CHALLENGE GRANTS: BIODEFENSE AND SARS PRODUCT DEVELOPMENT

RELEASE DATE:  September 22, 2003

RFA Number:  RFA-AI-03-016

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATIONS:

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

COMPONENTS OF PARTICIPATING ORGANIZATIONS:

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 1, 2003
APPLICATION RECEIPT DATE:  January 13, 2004

This RFA replaces PAR-03-025 
(http://grants.nih.gov/grants/guide/pa-files/PAR-03-025.html), 
which was terminated by NIAID on May 16, 2003.

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism 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 Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

Research supported and conducted by the National Institute of Allergy and 
Infectious Diseases (NIAID), National Institutes of Health, strives to 
understand, treat and ultimately prevent the myriad infectious, immunologic, 
and allergic diseases that threaten millions of human lives.  The NIAID 
Division of Microbiology and Infectious Diseases (DMID) and the Division of 
Allergy, Immunology and Transplantation (DAIT) support extramural research to 
control and prevent diseases caused by virtually all infectious agents. This 
includes basic biomedical research, such as studies of microbial physiology 
and antigenic structure; immunity; applied research, including the 
development of diagnostic tests; and clinical trials to evaluate experimental 
drugs and vaccines.  

In response to growing concerns about the use of biological agents in acts of 
terrorism, the further clinical development of new vaccines, therapeutics, 
adjuvants, diagnostics, and research resources against NIAID Category A, B, 
and C priority pathogens (see 
http://www.niaid.nih.gov/biodefense/bandc_priority.htm) is a high priority.  
In addition, while the long-term public health consequences of Severe Acute 
Respiratory Syndrome (SARS) are not known, its recent emergence, ease of 
transmission and disease severity warrant an immediate response from the 
biomedical research community.  

This program, CHALLENGE GRANTS:  BIODEFENSE AND SARS PRODUCT DEVELOPMENT, 
will support further development of already identified products against NIAID 
Category A, B and C high priority pathogens and all stages of product 
development against Severe Acute Respiratory Syndrome (SARS), including 
vaccines, adjuvants, therapeutics, diagnostics and research resources. To be 
responsive to this program for the development of biodefense products, the 
applicant must have already identified a candidate vaccine, therapeutic, or 
adjuvant, or have demonstrated proof-of-principle for a diagnostic method or 
research resource for biodefense. Phases of further development eligible for 
support include, but are not limited to:  early validation; pre-clinical 
stages; scale-up; production; regulatory requirements; and, where appropriate 
and feasible, clinical or field evaluation up to and including Phase II 
clinical studies.

NOTE:  Applications to support basic research or the "discovery" of new 
targets or the identification and validation of protective epitopes for NIAID 
Category A, B, and C priority pathogens will NOT be supported under this 
initiative, but are supported by other NIAID programs (see 
http://www.niaid.nih.gov/biodefense/research/funding.htm).

NIAID recognizes that product development against SARS is likely to be in the 
very early stages and that studies to demonstrate proof-of-principle for a 
diagnostic method or research resource may not be available.  Therefore, all 
stages of product development against SARS, including target identification, 
are responsive to this program.  

NOTE:  Only applications focused on the development of products against the 
SARS-associated coronavirus will be deemed responsive.  Applications for 
product development against other human coronaviruses or animal coronaviruses 
will be deemed unresponsive and returned to the applicant without review.

Challenge Grants

Under this program, Challenge (UC1) grant awards will be performance based 
for a period of up to three years.  That is, funds will be awarded in 
increments based on the attainment of interim research objectives 
(milestones) defined by the applicant and approved by the NIAID.  Because 
funding will be tied to the attainment of interim research objectives 
(milestones), funding will not be provided annually as is traditional for NIH 
grants, but will be linked to project timelines and interim objectives.  
Initial release of funds will be to support achievement of the first interim 
objective/milestone.  Release of the next funding increment will be based on 
the achievement of the previous interim objective, as determined by NIAID 
staff.

Partnerships

A key component of this initiative is the development of partnerships between 
the government and industry.  For the purpose of this program, "industry" is 
defined as large and small, domestic or foreign, pharmaceutical, 
biotechnology, bioengineering, and chemical companies.  Since academic 
organizations are often the source of new candidate products, this program 
can also support a partnership between industry and collaborator(s) as 
necessary from academic and non-profit research organizations.  The 
involvement of an academic or non-profit research organization is NOT a 
requirement; therefore, industry does not need a collaborator to submit an 
application to this program. 

All projects must demonstrate substantive involvement by industry 
participant(s).  "Substantive involvement" is defined, for the purposes of 
this program, as substantive commitment of any one or more of the following 
resources:  personnel, in kind contributions of materials and/or reagents, 
including but not limited to chemical libraries, innovative biotechnology 
platforms (i.e., for screening of drugs and inhibitors), scale up of GMP 
chemical synthesis or production, provision of animal or other laboratory 
models for evaluation, subcontracts, data management resources, and 
regulatory support.  

The Principal Investigator of the project may be affiliated with either 
industry or an academic organization (if academia is part of a partnership 
with industry).  See information under ELIGIBLE INSTITUTIONS below.

Product Development Plan

The applicant must describe a plan for the further commercial development of 
the candidate product(s) by specifying the stage of product development to be 
completed during the project period, the proposed overall project goal(s), 
interim objectives (milestones), a detailed schedule including a maximum of 
four milestones, and a timeline for their attainment.   See SUBMITTING AN 
APPLICATION below for instructions on what to include in the grant 
application.

The NIAID recognizes that the inherent nature and demands of the product 
development process may require funding large, complex grants with 
interdependent specific aims.  Furthermore, some aspects of the product 
development process (e.g., large-scale production) are inherently not 
innovative.  Recognizing that product development is often an iterative and 
sequential process, and that steps early in the process may not be successful 
and may need to be modified or reworked, NIAID staff, through this program's 
cooperative agreement grant mechanism, will be actively involved as a member 
of the partnership by evaluating the milestones of awardees and determining 
whether additional investment in the development is warranted.

Applicants proposing a project that contains or comprises a Phase I and/or 
Phase II clinical trial are strongly encouraged to contact appropriate NIAID 
staff prior to submission of the application to discuss the scope of the 
clinical research project, including the feasibility of completing the 
project within the maximum three-year project period.   

