This is a one time solicitation.  This PA expires after June 27, 2001.

INTEGRATED PRECLINICAL/CLINICAL PROGRAM FOR HIV TOPICAL MICROBICIDES

Release Date:  March 29, 2001

Receipt Date:  June 27, 2001

PA NUMBER:  PA-01-075

National Institute of Allergy and Infectious Diseases
 (http://www.niaid.nih.gov/)
National Institute of Child Health and Human Development
 (http://www.nichd.nih.gov/)

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.”

PURPOSE

The National Institute of Allergy and Infectious Diseases (NIAID) and 
the National Institute of Child Health and Human Development (NICHD), 
National Institutes of Health (NIH) invite multi-project, multi-
disciplinary applications whose goal is to advance novel topical 
microbicides and microbicide combination strategies to prevent the 
sexual transmission of HIV from preclinical to clinical studies. For 
the purposes of this Program Announcement (PA), topical microbicides 
are defined as vaginally or rectally applied biomedical products with 
or without contraceptive activity that directly or indirectly 
inactivate HIV or prevent HIV infection or spread from initial target 
cells.  The Integrated Preclinical/Clinical Program for HIV Topical 
Microbicides (IPCP-HTM) described in this PA links research with 
product development and initial clinical evaluation by supporting 
diverse research activities from multidisciplinary groups spanning 
advanced preclinical optimization and development through early 
clinical trials.  Applications that aim to further an innovative 
topical microbicide may propose to initiate research at one of the 
following points: (1) preclinical optimization of a lead microbicide 
candidate/combination and advanced preclinical development, (2) 
preclinical research that transitions to iterative clinical/laboratory 
research directed toward refinement of the microbicide 
candidate/combination during the award period, or (3) iterative 
clinical/laboratory research in which a pilot clinical trial will be 
implemented within the first year of award.  In combining these 
activities into a single PA, the IPCP-HTM provides a spectrum of 
research opportunities for collaborative groups pursuing any aspect of 
advanced development of new topical microbicides.  For applications in 
which clinical studies are proposed, the participation of industry is 
required.  For applications limited to advanced preclinical 
optimization and development, participation of industry is strongly 
urged.  Responsive applications will advance microbicide development 
with innovative microbicide research.  Excluded from this PA is 
research on, or development of, marketed spermicidal products and/or 
discovery of potential microbicides. 

HEALTHY PEOPLE 2010

The 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 PA, Integrated 
Preclinical/Clinical Program for HIV Topical Microbicides, is related 
to the focus area of HIV Infection and Sexually Transmitted Diseases.  
Potential applicants may obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic 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 (PIs).  

The involvement of industry is required for applications proposing 
clinical studies and strongly urged for preclinical applications 
because of the established and proven infrastructure and capital 
resources it brings to the program and its proficiency in rapidly 
mobilizing resources and expertise to move promising leads through the 
development pathway.  Investigators from the private sector are 
eligible to participate as PIs, Project or Core Leaders (PLs or CLs), 
or as collaborators.

MECHANISM OF SUPPORT

Program Project grants (P01) will be used to support projects in 
response to this announcement. 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 
integrated approach of the individual scientifically meritorious 
projects will result in a greater contribution to the overall program 
goals than if each project were pursued independently.  Normally, the 
program project grant consists of a minimum of three interrelated 
individual research projects that contribute to the program objective.  
However, for the purposes of this PA, the minimum number of individual 
research projects is two. It is important to note that applications for 
programs consisting of only 2 projects must have 2 fundable projects 
remaining as recommended for consideration for funding after the review 
is complete.  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.  Examples of cores include 
administrative, formulation or animal model cores.  The total project 
period for an application submitted in response to this PA that 
proposes clinical studies at any time during the award period may not 
exceed 5 years.  The total project period for an application limited to 
advanced preclinical optimization and development may not exceed 4 
years.  

NIAID and NICHD intend to support the following research groups through 
this PA:  (1) groups focusing exclusively on advanced preclinical 
optimization and IND-directed development of new topical microbicides 
[i.e., appropriately synthesized and manufactured microbicide products 
that will undergo safety testing as per U.S. Food and Drug 
Administration (FDA) Investigational New Drug (IND) guidelines], and 
(2) groups positioned to implement a pilot clinical study during the 
award period.  Pilot clinical studies are defined as early Phase I 
studies with small numbers of participants, exclusive of formal Phase I 
through Phase III clinical trials.  P01 applications submitted in 
response to this PA may not request in excess of $750,000 first-year 
direct costs for research involving preclinical studies, or $1,300,000 
first-year direct costs, exclusive of Facilities & Administrative (F & 
A) costs for consortium arrangements for translational 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.”  Applications with budgets 
exceeding these levels that are submitted without prior Program 
approval will be returned without review.  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 are encouraged therefore to develop 
plans to use existing infrastructure and organizational support to 
complement the award [including NIH-sponsored General Clinical Research 
Centers (GCRC), Centers for AIDS Research (CFAR), the HIV Prevention 
Trials Network (HPTN), the Adolescent Medicine Trials Network (ATN), 
the Contraceptive Clinical Trials Network (CCTN) and the Comprehensive 
International Program for Research on AIDS (CIPRA)].  These plans 
should be included in the application.

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 (August 2000); this brochure is available via the WWW 
at: http://www.niaid.nih.gov/ncn/grants/multibron.htm.


RESEARCH OBJECTIVES

Background

In the absence of a fully effective HIV vaccine, topical microbicides 
represent an important potential strategy for preventing the 
transmission of HIV through sexual intercourse, the predominant mode by 
which HIV is transmitted worldwide.  In particular, the number of women 
with HIV infection and AIDS has been increasing steadily worldwide and 
according to the World Health Organization (WHO), 15.7 million women 
are living with HIV/AIDS worldwide, accounting for 46 percent of the 
32.4 million adults living with HIV/AIDS.  The vulnerability of women 
of all ages for acquiring HIV infection - including older, 
postmenopausal women as well as adolescents - demands the development 
of effective and acceptable female-controlled chemical and physical 
barrier methods, including topical microbicides, to reduce HIV 
transmission.  In addition, recent statistics from several major cities 
in the U.S. show an increase in unsafe sexual practices as indicated by 
an increase in rectal gonorrhea.  Yet no effective anti-HIV topical 
microbicide is currently available.  Few products have been entered 
into clinical trials and only nonoxynol-9 (N-9)-containing products 
have advanced to efficacy trials.  Results from Phase III trials of 
vaginal N-9-containing products have indicated that N-9 does not 
provide protection against the sexual transmission of HIV.  Candidate 
microbicides currently under investigation include products that kill 
or inactivate HIV nonspecifically, those that inhibit HIV entry and 
cell fusion, and those that inhibit post-fusion events early in the 
viral replication cycle.  The nonspecific candidate products fall 
predominantly into the category of surfactants and detergents, whereas 
most products targeted against specific steps in the HIV life cycle 
have been developed exclusively as potential therapeutics.  In 
addition, no combination of microbicides has yet been evaluated in 
animal or human trials.  Therefore, there is a critical need to promote 
the advanced development of novel microbicides and combinations and to 
provide support for translational studies to advance existing/new 
candidates and combinations into early clinical trials.  This PA will 
support multi-project, multi-disciplinary research groups whose goal is 
to advance topical microbicides and microbicide combination strategies 
from preclinical to clinical studies by assembling the diverse 
scientific expertise and ancillary resources needed to translate basic 
discoveries to innovative applied entities. 

Scope

The purpose of the IPCP-HTM is: 1) to encourage advanced optimization 
and development of lead topical microbicide candidates and 
combinations, and 2) to foster translation of new 
microbicides/combinations from preclinical studies to pilot clinical 
studies.  The ultimate goal of this research is the development and 
exploratory clinical evaluation of new and potentially effective 
microbicides for the prevention of HIV sexual transmission.  Such 
research is expected to increase the array of approaches and 
availability of potential candidates and combinations suitable for 
evaluations of safety and effectiveness in human clinical studies.  In 
line with this objective, the PA will support diverse and creative 
microbicides/combinations with sound scientific rationale that are new 
and innovative or understudied.  The PA provides a continuous spectrum 
of research opportunities for interdisciplinary research groups to 
conduct, from preclinical to pilot clinical studies. 

