NOVEL HIV THERAPIES: INTEGRATED PRECLINICAL/CLINICAL PROGRAM

Release Date:  May 24, 2000

PA NUMBER:  PAR-00-098

National Institute of Allergy and Infectious Diseases
National Institute of Mental Health

Application Receipt Dates:  October 10, 2000, 2001, 2002

APPLICATIONS IN RESPONSE TO THIS PROGRAM ANNOUNCEMENT (PA) MUST BE PREPARED 
USING A MULTI-PROJECT GRANT APPLICATION FORMAT. SPECIFIC INSTRUCTIONS FOR 
COMPLETING THE APPLICATION ARE IN THE NIAID BROCHURE ENTITLED "INSTRUCTIONS 
FOR APPLICATIONS FOR MULTI-PROJECT AWARDS” (April 1999) -
http://www.niaid.nih.gov/ncn/grants/multibron.htm.

PURPOSE

The National Institute of Allergy and Infectious Diseases (NIAID), National 
Institutes of Health (NIH), invites applications for the discovery, 
preclinical evaluation, development, and pilot clinical studies of novel 
agents and strategies to suppress HIV replication, interfere with HIV 
transmission or disease progression, or ameliorate the consequences of 
infection.  The National Institute of Mental Health (NIMH), NIH, invites 
applications to identify and treat the nervous system complications of HIV 
infection that result in CNS dysfunction.  The Integrated Preclinical/ 
Clinical Program (IPCP) described in this Program Announcement (PA) supports 
a continuum of diverse research activities from multidisciplinary groups.  
Accordingly, applications may emphasize one of the following: (1) research 
involving preclinical discovery and development of new therapeutics; (2) 
preclinical research that transitions to clinical studies during the award 
period; or (3) clinical research of novel, pilot treatment strategies.  In 
combining these activities into a single PA, the IPCP provides a spectrum of 
research opportunities to collaborative groups interested in any aspect of 
the discovery and development of new modalities for the treatment of HIV 
disease.  The participation of the private sector is strongly urged.  
Responsive applications will involve creative and original therapeutic 
research that targets diverse facets of HIV infection.  Excluded from this PA 
are targets and approaches already under extensive investigation at academic 
or private sectors, non-targeted random screening of potential inhibitors, 
and research on AIDS-associated opportunistic pathogens and malignancies. 

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), NOVEL HIV THERAPIES: INTEGRATED PRECLINICAL/CLINICAL PROGRAM, is 
related to the focus area of HIV Infection.  Potential applicants may obtain 
a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic 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.  While foreign institutions are not eligible for to 
apply for Program Project Grant (P01) awards as the principal institution, 
they may participate under this PA as research projects or cores.  However, 
these components will not receive support for indirect costs.  Racial/ethnic 
minority individuals, women, and persons with disabilities are encouraged to 
apply as Principal Investigators.

The involvement of the private sector is strongly urged because of the 
infrastructure and capital resources it brings to the program and its 
potential to rapidly marshal resources and move therapeutic leads through the 
development pathway.  Investigators from the private sector are eligible to 
participate as Principal Investigators, Project or Core Leaders, or 
informally as collaborators.

MECHANISMS OF SUPPORT

The mechanism of support is the Program Project grant (P01).  Program Project 
grants support broadly based, multi-disciplinary research programs that have 
a well-defined, central research focus or objective.  An important feature is 
that the interrelationships of the individual scientifically meritorious 
projects will result in a greater contribution to the overall program goals 
than if each project were pursued individually.  The program project grant 
consists of a minimum of three interrelated individual research projects that 
contribute to the program objective.  This type of award also can provide 
support for certain common resources termed cores.  Such resources should be 
utilized by two or more projects within the award.  The total project period 
for P01 grants may not exceed four years.  At this time the NIAID is 
administratively limiting the duration of P01 grants to four years; this 
administrative limitation may change in the future.

Research groups supported by this PA include: (1) groups focusing exclusively 
on preclinical discovery and development of novel therapeutic entities and 
strategies; and (2) groups positioned to implement a proposed pilot clinical 
study during the award period.  P01 applications submitted in response to 
this PA may not request in excess of $725,000 first-year total (direct and 
indirect) costs for research involving preclinical studies, or $1,500,000 
first-year total (direct plus indirect) costs for research involving clinical 
studies.  Budgets exceeding these levels must be strongly justified and pre-
approved for submission by the Program contact person listed under 
"INQUIRIES".  Groups proposing to transition from preclinical to clinical 
studies during the award period should submit a budget for each phase that 
reflects the limits given above. 

The level of support for clinical research under this PA may be insufficient 
to provide all the funds necessary to conduct the proposed clinical study.  
Prospective groups should therefore develop plans to use existing 
infrastructure and organizational support to complement the award [including 
NIH sponsored General Clinical Research Centers (GCRC) and Centers for AIDS 
Research (CFAR)].

Responsibility for the planning, direction, and execution of the proposed 
research for all applicable mechanisms of support will be solely that of the 
applicant.

Applicants for P01 grants must follow special application guidelines in the 
NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT 
AWARDS (April 1999); this brochure is available via the WWW at:
http://www.niaid.nih.gov/ncn/grants/multibron.htm.

RESEARCH OBJECTIVES

Background

Research advances in recent years have yielded a wealth of information on HIV 
molecular biology, the pathogenesis of HIV disease, and the impact of disease 
progression on immune function.  Concomitantly, seminal technological 
advances have been realized.  Together, these advances offer exciting 
opportunities to develop and translate new therapeutic concepts to clinical 
application and complement current FDA approved therapies.  To assist in 
assembling the diverse scientific expertise and ancillary resources needed to 
translate basic discoveries to applied entities, this PA is designed to 
support multi-disciplinary preclinical and clinical research groups. 

Research Objectives and Scope

The objectives of the IPCP are: (1) to maintain a strong and diverse base in 
preclinical discovery and development of new therapeutics; and (2) to support 
the translation of innovative treatment concepts from preclinical studies to 
pilot clinical proof-of-concept studies.  The ultimate goal of this PA is the 
discovery, development, and exploratory clinical evaluation of new and 
effective therapeutic approaches for the treatment of HIV disease and 
prevention of HIV sexual transmission.  Such research is expected to yield 
long-term therapeutic returns as well as identify and open new research 
directions.  In line with this objective, the PA will support diverse and 
creative strategies of sound scientific rationale that are new or under-
studied, and provide a continuous spectrum of research opportunities from 
preclinical to pilot clinical studies.  Interdisciplinary research groups 
will conduct this comprehensive effort.

Examples of preclinical and clinical research areas of interest to the IPCP 
include: 

1.  Development of under-explored/new drugs and therapeutic concepts that 
target elements (viral or host) essential for HIV replication and/or 
pathogenic manifestation(s)
2.  Development of strategies or entities that target viral reservoirs 
(cellular, tissue, organ)
3.  Development of cytoreductive strategies as adjunct immune-therapies 
(e.g., to induce repopulation of immune components) or as preparative 
regimens for transplantation (hematopoietic stem cells, lymphoid cells, 
organs)
4.  Design and testing of therapeutic vaccines (e.g., DNA-based; vector-
based)
5  Identification of topical microbicide inhibitors of HIV sexual 
transmission (e.g., blockers of HIV fusion and/or entry; gene- and cell-based 
inhibitors)
6.  Evaluation of novel therapeutic strategies in combination with treatment 
paradigms [e.g., HAART plus cell-based therapy; structured treatment 
interruption (STI) in conjunction with a therapeutic vaccine, cytokines, 
others]
7.  Identification of molecular and cellular mechanisms underlying HIV-
associated CNS dysfunction and development of targeted therapeutics

[Current research areas supported by funded groups under the IPCP can be 
viewed at: http://www.niaid.nih.gov/daids/pdatguide/ipcp.htm.]