RESEARCH OBJECTIVES

Background

The National Institutes of Health and other agencies in the Department of 
Health and Human Services (DHHS) are currently supporting research to develop 
new products to protect the public from the health consequences resulting 
from the use of biological threat agents.  NIAID has recently convened three 
separate Blue Ribbon Panels to address research priorities.  The three NIAID 
Panels focused on:
          
o NIAID Category A Priority Pathogens (February 4-5, 2002; the full report is 
available at 
http://www.niaid.nih.gov/biodefense/research/biotresearchagenda.pdf 
o NIAID Category B and C Priority Pathogens (October 22-23, 2002; the full 
report is available at 
http://www.niaid.nih.gov/biodefense/research/categorybandc.pdf)
o Immunological aspects of biodefense preparedness research (June 17, 2002; 
the full report is available at 
http://www.niaid.nih.gov/publications/pdf/biodimmunpan.pdf) 

These Panels identified the development of new vaccines, adjuvants, 
therapeutics, and diagnostics as one of the highest priorities.  In addition 
to the NIAID research agenda, the DHHS has identified the highest priority 
products for biodefense preparedness 
(http://www.niaid.nih.gov/biodefense/high%5Fpriority.htm).

Potential applicants should also be aware of other biodefense research 
programs at NIAID that have different research scopes and requirements from 
those solicited in this program.  A complete list of the biodefense funding 
opportunities currently supported by NIAID can be found at: 
http://www.niaid.nih.gov/biodefense/research/funding.htm.  A similar RFA that 
supports earlier stages of development of new vaccines, therapeutics, 
adjuvants and diagnostics and does not require an industry collaborator 
(although applications with industry are responsive) and does not support 
clinical trials is RFA-AI-03-017 entitled "Cooperative Research for the 
Development of Vaccines, Adjuvants, Therapeutics, Immunotherapeutics and 
Diagnostics for Biodefense," and can be found at: 
http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-03-017.html.

The NIAID also recently convened a workshop to identify key research areas 
needed to address the potential global threat from SARS.  The workshop 
featured international experts in the fields of coronavirus biology, vaccine 
development, antiviral drug development, laboratory diagnosis, SARS 
epidemiology, etiology and clinical management.  Participants identified 
basic and applied research activities needed for the development of effective 
countermeasures for the control of SARS, including vaccines, adjuvants, 
therapeutics, diagnostics, and research resources.  A summary of the content 
of the information presented at that meeting is available at 
http://www.niaid.nih.gov/sars_meeting.htm.

To be responsive to this Program: CHALLENGE GRANTS: BIODEFENSE AND SARS 
PRODUCT DEVELOPMENT, the application must:

o  Identify and propose the further development of a previously identified 
candidate vaccine, therapeutic, adjuvant, diagnostic product or research 
resource with a proven technical approach against any of the NIAID Category 
A, B, and C priority pathogens (listed at 
http://www.niaid.nih.gov/biodefense/bandc_priority.htm) or a target for 
development of a product against the SARS coronavirus;
o  Demonstrate substantial involvement by a commercial sector (industry) 
component; and
o  Focus on the further development of the candidate product(s) or strategy 
for product development by specifying the proposed overall project goal(s), 
interim objectives (milestones), and a detailed timeline for milestone and 
goal attainment. It is suggested that an applicant propose no more than two 
or three interim objectives/milestones and a final objective (or product).  

VACCINES FOR BIODEFENSE

Vaccines are the most effective method of protecting the public against 
infectious diseases.  The development of vaccines against biological threat 
agents that can be administered quickly and can safely elicit a protective 
response in a broad range of recipients is a high priority.  Research 
approaches should begin with an identified and characterized vaccine 
candidate against a NIAID Category A, B, or C priority pathogen.  Only 
applications for vaccine development against one of these priority pathogens 
are responsive to this program.  Note:  Applications proposing the 
development of a vaccine that does not focus on an NIAID Category A, B, or C 
priority pathogen will be deemed unresponsive and will be returned to the 
applicant without review.

All applicants must develop a sound scientific rationale for the forward 
progression of the target or vaccine candidate through the product 
development pathway.  A research and development plan must be included that 
defines the potential ultimate product, proposed project goal, interim 
objectives (development milestones), identifies alternative approaches, and 
provides a timeline for milestone and goal attainment.  

Clinical development activities that can be supported under this program 
include, but are not limited to, the following areas:

o  Optimization of production methodology including process development;
o  Scale up and production of candidate vaccines including GMP production;
o  Evaluation of vaccine candidates against an NIAID Category A, B, or C 
priority pathogen formulated with or without adjuvants or immunomodulators;
o  Optimization of dose and route of delivery in pre-clinical evaluation;
o  Performing preclinical testing for safety and toxicity and efficacy in 
animal models and other benchmarks required for moving candidate vaccines 
into Phase I clinical trials;
o  Optimization of safety and immunogenicity or dose response studies in 
Phase I clinical trials; and,
o  Evaluation of dose-ranging and dosing intervals in Phase II clinical 
trials, including human challenge studies as appropriate. 

ADJUVANTS FOR BIODEFENSE

The development of an enhanced immune response may require the administration 
or co-administration of an adjuvant or immunostimulatory compound.  
Applications to support the further clinical development or clinical 
evaluation of molecules with documented ability to enhance the immune 
response are responsive to this program, and products capable of safely 
enhancing an innate immune response are particularly encouraged. 

This program supports the further clinical development and evaluation of 
vaccine adjuvants and immunomodulators against all NIAID Category A, B, and C 
priority pathogens (see 
http://www.niaid.nih.gov/biodefense/bandc_priority.htm) that have previously 
been shown to have promise in early stages of development.  Applications may 
propose the further clinical development of an adjuvant or immunomodulator as 
either a stand-alone product or in conjunction with a licensed or an 
investigational vaccine against a NIAID Category A, B, or C priority pathogen 
only.  Note:  Applications proposing the development of an adjuvant or 
immunomodulator in conjunction with a vaccine that does not focus on a NIAID 
Category A, B, or C priority pathogen will be deemed unresponsive and 
returned to the applicant without review.

Clinical development activities supported under this program may include, but 
are not limited to, one or more of the following areas:

o  Testing of previously evaluated adjuvants for their capacity to stimulate 
enhanced immune responses toward specific NIAID category A, B or C priority 
pathogens/toxins; 
o  Testing mixtures of adjuvants to evaluate additive or synergistic 
potential to safely stimulate desired immune responses;
o  GLP or GMP production;
o  Optimization of delivery platform(s), including antigen and adjuvant 
combinations/formulations;
o  Optimization of dose, dosing interval, and route of delivery in pre-
clinical evaluation;
o  Performing pre-clinical testing for safety and efficacy in animal models 
and other benchmarks required for moving candidate adjuvants into Phase I 
clinical trials;
o  Optimization of safety and immunogenicity or dose response studies in 
Phase I clinical trials; and,
o  Evaluation of dose-ranging and dosing interval Phase II clinical trials, 
including human challenge studies as appropriate.

