human
subjects. This policy announcement is in the NIH Guide for Grants and
Contracts Announcement, dated June 5, 2000, at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research
on hESCs can be found at http://stemcells.nih.gov/index.asp and at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only
research using hESC lines that are registered in the NIH Human Embryonic Stem
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).
It is the responsibility of the applicant to provide, in the project
description and elsewhere in the application as appropriate, the official NIH
identifier(s) for the hESC line(s)to be used in the proposed research.
Applications that do not provide this information will be returned without
review.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The
Office of Management and Budget (OMB) Circular A-110 has been revised to
provide public access to research data through the Freedom of Information Act
(FOIA) under some circumstances. Data that are (1) first produced in a
project that is supported in whole or in part with Federal funds and (2)
cited publicly and officially by a Federal agency in support of an action
that has the force and effect of law (i.e., a regulation) may be accessed
through FOIA. It is important for applicants to understand the basic scope
of this amendment. NIH has provided guidance at
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this RFA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the
application. In addition, applicants should think about how to structure
informed consent statements and other human subjects procedures given the
potential for wider use of data collected under this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The
Department of Health and Human Services (DHHS) issued final modification to
the Standards for Privacy of Individually Identifiable Health Information ,
the Privacy Rule, on August 14, 2002. The Privacy Rule is a federal
regulation under the Health Insurance Portability and Accountability Act
(HIPAA) of 1996 that governs the protection of individually identifiable
health information, and is administered and enforced by the DHHS Office for
Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside
with the researcher and his/her institution. The OCR website
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including
a complete Regulation Text and a set of decision tools on Am I a covered
entity? Information on the impact of the HIPAA Privacy Rule on NIH
processes involving the review, funding, and progress monitoring of grants,
cooperative agreements, and research contracts can be found at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals
for NIH funding must be self-contained within specified page limitations.
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs)
should not be used to provide information necessary to the review because
reviewers are under no obligation to view the Internet sites. Furthermore,
we caution reviewers that their anonymity may be compromised when they
directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of "Healthy
People 2010," a PHS-led national activity for setting priority areas. This
RFA is related to one or more of the priority areas. Potential applicants may
obtain a copy of "Healthy People 2010" at
http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS

This program is described in the Catalogue of Federal Domestic Assistance at
http://www.cfda.gov/ in the following citations: No. 93.855, Immunology,
Allergy, and Transplantation Research and No. 93.856, Microbiology and
Infectious Diseases Research. Awards are made under authorization of
Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241
and 284) and administered under NIH grants policies and Federal Regulations
42 CFR 52 and 45 CFR Parts 74 and 92. This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review.

The NIH Grants Policy Statement is available at
http://grants.nih.gov/grants/policy/policy.htm. This document includes
general information about the grant application and review process;
information on the terms and conditions that apply to NIH Grants and
cooperative agreements; and a listing of pertinent offices and officials at
the NIH. All awards are subject to the terms and conditions, cost
principles, and other considerations described in the NIH Grants Policy
Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free
workplace and discourage the 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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices