AUTOIMMUNITY CENTERS OF EXCELLENCE
RELEASE DATE: May 13, 2002
(see addendum NOT-AI-02-053)
RFA: AI-02-006 - (Reissued as RFA-AI-08-010)
PARTICIPATING INSTITUTES AND CENTERS (ICs):
National Institute of Allergy and Infectious Diseases
(http://www.niaid.nih.gov)
National Institute of Diabetes and Digestive and Kidney Diseases
(http://www.niddk.nih.gov/)
Office of Research on Women's Health, NIH
(http://www4.od.nih.gov/orwh)
LETTER OF INTENT RECEIPT DATE: September 17, 2002
APPLICATION RECEIPT DATE: October 16, 2002
APPLICATIONS IN RESPONSE TO THIS REQUEST FOR APPLICATIONS (RFA) MUST BE
PREPARED USING A MULTI-PROJECT GRANT APPLICATION FORMAT; SPECIFIC INSTRUCTIONS
FOR COMPLETING THE APPLICATION ARE IN THE NIAID BROCHURE ENTITLED
"INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS" at
http://www.niaid.nih.gov/ncn/grants/multibron.htm
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 Cooperative Agreement Terms and Conditions of Award
o Where to send Inquiries
o Letter of Intent
o Submitting an Application
o Special Instructions for Completion of Applications in Response to This RFA
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
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the
Office of Research on Women's Health (ORWH) invite applications for
Autoimmunity Centers of Excellence (ACEs). The purpose of this cooperative
research program is to support integrated basic, pre-clinical and clinical
research centers to: conduct single site and multi-site cooperative clinical
trials and studies of mechanisms of action of tolerance induction and new
immune modulation interventions in multiple autoimmune diseases; accelerate
early translation of basic findings into clinical application; facilitate the
utilization of clinical materials for basic research studies; enhance the
exchange of information between basic scientists and clinicians and among
various specialists involved in treating autoimmune diseases; and establish a
collaborative approach to clinical and basic research among multiple
institutions in various geographic areas. Each Center will include: 1) a
clinical component, incorporating multiple clinical specialists to conduct
trials and clinical studies of new immunotherapies for autoimmune diseases in
cooperation with other Center clinical components; and 2) two or more
multidisciplinary, interactive basic and/or pre-clinical research components,
focused on elucidation of the basic mechanisms of autoimmunity, self tolerance
and/or immune modulation. The basic and clinical components of all Centers
will work cooperatively to select, design, and perform the clinical
trials/studies and the adjunct basic mechanistic studies. All applicants must
comply with the Cooperative Agreement Terms and Conditions of Award presented
below.
RESEARCH OBJECTIVES
Background
Autoimmune diseases result from direction of an immune response towards the
body's own tissues. The most common of these diseases include systemic lupus
erythematosus, multiple sclerosis, type 1 diabetes mellitus, and rheumatoid
arthritis. However, the immune response toward self can affect any organ or
organ system, resulting in a wide variety of autoimmune diseases, including
autoimmune myositis, thyroid disease, oophoritis and orchitis, hepatitis,
hemolytic anemia, pemphigus, inflammatory bowel disease, and alopecia. Many
of these autoimmune diseases by themselves are considered orphan diseases, but
in toto autoimmune diseases disproportionately afflict millions of women in
this country. The costs of these diseases are enormous, including
hospitalizations, outpatient visits, lost productivity, and decreased quality
of life for patients and their families.
The underlying immune mechanisms of these multiple diseases may be
overlapping. Self-reactive T cells play an important role in the immune
responses leading to many of these clinically divergent diseases. The
presence, number, activity, and specificity of these self-reactive cells are
regulated by complex processes involving multiple molecules and mechanisms.