The application should comprise a clinical development plan that begins with 
an identified and characterized adjuvant or immunostimulatory compound and 
develops a sound scientific rationale for its forward progression through the 
product development pathway.  A research and development plan must be 
included that defines the potential ultimate product, proposed project goal 
and interim objectives (development milestones); identifies alternative 
approaches; and provides a schedule for milestone and goal attainment.  

THERAPEUTICS FOR BIODEFENSE

The need for safe and effective, broad-spectrum and specific, antimicrobials 
for biodefense against highly pathogenic agents or their toxins is a key 
national priority.  Applications for development of novel antivirals, 
antitoxins, immunotherapies, and antibiotics against NIAID Category A, B, and 
C priority pathogens are responsive to this initiative.  The further 
characterization of immunotherapeutics such as antimicrobial peptides, 
antibodies, lectins, or immune modulators that provide either broad 
protection or pathogen specific protection against antigens from NIAID 
category A, B, or C priority pathogens are also responsive.

Activities to support the further clinical development of previously 
identified therapeutics may include, but are not limited to, one or more of 
the following areas:

o  Lead optimization by structure activity studies, medicinal chemistry, 
molecular modeling and/or library screening to improve the antimicrobial 
activity, pharmacology, and safety of the drug candidate;  
o  Synthesis of sufficient quantities of a lead compound(s) for in analysis, 
including efficacy and toxicity in in vitro or in vivo models; 
o  Performing preliminary pharmacokinetics and pharmacodynamics; assessing 
bioavailability and mechanism of action;
o  Evaluating the potential for the emergence of drug resistance in model 
systems;
o  Determining drug interactions in host molecular processes;
o  Performing required benchmarks for moving a drug candidate into Phase I 
clinical trials (http://www.fda.gov/cder/regulatory/default.htm);
o  Optimization of safety in Phase I clinical trials; and,
o  Evaluation of dose-ranging and dosing interval in Phase II clinical 
trials, including human challenge studies as appropriate.

Applications should focus on the further clinical development and testing of 
the therapeutic identified in one of the above areas deemed responsive to 
this program.  The application should include a sound scientific rationale 
for the development of the product.  A research and development plan must be 
included that defines the proposed project goal, interim objectives 
(development milestones) and potential ultimate product, and provides a 
timeline for milestone and goal attainment.

DIAGNOSTICS FOR BIODEFENSE

There is an urgent need for rapid, highly sensitive, specific, easy to use, 
and cost-effective diagnostics for public health laboratories, hospital-based 
clinical laboratories, and point-of-care use to identify or diagnose 
individuals exposed to biological threat agents or their toxins. Diagnostic 
tools that will rapidly distinguish whether an individual is infected by a 
biological threat agent or a common infection with similar, generalized 
symptoms and determine drug sensitivities are of high priority, as are 
applications for the simultaneous detection and identification of a broad 
range of infectious agents in clinical specimens.  This program supports the 
further development of sensitive, specific, and rapid diagnostics against all 
NIAID Category A, B, and C priority pathogens.  To be responsive to this 
program, applications must focus on technologies that have previously been 
shown to have promise in early stages of development.  

NOTE: This program does NOT support applications solely for the development 
of environmental detection devices or their deployment.  As such, 
applications for the development of environmental detection devices and/or 
their deployment will be deemed unresponsive and returned without review to 
the applicant.
 
Applications that focus on the following areas are particularly encouraged:

o  Tests to evaluate antimicrobial resistance, enhanced virulence, or genetic 
manipulation;
o  Tests capable of high throughput screening (e.g. microchip-based 
platforms) containing microbial signature profiles;
o  Tests capable of identifying multiple pathogens simultaneously in a single 
sample;
o  Novel assays based on human immune or other physiological responses;
o  Tests capable of identifying novel biomarkers for human immune activation; 
and
o  In vivo imaging methods and development of contrast reagents for 
visualization of pathogens or host immune responses in vivo

Applications should focus on the further development and validation of a 
diagnostic test or diagnostic method.  Preliminary data should be presented 
to support the basis of the method.  Capabilities of the diagnostics should 
be described.  Plans for determining the sensitivity, specificity and 
validation of the diagnostic should be included in the application.  The 
application should include a sound scientific rationale for the development 
of the product.  A research and development plan must be included that 
defines the proposed project goal, interim objectives (development 
milestones) and potential ultimate product, and provides a timeline for 
milestone and goal attainment.

RESEARCH RESOURCES FOR BIODEFENSE

The availability of research resources and tools is often a critical 
component in the development of new vaccines, adjuvants, therapeutics, and 
diagnostics. Among the resources needed to conduct biodefense research are 
genomics, proteomics, appropriate in vitro and animal models, validated 
assays and standardized reagents. Applications for research resources in 
response to this RFA are limited to the following areas for NIAID Category A, 
B, and C Priority Pathogens.  Note applications proposing the development of 
a research resource that does not focus on an NIAID Category A, B, or C 
Priority Pathogen will be deemed unresponsive and returned to the applicant 
without review.  

o  Optimization of vaccine delivery systems and platform technologies;
o  Software development tools for genetic, genomic, and proteomic analysis 
and modeling of host-pathogen interactions;
o  Screening tools and services for high throughput antigen identification;
o  Development of appropriate standardized cell cultures for the testing, 
development, or production of vaccines; and
o  Validated assays needed for product licensure including assays to measure 
toxicity, safety, efficacy, immunogenicity and other host responses.

Applications should focus on the further development and testing of one of 
the above resources or tools deemed responsive to this program.  The 
application should include a sound scientific rationale for the development 
of the product.  A research and development plan must be included that 
defines the proposed project goal, interim objectives (development 
milestones) and potential ultimate product, and provides a timeline for 
milestone and goal attainment.

PRODUCT DEVELOPMENT FOR SARS

Although there have been more than 8,400 infected individuals and more than 
800 deaths from the SARS coronavirus, the long-term global public health 
impact of SARS is not known.  The potential for reemergence of the virus and 
its ease of transmission and disease severity, warrant the rapid development 
of effective products for the identification, prevention, treatment, and 
control of the SARS coronavirus.  The NIAID is accepting applications under 
this program, CHALLENGE GRANTS:  BIODEFENSE AND SARS PRODUCT DEVELOPMENT, to 
support the development of vaccines, adjuvants, therapeutics, diagnostic 
tests and research resources as effective countermeasures against the SARS 
coronavirus.  NIAID recognizes that product development against SARS is 
likely to be in very early stages and that studies to demonstrate proof-of-
principle for a diagnostic method or research resource may not be available. 
As such, NIAID is accepting applications to support all stages of product 
development (up to Phase II clinical trials), including target 
identification, for SARS vaccines, adjuvants, therapeutics, diagnostics, and 
research resources under this program.  

