This Program Announcement expires on May 2, 2004, unless reissued.
THERAPEUTICS RESEARCH ON AIDS-ASSOCIATED OPPORTUNISTIC INFECTIONS
AND MALIGNANCIES
Release Date: June 28, 2001
PA NUMBER: PA-01-113 (see replacement PA-04-157)
(see NOT-AI-04-014 and NOT-AI-04-010)
National Institute of Allergy and Infectious Diseases
(http://www.niaid.nih.gov)
National Cancer Institute
(http://www.nci.nih.gov)
National Institute of Dental and Craniofacial Research
(http://www.nidcr.nih.gov)
Application Receipt Dates: January 2, May 1, September 1
THIS RFA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT INCLUDES
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED
WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA/PA.
The purpose of this Program Announcement (PA) is to encourage research grant
applications aimed at novel approaches to discovery and preclinical
development of therapeutic agents against opportunistic infections (OIs) and
malignancies in people with AIDS. The intent of this PA is to seek
investigator-initiated grant applications that involve creative and original
preclinical research utilizing state-of-the-art technologies necessary to
propel advances in new or improved therapies. No clinical trials will be
supported under this PA.
This PA is being issued by NIAID, and co-sponsored by the National Cancer
Institute (NCI) and the National Institute of Dental and Craniofacial
Research (NIDCR). The National Heart, Lung, and Blood Institute (NHLBI), and
the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
also have an interest in and support research on opportunistic infections
associated with AIDS. Applicants may wish to contact these NIH components
listed under INQUIRIES to find out about other funding opportunities.
Applicants for Small Business Innovation Research (SBIR) projects on
investigational areas included in this PA should consider applying through
NIAID PAR 00-126, published in the NIH Guide for Grants and Contracts on July
26, 2000, which is available on the World Wide Web at:
http://grants.nih.gov/grants/guide/pa-files/PAR-00-126.html
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 Program Announcement
(PA), Therapeutics Research on AIDS-Associated Opportunistic Infections, 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/.
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State and local governments, and eligible
agencies of the Federal government. Racial/ethnic minority individuals,
women, and persons with disabilities are encouraged to apply as Principal
Investigators.
MECHANISM OF SUPPORT
This PA will use the National Institutes of Health (NIH) individual research
project grant (R01) and the exploratory/developmental grant (R21) mechanism.
A sound rationale and a well-designed research plan with limited preliminary
data are required for a R21. The R01 supports more advanced projects.
Responsibility for the planning, direction, and execution of the proposed
research for all applicable mechanisms of support will be solely that of the
applicant.
Specific application instructions have been modified to reflect "MODULAR
GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH.
Complete and detailed instructions and information on Modular Grant
applications can be found at
http://grants.nih.gov/grants/funding/modular/modular.htm.
A notice of modification and update (OD-00-046) regarding modular grants was
released on 7/24/00 and can be found at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-046.html.
SBIR applicants should refer to NIAID PAR-00-126 cited above.
Applicants for R01 grants will request direct costs in $25,000 modules, up to
a total direct cost request of $250,000 per year. This applies only up to
$250,000. Applications that request more than $250,000 direct costs in any
year must follow the traditional PHS 398 application instructions. A typical
modular grant application will request the same number of modules in each
year. Applications for R01 grants may request a maximum five years of
support.
Applicants for the R21 grant mechanism may request up to $150,000 (6- $25,000
modules) direct costs per year and support may not exceed two years. This
mechanism provides short-duration support for preliminary studies of a highly
speculative nature, which are expected to yield sufficient information upon
which to base a well-planned and rigorous series of further investigations.
The R21 grants are non-renewable and competitive continuation of projects
developed under this grant mechanism will be through the R01 research grant
mechanism. Funds and time requested should be appropriate for the research
proposed.
RESEARCH OBJECTIVES
AIDS-Associated Opportunistic Infections
The most notable advance in AIDS-associated opportunistic infections (OIs)
has been the decline in their incidence, which is a result of the effect of
potent antiretroviral therapy. Recent findings also suggest that although
the natural history of OIs in patients with HIV infection is changing, OIs
are still an important clinical and pathophysiological manifestation of HIV
disease. For example, HIV-infected patients have an elevated risk of primary
or reactivated tuberculosis, and such active infectious processes may enhance
HIV replication and increase risk of death.
The long-term effectiveness of antiretroviral therapy in developed countries
remains unknown, and it is unclear whether the reduced rates of OIs are
temporary or permanent. HIV/AIDS continues at an epidemic rate in developing
countries where antiretroviral therapy remains unavailable.