Preclinical Research 

The preclinical portion of the IPCP supports the discovery and development of 
specific therapeutic approaches or strategies.  The new therapeutic strategy 
should have relevance and future application to clinical evaluation.  The 
inclusion of an animal model for proof-of-concept is strongly encouraged.

Preclinical groups seeking to transition from preclinical to clinical 
research during the award period must detail the goals and milestones 
considered necessary to enter the clinical phase.  These goals and milestones 
should also include plans and a timetable for obtaining the required 
institutional and government approvals [Institutional review Board (IRB), 
Institutional Biosafety Committee (IBC), Food and Drug Administration (FDA), 
NIH Recombinant Advisory Committee (RAC)].  The peer review group will review 
the appropriateness of the goals and milestones.  When a request to 
transition to the clinical phase is made, these goals and milestones will be 
also be used to determine the successful completion of the preclinical 
development phase.  Release of funds for clinical research will be contingent 
upon the documented successful completion of the proposed and peer-reviewed 
goals and milestones.

Clinical Studies 

The clinical portion of the IPCP supports interdependent, iterative 
clinical/laboratory research designed to evaluate and optimize a clinical 
therapeutic approach.  Relative to the preclinical portion of the IPCP, human 
subjects concerns and regulatory issues substantially increase under the 
clinical phase.  These safety and clinical proof-of-concept studies of 
innovative therapeutic strategies may involve greater scientific risk than 
that practiced in larger clinical trials.  A successful group will develop 
and optimize a therapeutic strategy to a point at which it can be determined 
whether the strategy merits further clinical evaluation.  Moreover, analysis 
of outcome should explore reasons for failures as well as successes as part 
of an overarching objective to further advance the knowledge base and 
development of new therapeutic modalities.

A clinical application must be based on a strategy in an advanced stage of 
preclinical development that is suitable for evaluation in a small number (6-
12) of patients.  [When merited by the study, a larger number of patients may 
be considered; prior approval by the Program Officer (see INQUIRIES, below) 
is required.]  The application should include (1) a detailed plan of the 
iterative clinical and laboratory research to be conducted to optimize the 
proposed strategy; (2) a timetable to be followed; (3) plans for the clinical 
studies including the clinical protocol; and (4) institutional and government 
approvals (IRB, FDA, RAC).

SPECIAL REQUIREMENTS 

IPCP Group Scientific Advisory Panel

Each IPCP group will designate a Scientific Advisory Panel ("Panel") of 2-3 
investigators, not affiliated with any of the institutions comprising the 
group.  The Panel will attend one or more of the IPCP group meetings each 
year, review the group's activities, and evaluate progress, adherence to the 
original time frame of activities, and the continued relevance of each 
project to the group's overall goals.  The Panel will recommend new 
directions as appropriate and will provide the PI with a comprehensive 
written evaluation of the group's activities and recommendations after each 
meeting.  A copy of the report is to be sent to the DAIDS Coordinator within 
30 days of the meeting.  [The DAIDS Coordinator for each group will be the 
equivalent of a Project Officer, having either medical or scientific research 
expertise depending on the clinical or preclinical focus of the project.]

Meetings and travel

The NIAID organizes small meetings/workshops throughout the year on topics of 
interest to IPCP investigators.  Awardees are strongly encouraged to 
participate in these meetings held in the Washington DC area.  Applicants 
should include estimated travel expenses for one such meeting per year in the 
application budget.  Estimated expenses for travel of the Scientific Advisory 
Board members should be based on one group meeting per year and should be 
included in the budget.  No additional travel funds will be provided to attend 
other domestic or foreign meetings.