Examples of microbicide candidates of interest to the IPCP-HTM include, 
but are not limited to:

o  Development of combination microbicides containing a cocktail of 
active agents with diverse mechanisms of action, including those 
addressed below.  

o  Development of microbicides that target viral or host elements 
essential for (i) HIV entry, including attachment, receptor engagement 
or fusion; (ii) early post-entry events in the HIV life cycle prior to 
and including reverse transcription, such as uncoating or translocation 
of the pre-integration complex into the nucleus; and/or (iii) HIV 
capture by, and dissemination from, initial target cells

o  Development of microbicides that enhance or stimulate naturally 
occurring healthy mucosal defense mechanisms

o  Development of innovative virucidal agents that inactivate 
infectious HIV-1 particles or HIV-1-infected cells in the absence of 
host cell toxicity.

Preclinical Research

The preclinical component of the IPCP-HTM supports the advanced 
optimization and development of topical microbicides and combination 
microbicide approaches.  A new microbicide or combination, including 
pre-existing non-detergent microbicides, should have relevance and 
future application to clinical evaluation.  Advanced optimization may 
involve identification of the most favorable formulation for delivery 
or determination of the optimum concentrations of individual active 
agents in a candidate combination microbicide.  As part of an 
integrated approach to the critical path development of a specific 
candidate product and advancement into pilot clinical trials, 
applications may incorporate research in the areas of formulation 
science and development of new and/or improved ex vivo (e.g., tissue 
explants) and in vivo animal models for evaluating the safety and 
efficacy of new microbicides, including models for reproductive 
toxicity.  In addition, IND-enabling preclinical studies must comply 
with Good Laboratory Practice (GLP) regulations, as well as production 
and manufacture of microbicide products according to Good Manufacturing 
Practice (GMP) regulations, to be considered responsive to this PA.  A 
successful group proposing preclinical studies would move a candidate 
microbicide, or combination, through advanced preclinical development 
where it would be poised for clinical evaluation during the course of 
the award period.

Applicants 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), Office of Human Research Protection (OHRP), FDA].  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 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-HTM exploits interdependent, iterative 
clinical/laboratory research designed to evaluate and optimize a 
microbicide.  Research in the areas of identification of markers to 
establish product use compliance and assessment of state-of-the-art 
technologies to measure bio-adhesive and bio-dispersion characteristics 
may be included as part of an integrated approach to advance a specific 
microbicide candidate.  Examples of other scientific areas appropriate 
for pilot clinical studies include, but are not limited to, evaluation 
of pharmacokinetics and tissue distribution of the proposed microbicide 
candidate, and preliminary evaluation of potential activity on viral 
load (if relevant to the proposed mechanism of action) recovered in 
vaginal and rectal mucosal specimens.  Proposals with projects focusing 
on new strategies that exploit pre-existing non-detergent microbicides, 
especially as combination microbicides, would also be considered 
responsive.  A successful application proposing clinical studies would 
develop and optimize a microbicide candidate to the point of 
determining its merits for further clinical evaluation.

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 subjects in a pilot clinical study.  [When merited by 
the study, a larger number of subjects may be considered; prior 
approval by the Program Officer (see INQUIRIES, below) is required.]  
Conventional Phase I through Phase III clinical trials are not 
supported by this Program Announcement.  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 clinical studies, including a clinical 
concept, outline of a clinical protocol, or the clinical protocol, and 
(4) institutional and government approvals (IRB, FDA, OHRP), where 
applicable. 

SPECIAL REQUIREMENTS

IPCP-HTM Group Scientific Advisory Panel 

Each IPCP group will establish a Scientific Advisory Panel ("Panel") of 
2-3 investigators not affiliated with any of the institutions 
comprising the group.  Applicants must not name the prospective 
Advisory Panel members in their applications nor should prospective 
members be contacted by applicants prior to completion of review of 
applications. However, a proposal should include identification of the 
proposed expertise to be represented on the panel.  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 NIAID or NICHD 
Coordinator, as appropriate, within 30 days of the meeting.  [The 
Coordinator for each group will be the equivalent of a Program Officer, 
having medical and/or scientific research expertise depending on the 
preclinical and/or clinical focus of the project.]