Significant pathological consequences associated with OIs in AIDS include
tuberculosis (Mycobacterium tuberculosis), pneumonia (Pneumocystis carinii),
protracted diarrhea (Cryptosporidium parvum, Enterocytozoon bieneusi) and
painful oral ulcerative lesions.
Limitations of currently available drugs for treatment and prevention of OIs
include the static nature of most agents, toxicity, and emergence of
resistance. The discovery of more potent and less toxic compounds would
provide improved medical management of these AIDS-associated complications.
Furthermore, no standard treatments exist for opportunistic pathogens such as
C. parvum, and E. bieneusi.
AIDS-Associated Malignancies
As HIV-infected individuals survive longer, the number of cases of AIDS-
associated malignancies (AAMs) continues to increase. While the incidence of
Kaposi’s sarcoma and primary CNS lymphomas in HIV-infected individuals has
been reduced since the widespread use of potent antiretroviral therapy, there
has been no substantial change in the incidence of non-Hodgkin’s lymphomas,
cervical cancer and anogenital cancers. Many of these malignancies are
associated with viral infections such as Kaposi’s sarcoma herpesvirus (KSHV)
with Kaposi’s sarcoma, Epstein-Barr virus (EBV) with certain lymphomas, and
human papillomavirus (HPV) with cervical and anogenital cancers. Therapies
developed for cancers in the non-immunocompromised setting have not always
proven to be effective in patients with HIV/AIDS. Oral cancers may in fact
remain the same or increase following potent antiretroviral treatment. The
discovery of new therapies for AAMs remains an unmet need.
Research Objectives and Experimental Approaches
The goal of this PA is the development of agents for treatment of AIDS-
associated OIs and malignancies. Given present advances in molecular
biology, the principal objectives of the PA are to stimulate original and
innovative preclinical research to (1) identify and characterize new,
pathogen-specific or malignancy-specific molecular targets and (2) develop
promising therapeutic approaches. Applications directly linking disease
pathogenesis to molecular target identification are encouraged.
AIDS-associated opportunistic pathogens emphasized by this PA are:
Mycobacterium tuberculosis, Pneumocystis carinii, Cryptosporidium parvum, and
the microsporidia.
AIDS-associated malignancies emphasized by this PA are: Kaposi’s sarcoma,
lymphomas, cervical cancer, oral warts and cancers, and anogenital cancers.
Areas of study may include but are not restricted to the following examples:
o discovery and development of efficacious new therapeutic agents for
treatment of AIDS-associated OIs and malignancies,
o validation of molecular targets for therapeutic agents utilizing state-of-
the-art molecular genetic technology,
o discovery and evaluation of novel, selective chemical entities generated
by combinatorial chemistry or combinatorial genomics methodologies,
o development of improved delivery systems for therapeutic agents (improved
bioavailability, pharmacokinetics), and
o development of improved assays, in vitro (cell culture) and in vivo
(animal model) systems for drug evaluations.
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of the NIH that women and members of minority groups and
their subpopulations must be included in all NIH supported biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification is provided 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 research involving human subjects should read the
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical
Research," which have been published in the Federal Register of March 28,
1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol.
23, No. 11, March 18, 1994 available on the web at the following URL address:
http://grants.nih.gov/grants/guide/notice-files/not94-100.html
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of NIH 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 was published in the NIH Guide for
Grants and Contracts, March 6, 1998, and is available at the following URL
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html
Investigators also may obtain copies of these policies from the program staff
listed under INQUIRIES. Program staff may also provide additional relevant
information concerning the policy.
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. Reviewers are cautioned that their anonymity may
be compromised when they directly access an Internet site.
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.
Applications are to be submitted on the grant application form PHS 398 (rev.
4/98) at http://grants.nih.gov/grants/forms.htm and will be accepted at the
standard application deadlines (http://grants.nih.gov/grants/dates.htm) as
indicated in the application kit. Application kits are also available at most
institutional offices of sponsored research and may be obtained from the
Division of Extramural Outreach and Information Resources, National
Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-
7910, telephone 301/710-0267, email: GrantsInfo@nih.gov.
Applicants planning to submit an investigator-initiated new (type 1),
competing continuation (type 2), competing supplement, or any amended/revised
version of the preceding grant application types requesting $500,000 or more
in direct costs for any year are advised that he or she must contact the
Institute or Center (IC) program staff before submitting the application,
i.e., as plans for the study are being developed. Furthermore, the
application must obtain agreement from the IC staff that the IC will accept
the application for consideration for award. Finally, the applicant must
identify, in a cover letter sent with the application, the staff member and
Institute or Center who agreed to accept assignment of the application.