TERMS AND CONDITIONS OF AWARD

Patent Coverage

Since an application may include several institutions, including the private 
sector, complex patent situations may arise.  To avoid delays related to 
intellectual property issues in implementing new therapies for HIV, each 
multi-project group is required to provide a plan as part of the application, 
detailing (1) the approach, agreed to by all parties, to be used for 
obtaining patent coverage and for licensing, where appropriate; and (2) the 
procedures to be followed for the resolution of legal problems that 
potentially may develop.  Attention is drawn to the reporting requirements of 
35 U.S.C. Parts 200-212 and 37 CFR Part 401 or FAR 55.227-11.  Instructions 
were also published in the NIH GUIDE FOR GRANTS AND CONTRACTS, Vol. 19, No. 
23, June 22, 1990.  Note that non-profit organizations (including 
universities) and small business firms retain the rights to any patent 
resulting from Government grants or cooperative agreements.

It is also noted that a Presidential memorandum of February 18, 1983 extended 
to all business concerns, regardless of size, the first option to the 
ownership of rights to inventions as provided in P.L. 96-517.  As a result of 
this memorandum, the relationships among industrial organizations and other 
participants are simplified, since all group members can now be full partners 
in the research and in any inventions resulting there from.  The specific 
patenting arrangements among the institutions may vary and could include 
joint patent ownership, exclusive licensing arrangements, etc.  Applicants 
are encouraged to develop an arrangement that is most suitable for the 
group’s particular circumstances.  

The patent agreement among the institutions comprising the group, signed and 
dated by the organizational officials authorized to enter into patent 
arrangements for each group member and member institution, must be submitted 
with the application, and a copy submitted to Dr. Nava Sarver (address under 
INQUIRIES).  If the group wishes to place all inventions and discoveries 
resulting from these studies within the public domain, a letter to that 
effect must be submitted to Dr. Sarver in lieu of the patent agreement.  The 
letter must be co-signed by the Principal Investigator, each of the Project 
Leaders, and each of the business officials representing the respective 
institutions.

Federal regulation clause 37-CFR-401 and HHS Inventions regulations at 45 CFR 
Parts 6 and 8 require that NIH be informed of inventions and licensing 
occurring under NIH funded research.  Invention and licensing reports must be 
submitted to the Extramural Invention Reports Office at (301) 435-1986.

For awards including clinical studies 

When clinical studies or trials are a component of the research proposed, 
NIAID policy requires that studies be monitored commensurate with the degree 
of potential risk to study subjects and the complexity of the study.  Terms 
and Conditions of Award will be included with awards.  NIAID policy was 
announced in the NIH Guide on February 24, 2000 and is available at: 
http://grants.nih.gov/grants/guide/notice-files/NOT-AI-00-003.html.  The full 
policy including terms and conditions of award is available at:  
http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf
Terms of awards specific to this PA may also apply.  

Groups seeking to transition from preclinical to clinical studies during the 
award period must include a long-range development plan that details the 
preclinical, transitional, and clinical phases of the proposed studies and a 
budget appropriate to each phase.  Funds to accommodate the potentially more 
costly clinical study should be budgeted in the application.  The group must 
articulate a set of objectives and milestones to be completed prior to the 
transition to clinical research and include the clinical site and clinical 
investigators to be involved.  For purposes of peer review, the application 
must include a clinical protocol based on research findings available at the 
time of submission (although it is understood that the protocol may change as 
work progresses).  All the above components - the development plan, 
objectives and milestones, clinical site and clinical investigators - will be 
essential elements of the initial review by the peer review group.  The NIAID 
and/or NIMH will review requests to transition to clinical research and will 
use outside expertise to review the revised clinical protocol and budget and 
to assist in determining whether the group requesting transition is 
positioned to proceed to clinical studies.