These include: the binding and presentation of antigen by the molecules of the
major histocompatibility complex (MHC); the number and affinity of specific T
cell receptors for these complexes; the presence of co- stimulatory molecules,
including the B.7 and CD40 families; the activity of regulatory T cells, both
T helper and T cytotoxic cells; the presence and pattern of extracellular
mediators including cytokines, lymphokines, and chemokines; and the
intracellular pathways leading to apoptosis or cell death. Strategies to
interrupt the immune response at any of these sites could prevent or down
regulate the self-reactive response leading to autoimmune disease. In fact,
agents which block co-stimulatory signals (anti-CD40L, CTLA4-Ig) or cytokines
(anti-TNF-alpha, TNFR:Fc, IL-1Ra), interrupt or alter binding of antigen to
MHC (antigen peptides, MHC peptides, peptide oligomers), or modulate the
appearance and activity of regulatory cells (various cytokines and anti-
cytokines) are now being evaluated for treatment of multiple autoimmune
diseases. Equally, T cell independent mechanisms may be important mediators
of B cell tolerance. Thus, approaches that target various molecules in these
unique pathways, including complement, B cell receptor, PD-1, CD22, Fc?Rs,
CD19, and B lymphocyte stimulator (BlyS), are under evaluation. Other
approaches are likely to be discovered in the next few years. Clinical
evaluation of new immune interventions in various diseases has often been
performed without basic mechanistic studies to define the actions of the
experimental agents. Closer interactions between clinicians and basic
scientists should accelerate clinical testing of new approaches to tolerance
induction and immune modulation and enhance understanding of their underlying
mechanisms of action.
Since the affected organ systems vary in different diseases, autoimmune
diseases are usually treated by multiple clinical specialists. Thus, multiple
sclerosis is treated by neurologists; type 1 diabetes, Graves' disease, and
Hashimoto's thyroiditis by endocrinologists; systemic lupus erythematosus,
rheumatoid arthritis, and scleroderma by rheumatologists; idiopathic
thrombocytopenia purpura by hematologists; and inflammatory bowel disease by
gastroenterologists. Many of these diseases are treated by multiple
specialists. Because all these diseases will be increasingly approached with
immunologic interventions, a cooperative group with the capability to evaluate
a new agent in any of a number of diseases offers considerable advantages.
Increased interaction of clinical specialists in planning, performance, and
evaluation of trials/studies should lead to a more coordinated approach to
development of new immune-based therapies for all autoimmune diseases.
Research Objectives and Scope
The major goal of this program is to support an integrated basic and clinical
research program focused on tolerance induction and immune modulation to
prevent or treat autoimmune disease. The close interaction between basic
researchers and clinicians will accelerate the translation of basic advances
to the clinic and the utilization of patient materials for basic research.
NIAID is seeking multidisciplinary centers that emphasize new ideas, novel
approaches, and state of the art technology to increase our understanding of
the basic mechanisms of autoimmunity and self tolerance and the translation of
that knowledge to design and evaluate clinical interventions to prevent or
treat autoimmune diseases. The clinical components of the Autoimmunity Centers
of Excellence will perform pilot or exploratory clinical trials or clinical
studies, hereafter designated clinical trials/studies, in patients with
autoimmune disease(s) to test, evaluate, develop, or determine mechanism of
action of agents or interventions to prevent or treat autoimmune disease by
induction of tolerance or immune modulation. While industry has supported some
translational activities, industry-supported trials have generally not focused
on questions about the basic mechanisms of action of these agents.
Collaboration of the Autoimmunity Centers of Excellence with industry in
performance of clinical trials/studies and adjunct basic mechanistic studies
is encouraged.
Specific areas of interest include, but are not limited to:
o clinical trials of tolerogenic and immunomodulatory approaches and agents
to treat and prevent autoimmune disease, including co-stimulatory blockade,
such as anti-CD40 ligand antibody and CTLA4-Ig; cytokines and anti-cytokine
molecules, such as anti-TNF, IL-4, and IL-12; and peptide ligands, such as MHC
peptides, antigen-specific peptides, or peptide oligomers;
o clinical trials of novel approaches to modulate B cell tolerance, including
anti-CD19, anti CD22, anti-BlyS, and anti-apoptotic agents;
o immune ablation with or without reconstitution with hematopoietic stem cell
or bone marrow transplantation for treatment of autoimmune disease;
determination of course of development of tolerance and/or immunity, the cells
that are necessary for tolerance induction, and the role of chimerism;
o relationship of response to therapy and various parameters: stage of
disease, subsets of disease (i.e., relapsing vs. chronic progressive multiple
sclerosis), patient characteristics including race, ethnic background, and
genetic background, route of administration of agents;
o development of new clinically useful agents to modulate the immune response
and modification of currently available agents to enhance agonist or
antagonist activity, to enhance efficacy, and/or eliminate adverse effects;
o determination of the mechanism of action of agents utilized: the role of
cytokines, regulatory T cells, accessory cells (including macrophages, NK
cells, dendritic cells, and B cells), shifts in T cell subset response, T cell
anergy, T cell deletion, or induction of cell death pathways;
o mechanisms responsible for tolerance initiation, maintenance, or loss; and
o basic hypothesis driven research into mechanisms of self tolerance, the
pathogenesis of human autoimmune disease and/or its modulation.
MECHANISM OF SUPPORT
This RFA will use the NIH Multi-project Cooperative Agreement (U19) mechanism.
As an applicant you will be solely responsible for planning, directing, and
executing the proposed project. This RFA is a one-time solicitation. The
anticipated award date is September 2003.
The NIH (U19) 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."
Essential elements of the multi-project cooperative agreement mechanism also
include: (1) a minimum of three interrelated individual research projects
organized around a central theme; (2) collaborative efforts and interaction
among independent projects and their investigators to achieve a common goal;
(3) a single Principal Investigator who will be scientifically and
administratively responsible for the group effort; (4) a single applicant
institution that will be legally and financially responsible for the use and
disposition of funds awarded; and (5) support provided, as necessary, for
"Core" resources or facilities, each of which is expected to be utilized by at
least two research projects in order to facilitate the research effort.
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
or how this solicitation will be continued beyond the present RFA.
FUNDS AVAILABLE
The estimate total funds, direct and facilitites and administrative (F & A),
available from participating IC(s) for the first year of support of this
program are $6.25 million. In fiscal year 2003, the sponsoring institutes
intend plan to award 5 new and/or competitive continuation grants in response
to this RFA. First year budget requests may not exceed $800,000 total costs
for the basic projects and any proposed cores (excludes costs for clinical
component). The additional funds of approximately $2.5 million (ACE Clinical
Research Fund) will be available to successful applicants to support the
clinical components and new clinical trials. Although the financial plans of
the IC(s) 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.
ELIGIBLE INSTITUTIONS
You may submit (an) application(s) if your institution the following
characteristics:
o Domestic (US) for-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals,
and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any 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
Each Autoimmunity Center of Excellence must have a clinical research
component, two or more research projects and participate in cooperative and
collaborative projects within each Center and among the Centers. For detailed
information, see "Cooperative Agreement Terms And Conditions Of Award" and
"SPECIAL INSTRUCTIONS FOR COMPLETION OF APPLICATIONS IN RESPONSE TO THIS RFA"
below.
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 instrument used for this program is the
multiproject cooperative agreement (U19), an "assistance" mechanism rather
than an "acquisition" mechanism, in which substantial NIH scientific and/or
programmatic involvement with the awardee is anticipated during the
performance of the activity. Under the cooperative agreement, the NIH purpose
is to support and/or stimulate the recipient's activity by involvement in and
otherwise working jointly with the award recipient in a partner role, but it
is not to assume direction, prime responsibility, or 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 Research Coordinator.
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. Terms
and Conditions of Award will be included with awards. NIAID policy was
announced in the NIH Guide on February 24, 2000 and is available at:
https://grants.nih.gov/grants/guide/notice-files/NOT-AI-00-003.html. The full
policy including terms and conditions of award is available at:
http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf
All investigators proposing clinical research should comply with 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
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at
https://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.
DATA AND SAFETY MONITORING BOARD. The NIAID will appoint an independent Data
and Safety Monitoring Board to monitor the endpoint and safety data for all
trials/studies on an ongoing basis, but at least twice a year. This Board is
advisory to the Institute staff; feedback is provided to investigators as
well. This Board will be funded separately from the Centers.
2. Awardee Rights and Responsibilities
Awardees will have primary responsibility for defining the details of the
project within the guidelines of the RFA AI-02-006 and for performing the
scientific activity, and agree to accept close coordination, cooperation, and
participation of the NIAID staff in those aspects of the scientific and
technical management of the project described below. Specifically, awardees
have primary responsibility as described below.