This policy requires an applicant to obtain agreement for acceptance of both
any such application and any such subsequent amendment. Refer to the NIH
Guide for Grants and Contracts, March 20, 1998 at
http://grants.nih.gov/grants/guide/notice-files/not98-030.html
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS
BUDGET INSTRUCTIONS
Modular Grant applications will request direct costs in $25,000 modules, up
to a total direct cost request of $250,000 per year. (Applications that
request more than $250,000 direct costs in any year must follow the
traditional PHS 398 application instructions.) The total direct costs must
be requested in accordance with the program guidelines and the modifications
made to the standard PHS 398 application instructions described below:
PHS 398
o FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs (in
$25,000 increments up to a maximum of $250,000) and Total Costs [Modular
Total Direct plus Facilities and Administrative (F&A) costs] for the initial
budget period. Items 8a and 8b should be completed indicating the Direct and
Total Costs for the entire proposed period of support.
o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form Page 4
of the PHS 398. It is not required and will not be accepted with the
application.
o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the
categorical budget table on Form Page 5 of the PHS 398. It is not required
and will not be accepted with the application.
o NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget Narrative
page. (See http://grants.nih.gov/grants/funding/modular/modular.htm for
sample pages.) At the top of the page, enter the total direct costs requested
for each year. This is not a Form page.
o Under Personnel, List all project personnel, including their names, percent
of effort, and roles on the project. No individual salary information should
be provided. However, the applicant should use the NIH appropriation language
salary cap and the NIH policy for graduate student compensation in developing
the budget request.
For Consortium/Contractual costs, provide an estimate of total costs (direct
plus facilities and administrative) for each year, each rounded to the
nearest $1,000. List the individuals/organizations with whom consortium or
contractual arrangements have been made, the percent effort of all personnel,
and the role on the project. Indicate whether the collaborating institution
is foreign or domestic. The total cost for a consortium/contractual
arrangement is included in the overall requested modular direct cost amount.
Include the Letter of Intent to establish a consortium.
Provide an additional narrative budget justification for any variation in the
number of modules requested.
o BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by
reviewers in the assessment of each individual"s qualifications for a
specific role in the proposed project, as well as to evaluate the overall
qualifications of the research team. A biographical sketch is required for
all key personnel, following the instructions below. No more than three pages
may be used for each person. A sample biographical sketch may be viewed at:
http://grants.nih.gov/grants/funding/modular/modular.htm
- Complete the educational block at the top of the form page,
- List position(s) and any honors,
- Provide information, including overall goals and responsibilities, on
research projects ongoing or completed during the last three years.
- List selected peer-reviewed publications, with full citations,
o CHECKLIST - This page should be completed and submitted with the
application. If the F&A rate agreement has been established, indicate the
type of agreement and the date. All appropriate exclusions must be applied
in the calculation of the F&A costs for the initial budget period and all
future budget years.
o The applicant should provide the name and phone number of the individual to
contact concerning fiscal and administrative issues if additional information
is necessary following the initial review.
The title and number of the program announcement must be typed on line 2 of
the face page of the application form and the YES box must be marked.
Submit a signed, typewritten original of the application, including the
Checklist, and five 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)
REVIEW CONSIDERATIONS
Review Procedures
Applications will be assigned on the basis of established NIH referral
guidelines. Applications will be evaluated for scientific and technical merit
by an appropriate scientific review group convened in accordance with the
standard NIH peer review procedures. As part of the initial merit review, all
applications will receive a written critique and undergo a process in which
only those applications deemed to have the highest scientific merit,
generally the top half of applications under review, will be discussed,
assigned a priority score, and receive a second level review by the
appropriate national advisory council or board.
Review Criteria
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. 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 these 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. Does this study address an important problem? If the aims of
the application are achieved, how will scientific knowledge be advanced? What
will be the effect of these studies on the concepts or methods that drive
this field?
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?
3) Innovation. Does the project employ novel concepts, approaches or method?
Are the aims original and innovative? Does the project challenge existing
paradigms or develop new methodologies or technologies?
4) Investigator. Is the investigator appropriately trained and well suited to
carry out this work? Is the work proposed appropriate to the experience level
of the principal investigator and other researchers (if any)?
5) Environment. Does the scientific environment in which the work will be
done contribute to the probability of success? Do the proposed experiments
take advantage of unique features of the scientific environment or employ
useful collaborative arrangements? Is there evidence of institutional
support?
In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:
o The adequacy of plans to include both genders, minorities and their
subgroups, and children as appropriate for the scientific goals of the
research. Plans for the recruitment and retention of subjects will also be
evaluated.
o The reasonableness of the proposed budget and duration in relation to the
proposed research
o 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.
AWARD CRITERIA
Applications will compete for available funds with all other recommended
applications. The following will be considered in making funding decisions:
o scientific merit (as determined by peer review)
o availability of funds
o programmatic priorities.
