INNOVATIVE APPROACHES FOR COMBATING ANTIMICROBIAL RESISTANCE
RELEASE DATE: May 16, 2002
RFA: AI-02-009
National Institute of Allergy and Infectious Diseases
(http://www.niaid.nih.gov)
LETTER OF INTENT RECEIPT DATE: September 10, 2002
APPLICATION RECEIPT DATE: October 10, 2002
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 Disease (NIAID) solicits
exploratory/developmental (R21) and small research grant (R03) applications
for novel and innovative research, including high risk and high payoff studies
in nontraditional fields to enhance the understanding of the factors affecting
the development of resistant pathogens and spread of resistance genes, in
order to direct actions to diagnose, control and treat antimicrobial
resistance. Research conducted through this program may fall along a broad
spectrum of activities and scientific areas described below.
BACKGROUND
Antimicrobial resistance (AR) is growing and spreading worldwide, impacting
upon our ability to successfully treat respiratory, diarrheal, sexually
transmitted, healthcare-associated, and a great variety of infections caused
by viruses, bacteria, fungi, and parasites. From the first availability of
penicillin, microbes have developed mechanisms of resistance that thwart or
block the action of the antimicrobial drug. There are many examples of the
transfer of resistance determinants among the same species of microbes, among
different genera of organisms, from commensals to pathogens, and from animal
to human pathogens. It is not always possible to predict when and why this
transfer will occur. AR results in difficult to treat infections, increased
hospital stays and costs, and the need to use more toxic drugs. Novel and
innovative approaches are needed to advance the basic field of study,
providing a basis of knowledge for the development of new diagnostic,
therapeutic or preventive approaches.
In July of 1999 a public meeting was held under the auspices of the
Interagency Task Force on Antimicrobial Resistance, with expert consultants
from academia, industry, state and local health agencies, professional
societies, healthcare delivery organizations, agricultural groups, and
consumer advocacy groups to address what actions the federal government should
undertake to combat this growing problem. The Research Working Group
identified gaps in the understanding of microbial physiology, ecology,
genetics and mechanisms of antimicrobial resistance. The outcome of these
discussions was "A Public Health Action Plan To Combat Antimicrobial
Resistance Part 1: Domestic Issues"
(http://www.cdc.gov/drugresistance/actionplan/). In addition, at the NIAID"s
Summit on Development of Infectious Disease Therapeutics,
(http://www.niaid.nih.gov/dmid/drug/summit.htm)
pharmaceutical and biotechnology representatives and academicians supported
the need for more basic microbial physiology research and research directed at
antimicrobial resistance mechanisms, as an important underpinning of
pharmaceutical development.
RESEARCH OBJECTIVES
Additional novel and innovative research, including high risk and high payoff
studies in nontraditional fields, is needed to enhance the understanding of:
mechanisms of AR, its emergence, acquisition, spread, persistence, and decline
including mathematical modeling of these processes, effect of resistance
mutations on microbial fitness, and microbial ecology, co-infection, and the
role of normal flora as a repository of resistance factors, as well as the use
of susceptible bacterial populations in control strategies. Studies are also
needed leading to the development of: innovative molecular diagnostics for
identifying and characterizing drug resistant pathogen variants, and
resistance reversing agents and approaches including, combination therapies,
strategies for chronic treatment, and variations in antimicrobial use patterns
(e.g., drug cycling, duration and dosage, among others) that minimize the
emergence and spread of resistance, while optimizing treatment outcome.
Responsive research proposals will address the above basic and developmental
research areas and be applicable to the full spectrum of microbes including
bacteria, parasites, fungi or viruses, other than HIV. Applicants should note
that the significance of the organism, or model system to public health will
be evaluated.
MECHANISM OF SUPPORT
This RFA will use the NIH Small (Pilot) Research Project Grant, (R03) and/or
Exploratory/Developmental Research Project Grant, (R21) award. The total
requested project period for an application submitted in response to this RFA
may not exceed two years for an R21 and three years for an R03. As an
applicant you 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 2, 2003.
NIAID uses R03 grants to support small, highly innovative or pilot projects.
Applicants for R03 grants may request up to $50,000 annual direct costs for a
period not to exceed three (3) years. Funds and time requested should be
appropriate for the research proposed. Applicants may not request travel or
large equipment. R03 awards are not renewable.
NIAID uses R21 grants to provide short-duration support for preliminary
studies of a highly speculative nature, which are expected to yield, within
this time frame, sufficient information upon which to base a well-planned and
rigorous series of further investigations. Applicants for R21 grants may
request up to $150,000 annual direct costs for a period not to exceed two
years.
This RFA uses just-in-time concepts. It also uses the modular budgeting
format. (see https://grants.nih.gov/grants/funding/modular/modular.htm).
Specifically, if you are submitting an application with direct costs in each
year of $250,000 or less, use the modular format.
FUNDS AVAILABLE
The NIAID intends to commit approximately $ 3M in FY 03 to fund 12 to 25 new
grants in response to this RFA. 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 the 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.
ELIGIBLE INSTITUTIONS
You may submit (an) application(s) if your institution has any of the
following characteristics:
o 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
o Domestic or foreign
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
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
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:
Marissa A. Miller, DVM, MPH
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room 3112, MSC-7630
6700-B Rockledge Drive
Bethesda, MD 20892-7630
Telephone: (301) (496-7728)
FAX: (301) (402-2508)
E-Mail: mm459k@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:
Madelon Halula, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2215 MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) (402-2636)
FAX: (301) (402-2638)
E-Mail: mhalula@nih.gov
o Direct your questions about financial or grants management matters to:
Lesia A. Norwood
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2117, MSC-7614
6700-B Rockledge Drive
Bethesda, MD 20892-7614
Telephone: (301) (402-7146)
Fax: (301) (480-3780)
E-mail: ln5t@nih.gov
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that includes
the following information:
o Title and brief description 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:
Madelon Halula, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2215 MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) (402-2636)
FAX: (301) (402-2638)
E-Mail: mhalula@nih.gov
SUBMITTING AN APPLICATION
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.
SUPPLEMENTAL INSTRUCTIONS FOR R21 APPLICATIONS:
To apply, please follow NIH guidelines for submission of an R21 application as
listed below:
1. The description (abstract) must include a brief explanation of the
proposed activity, and how it is consistent with the exploratory/development
nature of the R21 mechanism as described in this notice.
2. Although preliminary data are neither expected nor required for an R21
application, they may be included.
3. Sections a-d of the Research Plan may not exceed 10 pages, including
tables and figures.
4. Appendix materials should be limited, as is consistent with the
exploratory nature of the R21 mechanism, and should not be used to circumvent
the page limit for the research plan. Copies of appendix material will only
be provided to the primary reviewers of the application and will not be
reproduced for wider distribution. The following materials may be included in
the appendix:
o Up to five publications, including manuscripts (submitted or accepted for
publication), abstracts, patents, or other printed materials directly relevant
to the project. These may be stapled as sets.
o Surveys, questionnaires, data collection instruments, and clinical
protocols. These may be stapled as sets.
o Original glossy photographs or color images of gels, micrographs, etc.,
provided that a photocopy (may be reduced in size) is also included within the
10-page limit of items a-d of the research plan.
Include five collated sets of all appendix material, in the same package with
the application, following all copies of the application. Identify each item
with the name of the principal investigator.
SUPPLEMENTAL INSTRUCTIONS FOR R03 APPLICATIONS:
For the NIH Small Grant (R03), Modular Grant applications will request direct
costs in $25,000 modules, up to a total direct cost request of $50,000 for up
to three years.
o Research Plan
Items a - d of the Research Plan (Specific Aims, Background and Significance,
Preliminary Studies, and Research Design and Methods) may not exceed a total
of 10 pages. Please note that a Progress Report is not needed, competing
continuation applications will be not accepted for an R03.
o Appendix
Appendix material may only include color and/or glossy pictures with
descriptions.
SUPPLEMENTAL INSTRUCTIONS: Responsive applicants will budget for
participating in one scientific meeting to occur at some point during the
award period. Provision must be made in the budget for the PI to travel to
Bethesda, Maryland, and prepare a presentation of his/her research findings
and outcomes with the group of recipients of this RFA. The NIAID will
organize this meeting and contact PI"s concerning timing and details of
attendance.
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications requesting
up to $250,000 per year in direct costs must be submitted in a modular grant
format. The modular grant format simplifies the preparation of the budget in
these applications by limiting the level of budgetary detail. Applicants
request direct costs in $25,000 modules. Section C of the research grant
application instructions for the PHS 398 (rev. 5/2001) at
https://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step
guidance for preparing modular grants. Additional information on modular
grants is available at https://grants.nih.gov/grants/funding/modular/modular.htm.
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:
Madelon Halula, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2215 MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) (402-2636)
FAX: (301) (402-2638)
E-Mail: mhalula@nih.gov
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.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the NIAID. Incomplete applications will be returned to the
applicant without further consideration. And, if the application is not
responsive to the RFA, CSR staff may contact the applicant to determine
whether to return the application to the applicant or submit it for review in
competition with unsolicited applications at the next appropriate NIH review
cycle.
Applications that are complete and responsive to the RFA will be evaluated for
scientific and technical merit by an appropriate peer review group convened by
the NIAID in accordance with the review criteria stated below. As part of the
initial merit review, all applications will:
o 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 Institute of 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.
(1) SIGNIFICANCE: Does your study address an important problem? What is the
significance of the organism, the resistance pattern, or the proposed approach
to public health and medicine?
If the aims of your application are achieved, how do they advance scientific
knowledge? What will be the effect of these studies on the concepts or
methods that drive this field?
(2) APPROACH: Are the conceptual framework, design, methods, and analyses
adequately developed, well integrated, and appropriate to the aims of the
project? Do you acknowledge potential problem areas and consider alternative
tactics?
(3) INNOVATION: Does your project employ novel concepts, approaches or
methods? Are the aims original and innovative? Does your project challenge
existing paradigms or develop new methodologies or technologies?
(4) INVESTIGATOR: Are you appropriately trained and well suited to carry out
this work? Is the work proposed appropriate to your experience level as the
principal investigator and to that of other researchers (if any)?
(5) ENVIRONMENT: Does the scientific environment in which your 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, 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 10, 2002
Application Receipt Date: October 10, 2002
Scientific Peer Review Date: February 3, 2003
Advisory Council Review: May 1, 2003
Earliest Anticipated Start Date: June 2, 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 and balance.
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.
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 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
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.