Designation of the Clinical Research Representative and the Basic Research
Representative
The Clinical Research Representative is the person responsible for the overall
management of the clinical research component, including: coordination of the
participating Center specialists, whether within a single institution or a
consortium of institutions; design and submission of proposed protocols for
clinical trials/studies; and implementation, monitoring, and data submission
and analysis of clinical trials/studies. This person must be a physician with
substantial training and experience in 1) clinical management of one or
multiple autoimmune diseases, 2) clinical immunology, and 3) the design,
implementation and evaluation of clinical trials.
The Basic Research Representative is the person responsible for coordination
of the Center's basic research scientists, whether within a single institution
or a consortium of institutions, in: development of proposed clinical
trials/studies and adjunct basic studies in cooperation with clinicians,
conduct of the basic studies in conjunction with ongoing clinical
trials/studies; and collaboration and sharing of basic resources and reagents
within a Center and with other Centers. The collaboration of clinicians
and/or basic scientists from different Centers is highly encouraged based on
shared interests and complementary talents.
Designation of the Clinical Research Representative and the Basic Research
Representative is the responsibility of the Center Principal Investigator, who
may serve as either representative, but not both.
Steering Committee Membership and Meeting Attendance
Each Center Principal Investigator will designate a Clinical Research
Representative and a Basic Research Representative to serve as voting members
of the Steering Committee and participate in all Committee activities and
decisions including, but not limited to, conference calls and special
subcommittees as may be necessary. The Steering Committee shall be
responsible for determining the frequency of meetings and scheduling the time
and location. The Steering committee will establish the procedures for the
function of the Centers network, as outlined in section "Steering Committee."
Data Coordination and Management
Each awardee will be responsible for providing the NIAID with all primary
study data for management, quality control and analysis, using procedures and
standards determined by the Steering Committee. All data will be available to
all awardees. Specific analysis to be performed by NIAID will be directed by
the Steering Committee or its designee. The awardees will retain custody of
and have primary rights to all data developed under these awards, subject to
Government rights of access consistent with HHS and NIH policies.
Publication and Presentation of Study Findings
Early publication of major findings is encouraged. Publications and oral
presentations of work performed under this agreement will require appropriate
acknowledgment of the Autoimmunity Centers of Excellence and NIAID support.
Analyses to be performed using collective data from multiple centers will be
determined by the Steering Committee. Centers wishing to perform analysis of
local data or of single site studies should inform the Steering Committee
prior to initiation to avoid duplication. The Steering Committee will
establish the procedures and criteria for presentation and publication of data
developed within the Centers network.
Federally Mandated Regulatory Requirements
Each institution participating in the Clinical component of an Autoimmunity
Center of Excellence is required to meet DHHS regulations for the protection
of human subjects and FDA requirements for the conduct of research using
investigational agents. At a minimum, these include:
o methods for assuring that each institution at which Autoimmunity Centers of
Excellence investigators are conducting clinical studies has registered with
the Office of Human Research Protections (OHRP; http://www.hhs.gov/ohrp/)
and has a Federalwide Assurance; that study protocols are reviewed and
approved by the responsible Institutional Review Board (IRB) prior to patient
entry; that active protocols are reviewed at least annually by the IRB, and
that amendments are approved by the IRB.
o methods for assuring or documenting that each patient, or patient's
parent/legal guardian, gives fully informed consent to participation in a
research protocol prior to the initiation of the experimental intervention.
3. NIAID Staff Responsibilities
NIAID staff assistance will be provided by an NIAID Autoimmunity Research
Coordinator, who 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.
Steering Committee Membership and Meeting Attendance
The NIAID Autoimmunity Research Coordinator will serve as a voting member of
the Steering Committee, will attend all Steering Committee meetings, and will
participate in other Committee activities, including, but not limited to,
conference calls, subcommittees, and special committees.
Monitoring Performance
The NIAID Autoimmunity Research Coordinator will provide assistance to the
Steering Committee in the development of procedures for monitoring the
performance of the clinical trials/studies. This includes participation in
periodic on-site monitoring with respect to compliance with protocol
specifications, quality control and accuracy of data recording, and accrual.
