Expired RFA-AI-08-006: Integrated Preclinical/Clinical Program for HIV Topical Microbicides (U19)

Department of Health
and Human Services (HHS)

NIH... Turning Discovery Into Health^®

Part I Overview Information

Department of Health and Human Services

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

Components of Participating Organizations
National Institute of Allergy and Infectious Diseases (NIAID) ( http://www.niaid.nih.gov)
National Institute of Mental Health (NIMH) (http://www.nimh.nih.gov)

Title: Integrated Preclinical/Clinical Program for HIV Topical Microbicides (U19)

Announcement Type
This is a re-issuance, with modifications, of RFA-AI-07-001, which was previously released September 29, 2006.

Update: The following update relating to this announcement has been issued:

August 2, 2010 - Competitive revisions for IPCP-HTM grants may be submitted on RFA-AI-10-007.
November 28, 2008 - This RFA has been reissued as (RFA-AI-08-057) .

Request For Applications (RFA) Number: RFA-AI-08-006

Catalog of Federal Domestic Assistance Number(s)
93.855, 93.856, 93.242

Key Dates
Release Date: March 4, 2008
Letters of Intent Receipt Date: June 17, 2008
Application Receipt Date: July 17, 2008
Peer Review Date: November, 2008
Council Review Date: January 2009
Earliest Anticipated Start Date: March 2009
Additional Information To Be Available Date (Url Activation Date): http://www.niaid.nih.gov/ncn/budget/qa/
Expiration Date: July 18, 2008

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Purpose. The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH) invites applications from single institutions and consortia of institutions to participate in this Funding Opportunity Announcement (FOA) ; Integrated Preclinical/Clinical Program for HIV Topical Microbicides (IPCP-HTM). The purpose of this FOA is to support integrated and iterative multi-project, multi-disciplinary preclinical and exploratory clinical studies with the goal of advancing safe, novel topical microbicides and microbicide combination strategies for the prevention of sexual transmission of HIV. A minimum of two research projects and an Administrative Core must be proposed. At least one component (research project or scientific core) must be derived from industry (i.e., pharmaceutical, chemical, bioengineering or biotechnological companies). A Scientific Advisory Panel (SAP) for each award under this RFA will be constituted post award but no later than 12 months after award.
Mechanism of Support. This RFA will use the multi-project Cooperative Agreement (U19) award mechanism.
Funds Available and Anticipated Number of Awards. NIAID and NIMH anticipate awarding a total of $4.5 million in FY 2009. NIMH and NIAID will contribute ~ $0.5 million and $4.0 million to the IPCP-HTM respectively. Two to three new awards are anticipated in response to this RFA.
Budget and Project Period. An applicant may request a project period of up to 4 years for applications without pre-Phase 1 clinical trials, and up to 5 years for applications with pre-Phase 1 clinical trials. Budget requests may not exceed the stated upper limits for each of the categories listed. The total annual direct costs for current IPCP HTM awards with the following activities range from: 1) $0.5 million to $0.9 million for basic and preclinical research; 2) $0.9 million to $1.2 million for basic and preclinical research that involves non-human primate studies designed to assess the efficacy or safety of a microbicide candidate or strategy; and 3) $1.2 million to $1.6 million for awards involving exploratory pre-Phase 1 clinical trials.
Eligible Institutions/Organizations. Public/State Controlled Institution of Higher Education; Private Institution of Higher Education; Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education); Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education); Small Business; For-Profit Organization (Other than Small Business); State Government; U.S. Territory or Possession; Indian/Native American Tribal Government (Federally Recognized); Indian/Native American Tribal Government (Other than Federally Recognized); Indian/Native American Tribally Designated Organization; Non-domestic (non-U.S.) Entity (Foreign Organization); Hispanic-serving Institution; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); Alaska Native and Native Hawaiian Serving Institutions; Regional Organization; Other(s): Eligible agencies of the Federal government; Faith-based or community based organizations.
Eligible Project Directors/Principal Investigators (PDs/PIs): Individuals with the skills, knowledge, and resources necessary to carry out the proposed research. PIs are invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
Resubmissions. Resubmissions (formerly revisions/amendments") of a previously reviewed IPCP-HTM grant application may be submitted.
Renewal Applications. Renewals (formerly competing continuations) will not be accepted.
Number of Applications. A PI may submit only one application; however, a PI may serve as a Project Leader and/or Scientific Core Leader in multiple applications, provided there is no scientific overlap with the application submitted by the PI.
Application Materials. See Section IV.1 for application materials.
Hearing Impaired. Telecommunications for the hearing impaired is available at: TTY 301-451-5936.
Special Date(s). This FOA uses a non-standard due date. See Receipt, Review and Anticipated Start Dates

