and Human Services (HHS)
EXPIRED
INTERNATIONAL STUDIES OF AIDS-ASSOCIATED CO-INFECTIONS (ISAAC)
RELEASE DATE: August 19, 2003
RFA Number: RFA-AI-03-036
National Institute of Allergy and Infectious Diseases (NIAID)
(http://www.niaid.nih.gov)
CATALOGUE OF FEDERAL DOMESTIC ASSISTANCE NUMBERS:
No. 93.855, Immunology, Allergy, and Transplantation Research
No. 93.856, Microbiology and Infectious Diseases Research
LETTER OF INTENT RECEIPT DATE: December 12, 2003
APPLICATION RECEIPT DATE: January 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
The National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH), invites applications for cooperative agreement
(U01) grants from US based investigators to conduct International Studies of
AIDS-associated Co-infections (ISAAC). The ISAAC grant will support clinical
studies of co-infections with HIV and one or more pathogens (including but not
limited to tuberculosis, other AIDS-defining opportunistic infections, malaria
and other parasitic infections) endemic among adults and children in resource-
constrained tropical countries (countries that have territories within the
geographically defined tropical zones, i.e. the countries with territories
between the tropic of Cancer and the tropic of Capricorn characterized by hot
climate) . The initial goal of this program is to conduct clinical research to
determine the spectrum, incidence, clinical manifestations, and outcomes of
these co-infections in a specific region, and evaluate the pathogenic
interactions between HIV and endemic infections. Applications for projects
addressing therapeutic goals will be acceptable if the epidemiology of the co-
infections is already adequately defined in the region. Long-term goals are to
develop effective and sustainable clinical management strategies to improve
local standards of care and to foster the integration of research for HIV and
the relevant co-pathogens. In reviewing applications, a major emphasis will be
placed on training, technology development, and enhancing independent research
capacities in host country sites. Collaborative teams inclusive of research
expertise in HIV and in tropical pathogens are required. Projects must be
designed to increase relevant research experience of host country
investigators and to enhance their ability to pursue scientific opportunities
by training, study planning and performance, and improving technical ability.
RESEARCH OBJECTIVES
Background
The overlapping endemicity of infection by HIV and tropical pathogens in
resource-constrained countries (annual per capita gross national product of
$7,500 or less) results in a high rate of co-infection. Per capita gross
national product (GNP) is based on World Bank data. Additional information on
GNP can be obtained from the World Bank website at
http://www.worldbank.org/depweb/english/modules/economic/gnp/data.html. HIV
co-infections/opportunistic infections have been well characterized in the US
and other industrialized countries. Prior to effective antiretroviral therapy,
standards of care for HIV positive persons in the US focused on prevention and
treatment of co-infections to reduce morbidity, slow HIV progression, and
prevent death. Similar characterization and clinical study of co-infections
in tropical countries have been limited and standards of care have not been
developed. Characterization of the interactions of HIV and endemic co-
infections and development of approaches for the effective clinical management
of co-infected persons will be crucial in the effort to improve health care in
resource-constrained tropical countries.
Infectious diseases cause nearly half of all mortality in resource-constrained
countries and approximately half of this mortality is attributed to HIV
infection, tuberculosis and malaria. Co-infections with HIV and other endemic
pathogens are common causes of morbidity and mortality. In addition,
progression of HIV infection is accelerated by many co-infections, and the
risk, severity, and complications of co-infections often are increased in the
presence of HIV infection. Tuberculosis and malaria are examples of co-
infections for which previous methods of control and treatment are no longer
as effective. These common co-infections also cripple economic development,
perpetuate or exacerbate poverty, create substantial social burdens, and
contribute to political instability.
The majority of the HIV epidemic occurs in tropical countries, with 71% of
HIV-infected persons worldwide living in sub-Saharan Africa. Although co-
infections with endemic pathogens are extremely common, the spectrum of co-
infections, co-pathogenesis, and the course and outcomes of co-infection with
HIV and endemic pathogens have not been adequately studied in most regions.