NOTE:  Only applications focused on the development of products against the 
SARS-associated coronavirus will be deemed responsive; applications focused 
on other coronaviruses will be returned to the applicant without review.  

MECHANISM OF SUPPORT

This RFA will use the NIH Challenge Grant - Cooperative Agreement (UC1), an 
"assistance" mechanism, rather than an "acquisition" mechanism.  In the 
cooperative agreement mechanism, 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 anticipated 
award date is September 2004.  Essential elements of the challenge grant 
cooperative agreement mechanism include:  (1) interim research and 
development targets upon whose achievement the next increment of funds will 
be released to the awardee; (2) a single Principal Investigator who will be 
scientifically and administratively responsible for the research and 
development effort; and (3) a single applicant organization that will be 
legally and financially responsible for the use and disposition of funds 
awarded.  
  
Awards will be made for a period of up to three years and will be 
performance-based.  That is, funds will be awarded in increments based on the 
attainment of interim research objectives defined by the applicant and 
approved by the NIAID (See APPLICATION INSTRUCTIONS and TERMS AND CONDITIONS 
OF AWARD below).  Because funding will be tied to the attainment of interim 
research objectives, funding will not be provided annually as is traditional 
for NIH grants, but will be linked to project timelines and interim 
objectives.  Initial release of funds will be to support achievement of the 
first interim objective/milestone.  Release of the next funding increment 
will be based on the achievement of the previous interim objective as 
determined by NIAID staff.  

The total project period for applications submitted in response to this RFA 
may not exceed three 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 but not modular grant budgets.

FUNDS AVAILABLE

The estimated total funds [direct and facilities and administrative (F&A) 
costs] available for all awards for the entire length of the program will be 
$100 million to be awarded in fiscal year 2004.  As a result, in FY2004, the 
NIAID plans to fund approximately 10-20 awards.  It is anticipated that 
awarded budgets will vary widely in amount from hundreds of thousands to 
millions of dollars. The NIAID is seeking to fund a range of product 
development projects based on scientific merit and public health needs and 
priorities.  To ensure that research aims can be met and biohazards can be 
contained, an applicant may request up to $500,000 for significant 
alterations and renovations and/or up to $300,000 for major equipment.  
Although this program is provided for in the financial plans of the NIAID, 
awards pursuant to this RFA are contingent upon the availability of funds for 
this purpose and the receipt of a sufficient number of applications of high 
scientific merit. Continued funding will be contingent upon satisfactory 
progress on timelines and milestones.  At this time, the NIAID has not 
determined whether and how this solicitation will be continued beyond this 
present program.

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 and foreign institutions/organizations
o Faith-based or community-based organizations

Institutions must be in compliance with U.S. laws and regulations and DHHS 
and NIH policies in effect at the time of grant award and during the period 
of performance of the research.  

FOREIGN ORGANIZATIONS

Several special provisions apply to applications submitted by foreign 
organizations.
 
o Funds for alterations or renovations cannot be requested.
o Charge back of customs and import fees is not allowed.
o Format: every effort should be made to comply with the format 
specifications, which are based upon 
a standard US paper size of 8.5" x 11."
o Funds for up to 8% administrative costs can now be requested, 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-028.html)
o Organizations must comply with federal/NIH policies on human subjects, 
animals, and biohazards. 
o Organizations must comply with federal/NIH biosafety and biosecurity 
regulations. See TERMS AND CONDITIONS OF AWARD below.

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

This program responds to the urgent public health need to advance new and 
promising high-priority products for biodefense and for the control of SARS 
by supporting partnerships between the private sector and the Federal 
Government.  Applications in response to this program are limited to the 
development of vaccines, adjuvants, therapeutics diagnostics, and research 
resources against NIAID Category A, B, and C priority pathogens and the SARS 
coronavirus only, and each application must propose a milestone-driven, 
timeline-based project whose goal is to further the development of that 
product as specified above.  

NOTE:  Because awards made under this program will be performance-based and 
milestone-driven, funding will be tied to the successful attainment of 
interim research objectives, and may not be provided annually as is 
traditional for NIH grants.  Initial release of funds will be to support 
achievement of the first interim objective/milestone.  Release of the next 
funding increment will be based on the achievement of the previous interim 
objective as determined by NIAID staff.  As a result of this structure of the 
program, the following issues must be addressed in the application to ensure 
a clear understanding of the proposed objectives.

Applicants submitting proposals for the development of products under this 
program must provide the following information in a separate section of the 
application:

o A clear description of the goal(s) of the project, including one (or more) 
final product(s) or stage(s) of development to be completed during the award 
period.  This section must also state all interim milestones to be achieved 
during the course of the project and identify any impediments that could 
require a revision in the work plan or milestones with alternative 
approaches.  It is suggested that an applicant propose no more than four 
interim objectives/milestones and a final objective.  An example of an 
interim milestone could be the production of a GMP vaccine candidate or a 
decision as to which drug candidate will advance to pre-clinical testing.  
This section should include information that demonstrates that the applicant 
understands the steps that are required for advancing a candidate product as 
proposed in this application. 

For additional details on vaccines see: 
http://www.fda.gov/cber/vaccine/vacappr.htm 
For additional details on therapeutics see: 
http://www.fda.gov/cder/regulatory/default.htm 
For additional details on diagnostics see:   www.fda.gov/cdrh 

o A detailed schedule or timeline for the anticipated attainment of each 
milestone and the overall goal(s).

o Criteria that clearly describe how decisions will be made to advance a 
product through the proposed product development pathway. In other words, 
provide criteria by which "go" or "no go" decisions will be made throughout 
the project as applicable.  

o  Applications must address any clinical safety issues related to the 
further clinical development of the candidate product(s) as appropriate in 
their applications.

o  Applications must address issues related to physical or facility security, 
use of select agents, biocontainment and biosafety in the Resources section 
of the application.

When appropriate, research plans should include an awareness of the 
guidelines that govern GLP as defined by 21 CRF (58) and GMP, as defined by 
21 CRF (211), manufacturing and/or IND enabling studies that will be 
performed with this award as they would be applicable to eventual product 
licensure in the U.S.