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt and Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Arbitration Process
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose

The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH) invite applications from single institutions and consortia of institutions to participate in the Integrated Preclinical/Clinical Program for HIV Topical Microbicides (IPCP-HTM) for the advancement of novel single and combination safe, effective and acceptable microbicides and microbicide strategies to prevent sexual transmission of HIV. The types of microbicide research that will be supported by the IPCP-HTM include basic microbicide science, focused preclinical development and exploratory small scale clinical trials hereinafter referred to as pre-Phase I clinical trials. The IPCP-HTM is specifically designed to serve as a platform for microbicide development through support for integrated and iterative research projects and activities including but not limited to: microbicide-relevant basic science; drug discovery-driven development of microbicides; preclinical virologic and toxicologic assessment of lead candidates; development and validation of Good Laboratory Practice (GLP)-compliant analytical assays; and Good Manufacturing Practice (GMP)-manufacturing activities in support of pre-Phase I clinical trials. Applications may include any combination of these activities. Proposed programs are not required to include all activities that might constitute the complete development path from discovery to pre-Phase I clinical trials.

NOTE: While pre-Phase I clinical trials may be supported under the IPCP-HTM, this FOA will NOT support Phase I, II, or III clinical trials.

Background

With current global HIV infection estimates exceeding 42 million people, the development of a safe, effective, and acceptable topical microbicide to prevent the sexual transmission of HIV could play a major role in world-wide reduction of the over 12,000 new HIV infections per day, and potentially save millions of lives. Topical microbicides are agents which when applied vaginally and/or rectally can result in inhibition of the transmission of HIV and/or other sexually transmitted infections (STIs) that may be co-factors in HIV transmission. Progress has been made in the field of microbicides as evidenced by the proof-of-concept studies of the effectiveness and safety of multiple microbicides in non-human primates and the initiation of large-scale effectiveness trials to test five microbicide candidates. These human trials, whose outcomes will become available in the next two to four years, will be essential in guiding future microbicide development by providing critical information regarding potential proof-of-concept for microbicide safety, efficacy, and acceptability in humans. NIAID is sponsoring the Phase II/IIB safety and effectiveness trial of BufferGel and PRO2000/5 gel (HPTN 035, http://www.hptn.org/research_studies/hptn035.asp), and the Phase II safety trial of daily and coitally-associated use of tenofovir gel in HIV negative women (HPTN059, http://www.hptn.org/research_studies/hptn059.asp).

Although progress has been made in the field of microbicides since the IPCP-HTM (RFA AI-07-001, http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-07-001.html), PAR-03-137 (http://grants.nih.gov/grants/guide/pa-files/PAR-03-137.html ), and its predecessor, the Microbicide Preclinical Development Program (RFA HD-00-018, http://grants.nih.gov/grants/guide/rfa-files/RFA-HD-00-018.html ), were released (September 29, 2006, June 9, 2003 and November 7, 2000, respectively) the microbicide field still faces significant challenges in the following areas:

The role of vaginal and rectal microenvironment and physiology in the biology of HIV transmission;
The role of STIs in HIV transmission;
The development of additional rational targets to prevent transmission;
The identification of new inhibitors and inhibitor strategies to provide a future generation(s) of microbicide lead candidates;
The measurement and role of product adherence and acceptability in determining the effectiveness of proposed microbicide strategies;
The development of combination microbicides and complex microbicide strategies that incorporate other modes of prevention, i.e. mucosal vaccines; and
The development of microbicide delivery strategies (gel formulations, rings, etc.) whose use can be disassociated from the sex act.

Central to developing a rational approach to these many challenges is the development of collaborative platforms for the integration of the diverse scientific disciplines required to discover and advance microbicide candidates toward general use and distribution. The IPCP-HTM program was initiated to provide such a platform by supporting the establishment and implementation of integrated and interactive research projects for identifying and advancing novel single microbicides and combination strategies from the basic/preclinical stage to pre-Phase I clinical trials. NIAID is currently supporting fourteen IPCP-HTM awards. Current IPCP-HTM awards include development of microbicide candidates covering potential targets from virucidal activity on cell-free virus, inhibition of entry (gp120, Coreceptor, gp41) to reverse transcriptase as single or combination microbicides for vaginal and/or rectal use. Currently supported microbicide candidate studies include small chemically-defined molecules, peptides, proteins, siRNA strategies and bioengineered Lactobacilli expressing a variety of protein-based microbicides. Integral to accomplishing the goal of the IPCP-HTM is the inclusion of milestones and industry partners in planning and executing projects.