Release of funds for clinical research will be contingent on successful 
accomplishment of milestones and criteria stated in the original application 
as reviewed and approved by the peer review group, and include compliance 
with all applicable laws and regulations.  To initiate clinical studies 
awardees must have IRB, FDA and RAC (if applicable) approvals.  Funds for 
clinical studies will be withheld until the required approvals are obtained 
and copies provided to NIAID (Dr. Nava Sarver, address under INQUIRIES).  
Additional details for applications including a clinical component are listed 
as follows.

The Principal Investigator is responsible for:

1.  Assuming responsibility for developing protocols and monitoring study 
performance; participant recruitment and follow-up; interim data and safety 
analysis and monitoring.  All protocols will be submitted by the Principal 
Investigator to the NIAID (Dr. Nava Sarver, address below) for review for 
safety issues by the DAIDS Clinical Science Review Committee (CSRC) prior to 
implementation.  The Principal Investigator will be responsible for reporting 
recruitment, retention, and other similar information to DAIDS/NIAID at six-
month intervals, on January 1 and July 1 of each year.  Adverse event reports 
will be forwarded to Dr. Sarver at the same time as to the FDA.

2.  Establishing procedures to comply with FDA regulations for studies 
involving investigational agents and strategies and to comply with the 
requirements of 45 CFR Part 46 for the protection of human subjects.  Terms 
of award for any human clinical trial component will be developed to ensure 
volunteer safety and monitoring of compliance with regulations and Good 
Clinical Practices.  NIAID staff will provide guidance and technical advice 
on meeting FDA requirements for investigational substances.

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 sub-populations must be included in all NIH supported biomedical and 
behavioral research projects involving human subjects, unless a clear, 
compelling rationale, and justification are 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", published in the Federal Register of March 28, 1994 (FR 59 14508-
14513) and the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 18, 
1994 which is available via the WWW at: 
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 which is available at the following 
URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html

Investigators may obtain copies from these sources or from Dr. Nava Sarver 
(listed in INQUIRIES below) who 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.

APPLICATION PROCEDURES

Applicants for P01 grants must follow special application guidelines in the 
NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT 
AWARDS (April 1999); this brochure is available via the WWW at: 
http://www.niaid.nih.gov/ncn/grants/multibron.htm

Applications are to be submitted on the grant application form PHS 398 (rev. 
4/98) and will be accepted at the standard application deadlines as indicated 
in this Program Announcement.  Application kits are available at most 
institutional offices of sponsored research and from the Division of 
Extramural Outreach and Information Resources, National Institutes of Health, 
6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 435-
0714, email: GrantsInfo@nih.gov.
In addition, applications are available at the following URL: 
http://grants.nih.gov/grants/forms.htm. 

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. 4/98) 
Application Kit (as modified in, and superseded by, the NIAID BROCHURE 
ENTITLED "INSTRUCTIONS FOR APPLICATIONS FOR -PROJECT AWARDS" 
(http://www.niaid.nih.gov/ncn/grants/multibron.htm) will be judged non-
responsive and will be returned to the applicant.  

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 to 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.

For purposes of identification and processing, item 2a on the face page of 
the application must be marked "YES" and the PA number listed on the face 
page of this PA and the words "NOVEL HIV THERAPIES: INTEGRATED 
PRECLINICAL/CLINICAL PROGRAM" must be typed in.

Submit a signed, typewritten original of the application, including the 
checklist, and three signed, exact, single-sided 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 mail or 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 Dr. 
Dianne Tingley at the address listed under INQUIRIES.

Concurrent submission of an R01 and a Component Project of a Multi-project 
Application:  Current NIH policy permits a component research project of a 
multi-project grant application to be concurrently submitted as a traditional 
individual research project (R01) application.  If, following review, both 
the multi-project application and the R01 application are found to be in the 
fundable range, the investigator must relinquish the R01 and will not have 
the option to withdraw from the multi-project grant.  This is an NIH policy 
intended to preserve the scientific integrity of a multi-project grant, which 
may be seriously compromised if a strong component project(s) is removed from 
the program.  Investigators wishing to participate in a multi-project grant 
must be aware of this policy before making a commitment to the Principal 
Investigator and awarding institution.