Very few studies have effectively addressed the safety and efficacy of
treatment strategies for individuals co-infected with HIV and tropical
pathogens. Data from well-designed studies are urgently needed to develop
guidelines for treatment of co-infections in tropical countries with and
without the ability to provide antiretroviral therapy.
Research Objectives and Scope
Applications submitted in response to this RFA should focus on hypothesis-
driven, discrete objectives. Clinical research in resource-constrained
tropical countries that address one or more of the following objectives will
be considered responsive: 1) Define the spectrum, incidence, and course of co-
infection with HIV and other pathogens disproportionately affecting
populations living in tropical countries as they present with infectious
syndromes, 2) Characterize the effect of endemic co-infections on HIV
replication, disease progression, and transmission, and, reciprocally, the
effects of HIV infection on disease expression and outcomes of endemic co-
infections, 3) Assess the safety, efficacy, and optimal therapeutic strategies
for antiretroviral therapy in the presence of endemic co-infections, 4) Assess
practical means for therapeutic monitoring, and for studying possible
pharmacological interactions between therapeutic drugs targeting the different
pathogens, 5) Improve the practical therapeutic management of endemic
infections in the presence of HIV infection, including the development of
affordable means of diagnosis and therapeutic monitoring and the evaluation of
vaccines and chemoprophylaxis for eventual use in local primary care settings,
6) Monitor the emergence of antimicrobial resistance among HIV and endemic
pathogens in co-infected study subjects and the wider community, determine the
relevant risk factors, and evaluate strategies to reduce the development of
resistance to therapy and to manage resistant infections, 7) Characterize
changes in immune response patterns in the presence of infection by HIV and
endemic pathogens and the role of host immunity in the response to therapy of
co-infections.
Studies may be proposed on the epidemiology, pathogenesis, immunopathogenesis
of co-infections and may include phase II - IV preventive and therapeutic
clinical trials. Basic epidemiological data for the co-infections occurring
in the region should be known, and is a pre-requisite for proceeding with
therapeutic studies. In the absence of such data, gathering epidemiological
data for co-infections in the region being studied should be a priority before
any therapeutic studies are proposed. Examples of research projects that would
be appropriate in response to this RFA include:
o epidemiologic studies to define the incidence, clinical presentations, and
outcomes of co-infections with HIV and endemic pathogens in a specific
region,
o studies to determine how specified co-infection(s) accelerate(s) HIV
disease progression and practical interventions that may interrupt this
response, such as the optimal strategy for application of antiretroviral
therapy,
o how HIV infection impacts co-infection outcomes, and
o defining the optimal therapy for co-infections at different stages of HIV
infection, and the role of primary and secondary prophylaxis.
Collaborative partnerships between institutions in the US and the host
countries are required. The US institutions must develop these collaborations
such that host country (outside the US) investigators have substantial
involvement in all aspects of the research, including planning, design,
implementation, analysis, and reporting of each study. The majority of support
must be expended in the host country. Performance of clinical studies in
developed countries will not be supported. This RFA will support clinical
studies requiring access to co-infected populations in resource-constrained
tropical countries, and is not meant to support the conduct of research that
can be done in US based centers. US applicant institutions will make their own
arrangements for mutually acceptable affiliations with one or more
collaborating institution(s) in resource-constrained tropical countries as
well as other institutions in the US or other developed countries.
A major goal of all projects must be to enhance the independent research
capacity of the host country. Projects should be relevant to the health needs
of the local population. Appropriate expertise in epidemiology, clinical
research, adult/pediatric HIV/AIDS management, tropical medicine, and
microbiology will be required. One goal of the project will be to help to
develop local specialized microbiology laboratory capabilities needed to
accomplish the objectives of the proposed studies, if these capabilities are
not currently available. The project sites will be required to interact with
other appropriate NIAID-sponsored treatment, prevention, and vaccine research
units in the same locality, and with the local HIV voluntary counseling and
testing facilities and HIV care agencies.