Milestones

Milestones will be used to measure the progress of the individual projects and scientific cores, as well as the IPCP-HTM as a whole. Milestones should identify research outcomes by providing measures of success within specified timelines. In addition to providing a quantifiable measurement of program outcome, it is expected that milestones will facilitate tracking of the successes and failures of individual activities within the IPCP-HTM. Assigned NIAID staff, through the Cooperative Agreement grant mechanism, will monitor progress toward achieving milestones and work with the IPCP-HTM PI to adjust or modify established milestones as needed to adapt to changes supported by strong scientific rationale.

Industry Partnerships

A key component of this initiative is the development of partnerships with industry. For the purposes of this RFA, industry is defined as large or small, domestic or foreign, pharmaceutical, biotechnology, bioengineering, or chemical companies. Since academic organizations are often the source of new candidate products, this RFA will support a partnership between industry and collaborators from academic and non-profit research organizations. The involvement of an academic or non-profit research organization is not a requirement; therefore industry may submit an application to this program without a collaborator.

The PI may be affiliated with industry, an academic institution or a non-profit organization.

Research Objectives and Scope

The objectives of the IPCP-HTM are to:

Stimulate a strong and diverse base in preclinical discovery and development of novel single microbicides, combination microbicides and microbicide strategies for vaginal and/or rectal use
Support translation of novel microbicides and microbicide strategies from preclinical studies to pre-Phase I clinical trials
Facilitate entry of new methods and expertise into microbicide development such as:

(1) Integration of behavioral research into early microbicide formulation development

(2) Modulation of innate and adaptive vaginal defenses to promote coital-disassociated microbicide usage

(3) Validation of models and surrogate markers for safety, efficacy, and acceptability.

A minimum of two research projects and an Administrative Core must be proposed. Scientific cores may also be proposed and each core must support two or more research projects.

The scope of microbicide strategies eligible for support includes strategies developed around a novel single microbicide and/or combination microbicides incorporating optimized mixtures of two or more compounds that may:

(1) Block virus entry;

(2) Inhibit virus replication;

(3) Modulate adaptive and/or innate immunity; and/or

(4) Prevent HIV transmission through a novel target(s) that is compatible with the concept of a microbicide.

Transmission-inhibitory strategies should be focused on microbicides as the primary mode of inhibition; however the microbicide candidates/strategies may also (1) inhibit STIs associated with HIV acquisition in addition to HIV, while maintaining anti-HIV activity, and (2) be composed of complex strategies incorporating other modes of prevention in support of the microbicide component (single or combination), where the microbicide strategy is the dominant mode of prevention being developed within the IPCP-HTM.

The IPCP-HTM is a development platform for single and combination microbicides and microbicide strategies where innovation should be established in the context of the global need for a microbicide to prevent HIV transmission. Innovation may be realized through incremental advancement of a microbicide or strategy. Thus, innovation in those cases will consist of the value added to the field of microbicides by the individual research projects and scientific cores, as well as the integration of the overall program.

The IPCP-HTM, through the value-added aspect of the integrated multi-project environment, will support research and development projects in the following three main areas of microbicide science:

1. Basic Science: Although the overarching goal of the IPCP-HTM is to advance novel microbicides toward clinical studies, a basic science program integrated with microbicide development may be proposed to address hypotheses essential to the understanding and development of safe, effective, and acceptable microbicides. All basic science projects must be carried out in the context of an identified microbicide candidate(s) or strategy and the outcomes of the research should directly support preclinical and/or clinical projects that further advance the microbicide or strategy forming the thematic basis of the application. Examples of responsive basic science projects include: the role of the vaginal microenvironment; the role of biofilms and hormone fluxes in HIV acquisition; the role of adaptive and/or innate immunity in promotion and/or inhibition of HIV acquisition; the development of new technologies that directly support microbicide development, i.e. novel formulation strategies, safety techniques; and the investigation of the mechanism of cell-free and/or cell-associated HIV transmission in the presence of vaginal and seminal plasma factors.

2. Preclinical Development: Projects that focus on preclinical development of a microbicide candidate or microbicide strategy should incorporate activities that (1) prove the feasibility of a microbicide candidate/strategy, and (2) meet minimal requirements for preclinical virology as identified by the Food and Drug Administration (FDA) (http://www.fda.gov/OHRMS/DOCKETS/98fr/05d-0183-gdl0002-01.pdf).