Clinical Data Coordination and Management
The NIAID will be responsible for ensuring the provision of centralized data
management and coordination assistance, including analysis support. Under the
direction of the Steering Committee, the NIAID will provide technical
assistance and data management services to the Autoimmunity Centers of
Excellence with respect to quality control, uniformity of data collection,
management of the collective data base, and data analysis.
Publication and Presentation of Clinical Trials/Studies Findings
The NIAID Autoimmunity Research Coordinator may contribute, through review,
comment, analysis, and/or co-authorship, to reporting results of the clinical
studies and trials/studies to the investigator community and other interested
scientific and lay organizations. Co-authorship by the NIAID Autoimmunity
Research Coordinator will be subject to approval in accordance with the NIH
policies regarding staff authorship of publications resulting from extramural
awards.
NIAID Program Director
The NIAID Autoimmunity Research Coordinator, who is an NIAID Program Director,
will be responsible for normal programmatic stewardship and monitoring of this
award. These duties include:
The Government, via the NIAID Program Director, will have access to data
generated under this Cooperative Agreement and may periodically review the
data and progress reports. Information obtained from the data may be used by
NIAID staff for the preparation of internal reports on the activities of the
clinical trials/studies. However, awardees will retain custody of and have
primary rights to all data developed under these awards.
Study Materials: The NIAID may negotiate with companies interested in
participating in trials or studies. The NIAID may facilitate the appropriate
approvals (when necessary) from the Food and Drug Administration with respect
to the use of investigational drugs.
4. Collaborative Responsibilities
Each clinical and basic component of each Center must be willing to work
cooperatively and collaboratively both within their Center and with other
Centers.
Steering Committee
A Steering Committee will be established to serve as the main governing body
of the cooperative network. At a minimum, the Steering Committee will be
composed of the NIAID Autoimmunity Research Coordinator and two
representatives from each of the Centers: one Clinical Research Representative
and one Basic Research Representative. Each Basic and Clinical Research
Representative will be expected to actively participate in all Steering
Committee activities.
The Chairperson of the Steering Committee will be selected by the Steering
Committee from among the non-Federal members during one of the early meetings
of the Committee to be convened by the NIAID Autoimmunity Research
Coordinator. All major scientific decisions will be determined by the
Steering Committee, with each Clinical Research Representative, Basic Research
Representative, and the NIAID Autoimmunity Research Coordinator having one
vote. The Committee will meet at least three times during the first 12 months
of the program and at least semi-annually thereafter.
The Steering Committee will have responsibility for facilitating the conduct
of clinical trials/studies and basic research related to these trials/studies,
promoting trans-Center collaboration among and between clinical and basic
components, analyzing and interpreting Center-wide study data, and
establishing procedures for reporting results of Center trials/studies.
Proposed protocols for clinical trials/studies to be performed by a single
Center or groups of Centers will be submitted to the Steering Committee for
review and evaluation. Protocols to be implemented will be selected by the
Steering Committee in accordance with criteria and procedures established by
the Steering Committee. Timely review and evaluation are expected. After
approval, those clinical investigators participating in the trial/study in
collaboration with investigators from the basic components who will be
performing adjunct basic mechanistic studies will develop detailed protocols.
As needed, the Steering Committee may establish subcommittees for special
purposes. It is expected that most of the work of the Steering Committee will
be performed in these subcommittees.
Clinical trials/studies will proceed into the implementation stage only with
the concurrence of the Steering Committee and the NIAID Autoimmunity Research
Coordinator. The Steering Committee will be responsible for management of the
ACE Clinical Research Fund.
5. 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. This panel
will be composed of three members -- one selected by the Steering Committee or
by the individual awardee in the event of an individual disagreement, a second
member selected by the NIAID, and a 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.
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:
Elaine Collier, MD
Division of Allergy, Immunology, and Transplantation
National Institute of Allergy and Infectious Diseases
6700-B Rockledge Drive, Room 5135, MSC-7460
Bethesda, MD 20892-7640
Telephone: (301) 496-7104
FAX: (301) 402-2571
E-Mail: ECollier@niaid.nih.gov
Beena Akolkar, Ph.D.