MECHANISM OF SUPPORT
This RFA will use the NIH cooperative agreement (U01), 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. The applicant will be solely
responsible for planning, directing, and executing the proposed project. This
RFA is a one-time solicitation. Future unsolicited, competing-continuation
applications based on this project will compete with all investigator-
initiated applications and will be reviewed according to the customary peer
review procedures. The anticipated award date is June 2004. 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.
The NIH U01 is a cooperative agreement award mechanism 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. At this time, the NIAID has not determined whether
and how this solicitation will be continued beyond the present RFA.
This RFA uses just-in-time concepts. It also uses the modular as well as the
non-modular budgeting formats (see
http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if
the investigator is submitting an application with direct costs in each year
of $250,000 or less, use the modular format. Otherwise follow the
instructions for non-modular research grant applications. This program does
not require cost sharing as defined in the current NIH Grants Policy Statement
at http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.
The US applicant institutions will support research at the institutions in
resource-constrained countries 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. Travel, salaries, and fringe benefits will
be subject to the applicant institution's rules and regulations. Only host
countries with annual per capita gross national product (GNP) of $7,500 or
less will be considered in response to this application. Annual per capita
gross national product is based on World Bank data, and additional information
can be obtained from the World Bank website at
http://www.worldbank.org/depweb/english/modules/economic/gnp/data.html .
FUNDS AVAILABLE
NIAID intends to commit approximately $3.0 Million in FY 2004 to fund 3 to 4
new grants in response to this RFA. An applicant may request a project period
of up to 5 years and a budget for total costs of up to $1.0 Million per year.
At least 60% of the direct costs for this project should be expended in the
host country, with no more than 40% of the direct costs expended in the US.
Travel costs for US site staff should be included in the US budget. 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, it is not known if this RFA will be reissued. Continued funding
will be contingent upon satisfactory progress during the preceding year and
availability of funds.
ELIGIBLE INSTITUTIONS
You may submit (an) application(s) if your institution has any of the
following characteristics:
o Applications may be submitted by domestic (US-based), for-profit and non-
profit organizations, public and private institutions, such as universities,
colleges, hospitals, laboratories, etc.
o Foreign institutions are not eligible to participate as the primary
applicant.
o Racial/ethnic minority individuals and women are encouraged to apply as
Principal Investigators.
o The US 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.
o Research activities on this project conducted at the foreign affiliate
must be supported under a consortium arrangement by the award made to the US-
based institution. "Intent to create consortium" is located at
http://odoerdb2-1.od.nih.gov/gmac/topics/consortium_main.html
o The host country investigators must have substantial input into all
aspects of proposed research studies and programs and all projects must be
acceptable to the overseas institutions. The application will not be reviewed
unless documentation of such affiliation and involvement is included.
Linkages with host country health care policy and provision agencies are
highly encouraged.
o A plan must be submitted to outline how the US primary applicant plans to
enhance and develop research abilities and increasingly transfer capacity to
the host country.
o Proposed studies will be reviewed to ensure that all study subjects must
receive treatment and care for HIV infection and related complications and co-
infections at levels at least as high as that which is generally available in
the host country.
INDVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, experience, 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
Travel: It is expected that investigators and research staff from the US
institution will travel to the foreign research site(s) for substantial
periods of time in support of the research funded through this RFA. It is
expected that the Principal Investigator will travel to the foreign research
site(s) at least once a year. The application must include a plan describing
how much time the US collaborators plan to spend in the host country. The
applicant must present a comprehensive and convincing package to include the
expertise of the research team (both in the US and in the host country),
outlining the level of effort of key personnel and how much time they will
spend at the host site, to demonstrate that there will be adequate expertise
and oversight on the team at all times, to successfully conduct the research
proposed. The Principal Investigators (from both the US and the host country)
and 1 or 2 key staff should plan on traveling to the Washington DC
metropolitan area at least once a year to discuss progress and findings with
the Scientific Coordinator and other NIAID Program staff.
Available infrastructure, including experience level of staff, availability of
major pieces of equipment and or support required for these should be clearly
stated in as much detail as possible.