Feasibility of a microbicide candidate is defined as the demonstration of attributes compatible with:

In vitro efficacy with minimal or no toxicity for newly discovered leads;
Activity (single dose) and/or lack of toxicity (multiple dose) in relevant animal models; and
Efficacy and lack of toxicity in ex vivo tissue models.

Preclinical studies are expected to be incremental and iterative in nature, resulting in the optimization of the microbicide candidate. The proposed studies should be developed such that a strong scientific rationale can be established for its use as a vaginal and/or rectal microbicide. Applicants are encouraged to include preliminary studies that assess toxicity (acute and/or chronic vaginal or rectal), immunotoxicity (for protein or peptide-based microbicides), and genotoxicity and/or systemic absorption in animal models. In all cases, projects must work toward defined milestones that specify the predicted range and magnitude of potency and/or antiviral activity of the microbicide and/or strategy to be developed.

Preclinical studies also may include those FDA-required activities associated with supporting the filing of a Pre-Investigational New Drug (IND) or IND application, such as acute and chronic toxicology, pharmacokinetic [absorption, distribution, metabolism and excretion (ADME)] studies, reproductive toxicology, analytical methods development, and limited GMP manufacturing (provision of investigational product for proposed pre-Phase I clinical trials). Given the nature and complexity of FDA-required preclinical activities, applicants are encouraged to seek in-kind support for specialized facilities and resources required to carry out these preclinical studies. In addition, applicants are encouraged to incorporate pre-IND meetings/conference calls with the FDA early in their development plans and incorporate such meetings/conference calls and IND filing as milestones.

3. Exploratory Clinical Development: Inclusion of pre-Phase I clinical trials allow the pursuit of microbicide-derived clinical hypotheses that are critical to the advancement of a specific microbicide and/or are broadly applicable to microbicide development. Proposed trials should follow the FDA Guidance for Exploratory IND Studies found at: http://www.fda.gov/cder/guidance/7086fnl.htm. Under these guidelines, pre-Phase I studies are (i) to be conducted early in Phase I prior to traditional dose-escalation, safety, and tolerance studies that ordinarily initiate a clinical drug development program; (ii) involve very limited human exposure; and (iii) have no therapeutic or diagnostic intent (e.g., vaginal absorption studies, screening studies, micro-dose and gel distribution studies). The number of participants should be commensurate with the intent of the pre-Phase I clinical trial concept and the scope of the secondary and tertiary objectives. It is not the intent of pre-Phase I clinical trials to provide powered statistical assessments of the proposed hypothesis or a microbicide candidate or strategy, but rather to be an initial determination of whether additional (more adequately powered) trials are needed. It is intended that these larger trials be performed outside the framework of the IPCP-HTM. Phase I, II or III trials WILL NOT BE supported under this FOA. Examples of responsive clinical projects include:

Identification and measurement of potential surrogate markers for safety, efficacy acceptability and/or adherence;
Assessment of the acceptability of a microbicide formulation or strategy;
Deployment of a microbicide formulation in the female reproductive tract and/or the gastrointestinal compartment;
Assessment of baseline health conditions that could modify microbicide safety and/or acceptability;
Tissue and/or systemic absorption from vaginal, rectal and/or penile tissues; and
Studies of HIV positive cohorts or specific at-risk populations which may include, but are not limited to, intravenous drug users (IDUs), where scientifically appropriate and within the scope of an exploratory clinical development program.

Clinical projects may start as early as year 1 but no later than year 3.5 of the project period. Applicants are encouraged to use clinical trial sites affiliated with the NIAID HIV/AIDS Clinical Trials Networks when possible (http://www3.niaid.nih.gov/news/newsreleases/2006/leadership.htm).