Applicants from institutions that have a General Clinical Research Center 
(GCRC) funded by the NIH National Center for Research Resources may wish to 
identify the GCRC as a resource for conducting the proposed research.  If so, 
a letter of agreement from either the GCRC program director or principal 
investigator could be included with the application.

REVIEW CONSIDERATIONS

Review Procedures

Applications will be assigned on the basis of established NIH referral 
guidelines.  Upon receipt, the NIH Center for Scientific Review will review 
applications for completeness.  Incomplete applications will be returned to 
the applicant without further consideration.

P01 applications that are complete and responsive to this PA will be 
evaluated for scientific and technical merit by an appropriate peer review 
group convened by the NIAID.

Review Criteria

Applicants are urged to become familiar with the NIAID brochure "INSTRUCTIONS 
FOR APPLICATIONS FOR MULTI-PROJECT AWARDS” 
http://www.niaid.nih.gov/ncn/grants/multibron.htm (April 1999) for specific 
review criteria for P01 applications.  This brochure details the review 
criteria applicable to the individual projects, individual cores, and the 
overall application as a whole.  These criteria are contained in instructions 
provided to the peer review panel and will be used as the working frame by 
which the applications will be evaluated. 

Specifically, the reviewers will be asked to comment on specific criteria as 
detailed in the brochure for multi-project application in order to judge the 
likelihood that the proposed research will have a substantial impact on the 
pursuit of these goals.  Each of these review 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. 

In addition to (not in lieu of) the review criteria detailed in the 
instruction brochure (see above), review criteria specific to this PA (mainly 
bearing to the review of the individual preclinical and clinical projects) 
include, as follows:

1. The medical significance and originality of the project. 

2. The likelihood that the research will open new directions in the treatment 
of HIV disease or containment of HIV infection, demonstrate a capacity to be 
reduced to clinical practice, or merit evaluation in clinical studies for 
safety and proof-of-concept. 

3. Appropriateness of the experimental approach, development plan, and 
methodology proposed, including laboratory capabilities (preclinical and/or 
clinical) in immunology, virology, cell biology; assays to detect changes in 
parameters related to HIV infection based on state-of-the-art methods, and 
choice of end-points.  For previously funded preclinical groups: evidence of 
significant progress in the previous award (e.g. design, formulation, or 
development of therapeutic entities/strategies that merit clinical 
evaluation).

4. The Principal Investigator's and Project Leaders' commitment to devote 
substantial time and effort to the program.  [Due to the complexity and time 
required to maintain a well-coordinated and productive research effort, a 
minimum 20% (time) commitment by the PI and PLs is strongly suggested unless 
there are compelling arguments to the contrary.]

5. For groups focusing on preclinical research:

o  Choice of the therapeutic target or strategy, its contribution to the 
diversity of potential therapeutics, and the likelihood that the 
target/strategy can be developed (e.g., following a prescribed preclinical 
development plan; selecting a clinical candidate compound) during the award 
period.

6. For groups proposing clinical research:

o  Adequacy and validity of the proposed milestones for determining the 
readiness of the group to transition to clinical research; iterative research 
plan to develop and optimize the proposed strategy; protocol design (clinical 
and scientific); short and long term development plans; contingency plans 
addressing the specific objectives; plans to guard the safety of subjects; 
plans to evaluate outcome even if negative; and provisions to obtain the 
required institutional and regulatory approvals (IRB, FDA, RAC) to conduct 
the clinical study.

o  Experience of the Principal Investigator and Project Leaders in the 
planning, design, and conduct of small clinical studies in HIV-infected 
patients; availability of a General Clinical Research (GCRC), Center for AIDS 
Research (CFAR), or other additional source of institutional support and/or 
statistical support; the infrastructure required for the conduct of safe and 
efficient clinical research; and short and long range plans that will result 
in the successful implementation of clinical studies during the award period.

o If a previously funded clinical group: a clinical concept that is new, 
substantially improved, or that represents a new opportunity/direction 
resulting from the preceding funding period.  

