PARTNERSHIPS: HEPATITIS B AND VECTOR BORNE DISEASES CONTROL

RELEASE DATE:  November 13, 2002

RFA NUMBER:  AI-03-003 

Letter of Intent Receipt Date:  February 24, 2003

Application Receipt Date:   March 24, 2003

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

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the RFA
o Research Objectives
o Mechanism(s) of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Terms and Conditions of Award
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THE RFA

Research of 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) supports 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; applied research, including the development of 
diagnostic tests; and clinical trials to evaluate experimental drugs and 
vaccines.

This Partnership program will use the cooperative agreement (U01) funding 
mechanism to support the development and testing of products for selected 
human infectious diseases of public health importance. A key component of the 
Partnership initiatives is the development of appropriate partnerships among 
government, academia, and the biotechnology, chemical or pharmaceutical 
industries. 

This RFA is specifically focused on:

A)  Development of novel therapies against hepatitis B virus (HBV); 
B)  Development of products/strategies for controlling the transmission of 
infectious agents by Ixodes ticks; and 
C)  Assessing and/or extending the effectiveness of other arthropod vector 
control tools or strategies. 

For the purpose of this RFA, "industry" is defined as large and small 
pharmaceutical, biotechnology, and chemical companies.  All projects must 
demonstrate substantive involvement by a commercial sector (industry) 
component.  For the purpose of this RFA,  "substantive involvement" is 
defined as the commitment of any one or more of the following resources: 
funds; personnel; or in-kind contributions of materials and reagents, 
including but not limited to chemical libraries, innovative biotechnology 
platforms for screening drugs and inhibitors, scale up GMP chemical 
synthesis, access to tick colonies, provision of animal or other laboratory 
models, and data management resources. The Principal Investigator may be 
affiliated with either a commercial or academic organization.

PARTNERSHIPS

The Partnership Program is intended to support all phases of development of a 
candidate product or platform technology including, but not limited to, early 
validation, pre-clinical stages, scale-up, production, regulatory 
requirements, and, where appropriate, clinical or field evaluation. 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 of cGMP product) 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 the cooperative 
agreement grant mechanism, will be actively involved in evaluating the 
milestones of awardees and determining whether additional investment in the 
development is warranted.

RESEARCH OBJECTIVES

Background

In late 2000, the NIAID convened a panel of experts to discuss the role and 
nature of NIAID/industry collaborations in antimicrobial drug development for 
public health needs and to learn how NIAID could better assist industry and 
academia in these endeavors ("Summit on Drug Development for Infectious 
Diseases.") One of the recommendations from this meeting was the need to 
continue to pursue innovative opportunities to form partnerships with the 
private sector for the control of a number of infectious diseases with public 
health importance.  A report of this meeting is available at 
http://www.niaid.nih.gov/dmid/drug/#7.  The need to support the research 
specified by this RFA has been emphasized by the NIAID-convened review of its 
Clinical Antiviral Programs in 1995 and a review of the NIAID vector biology 
research agenda in 2000.

Investment by industry in the commercialization of products for the control 
of a number of infectious diseases of public health importance remains 
limited.  This initiative is meant to help stimulate industry participation 
in decreasing the impact of these targeted important diseases for which 
effective new therapeutics or control measures are lacking.  This program is 
seeking applications that propose to:

A.  Exploit known or to-be-discovered targets for the design and testing of 
new classes of drugs/therapies against chronic HBV infection;

B.  Develop novel, environmentally safe strategies for limiting the ability 
of Ixodes ticks to transmit pathogens. Projects responsive to this area could 
include, but are not necessarily limited to, the development and/or proof of 
principle testing of novel immunological, genetic or molecular approaches 
that interfere with tick physiology and/or reproduction or the ability of 
ticks to transmit specific infectious agents; or 

C.  Evaluate the epidemiological impact of vector control products; and/or 
identify entomological correlates of prevention that can be monitored, and 
that have significance for public health vector control (e.g., insecticide 
resistance). 

Research Objectives and Scope

Responsive research applications should focus on the development of a single 
ultimate product or strategy for one of the following three areas of high 
public health importance:

A.  Development of novel therapies against hepatitis B virus 

Therapies for chronic hepatitis B viral infection are few, require protracted 
treatment, and are generally not curative.  Currently there are only two 
licensed therapies: interferon alpha and the nucleoside analogue, lamivudine.  
Most drugs in development are similar to lamivudine, essentially targeting 
the same function in viral replication.  Although some drugs may reduce 
viremia more than others, most have limited efficacy against evasive mutant 
viruses. 

Concerted efforts are needed to define key steps in the infection, 
replication and assembly of New analytical methods could identify these steps 
and open pathways to the design and testing of new classes of curative 
antivirals or immunostimulators. Applications are sought that include, the 
following areas of research:

o The use of emerging analytical technologies and methodologies to identify 
and verify viral/host targets for new designs for HBV therapies;
o The design, synthesis, purification, validation and testing of 
drugs/immunostimulators for efficacy and toxicity in model assays and in 
relevant animal models. Part of this work may involve a reiterative process 
of redesign and revalidation;
o The performance of pharmacokinetic and pharmacodynamic studies of lead 
candidates and the assessment of their bioavailability and mechanism(s) of 
action;
o The identification of optimal host conditions and delivery systems for the 
administration of therapeutics; and,
o The determination of drug interactions in the molecular processes of the 
host and efficacy against evolving viral mutants.

NOTE:  Chemically defined active component(s) of natural products can be 
explored as potential drug sources for development. The screening of natural 
products for biological activities will not be supported under Part A of this 
initiative.

B.  Development of products/strategies to prevent the transmission of Ixodes 
tick-borne diseases.    

Tick-borne infectious diseases are an increasing threat to human health, and 
new, more efficient approaches are required to prevent transmission to 
humans.  To be considered responsive,  an application must identify  a novel 
molecular, genetic, and/or immunological approach that is, or can be 
demonstrated to be, effective in preventing the transmission of tick-borne 
infectious diseases.  The application should include a well-defined and 
controlled experimental laboratory animal model to prevent the transmission 
of infection by Ixodes ticks.  The goal is to acquire preliminary data on 
transmission-interruption approaches that will ultimately support future 
field trials.  The conduct of field trials will not be supported under this 
part of this initiative.

C. Evaluation of the ongoing epidemiological effects of vector control 
approaches or products currently in use and/or identification of 
entomological correlates or surrogate markers of prevention that can be 
monitored, and that have significance for public health vector control, (e.g. 
insecticide resistance).  

Applications are sought that include, but are not limited to:
  
o Assessments of the effectiveness of arthropod vector control tools and 
strategies used in public health programs.  Specifically, this research would 
include studies that establish links between entomological (e.g. insect 
killing, repellency, blood feeding,) and epidemiological parameters (e.g., 
disease incidence or prevalence, infection status of humans or sentinel 
animals) as the basis for ongoing monitoring of vector- and disease-control 
impact.
o Collection of standardized, Geographic Information Systems (GIS)-based data 
on the incidence of insecticide resistance and other forms of control 
failures, the distribution of vector species and sub-species, environmental 
factors, patterns of agricultural insecticide use, vector migration patterns, 
and other key factors determining the development of insecticide resistance 
or the impact of vector control. 
o Studies to evaluate and limit the effects of pesticide resistance on 
practical control measures.
o Studies to develop or refine pesticide resistance management strategies 
(e.g., rotational use of insecticides, inclusion of refugia, altered duration 
or pattern of application).
o Creation of predictive regional models of the spread of insecticide 
resistance related to disease transmission.

NOTE:  Field studies may be supported for applicants responding to Part C.

MECHANISM OF SUPPORT

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

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

FUNDS AVAILABLE  
The estimated total funds [direct and facilities and administrative (F&A) 
costs] available for the first year of support for all awards made under this 
RFA will be $4 million.  In Fiscal Year 2003, the NIAID plans to fund 
approximately 6-10 awards with a mixture of both large and small grants. 
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. Funding beyond the first and subsequent years of the grant 
will be contingent upon satisfactory progress during the preceding years and 
availability of funds.