Examples of the types of research projects that are responsive to the IPCP-HTM Program include:

Exploration and/or development of new and/or improved existing in vitro, ex vivo and in vivo safety and efficacy models. Model development also may include the development and validation of models of HIV/SIV/SHIV co-infection with STIs that are associated with increased HIV susceptibility.
Performance of in vitro assays to establish the feasibility of a lead microbicide such as those specified under the FDA guidance for preclinical development of an antiviral: http://www.fda.gov/OHRMS/DOCKETS/98fr/05d-0183-gdl0002-01.pdf . Applicants are encouraged to demonstrate feasibility through the appropriate performance of iterative state-of-the-art in vitro safety and efficacy assessments.
Formulation of a single or combination microbicide. Formulation may include optimization of existing microbicide formulations or delivery methods, or development of new approaches that may incorporate unique formulary agents and vehicles.
Use of adaptive and/or innate immunity manipulations/immunomodulators as a means of modifying susceptibility to transmission, either as a stand alone microbicide or in combination with a more traditional single or combination microbicide. If a vaccination strategy is proposed to modify immunity, the primary mode of prevention must be the microbicide strategy and not the development of a new mucosal vaccine, vector or delivery system. Microbicide formulations with established efficacy and/or safety may be used to deliver mucosal immunogens. Applicants proposing vaginal and/or rectal microbicide strategies in which a mucosal vaccine is proposed are strongly urged to contact Program to determine responsiveness. Assessments of microbicide products, formulations or their constitutive elements on innate and adaptive immune responses, as correlates of product safety, efficacy, or feasibility of a microbicide strategy.
Projects designed to identify and provide, through iterative in vitro, ex vivo explant, and/or in vivo animal studies, validation of a potential surrogate safety and/or efficacy marker(s) that can be used to advance the lead microbicide/combination or strategy.
Development of single or combination microbicides with activity against HIV, or HIV and an STI associated with increased risk of HIV acquisition.
Microbicide strategies that focus on the development of coitally-disassociated use of products through delivery or chemical characteristics.
Development of an uncharacterized or standardized natural product if the application describes plans to deconstruct the natural product, identifying the microbicidal components and/or provide a rational scientific basis for standardization or significant refinement of the initial product. It is important that other projects within the IPCP-HTM further demonstrate feasibility (as defined above) of the product(s) as microbicides.
Microbicide strategies proposing development of sulfonated polysaccharides or other large molecular weight charged polyanions in combination with other microbicide candidates. Such studies may propose chemical modifications of a sulfonated polysaccharide as a means to enhance solubility, reduce production costs and/or assist in formulation, but these efforts should be closely linked to combination or complex microbicide strategy development.
Assessment of baseline behavioral and social parameters that could directly affect microbicide adherence or acceptability. This may include development of specific tools or measurements designed to identify acceptability of formulated microbicides or delivery strategies, and preliminary assessments of baseline conditions or practices within specific target populations that could directly inform the development of a microbicide product or strategy. In the latter case, it is essential for the applicant to demonstrate the relevance and need of the study(ies) to the proposed microbicide strategy.

Applications focusing on the following areas will not be considered responsive and will not be reviewed:

Proposed development or an incremental modification of a detergent, surfactant or non-specific -active agents, such as reactive oxygen, metal ions or oxidizing/reducing agents, as a single or combination microbicide agent.
Combination microbicides derived solely from detergents, surfactants or non-specific actives agents. Incorporation of these agents into combinations with other microbicides active against other relevant microbicide targets may be considered responsive when accompanied by sufficient preliminary safety data to demonstrate lack of toxicity.
Further development of over-the-counter products (OTC) or non-specific vaginal and/or female/male rectal health products to prevent HIV transmission as a microbicide. It is acceptable to use OTC or health products as a delivery vehicle for a specific microbicide strategy where the constituents of the formulary are addressed for safety and potential efficacy.
Development of N-9 (Nonoxynol-9).
Development of a new mucosal vaccine or vaccine vector. Incremental modification or optimization for use with a microbicide strategy may be considered responsive. Applicants are strongly urged to discuss applications incorporating a vaccine strategy with Program staff to determine their responsiveness to the FOA.
Studies where pre-exposure prophylaxis (PrEP) is the primary mode of HIV prevention. Oral microbicides may be proposed, but only in the context of a complex strategy involving a vaginal and/or rectal strategy of HIV prevention, where the vaginal or rectal microbicide represents the primary mode of prevention and the oral strategy is used to enhance microbicide efficacy. Applicants are strongly encouraged to discuss applications with oral dosing strategies with Program staff to determine their responsiveness to this FOA.
Applications proposing microbicides without activity to HIV, or that show activity to STIs with no concomitant activity to HIV, or to STIs that do not increase the risk of HIV transmission when present as a co-infection. This includes solely spermicidal products.
Random screening of chemical or natural product libraries or collections to identify new or uncharacterized microbicide candidates.
Proposed development of an uncharacterized natural product such as lime or lemon juice.
Development of sulfonated polysaccharides or other large molecular weight charged polyanions as a single microbicide product.
Phase I, II or III clinical trials.
Basic behavioral research to develop broadly usable measures of microbicide acceptability or sustained use, or other behavioral parameters.