Intellectual Property:  

The successful development of high priority products for biodefense and SARS 
will require substantial involvement and support of private sector industries 
and may also involve collaborations with multiple organizations, including 
academic and/or non-profit research institutions.  It is the intent of this 
initiative to support the formation of the appropriate public-private 
partnerships that are essential to meet these urgent public health needs.  
NIAID recognizes that intellectual property rights are likely to play an 
important role in achieving the goals of this program.  To this end, the 
NIAID requires that at the time of application, all applicants must provide a 
letter ("Proprietary Rights Assurance Letter") containing the following 
assurances, which is signed by a representative who is duly authorized to 
provide such assurances on behalf of the applicant organization:

o  Applicant is solely responsible for the timely acquisition of all 
proprietary rights, including intellectual property rights, and all materials 
needed for applicant to perform the project;
o  Applicant acknowledges that prior to, during, and subsequent to the award, 
the U.S. Government is not required to obtain for applicant any proprietary 
rights, including intellectual property rights, or any materials needed by 
applicant to perform the project;
o  Applicant acknowledges the requirement to report to the U.S. Government 
all inventions made in the performance of the project, as specified at 35 
U.S.C. Sect. 202.

Apart from the Proprietary Rights Assurance Letter, applicants are expected 
to exercise their Bayh-Dole rights in a manner that does not conflict with 
the goals of this award or the intent of the Bayh-Dole Act to promote the 
utilization, commercialization and availability of U.S. Government-funded 
inventions for public benefit.  In addition, applicants are expected to make 
new information and materials known to the research community in a timely 
manner through publications, web announcements, and reports to the NIAID or 
other mechanisms.

Select Agents: 

All awardee institutions, foreign and domestic, must confirm that they are in 
compliance with Select Agent regulations http://www.cdc.gov/od/sap/  and NIH 
Guidelines for Research Involving Recombinant DNA Molecules  
(http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html ) to receive 
funding from NIAID. See TERMS AND CONDITIONS OF AWARD below.

Application Requirements for Phase I and/or Phase II Clinical Trials:

o While this program supports Phase I and Phase II clinical trials, 
applicants DO NOT have to propose a clinical trial as part of the application 
to be responsive to this program.  

o Since awards are limited to a total of three years of support, it is 
anticipated that applications that contain or comprise a clinical trial will 
have an Investigational New Drug Application (IND) submitted to the FDA 
within the first 12 months after award.  As the appropriateness and 
feasibility of conducting a clinical trial will be a review criteria, 
applicants are strongly encouraged to contact appropriate NIAID staff in 
advance of submission of their application to discuss the scope of the 
proposed clinical trial (see ADDITIONAL REVIEW CRITERIA).
  
o A mandatory milestone that must be included in all applications that 
contain or comprise a clinical trial is the approval of the final clinical 
protocol(s) by NIAID prior to submission of the IND.  Applicants must build 
this mandatory milestone into their application.   

o A clinical protocol, consent form, and several representative case report 
forms as part of the application.  The clinical protocol, consent form, and 
case report forms should be submitted as an Appendix to the grant 
application; however, sufficient descriptive information about the protocol 
should also be included in the application.  

o For applications that contain or comprise a Phase I and/or Phase II 
clinical trial, the NIAID will also require the establishment of an 
Independent Safety Monitor (ISM), a Safety Monitoring Committee (SMC), or a 
Data and Safety Monitoring Board (DSMB), as deemed appropriate by NIAID, to 
monitor the safety of study participants.  Applicants proposing a project(s) 
that contains or comprises a clinical trial(s) should discuss this aspect of 
the proposed project(s) with NIAID Program Staff before submission of the 
application.  If a DSMB is required, funds to convene and support the DSMB 
must be included in the proposed budget.

For guidance on protocol format and/or other issues related to clinical 
studies and monitoring the safety of human subjects, applicants should 
contact the DMID Office of Clinical Research Affairs (Contact information is 
provided below).

Meetings:

A critical determinant of success of the project is likely to be the degree 
of communication among the grantee organization, any collaborating 
institutions (if applicable), and the NIH and/or other U.S. government 
agencies.  It is mandatory that the Principal Investigator, one or two key 
personnel designated by the Principal Investigator, two external advisors, 
and the NIAID Program Officer meet once a year to review progress and aid 
program development.  To facilitate this mandatory meeting, proposed budgets 
must include funds to travel the Principal Investigator, key personnel, and 
two external advisors (to be named after award by NIAID in consultation with 
the Principal Investigator) to an annual two-day meeting in Bethesda, 
Maryland, or at a relevant scientific meeting, as determined by NIAID Program 
staff.  Names of suggested external advisors should not be included in the 
application.

Where scientifically appropriate, NIAID may ask grant recipients to 
collaborate or cooperate with other NIAID funded projects and/or US 
government agencies, for example, the Food and Drug Administration, the 
Centers for Disease Control and Prevention, and the United States Department 
of Agriculture.

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 
challenge grant cooperative agreement (UC1), 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 
partnership role, but it is not to assume direction, prime responsibility, or 
a dominant role in the activity.  Consistent with this concept, the dominant 
role and prime responsibility for the activity resides with the awardees for 
the project as a whole, although specific tasks and activities in carrying 
out the research will be shared among the awardees and the NIAID Program 
Officer.  

1.  Clinical Terms of Award

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 may be from industry or academia; however, the industrial portion of 
the partnership is critical for compliance and substantive involvement by 
industry directed to the specific project being proposed must be clearly 
defined.  

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.

The awardee must be in compliance with Select Agent Rule 
(http://www.cdc.gov/od/sap/) and NIH Guidelines for Research Involving 
Recombinant DNA Molecules 
(http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html).

The NIH has established a new policy regarding the use of NIH funds for 
research involving Select Agents.  This policy is being implemented using 
Terms of Award that are to be included in any grant, cooperative agreement, 
or contract in which select agents are or will be used.

Award to a U.S. Institution: This award includes research involving Select 
Agents (see 42 CFR 73 for the Select Agent list; and 7 CFR 331 and 9 CFR 121 
for the relevant animal and plant pathogens).  Before using NIH funds, the 
awardee must complete registration with CDC (or USDA, depending on the 
agent).  No funds can be used for research involving Select Agents if the 
final registration certificate is denied.

Award to Foreign Institution: This award includes research involving Select 
Agents (see 42 CFR 73 for the Select Agent list; and 7 CFR 331 and 9 CFR 121 
for the relevant animal and plant pathogens). Before using NIH funds for any 
work directly involving the Select Agents, the awardee must provide 
information satisfactory to the NIH that a process equivalent to that 
described in 42 CFR 73 for US institutions is in place and will be 
administered on behalf of all Select Agent work sponsored by these funds.  
The awardee must be willing to address the following key elements appropriate 
for their institutions: safety, security, training, procedures for ensuring 
that only approved/appropriate individuals have access to the Select Agents, 
and any applicable laws, regulations and policies equivalent to 42 CFR 73.