5. In addition to evaluating the scientific merit of the application, all 
multi-project applications are also assessed for the soundness of the 
administrative and organizational structure that facilitates attainment of 
the objective(s) of the program.

Thus, the Administrative Core should detail the short and long term 
management of the Program such as: communication, group meetings, sharing and 
transmission of information and reagents, awareness of development at other 
projects within the program, progress, problems and how will they be 
addressed, engagement of the Scientific Advisory Panel and NIAID in the 
group's research activities/meeting, consideration and integration of 
scientific input/recommendation from the Scientific Advisory Panel and NIAID 
into scientific direction and decision-making, timely reporting as required 
in the Terms of Award (provided at the time of award), HHS, NIH Office of 
Biotechnology Activities - Recombinant Advisory Committee (OBA-RAC), and FDA 
as applicable, and other aspects relevant to the cohesiveness and interactive 
nature of group activities 

The initial review group will also examine: the adequacy of plans to include 
children and both genders and minorities and their subgroups as appropriate 
for the scientific goals of the research and plans for the recruitment and 
retention of subjects; the provisions for the protection of human and animal 
subjects; and the safety of the research environment.

AWARD CRITERIA

Applications will compete for available funds with all other recommended 
applications.  The following will be considered when making funding 
decisions: quality of the proposed project as determined by peer review, 
overall program balance among research areas of the announcement, balance of 
preclinical and clinical studies, and availability of funds.

INQUIRIES

Written and telephone inquiries are encouraged.  The opportunity to clarify 
any issues or questions from potential applicants is welcome.

Requests for the NIAID brochure “INSTRUCTIONS FOR APPLICATIONS FOR MULTI-
PROJECT AWARDS” 
http://www.niaid.nih.gov/ncn/grants/multibron.htm.
(April 1999) as well as inquiries regarding programmatic (research scope, 
eligibility and responsiveness) issues may be directed to:

Nava Sarver, Ph.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases
Room 4216, MSC 7626
6700-B Rockledge Drive
Bethesda, MD 20892-7626
Telephone:  301-496-8197
Fax:	  301-402-3211
EMAIL:  nsarver@niaid.nih.gov

Programmatic issues specific to CNS-related applications may be directed to:

Dianne Rausch, Ph.D.
Center for Mental Health Research on AIDS
National Institute of Mental Health
Room 6209
6001 Executive Boulevard, MSC 9619
Bethesda, MD 20892-9619
Telephone:  301-443-7281
Fax:	 301-443-9719
EMAIL:  dr89b@nih.gov

Direct inquiries regarding review to:

Dianne Tingley, Ph.D.
Division of Extramural Activities 
National Institute of Allergy and Infectious Diseases
Room 2148, MSC 7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone:  301-496-0818
Fax:	 301-402-2638
EMAIL:  dtingley@niaid.nih.gov 

Direct inquiries regarding NIAID fiscal matters to:

Ms. Linda Shaw
Division of Extramural Activities 
National Institute of Allergy and Infectious Diseases
Room 2125, MSC 7614
6700-B Rockledge Drive
Bethesda, MD 20892-7614
Telephone:  301-402-6611
Fax:	 301-480-3780
EMAIL: shaw@niaid.nih.gov  

Direct inquiries regarding NIMH fiscal matters to:

Ms. Diana S. Trunnell
Division of Extramural Activities 
National Institute of Mental Health
Room 7C-08
Parklawn Bldg
5600 Fishers Lane
Rockville, MD 20857
Telephone: 301-443-2805
Fax:	 301-443-6885
EMAIL: diana_trunnell@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalogue of Federal Domestic Assistance No. 
93.856.  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 Public Health Service 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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Research (OER)
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Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
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