ELIGIBILE 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  

Both domestic and foreign organizations are eligible.  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.

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

All applications must include substantive involvement by industry (as defined 
above).  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

Depending upon the scientific area, each application must propose a research 
and development project whose ultimate goal is to produce a novel therapeutic 
against HBV, an approach to limit the ability of Ixodes ticks to transmit 
infectious agents to humans, or a strategy to evaluate the epidemiological 
effects of other vector control products.   

Applications must propose clear project goal(s), including one (or more) 
final product or stage of development to be completed during the award 
period.  The applicant must clearly state the interim objectives 
(developmental milestones) to be achieved during the project, identify 
impediments or critical decision points that could require a revision in the 
work plan or milestones, and provide a detailed schedule or timeline for the 
attainment of each milestone and/or goal.  For applications that contain a 
clinical or field study (Part C only), a mandatory milestone that must be 
included is the approval of the final clinical protocol by NIAID.  Applicants 
must build this milestone into their application. 

Clinical or field studies will only be supported for applicants responding to 
scientific area C (Arthropod vector control) Any applicant proposing a 
clinical or field study for Part C must submit a study protocol as part of 
the application.  For guidance on protocol format and/or other issues related 
to clinical or field studies for Part C contact Dr. Kate Aultman (contact 
information provided below).

Intellectual Property

The successful development of these high priority products for biodefense 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.  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, reports to the NIAID or other 
mechanisms.

Mandatory Meetings

Proposed budgets must include funds for travel by the Principal Investigator, 
other key personnel as needed, and two external advisors to an annual two-day 
progress review meeting in Bethesda, MD.  Progress will be reviewed annually 
by NIAID with the help of external advisors, to be named after award by NIAID 
in consultation with the Principal Investigator.  Names of suggested advisors 
should not be included in the application, nor should these individuals be 
contacted prior to the review.

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 
cooperative agreement (U01), [an "assistance" mechanism (rather than an 
"acquisition" mechanism), in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during the 
performance of the activity.  Under the cooperative agreement, the NIH 
purpose is to support and/or stimulate the recipient's activity by 
involvement in and otherwise working jointly with the award recipient in a 
partner role, but it is not to assume direction, prime responsibility, or a 
dominant role in the activity.  Consistent with this concept, the dominant 
role and prime responsibility for the activity resides with the awardees for 
the project as a whole, although specific tasks and activities in carrying 
out the research will be shared among the awardees and their NIAID Program 
Officers.

1.  Clinical Terms of Award

When human subjects or human samples are a component of the research 
proposed, NIAID policy requires that studies be monitored commensurate with 
the degree of potential risk to human subjects.  Terms and Conditions of 
Award will be included with awards. The NIAID policy including terms and 
conditions of award is available at: 
http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf.

2.  Awardee Rights and Responsibilities

Awardees will have primary responsibility for defining the research 
objectives, approaches and details of the projects within the guidelines of 
the RFA and for performing the scientific activity. Specifically, awardees 
have primary responsibility as described below.

Awardees may be from academia or industry.  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 comply with the approved intellectual property disposition plan 
that details (1) the approach agreed to by all parties for disposition of 
intellectual property, including but not limited to obtaining patent coverage 
and licensing, where appropriate, and (2) procedures to be followed for the 
resolution of legal problems that potentially may develop.

For 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 
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm; 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 of Medical Sciences (CIOMS) International Ethical 
Guidelines 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.

When experimental field applications of chemical pesticides are included in 
the scope of work (Part C ONLY) the awardee must abide by all of the 
pertinent regulations and laws that exist in the jurisdiction where the work 
will take place. In the United States, that usually involves application for 
and receipt of an Experimental Use Permit from the Environmental Protection 
Agency (EPA). When such work would take place outside the Untied States, 
NIAID may also solicit the advice of appropriate experts, and awardees will 
be expected to provide the same level of protection for the environment as 
would be afforded if the work were being done in the United States.