Award to U.S. Institution with Foreign Institution Participation: This award 
includes research involving Select Agents (see 42 CFR 73 for the Select Agent 
list; and 7 CFR 331 and 9 CFR 121 for the relevant animal and plant 
pathogens). Before using NIH funds for any work directly involving the Select 
Agent at the US institution, the awardee must complete registration with CDC 
(or USDA, depending on the agent).  No funds can be used for research 
involving Select Agents if the final registration certificate is denied. 
Before using NIH funds for any work directly involving the Select Agents at 
the foreign institution, the US awardee must provide information from the 
foreign institution satisfactory to the NIH that a process equivalent to that 
described in 42 CFR 73 for US institutions is in place and will be 
administered on behalf of all Select Agent work sponsored by these funds.   
The awardee must be willing to address the following key elements appropriate 
for the foreign institution: safety, security, training, procedures for 
ensuring that only approved/appropriate individuals have access to the Select 
Agents, and any applicable laws, regulations and policies equivalent to 42 
CFR 73.

The Principal Investigator retains primary responsibility for the performance 
of the scientific activity, and agrees to accept close assistance in 
coordination, cooperation and participation of NIAID staff in scientific and 
technical management of the project in accordance with the terms formally and 
mutually agreed upon prior to the award.  The responsibility for the 
planning, direction, and execution of the proposed project will be solely 
that of the Principal Investigator.

For clinical research conducted in foreign countries, the awardee must assure 
compliance with the host country regulations for human subjects, and must 
assure that the trials are conducted according to one of the following:  the 
US Federal Policy (Common Rule) for the Protection of Human Subjects and/or 
the US Department of Health and Human Services (HHS) regulations at 45 CFR 
46; the May 1, 1996 International Conference on Harmonization E-6 Guidelines 
for Good Clinical Practice (ICH-GCP-E6) Sections 1 through 4; The 1993 
Council for International Organizations for Biomedical Research Involving 
Human Subjects; the 1998 Medical Research Council of Canada Tri-Council 
Policy Statement on Ethical Conduct for Research Involving Humans; the 2000 
Indian Council of Medical Research Ethical Guidelines for Biomedical Research 
on Human Subjects; or other internationally recognized standards for the 
protection of human subjects.

Meetings: One mandatory progress review meeting of the awardees will be held 
annually at the NIH, or at a site designated by the NIH, during which the 
Principal Investigator and Project Leaders will present significant findings.  
The NIAID Program Officer and External Advisors (when applicable) will be 
present.  A critical determinant of success will be the degree of 
communication between the Principal Investigator, Project Leaders and other 
significantly involved parties. Therefore, in addition to the one meeting 
listed above, additional meetings, which may be necessary for coordination of 
cooperative agreement activities, may be scheduled if justified.  Regular 
telephone and written communication will be important and are encouraged.

Publications: The Principal Investigator will be responsible for the timely 
submission of all abstracts, manuscripts and reviews (co)authored by members 
of the grant and supported in part or in total under this Agreement.  The 
Principal Investigator and Project Leaders are requested to submit 
manuscripts to the Program Officer within two weeks of acceptance for 
publication so that an up-to-date summary of program accomplishments can be 
maintained and joint press conferences and press releases prepared.  
Publications or oral presentations of work performed under this Agreement are 
the responsibility of the Principal Investigator and appropriate Project 
Leaders and will require appropriate acknowledgement of NIAID support.  
Timely publication of major findings is encouraged.

While the NIAID Program Officer has a right of access to the data (see NIAID 
staff responsibilities below) the awardee will retain custody of and right to 
the data. For more information on data sharing go to: 
http://grants.nih.gov/grants/policy/data_sharing/index.htm.  

3. NIAID Staff Responsibilities
     
The NIAID Program Officer will provide normal stewardship and 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.

The NIAID Program Officer will serve as a liaison/facilitator between the 
awardee, pharmaceutical and  biotechnology industries, and other government 
agencies (e.g., FDA, USDA, CDC), and will serve as a resource of scientific 
and policy information related to the goals of the awardee's research. The 
NIAID Program Officer will facilitate coordination of project activities 
during the course of the project.

The NIAID Program Officer will assist the awardee with access to other NIAID-
supported resources and services, including resources for preclinical 
development such as animal models, screening facilities, standardized 
research reagents, and a genomics resource center, where available.

4.  Collaborative Responsibilities

The specific timelines, interim objectives and funding levels agreed to by 
the awardee and the NIAID shall be included in the terms and conditions of 
award.  Given the nature of product development, it is recognized that 
timelines and interim objectives may require revision and renegotiation 
during the course of the project period.  The Principal Investigator and 
NIAID must agree to all such revisions. Release of each funding increment by 
NIAID will be based on a NIAID review of progress towards achieving the 
previously agreed upon interim objective.   Where scientifically appropriate, 
NIAID may ask recipients to collaborate or cooperate with other NIAID funded 
projects and/or US government agencies, for example CDC, FDA, and/or USDA.

5.  Arbitration

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

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

WHERE TO SEND INQUIRIES

We encourage your 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 on VACCINES to:

Dr. Linda Lambert
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases  
Room 5051, MSC-6603
6610 Rockledge Drive
Bethesda, MD  20892-6603
Telephone: (301) 496-5305
FAX:  (301) 496-8030
E-Mail: ll153p@nih.gov

o Direct your questions about scientific/research issues on ADJUVANTS to:

Dr. Charles Hackett  
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases  
Room 3009, MSC-6601
6610 Rockledge Drive
Bethesda, MD  20892-6601
Telephone:  (301) 496-7551
FAX:  (301) 402-2571
E-Mail: ch187q@nih.gov

o Direct your questions about scientific/research issues on THERAPEUTICS to:

Dr. Mark Challberg
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases  
Room 4095, MSC-6603
6610 Rockledge Drive
Bethesda, MD  20892-6603
Telephone:  (301) 496-7453
FAX:  (301) 480-1594
E-Mail:  mc37e@nih.gov 

Dr. Alison Deckhut (IMMUNOTHERAPEUTICS) 
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases  
Room 3007, MSC-6601
6610-B Rockledge Drive
Bethesda, MD  20892-6601
Telephone:  (301) 496-7551
FAX:  (301) 402-2571
E-Mail:  ad122x@nih.gov 

o  Direct your questions about scientific/research issues on DIAGNOSTICS to:

Dr. Maria Giovanni
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room 6007, MSC-6603  
6610 Rockledge Drive
Bethesda, MD  20892-6603
Telephone: (301) 496-5305
FAX: (301) 496-8030 
E-Mail:  mg37u@nih.gov

o Direct your questions about scientific/research issues on RESEARCH 
RESOURCES to :

Dr. John Rogers
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases  
Room 5069, MSC-6603
6610 Rockledge Drive
Bethesda, MD  20892-6603
Telephone:  (301) 496-2544
FAX: (301) 402-0659
E-Mail: mr92i@nih.gov

o Direct inquiries about scientific/research on PROTOCOL FORMAT and/or other 
issues related to CLINICAL STUDIES to: 