INQUIRIES
Written and telephone inquiries are encouraged. The opportunity to clarify
any issues or questions from potential applicants is welcome.
The National Institute of Allergy and Infectious Diseases has an interest in
the validation of novel molecular targets for drug development programs and
the evaluation of new and novel therapies against AIDS-associated
opportunistic infections. Inquiries regarding programmatic issues may be
directed to:
Chris Lambros, Ph.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases
6700B Rockledge Drive, Room 5227, MSC 7624
Bethesda, MD 20892-7624
Telephone: 301-435-3769
FAX: 301-402-3171
Email: clambros@niaid.nih.gov
The National Cancer Institute (NCI) has an interest in the discovery and
validation of novel molecular targets for drug discovery programs and the
evaluation of new and novel therapies against AIDS-associated malignancies.
Therefore, applications of interest on AIDS-associated malignancies are
likely to be given primary assignment to NCI in accordance with the NIH
referral guidelines. Inquiries regarding NCI programmatic issues may be
directed to:
Kenneth Cremer, PhD
Division of Cancer Biology
National Cancer Institute
Room 5016
6130 Executive Boulevard, MSC 7398
Bethesda, MD 20892-7398
Telephone: 301-496-6085
FAX: 301-496-2025
Email: kc47i@nih.gov
The National Institute of Dental and Craniofacial Research (NIDCR) has an
interest in opportunistic infections in the oral cavity. Therefore,
applications of interest will be assigned to NIDCR in accordance with the NIH
referral guidelines. Inquiries regarding NIDCR programmatic issues may be
directed to:
Dennis F. Mangan, Ph.D.
Division of Extramural Research
National Institute of Dental and Craniofacial Research
Building 45, Room 4AN-32F, MSC 6402
Bethesda, MD 20892-6402
Telephone: 301-594-2421
FAX: 301-480-8318
Email: dennis.mangan@nih.gov
The National Heart, Lung, and Blood Institute (NHLBI) has an interest in
supporting research on the pulmonary, cardiovascular and hematologic aspects
of opportunistic infections associated with HIV infection. Therefore,
applications of interest are likely to be given a may be primary or secondary
assignment to NHLBI in accordance with the NIH referral guidelines.
Inquiries regarding NHLBI programmatic issues may be directed to:
Hannah H. Peavy, M.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Suite 10018, MSC 7952
Bethesda, MD 20892-7952
Telephone: 301-435-0222
FAX: 301-480-3557
Email: hannah_peavy@nih.gov
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
has an interest in supporting research on the influence of opportunistic
pathogens on the enterocytes in the gastrointestinal tract as well as the
hepatocytes in the liver in liver disease expression. Therefore,
applications of interest are likely to be given a may be primary or secondary
assignment to NIDDK in accordance with the NIH referral guidelines.
Inquiries regarding NIDDK programmatic issues may be directed to:
Frank A. Hamilton, M.D., Ph.D.
Chief, Digestive Diseases Program Branch
Room 6AN12B
DDDN/NIDDK
Natcher Building 45
45 Center Drive, MSC 6600
Bethesda, MD 20892-6600
Telephone: 301-594-8877
FAX: 301-480-8300
Email: hamiltonf@extra.niddk.nih.gov
Direct inquiries regarding fiscal matters to:
Ms. Linda Shaw
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2125
6700B Rockledge Drive, MSC 7614
Bethesda, MD 20892-7614
Telephone: 301-402-6611
FAX: 301-480-3780
Email: lshaw@niaid.nih.gov
Mr. Bill Wells
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
6120 Executive Boulevard, MSC 7150
Bethesda, MD 20892-7150
Telephone: 301-496-8796
FAX: 301-496-8601
Email: wellsw@mail.nih.gov
Mr. Martin R. Rubinstein
Grants Management Branch
Division of Extramural Research
National Institute of Dental Research
Natcher Building, Room 4AN-44A
Bethesda, MD 20892-6402
Telephone: 301-594-4800
FAX: 301-480-8301
Email: martin.rubinstein@nih.gov
AUTHORITY AND REGULATIONS
This program is supported under authorization of the Public Health Service
Act, Sec. 301 (c), Public Law 78-410, as amended. The Catalogue of Federal
Domestic Assistance Citations are Sec. 93.856, Microbiology and Infectious
Diseases Research, No. 93.855 - Immunology, Allergy, and Transplantation
Research, and 93.121, Oral Diseases and Disorders Research Awards. Awards
will be administered under PHS grants policies and Federal Regulations 42 CFR
Part 52 and 45 CFR Part 74. This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems review.
The PHS strongly encourages all grant and contract recipients to provide a
smoke-free workplace and promote the non-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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