3. NIAID Staff Responsibilities
     
The NIAID Program Officer will provide normal stewardship and will also have 
substantial scientific/programmatic involvement during the conduct of this 
activitiy 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 biotech industries, and other government agencies 
(e.g., FDA, USDA, CDC), and will serve as a resource of scientific and policy 
information related to the goals of the awardee's research. 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.  All such revisions must be agreed 
to by the awardee and NIAID. Release of each funding increment by NIAID will 
be based on a NIAID review of progress towards achieving the previously 
agreed upon interim objective. 

5.  Arbitration

Any disagreement that may arise on scientific or programmatic matters (within 
the scope of the award) between award recipients and the NIAID may be brought 
to arbitration.  An arbitration panel will be composed of three members -- 
one selected by the Steering Committee or by the individual awardee in the 
event of an individual disagreement, a second member selected by the NIAID, 
and the third member with expertise in the relevant area and selected by the 
two prior members will be formed to review any scientific or programmatic 
issue that is significantly restricting progress.  While the decisions of the 
Arbitration Panel are binding, these special arbitration procedures will in 
no way affect the awardee's right to appeal an adverse action in accordance 
with PHS regulations at 42 CFR Part 50, subpart D, and HHS regulations at 45 
CFR Part 16.

WHERE TO SEND INQUIRIES

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

o Direct your questions about scientific/research issues to:

Part A:  Hepatitis B Therapies
Diana S. Berard
Division of Microbiology & Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room Number 6002, MSC-6603
6610 Rockledge Drive
Bethesda, MD 20892-6603
Telephone: (301) 402-8617
FAX: (301) 402-1456
Email: dberard@niaid.nih.gov 

Part B:  Tick-borne diseases transmission prevention
Dr. Phillip Baker
Division of Microbiology & Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room Number 3114, MSC-7630
6700B Rockledge Drive
Bethesda, MD 20892-7630
Telephone: (301) 435-2855
FAX: (301) 402-2508
Email: pbaker@niaid.nih.gov 

Part C:  Arthropod vector control epidemiology
Dr. Kate Aultman
Division of Microbiology & Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room Number 6014, MSC-6603
6610 Rockledge Drive
Bethesda, MD 20892-6603
Telephone: (301) 435-2854
FAX: (301) 402-0659
Email: kaultman@niaid.nih.gov 

o Direct inquiries regarding protocol format and/or other issues related to 
clinical or field studies to: 

Dr. Kate Aultman
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases  
Room Number 6014, MSC-6603
6610 Rockledge Drive
Bethesda, MD 20892-6603
Telephone: (301) 435-2854
FAX: (301) 402-0659
Email: kaultman@niaid.nih.gov 

Direct inquiries regarding review issues, address the letter of intent, and 
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 2150, MSC-7614
6700-B Rockledge Drive  
Bethesda, MD  20892-7614
Telephone:  (301) 496 2550
FAX:  (301) 402-2638
E-Mail:  mhalula@niaid.nih.gov

Direct inquiries regarding fiscal matters to:  

Ms Sharie Bernard               
Division of Extramural Activities  
National Institute of Allergy and Infectious Diseases  
Room 3219, MSC-7614
6700-B Rockledge Drive  
Bethesda, MD  20892-7614
Telephone:  (301) 402-5540
Fax:  (301) 480-3780
E-mail:  sb34k@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 PAR 

Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows IC staff to estimate the potential review workload and plan 
the review.
 
The letter of intent is to be sent by the date listed at the beginning of 
this document.  The letter of intent should be sent to:

Madelon Halula, Ph.D.  
Division of Extramural Activities  
National Institute of Allergy and Infectious Diseases  
Room 2150, MSC-7614
6700-B Rockledge Drive  
Bethesda, MD  20892-7614
BETHESDA, MD  20817 (for express mail or courier service)

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html  in an interactive 
format.  Please refer to SPECIAL REQUIREMENTS list above.  For further 
assistance contact GrantsInfo, Telephone (301) 435-0714, Email: 
GrantsInfo@nih.gov.  

APPLICATION RECEIPT DATES: Applications submitted in response to this RFA 
must be received by the date listed on the first page.