Dr. Holli Hamilton
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room 6045, MSC-6603  
6610 Rockledge Drive
Bethesda, MD 20892-6603
Telephone: (301) 402-8412
FAX:  (301) 480-0728
Email: hh88f@nih.gov

Direct your questions about peer review issues to:

Madelon Halula, Ph.D.
Division of Extramural Activities 
National Institute of Allergy and Infectious Diseases
Room 3116, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (20817 for express mail or courier service)
Telephone: (301) 496-2550
FAX: (301) 402-2638
Email:   mh30x@nih.gov  

o  Direct your questions about financial or grants management matters to:  

Ms. Pamela Fleming
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2119, MSC-7614
6700-B Rockledge Drive
Bethesda, MD 20892-7614
Telephone:  (301) 496-7075
FAX:  (301) 480-3780
E-Mail: pf49e@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 must be received by December 1, 2003. Send the letter of 
intent to:

Madelon Halula, Ph.D.
Division of Extramural Activities 
National Institute of Allergy and Infectious Diseases
Room 3116, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (20817 for express mail or courier service)
Telephone: (301) 496-2550
FAX: (301) 402-2638
Email:   mh30x@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) 435-0714, 
Email: GrantsInfo@nih.gov. 

SUPPLEMENTARY INSTRUCTIONS:

Applications must address each item described under the SPECIAL REQUIREMENTS 
section, as applicable.  

Due to the performance based and milestone driven nature of this program:

o Applicants must identify the final product(s) including the stage of 
development to be completed during the period of the grant.  Some examples 
could be: an Ebola vaccine ready for clinical studies; or, an anthrax drug 
ready for clinical testing (IND process completed); or, a new SARS diagnostic 
test ready for clinical evaluation. 

o Applicants must identify interim objectives to be achieved during the 
project period of performance.  Initial release of funds will be to support 
achievement of the first interim objective/milestone; with the achievement of 
that interim objective, funds will be released to meet the next objective 
(interim or final product).  Some examples of interim objectives could be: 
completion of a prototype of a diagnostic tool; submission of an NDA to FDA; 
or initiation of a Phase I clinical trial.

o Given the anticipated complexity of applications and the likelihood for 
multi-organizational arrangements, applicants should pay special attention to 
the preparation of a detailed budget which provides a thorough justification 
for all key personnel, equipment, consultant costs, and travel expenses.  
Budget materials do not count against the page limitations.  Continuation 
pages should be used when necessary to provide a complete budget 
justification.  This RFA does not use the modular budget format. 

Responses to this RFA should follow the PHS 398 instructions with the 
following modifications:  

Form Page 4 - Detailed Budget for Initial Budget Period - The budget 
submission must be linked to the interim objectives and final product(s) 
rather than the traditional annual budget periods requested in NIH grants.  
The initial budget period is defined as the time period needed to complete 
the first interim objective and the funds requested should be those needed to 
attain the first interim milestone.  In the upper right-hand corner of this 
page, enter the proposed "From" and "Through" dates for research to complete 
the first interim objectives.  Complete the balance of the form based on the 
efforts to be performed during this interval.

Form Page 5 - Budget for Entire Proposed Period of Support - The budgets for 
a second and subsequent budget periods must be based on the funds needed to 
attain the next objective not on an annual period.  The budget for the second 
budget period should be that needed to attain the second interim objective 
(or the final products if there is no second interim objective), and the 
third budget period shows the funds needed to complete the R&D effort (if 
there were two interim objectives).  Again, these budget periods are tied to 
performance and not to the calendar, so the budgets can be for periods of 
more than or less than one year.

Research Plan: Must have the following five sections and may not exceed 25 
pages:

1. Specific Aims - What do you intend to do?  What product or products will 
be developed?

2. Background and Significance - Why is the R&D important? What is the 
potential public health benefit? What is the probability of a beneficial 
product?

3. Preliminary Studies - What has already been done? How does this support 
the proposed R&D effort?

4. Research Methods - How are you going to perform the R&D effort?

5. Management Plan - What are the major segments of the research effort and 
the timeline for completion of each and for completion of the research 
project?  What interim objectives are proposed to measure progress? 

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 same time, 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 3116, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (20817 for express/courier service)

APPLICATION RECEIPT DATE: Applications submitted in response to this 
announcement must be received ON OR BEFORE January 13, 2004.
 
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, will be judged non-responsive and will be returned to the 
applicant.  
APPLICATION PROCESSING:  Applications must be received on or before 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. 

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.

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

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by NIAID. Incomplete and/or nonresponsive applications will 
not be reviewed.  
  
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 Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the National Advisory Allergy and 
Infectious Diseases Council

Depending on the total number and research topics of applications received in 
response to this RFA, applications may be separated into subgroups for review 
by different peer review committees.

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 evaluate the application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals. The scientific review group 
will address and consider each of the following criteria in assigning the 
application's overall score, weighting them as appropriate for each 
application. 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The application does not need to be strong in all categories to be judged 
likely to have major scientific impact and thus deserve a high priority 
score.  For example, an investigator may propose to carry out important work 
that by its nature is not innovative but is essential to move a field 
forward.

o SIGNIFICANCE:  Is this project likely to significantly advance the 
development of a vaccine, adjuvant, therapeutic, or diagnostic against the 
specific biologic threat agent identified in this initiative? If the aims of 
the application are achieved, are important biomedical agents or products 
likely to result?  What will be the effect of these studies on the concepts 
or methods that drive this field? 

o APPROACH:  Does the application clearly articulate the development of a 
candidate product?  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? Is the industry commitment adequate to have an 
impact on the success of the proposed research objectives? Is the likelihood 
of successful project completion high given the current state of research and 
development and the technical approach? Does the application clearly 
delineate appropriate timelines and interim milestones and are they 
appropriate, feasible and technically sound? 

o INNOVATION:  If appropriate, 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?

o INVESTIGATOR:  Is the research and development team appropriately trained 
and experienced 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)? Is there strong evidence of substantive industrial 
commitment?

o ENVIRONMENT:  Does the 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 environments, including 
partnerships with industry, or employ useful collaborative arrangements?  Is 
there adequate 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 in the sections on Federal Citations, 
below).

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

ADDITIONAL REVIEW CONSIDERATIONS

RFA-specific review criteria:

o The scientific rationale and basis for the candidate product, including the 
strength of existing data on product feasibility, safety and potential 
efficacy
o The appropriateness of the proposed project in terms of the stage of 
development of the candidate product
o The appropriateness and feasibility of defined objectives/milestones
o Feasibility of future product development
o The appropriateness and feasibility of conducting any proposed clinical 
trial or field evaluation during the period of award, including for example, 
the timelines proposed for IND preparation and filing, patient recruitment, 
and completion of the study.