Program Director, Immunopathogenesis and Genetics of Type 1 Diabetes
Division of Diabetes, Endocrinology, and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 681
Bethesda, MD 20892
Phone: 301 594-8812
FAX: 301 480-3503
Email: ba92i@nih.gov
o Direct your questions about peer review issues;
Priti Mehrotra, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2100, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) 435-9369
FAX: (301) 402-2638
E-Mail: pm158b@nih.gov
o Direct your questions about financial or grants management matters to:
Ann Devine
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2118, MSC-7614
6700-B Rockledge Drive
Bethesda, MD 20892-7614
Telephone: (301) 402-5601
Fax: (301) 480-3780
E-mail: ad22x@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
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:
Priti Mehrotra, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room (insert), MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) 435-9369
FAX: (301) 402-2638
E-Mail: pm158b@nih.gov
SUBMITTING AN APPLICATION
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
Applications must be prepared using the PHS 398 research grant application
instructions and forms (rev. 5/2001). The PHS 398 is available at
https://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.
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:
https://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:
Priti Mehrotra, Ph.D.
Division of Extramural Affairs
National Institute of Allergy and Infectious Diseases
Room Number 2100, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
BETHESDA, MD 20817 (for express mail or courier service)
Applications that are not received as a single package on the receipt date or
that do not conform to the instructions contained in PHS 398 (rev. 5/01)
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
Applicants for U19 cooperative agreements must follow special application
guidelines in the NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR
MULTI-PROJECT AWARDS; this brochure is available from NIAID listed under
INQUIRIES 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.
For this RFA, the description of each basic project is limited to 25 pages
each. The description of the clinical component is also limited to 25 pages.
Within the 25 page limit for the clinical component, the description of each
proposed clinical trial is limited to not more than 10 pages each.
CLINICAL RESEARCH COMPONENT. Each Autoimmunity Center of Excellence
application must describe a SINGLE clinical research component that
encompasses significant participation by multiple clinical specialists who
have access to patient populations in which to conduct clinical trials/studies
in autoimmune diseases. This component must include a minimum of three
clinical specialties and demonstrate the ability to perform clinical
trials/studies in at least three different autoimmune diseases. The clinical
component may represent a single institution or a consortium of institutions.
Diseases amenable to clinical intervention and of interest to the NIAID
include, but are not limited to: systemic lupus erythematosus, multiple
sclerosis, rheumatoid arthritis, type 1 diabetes mellitus, idiopathic
thrombocytopenia purpura, inflammatory bowel disease, and scleroderma.
Specialists that could participate in the clinical component include, but are
not limited to: endocrinologists, neurologists, rheumatologists,
gastroenterologists, and hematologists. The multiple specialists in the
clinical component must be willing and able to work collaboratively and
cooperatively, both within their Center and with clinical and basic components
of other Centers to facilitate clinical and adjunct basic studies. The
application should include written letters of commitment to this principal.
Applications proposing clinical components that do not meet the above criteria
concerning the number of clinical specialties represented and available
disease populations will be judged non-responsive and returned to the
applicant without review.
The application for the clinical component should describe the populations of
patients available for utilization in clinical trials/studies, and demonstrate
the ability to perform clinical trials/studies, including the ability to
recruit and retain subjects for at least three different autoimmune diseases.
The application should include two proposed clinical trial/study protocols for
immune interventions for autoimmune diseases. These protocols should include
the rationale for the agent(s) and disease(s) selected, patient population,
study design, and primary and secondary outcome measures. These two protocols
may utilize the same or different agents, but must intervene on different
autoimmune diseases. Award of a Center does not imply that the proposed
protocols will be implemented. Since the clinical trials/studies that are
ultimately undertaken by the Centers will be selected by the Steering
Committee (see TERM AND CONDITIONS OF AWARD), the trials/studies selected for
implementation may not be identical to any single protocol submitted in
response to this RFA. Funding for clinical components will be contingent upon
participation in approved clinical studies or trials.
In addition to the two proposed clinical trials/studies submitted with the
application, proposals for adjunct basic studies related to these clinical
trials/studies should be included in the application. The submitting Center's
basic components do not necessarily need to include the expertise to perform
these studies, however, the studies must be feasible, i.e., the techniques
must be established.