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.  

For purposes of identification and processing, item 2a on the face page of 
the application must be marked "YES," the RFA number and the words " 
PARTNERSHIPS: HEPATITIS B AND VECTOR BORNE DISEASES CONTROL" must be entered 
on the face page.

Submit a signed, typewritten original of the application, including the 
checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

At the time of submission, two additional exact copies of the grant 
application and all five sets of any appendix material must be sent to:

Madelon Halula, Ph.D.  
Division of Extramural Activities  
National Institute of Allergy and Infectious Diseases  
Room 2150, MSC-7614
6700-B Rockledge Drive  
Bethesda, MD  20892-7614
BETHESDA, MD  20817 (for express mail or courier service)

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.

APPLICATION PROCESSING:  Applications must be received by the date listed on 
the first page.  The CSR will not accept any application in response to this 
RFA that is essentially the same as one currently pending initial review 
unless the applicant withdraws the pending application.  The CSR will not 
accept any application that is essentially the same as one already reviewed.  
This does not preclude the submission of a substantial revision of an 
application already reviewed, but such application must include an 
Introduction addressing the previous critique.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by NIAID.

Incomplete or late applications will be returned to the applicant without 
further consideration. 
Applications that are complete and responsive to the RFA will be evaluated 
for scientific and technical merit by appropriate peer review groups convened 
by the NIAID in accordance with the review criteria stated below. There will 
be three different review groups to handle the three subject areas described 
in Parts A, B, and C above. As part of the initial merit review, all 
applications will:

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

REVIEW CRITERIA

The criteria to be used in the evaluation of grant applications are listed 
below.  To put those criteria in context, the following information is 
contained in instructions to the peer reviewers.

The reviewers will comment on the following aspects of the application in 
their written critiques in order to judge the likelihood that the proposed 
research will have a substantial impact on the pursuit of the PAR goals.  
Each of these criteria will be addressed and considered by the reviewers in 
assigning the overall score weighting them as appropriate for each 
application.  Note that the application does not need to be strong in all 
categories to be judged likely to have a 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.

1. Significance.  Is this project likely to result in or significantly 
advance development of (Part A) a novel HBV therapeutic, (Part B) a tick 
borne infectious agent preventative, or (Part C) an arthropod vector control 
agent/strategy that will add substantively to our ability to treat or control 
an infectious disease of public health importance? Is the industry commitment 
adequate to have an impact on the success of the proposed research 
objectives? 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? 

2. Approach.  Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project?  Does the applicant acknowledge potential problem areas and consider 
alternative tactics? Is the likelihood of successful project completion high 
given the current state of research and development and the technical 
approach? Are the proposed timeline and interim milestones appropriate, 
feasible and technically sound? 

3. Innovation.  Many aspects of drug and arthropod vector control method 
development are not inherently innovative.  However, each project will be 
judged on whether, if successful in completing its aims, the project will add 
substantially to our ability to treat or control an infectious disease that 
currently causes a public health burden and is not currently considered an 
attractive investment by the private sector (i.e., biotechnology, chemical or 
pharmaceutical industry).

4. 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?

5. 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, your 
application will also be reviewed with respect to the following:

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

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

o DATA SHARING: The adequacy of the proposed plan to share data. 

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

RECEIPT AND REVIEW SCHEDULE:

Letter of Intent Receipt Date: February 24, 2003
Application Receipt Date:  March 24, 2003
Scientific Peer Review Date:  May, 2003
Advisory Council Date:  June, 2003
Earliest Anticipated Award Date: September 2003

AWARD CRITERIA

The following will be considered in making funding decisions: 

o scientific merit (as determined by peer review)
o availability of funds
o programmatic priorities
  
REQUIRED FEDERAL CITATIONS 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures.  In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (NIH Policy for 
Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 
1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

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

All investigators proposing clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines 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.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research 
on hESCs can be found at http://grants.nih.gov/grants/stem_cells.htm 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 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 PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

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

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

AUTHORITY AND REGULATIONS

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

The NIH Grants Policy Statement is available at 
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.

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.

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