SHARING RESEARCH DATA: Applicants requesting more than $500,000 in direct 
costs in any year of the proposed research must include a data sharing plan 
in their application. The reasonableness of the data sharing plan or the 
rationale for not sharing research data will be assessed by the reviewers. 
However, reviewers will not factor the proposed data sharing plan into the 
determination of scientific merit or priority score. See 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html and the 
policy under Federal Citations below.
 
BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

PROTECTIONS: The adequacy of the proposed protections for humans, animals, or 
the environment, to the extent they may be adversely affected by the project 
proposed in the application.  

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:      December 1, 2003
Application Receipt Date:           January 13, 2004
Peer Review Date:                   May 2004
Council Review:                     August 2004
Earliest Anticipated Start Date:    September 2004

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 High priority public health needs  
  
REQUIRED FEDERAL CITATIONS 

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

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

SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking more than $500,000 or 
more in direct costs in any single year are expected to include a plan for 
data sharing or state why this is not possible.  
http://grants.nih.gov/grants/policy/data_sharing Investigators should seek 
guidance from their institutions, on issues related to institutional 
policies, local IRB rules, as well as local, state and Federal laws and 
regulations, including the Privacy Rule. Reviewers will consider the data 
sharing plan but will not factor the plan into the determination of the 
scientific merit or the priority score.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of 
the research. This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).

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

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: 
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them. 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.  This policy announcement is in the NIH Guide for Grants and 
Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

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

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

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

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

Form Page 5 - Budget for Entire Proposed Period of Support - The budgets for 
a second and subsequent budget periods must be based on the funds needed to 
attain the next objective not on an annual period.  The budget for the second 
budget period should be that needed to attain the second interim objective 
(or the final products if there is no second interim objective), and the 
third budget period shows the funds needed to complete the R&D effort (if 
there were two interim objectives).  Again, these budget periods are tied to 
performance and not to the calendar, so the budgets can be for periods of 
more than or less than one year.

Research Plan: Must have the following five sections and may not exceed 25 
pages:

1. Specific Aims - What do you intend to do?  What product or products will 
be developed?

2. Background and Significance - Why is the R&D important? What is the 
potential public health benefit? What is the probability of a beneficial 
product?

3. Preliminary Studies - What has already been done? How does this support 
the proposed R&D effort?

4. Research Methods - How are you going to perform the R&D effort?

5. Management Plan - What are the major segments of the research effort and 
the timeline for completion of each and for completion of the research 
project?  What interim objectives are proposed to measure progress? 

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 same time, 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 3116, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (20817 for express/courier service)

APPLICATION RECEIPT DATE: Applications submitted in response to this 
announcement must be received ON OR BEFORE January 13, 2004.
 
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, will be judged non-responsive and will be returned to the 
applicant.  
APPLICATION PROCESSING:  Applications must be received on or before 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. 

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.

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

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by NIAID. Incomplete and/or nonresponsive applications will 
not be reviewed.  
  
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 Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the National Advisory Allergy and 
Infectious Diseases Council

Depending on the total number and research topics of applications received in 
response to this RFA, applications may be separated into subgroups for review 
by different peer review committees.

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 evaluate the application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals. The scientific review group 
will address and consider each of the following criteria in assigning the 
application's overall score, weighting them as appropriate for each 
application. 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The application does not need to be strong in all categories to be judged 
likely to have major scientific impact and thus deserve a high priority 
score.  For example, an investigator may propose to carry out important work 
that by its nature is not innovative but is essential to move a field 
forward.

o SIGNIFICANCE:  Is this project likely to significantly advance the 
development of a vaccine, adjuvant, therapeutic, or diagnostic against the 
specific biologic threat agent identified in this initiative? If the aims of 
the application are achieved, are important biomedical agents or products 
likely to result?  What will be the effect of these studies on the concepts 
or methods that drive this field? 

o APPROACH:  Does the application clearly articulate the development of a 
candidate product?  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? Is the industry commitment adequate to have an 
impact on the success of the proposed research objectives? Is the likelihood 
of successful project completion high given the current state of research and 
development and the technical approach? Does the application clearly 
delineate appropriate timelines and interim milestones and are they 
appropriate, feasible and technically sound? 

o INNOVATION:  If appropriate, 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?

o INVESTIGATOR:  Is the research and development team appropriately trained 
and experienced 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)? Is there strong evidence of substantive industrial 
commitment?

o ENVIRONMENT:  Does the 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 environments, including 
partnerships with industry, or employ useful collaborative arrangements?  Is 
there adequate 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 in the sections on Federal Citations, 
below).

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

ADDITIONAL REVIEW CONSIDERATIONS

RFA-specific review criteria:

o The scientific rationale and basis for the candidate product, including the 
strength of existing data on product feasibility, safety and potential 
efficacy
o The appropriateness of the proposed project in terms of the stage of 
development of the candidate product
o The appropriateness and feasibility of defined objectives/milestones
o Feasibility of future product development
o The appropriateness and feasibility of conducting any proposed clinical 
trial or field evaluation during the period of award, including for example, 
the timelines proposed for IND preparation and filing, patient recruitment, 
and completion of the study.

SHARING RESEARCH DATA: Applicants requesting more than $500,000 in direct 
costs in any year of the proposed research must include a data sharing plan 
in their application. The reasonableness of the data sharing plan or the 
rationale for not sharing research data will be assessed by the reviewers. 
However, reviewers will not factor the proposed data sharing plan into the 
determination of scientific merit or priority score. See 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html and the 
policy under Federal Citations below.
 
BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

PROTECTIONS: The adequacy of the proposed protections for humans, animals, or 
the environment, to the extent they may be adversely affected by the project 
proposed in the application.  

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:      December 1, 2003
Application Receipt Date:           January 13, 2004
Peer Review Date:                   May 2004
Council Review:                     August 2004
Earliest Anticipated Start Date:    September 2004

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 High priority public health needs  
  
REQUIRED FEDERAL CITATIONS 

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

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

SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking more than $500,000 or 
more in direct costs in any single year are expected to include a plan for 
data sharing or state why this is not possible.  
http://grants.nih.gov/grants/policy/data_sharing Investigators should seek 
guidance from their institutions, on issues related to institutional 
policies, local IRB rules, as well as local, state and Federal laws and 
regulations, including the Privacy Rule. Reviewers will consider the data 
sharing plan but will not factor the plan into the determination of the 
scientific merit or the priority score.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of 
the research. This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).

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

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: 
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them. 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.  This policy announcement is in the NIH Guide for Grants and 
Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

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

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

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

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


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
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and Human Services (HHS)
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