The applicant must submit concept sheet(s) describing at least one proposed
clinical study. A sample outline of a concept sheet is available for review,
and is included in the "SUPPLEMENTAL INSTRUCTIONS" section of this document.
The concept sheet(s) should be included as an appendix to the application, and
it will be considered in evaluating the application.
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.
For all studies involving human subjects, the following special requirements
apply:
Awardees must comply with the Clinical Terms of Award that will be
incorporated in their Notices of Grant Award. Potential applicants are
encouraged to contact appropriate National Institute of Allergy and Infectious
Diseases (NIAID) program staff concerning this Policy. NIAID's Clinical Terms
of Award delineate awardee responsibilities including submission of the
required documentation to NIAID. These terms apply to all NIAID-supported
clinical research involving human subjects, including the development of new
technologies using human subjects or materials derived from patients or
volunteers; studies into the mechanisms of human disease using patient or
volunteer samples; therapeutic interventions, clinical trials, and any studies
that require institutional review board (IRB) or independent ethics committee
(IEC) approval to collect samples from patients or volunteers; epidemiologic
and behavioral studies; and outcomes and health services research. These
Clinical Terms of Award define specific timelines for approvals related to the
initiation of a trial or study and timelines for reporting events related to
its progress. It is the responsibility of the awardee to submit required
documentation to the responsible program or project officer according to these
timelines. 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.
The administrative and funding instrument used for this program is a
cooperative agreement (U01), an "assistance", 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 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 Scientific Coordinator(s) from the Division of Acquired
Immunodeficiency Syndrome (DAIDS) and the Division of Microbiology and
Infectious Diseases (DMID).
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.
2. Awardee Rights and Responsibilities
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, awardees
have primary responsibility as described below:
(a) Clearly stating the rationale, objectives and methods for proposed
research projects in the research design and protocol development. This
includes, 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.
(b) Maintaining a mutually acceptable arrangement with the host country
affiliate institutions and any relevant governmental agencies. Communicating
with, seeking required approvals, and complying with all requirements of
regulatory and health governmental agencies in the host country.
(c) Preparing detailed protocols, informed consent documents, and relevant
procedure manuals for timely submission of initial versions and all required
amendments to the Scientific Coordinator (Program Officer/Medical Officer),
Institutional Review Boards at relevant US and foreign institutions, and all
relevant regulatory agencies for approval. Decisions regarding the need for a
US FDA IND, (and who would hold the IND when needed), will be made by NIAID.
When NIAID holds the IND, the Principal Investigator will be required to
provide NIAID with all the necessary information and documentation for filing
the IND with the FDA, to amend as necessary after comments are provided by the
Program Officer, local IRB, and regulatory authorities, and to submit safety
reports and annual IND reports.
(d) Establishing procedures, where applicable, for all participating
institutions 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.
(e) Investigators and performance sites must demonstrate the ability to
perform overall project management and implement the proposed clinical
research protocol. This includes the development of adequate plans for
quality assurance/quality control, data management, drug distribution and drug
accountability (pharmacy plans), and appropriate laboratory procedures and
standards. Plans will be required to provide and document necessary training
for clinical research staff in protection of human subjects, Good Clinical
Practices, regulatory adherence, protocol specific procedures, and other
training as needed, e.g., for trial-related medical management issues.
(f) Awardees must present and carry out plans for a data management and
analysis center, and preparation of statistical reports for Data and Safety
Monitoring Boards (DSMBs). The requirements, criteria, and procedures for SAE
reporting and any other types of study safety monitoring reporting as
determined by NIAID must be followed for each study.
(g) Awardees are responsible for ensuring the accurate and timely assessment
of the progress of research. This includes, but is not limited to the
development of adequate internal QA/QC procedures for data collection and
management and laboratory performance, and generation of periodic reports
addressing study conduct quality and progress. Clinical research support
services under contract with DAIDS may be tasked to provide training,
expertise and assistance with the development of these procedures. The
investigator will make study documents (e.g., consent forms, drug distribution
forms, CRFs) and pertinent hospital or clinic records readily available for
inspection by the local IRB, the site monitors under contract to NIAID, the
FDA, the NIAID, the Office for Human Research Protections (OHRP), the
pharmaceutical sponsors, or the sponsor's designee for confirmation of the
study data.