Meetings and travel

All awardees will be strongly encouraged to attend a scientific 
conference of IPCP-HTM investigators, organized by NIH and held every 
12-18 months in the Washington, D.C. area.  Applicants should include 
estimated travel expenses for one such meeting per year to the 
applicant organization or the Washington, D.C. metropolitan area in the 
application budget.  Estimated expenses for travel of the Scientific 
Advisory Panel members should be based on one group meeting per year 
and should also 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, each multi-project group is 
required to provide, as part of the application, a plan detailing (1) 
the approach agreed to by all parties for obtaining patent coverage and 
licensing, where appropriate; and (2) 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 for intellectual property issues.  
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, 
should be submitted to Dr. Roberta Black (listed under INQUIRIES) prior 
to review.  The patent agreement should not be submitted with the 
application.  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. Black in lieu of the 
patent agreement.  The letter must be co-signed by the PI, each of the 
PLs, and each of the business officials representing the respective 
institutions.

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

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 transition to 
clinical research and include the clinical site(s) and clinical 
investigators to be involved.  For purposes of peer review, the 
application must include, at a minimum, a clinical concept for a future 
protocol or an outline of a clinical protocol (as an Appendix to the 
application) based on research findings available at the time of 
submission (although it is understood that the concept/protocol may 
evolve as work progresses).  The concept/outline must contain 
information regarding the design of the protocol including objectives 
and rationale, the size and characteristics of the patient population, 
medical (including safety) and site monitoring plans, statistical 
analysis, if appropriate, and a list and time course for associated 
laboratory evaluations.  All the above components - the development 
plan, objectives and milestones, clinical concept/protocol outline, 
clinical site and clinical investigators - will be essential elements 
of the initial review by the peer review group.  The NIAID and NICHD 
will review requests to transition to clinical research and will use 
the Division of AIDS (DAIDS) Prevention Sciences Review Committee 
(PSRC) to review the 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 OHRP 
approvals.  Funds for clinical studies will be withheld until the 
required approvals are obtained and copies provided to NIAID (Dr. 
Roberta Black, listed under INQUIRIES) or NICHD (Dr. Patricia 
Reichelderfer, listed under INQUIRIES), as appropriate.  

Additional details for applications that include a clinical component 
are listed as follows.

The PI is responsible for:

o  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 PI to the NIAID (Dr. Roberta Black, listed under INQUIRIES) for 
review for safety issues by the DAIDS PSRC prior to implementation.  
The PI will be responsible for reporting recruitment, retention, and 
other similar information to DAIDS, NIAID (or Center for Population 
Research, NICHD, as appropriate) at six-month intervals, on January 1 
and July 1 of each year.  Adverse event reports will be forwarded to 
Dr. Black or Dr. Reichelderfer at the same time as to the FDA.

o  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 and NICHD staff will 
provide guidance and technical advice on meeting FDA requirements for 
investigational agents.

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 UPDATED "NIH Guidelines For Inclusion of Women and Minorities 
as Subjects in Clinical Research," published in the NIH Guide for 
Grants and Contracts on August 2, 2000 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html.  
The revisions relate to the NIH-defined Phase III clinical trials and 
require: a) all applications or proposals and/or protocols to 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) all investigators to report accrual, 
and to conduct and report analyses, as appropriate, by sex/gender 
and/or racial/ethnic group differences.

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 may obtain copies from these sources or from Dr. Roberta 
Black (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 (August 2000); 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 up to and including the application 
receipt date as indicated in this PA.  Application kits are 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 301/435-0714, 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 MULTI-
PROJECT AWARDS"), will be judged non-responsive and will be returned to 
the applicant.

For purposes of this PA, the following procedures and policies will 
apply.  Applicants planning to submit a grant application requesting in 
excess of $750,000 in direct costs if preclinical research is proposed, 
or in excess of $1,300,000 in direct costs if a clinical trial is 
proposed, for any year, are advised that he or she must contact the 
Institute or Center (IC) program staff listed in INQUIRIES below, 
before submitting the application, i.e., as plans for the study are 
being developed.  Furthermore, the applicant 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 and the 
words, “INTEGRATED PRECLINICAL/ CLINICAL PROGRAM FOR HIV TOPICAL 
MICROBICIDES” 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/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. Vassil St. Georgiev 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 PI and awarding institution.