BASIC RESEARCH COMPONETS. Each Autoimmunity Center of Excellence application
must include TWO or more basic research components. The basic components must
be multi-disciplinary, interactive basic or pre-clinical research projects
focused on elucidation of the basic mechanisms and pathogenesis of
autoimmunity, self tolerance, and/or immune modulation. In addition, the
basic research components must have the interest and capability to carry out
adjunct basic studies related to clinical trials/studies in the context of an
overall Centers' program; work cooperatively with basic and clinical
components from their and other Centers; work with clinicians in development
of clinical trials/studies; and attend biannual Centers' meetings. These
basic research projects may utilize animal models, but must also incorporate
basic research in humans.
To promote the development of an interactive integrated network, a minimum
number of issues need to be addressed in the applications, as outlined below.
a. Intra- and Inter-Institutional Arrangements
Single institutions or consortia of institutions may submit applications.
However, the application must identify a single applicant organization that
will be legally and financially responsible and accountable for the use and
disposition of funds awarded to the other institutions. The development of
Centers, which include multiple institutions and geographic areas, is
encouraged when such an institutional arrangement provides the most
appropriate mixture of clinical and basic science components. Evidence that
the components can work together effectively must be provided in all
applications regardless of whether the applicant is a single institution or a
consortium of institutions.
b. Cooperative and Collaborative Responsibilities
Each clinical and basic component of each Center must be willing to work
cooperatively and collaboratively both within their Center and with other
Centers. The application must indicate commitment/willingness to the
collaborative organization, steering committee, and participation of NIAID
staff as described in the Cooperative Agreement Terms And Conditions Of Award.
The Steering Committee as defined in section entitled "Steering Committee"
will be the main governing body of the Centers network and will have
responsibility for establishing procedures for the selection of clinical
trials/studies and adjunct basic studies to be performed; developing
procedures for prioritization of use of samples from patients for basic
studies; implementing clear, inclusive, and effective communication among the
components of all Centers; establishing procedures for the monitoring of
performance and progress of the clinical trials/studies, including accrual,
timely submission and quality of data and samples, and conscientious
observance of protocol requirements; and instituting procedures for data
collection, management, quality control, and reporting results of clinical
trials/studies.
c. Budgets
All costs requested for the proposed basic studies must be included in the
application. Requested budgets should include: 1) travel for three one-day
Steering Committee meetings during the first 12 months of the program and
semiannual Steering Committee meetings thereafter for the Clinical and Basic
Research Representatives of each Center; and 2) travel for the Principal
Investigator of the Center components to a two-day biannual meeting (usually
in Washington, DC area), beginning in the second year. Funding for clinical
trials (including basic mechanistic studies associated with that trial) will
be provided out of the ACE Clinical Research Fund.The Steering Committee must
approve all clinical trials and will administer the ACE clinical research
fund.
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.
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.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the 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 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
In addition, the following review criteria specific to this RFA will be used
in evaluation of applications:
o the scientific and clinical expertise of the Principal Investigator,
Project Leaders, and key personnel;
o a documented commitment to the clinical and basic study of multiple
autoimmune diseases by the investigators and their institutions;
o willingness to work cooperatively and collaboratively both within the
proposed Center and with other Centers and to accept the participation and
assistance of the NIAID staff in accordance with the guidelines outlined under
"Terms and Condidtions of Award."
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your
application will also be reviewed with respect to the following:
o PROTECTIONS: The adequacy of the proposed protection for humans, animals, or
the environment, to the extent they may be adversely affected by the project
proposed in the application.
o INCLUSION: 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)
o DATA SHARING: The adequacy of the proposed plan to share data.
o 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 17, 2002
Application Receipt Date: October 16, 2002
Scientific Review Date: February 12, 2003
Advisory Council Date: May 29, 2003
Earliest Date of Award: September 2003
AWARD CRITERIA
Award criteria that will be used to make award decisions include:
o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
REQUIRED FEDERAL CITATIONS
MONITORING PLAN AND DATA SAFETY AND 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:
https://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
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at
https://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
https://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
https://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 https://grants.nih.gov/grants/stem_cells.htm and at
https://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 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
https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this PA 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.
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 in the following citations: No. 93.855,
Immunology, Allergy, and Transplantation Research, No. 93.847, Diabetes,
Endocrinology, and Metabolism Research, and . 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
https://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.
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.