(h) Awardees must adhere to the NIH policy regarding sharing of data.
Guidance regarding this policy is available at
http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm.
(i) Where relevant, 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.
(j) Cooperate in the reporting of the study findings. It is specifically
intended that publications resulting from collaborative research will be 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.
3. NIAID Staff Responsibilities
NIAID staff assistance will be provided by the Division of Acquired
Immunodeficiency Syndrome (DAIDS) and the Division of Microbiology and
Infectious Diseases (DMID) program staff , who will serve as NIAID's
Scientific Coordinators. The NIAID Scientific Coordinator will have
substantial scientific/programmatic involvement during the conduct of the
project through technical assistance, advice, and coordination above and
beyond normal program stewardship for grants, as described below.
Other program staff will be assigned as needed. NIAID staff will serve as a
resource with respect to relevant ongoing NIAID-sponsored research in order to
facilitate compatibility, information sharing, and avoidance of unnecessary
duplication. The NIAID will provide on-site study monitoring of clinical
research projects as required.
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 research teams, and (c) observation of field
data collection and management, quality control, fiscal review, and other
relevant matters. The NIAID retains, as an option, periodic external review
of progress.
The Scientific Coordinator will provide substantial assistance in the design
and conduct of research activities, including provision of: (a) advice on the
design, development, and technical performance of clinical protocols and
statistical evaluations of data, (b) access to and use of reagents, assays,
and other resources available through NIAID contractors and awardees, as
appropriate, and (c) advice and assistance with meeting FDA requirements for
investigational agents (with the assistance of Regulatory Affairs staff).
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.
The Scientific Coordinator or other appropriate NIAID staff will provide
timely review of all submitted documents (initial and amended protocols,
informed consent documents, IRB approvals and adverse events and study
progress reports) and promptly notify the PI of the outcome of such reviews.
The NIAID Program Director will review progress through consideration of
annual progress reports and periodic reports on ongoing progress, findings,
and future plans presented during meetings and conference calls, publications,
site visits, etc., and 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., compliance with regulations, terms of award and reporting
requirements); and/or (c) maintenance of a high quality of research.
4. 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 formed to review any scientific
or programmatic issue that is significantly restricting progress. The panel
will be composed of three members -- one selected by the awardee, a second
member selected by the NIAID, and the third member with expertise in the
relevant area and selected by the two prior members. 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.
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 your questions about scientific/research issues to:
Dr. Elizabeth Higgs
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room 5067, MSC-6603
6610 Rockledge Drive
Bethesda, MD 20892-6603
Telephone: (301) 496 2544
FAX: (301) 402 0659
Email: eh63a@nih.gov
Dr. Richard Hafner, M.D.
Division of Acquired Immunodeficiency Syndrome
National Institute of Allergy and Infectious Diseases
Room 5107, MSC-7624
6700-B Rockledge Drive
Bethesda, MD 20892-7624
Telephone: (301) 435-3766
FAX: (301) 402-2304
Email: rh23v@nih.gov
o Direct your questions about peer review issues; address the letter of
intent; mail two copies of the application and all five sets of appendices to:
Dianne Tingley, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2148, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) 496-0818
FAX: (301) 402-2638
Email: dt15g@nih.gov
o Direct your questions about financial or grants management matters to:
Laura Eisenman
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2120, MSC-7614
6700-B Rockledge Drive
Bethesda, MD 20892-7614
Telephone: (301) 402-5541
Fax: (301) 480-3780
Email: le55d@nih.gov
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 (locally
in the US as well as in the host country)
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:
Dianne Tingley, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2148, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) 496-0818
FAX: (301) 402-2638
Email: dt15g@nih.gov
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: GrantsInfo@nih.gov.