Applicants from institutions that have a GCRC funded by the NIH 
National Center for Research Resources or an HIV Prevention Trials Unit 
(HPTU), a CFAR, or a CIPRA award funded by NIAID or an ATN or CCTN 
award funded by NICHD may wish to identify the GCRC, HPTU, CFAR, ATN, 
CCTN or CIPRA as a resource for conducting the proposed research.  If 
so, a letter of agreement from either the GCRC program director or PI 
for the other relevant program(s) should be included with the 
application.

REVIEW CONSIDERATIONS

Review Procedures

Upon receipt, applications will be reviewed for completeness by the NIH 
Center for Scientific Review.  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 should see the NIAID brochure "INSTRUCTIONS FOR APPLICATIONS 
FOR MULTI-PROJECT AWARDS”(August 2000) for review criteria for P01 
applications.  Additional review criteria specific to this PA that the 
initial review group will also examine are: 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.  It may be beneficial to contact staff for advice 
regarding human subjects concerns prior to submission.

The reviewers will be asked to comment on specific criteria as detailed 
in the brochure for multi-project applications in order to judge the 
likelihood that the proposed research will have a substantial impact on 
the pursuit of these goals.  These specific criteria are:
 
o  The biomedical significance and originality of the project. 

o  The likelihood that the research will open new directions in the 
prevention of HIV sexual transmission or containment of HIV infection, 
demonstrate a capacity to be translated to clinical practice, or merit 
evaluation in IND-directed clinical trials for safety and proof-of-
concept. 

o  Appropriateness of the experimental approach, development plan, and 
methodology proposed, including laboratory capabilities (preclinical 
and/or clinical).

o  The PI's and PLs' 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.]

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 an evaluation of the following:

For groups focusing on preclinical research:

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

o  Likelihood that work will progress through advanced development 
during the award period

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 microbicide 
candidate; 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 unanticipated; and provisions to obtain the required 
institutional and regulatory approvals (IRB, FDA, OHRP) to conduct the 
clinical study.

o  Experience of the PI and PLs in the planning, design, and conduct of 
small pilot clinical studies in healthy individuals and/or in the 
conduct of topical microbicide clinical trials, availability of a GCRC, 
CFAR, CIPRA, HPTN clinical site, ATN site, CCTN site 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.

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 of other projects within the program, progress, problems 
and how will they be addressed, engagement of the Scientific Advisory 
Panel and NIAID and NICHD, as appropriate, in the group's research 
activities/meetings, consideration and integration of scientific 
input/recommendation from the Scientific Advisory Panel and NIAID and 
NICHD, as appropriate, into scientific direction and decision-making, 
timely reporting as required in the Terms of Award (provided at the 
time of award), Health and Human Services, 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.

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o  The reasonableness of the proposed budget and duration in relation 
to the proposed research

AWARD CRITERIA

The following will be considered in making funding decisions: quality 
of the proposed project as determined by peer review, 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” as well as inquiries regarding programmatic 
(research scope, eligibility and responsiveness) issues may be directed to:

Roberta Black, Ph.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases
Room 4110, MSC-7628
6700-B Rockledge Drive
Bethesda, MD 20892-7628
Telephone: (301) 496-8199
FAX: (301) 402-3684
Email: rblack@niaid.nih.gov

Requests for inquiries related to the NICHD contraceptive microbicide 
research interests may be directed to:

Patricia Reichelderfer, Ph.D.
Contraception and Reproductive Health Branch (CRH)
National Institute of Child Health and Human Development 
6100 Executive Boulevard, Room 8B13G, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 496-1661
FAX: (301) 480-1972
Email: pr20f@nih.gov

Direct inquiries regarding review issues to: 

Vassil St. Georgiev, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2102, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) 496-8206
FAX: (301) 402-2638
Email: vg8q@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Celeste Kerner
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2248, MSC-7614
6700-B Rockledge Drive
Bethesda, MD 20892-7614
Telephone: (301) 402-6213
FAX: (301) 480-3780
Email: ck103k@nih.gov

AUTHORITY AND REGULATIONS 

This program is described in the Catalog of Federal Domestic Assistance 
No. 93.856 and 93.864. 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 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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