SUPPLEMENTAL INSTRUCTIONS
A Sample outline of a concept sheet appears below, and must be submitted with
the application as requested in the "SPECIAL REQUIREMENTS" section of this
document.
Sample Outline of a concept
Title:
Population:
Co-infection(s):
Intervention (if any):
Test agents/interventions and comparators:
Dosing:
Duration of therapy:
Duration of administration:
Background/rationale:
Study objectives:
Hypothesis to be tested:
Study design (not all parts may be relevant):
Eligibility/exclusion criteria:
Randomization/stratification plan:
Sample size with justification:
Anticipated duration of recruitment phase:
Anticipated duration of study:
Interim study progress and safety monitoring plan, if applicable:
Primary endpoints/outcomes:
Secondary endpoints/outcomes:
Study visit schedule and primary evaluations (including any
performed by a central laboratory):
Any proposed sub-studies:
Data analyses planned:
Party responsible for data management and site monitoring:
Clinical sites:
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:
Dianne Tingley, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2148, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Bethesda, MD 20817 (for express mail or courier service)
Applications must be received on or before January 13, 2004. Applications
that are not received as a single package on the receipt date 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).
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. The
CSR will not accept any application that is essentially the same as one
already reviewed. This does not preclude the submission of substantial
revisions of applications already reviewed, but such applications must include
an Introduction addressing the previous critique. 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. While the investigator may still
benefit from the previous review, the RFA application is not to state
explicitly how.
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 NIAID.
Incomplete and/or non-responsive 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
NIAID in accordance with the review criteria stated below. As part of the
initial merit review, all applications will:
o Receive a written critique
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 second level review by the National Advisory Allergy and
Infectious Diseases Council
REVIEW CRITERIA
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 discuss the following aspects
of your application in order to judge the likelihood that the proposed
research will have a substantial impact on the pursuit of these goals:
o Significance
o Approach
o Innovation
o Investigator
o Environment
The scientific review group will address and consider each of these criteria
in assigning your application's overall score, weighting them as appropriate
for each application. Your 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, you 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?
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following
items will be considered in the determination of scientific merit and the
priority score:
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 included in the section on Federal
Citations, below).
ADDITIONAL CONSIDERATIONS
DATA SHARING: The adequacy of the proposed plan to share data. FINAL NIH
STATEMENT ON SHARING RESEARCH DATA can be found in
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.
BUDGET: The reasonableness of the proposed budget and the requested period of
support in relation to the proposed research.
OTHER REVIEW CRITERIA
(a) Strength of the proposed collaborative relationships including
administrative structure, communications, defined roles and responsibilities
and decision-making processes
(b) The 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
(c) Adequacy of the proposed plans for the conduct of clinical research.
Applicants may wish to include a concept document or abbreviated protocol
document that specifically identifies the rationale, primary and secondary
objectives for the study, primary study endpoint, study design, a description
of the proposed population, the number of subjects and the duration of follow-
up.
(d) Adequacy of the time and effort proposed by the Principal Investigator and
host country lead investigator(s)
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: December 12, 2003
Application Receipt Date: January 13, 2004
Peer Review Date: May, 2004
Council Review: June, 2004
Earliest Anticipated Start Date: July, 2004
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
MONITORING PLAN AND DATA AND SAFETY MONITORING BOARD: Research components
involving Phase I and II clinical trials must include provisions for
assessment of patient eligibility and status, rigorous data management,
quality assurance, and auditing procedures. In addition, it is NIH policy
that all clinical trials require data and safety monitoring, with the method
and degree of monitoring being commensurate with the risks (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).
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 is 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.
This policy applies to all initial (Type 1) applications submitted for receipt
dates after October 1, 1998.
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.
You will find this policy announcement 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.
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. NIH has provided guidance in the
FINAL NIH STATEMENT ON SHARING RESEARCH DATA at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.
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). Those who must comply with the Privacy Rule (classified
under the Rule as "covered entities") must do so by April 14, 2003 (with the
exception of small health plans which have an extra year to comply).
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
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