IPCP-HTM Scientific Cores

Scientific cores to support the research and development projects may be proposed if they will be utilized by at least two of the proposed projects. Such cores should provide services and/or facilities that are either new or can not be funded through other means. The services rendered should be well justified within the description of the proposed scientific core and also within each relevant project description. Examples of scientific cores include defined and routine in vitro and in vivo screening/testing, statistical, data management, and regulatory support for pre-Phase I clinical trials, product manufacturing, and product formulation services/facilities. Scientific cores should not be solely concerned with coordinating contractual activities to support preclinical development of a microbicide, such as those associated with fee-for-service support, i.e. GLP toxicology, GMP manufacturing, etc. The required administrative core is not considered a scientific core and should not incorporate scientific activities, but may coordinate fee-for-service services for the overall program.

NOTE: Any pre-Phase I clinical trial should be conducted as a research project and not as a scientific core.

IPCP-HTM Scientific Advisory Panel

Each IPCP-HTM awardee will be required to establish a Scientific Advisory Panel (SAP) no later than 12 months after award. The SAP will consist of 3-5 investigators not affiliated with any of the institutions comprising the IPCP-HTM. Membership will be determined in consultation with the NIAID Project Scientist. The SAP will attend the IPCP-HTM annual meetings to review program activities and evaluate progress, adherence to the original milestones and timelines, and the continued relevance of each project to the overall goals. The SAP will recommend new directions as appropriate and will provide the PI and NIH Project Scientist with a comprehensive written evaluation of the group s activities and the Panel’s recommendations following each annual meeting. See Section 2.A.3, Collaborative Responsibilities.

NOTE: The SAP MAY NOT BE CONSTITUTED PRIOR TO AWARD AND RECOMMENDATIONS FOR POTENTIAL SAP MEMBERS ARE NOT TO BE PROVIDED IN THE APPLICATION. Applications identifying SAP members will not be considered responsive and will not be reviewed.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism(s) of Support

This Funding Opportunity Announcement will use the U19 award mechanism.

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

The NIH U19 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award". At this time, the NIAID has not determined whether this funding opportunity will be reissued.

2. Funds Available

The NIAID and NIMH intend to commit approximately $4.5 million ($4.0 Million ~NIAID and $0.5 Million ~ NIMH) dollars in FY 2009 to fund 2-3 new applications in response to this FOA. An applicant may request a project period of up to 4 years for applications without pre-Phase 1 clinical trials, and up to 5 years for applications with pre-Phase 1 clinical trials. The budget should reflect the proposed research activity.

Budget requests may not exceed the stated upper limits for each of the categories below.

The total annual direct costs for current IPCP HTM awards with the following activities range from:

$0.5 million to $0.9 million for basic and preclinical research
$0.9 million to $1.2 million for basic and preclinical research that involves non-human primate studies designed to assess the efficacy or safety of a microbicide candidate or strategy
$1.2 million to $1.6 million for awards involving exploratory pre-Phase 1 clinical trials

Applications with budget requests in excess of the stated upper limits will be considered non-responsive and will not be reviewed.

The anticipated start date for awards is March 2009.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) is to provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation; see NOT-OD-05-004.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

Public/State Controlled Institution of Higher Education
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education)
Small Business
For-Profit Organization (Other than Small Business)
State Government
U.S. Territory or Possession
Indian/Native American Tribal Government (Federally Recognized)
Indian/Native American Tribal Government (Other than Federally Recognized)
Indian/Native American Tribally Designated Organization
Non-domestic (non-U.S.) Entity (Foreign Organization)
Hispanic-serving Institution
Historically Black Colleges and Universities (HBCUs)
Tribally Controlled Colleges and Universities (TCCUs)
Alaska Native and Native Hawaiian Serving Institutions
Regional Organization
Other(s): Eligible agencies of the Federal government; Faith-based or community based organizations

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

A PI may submit only one application; however, a PI may participate in multiple IPCP-HTM applications as a Project Leader and/or Scientific Core Leader, provided there is no scientific overlap with the application submitted by the PI.

Renewals (formerly competing continuation ) submitted in response to this FOA or competitive supplements to existing IPCP-HTM awards will not be accepted. Recipients of previous IPCP-HTM awards may reapply with a new IPCP-HTM application; however, the scope and specific aims of the new application must differ substantially from the previous award. Applications proposing the next step in development subsequent to a previous award will not be considered different from the previous award and, therefore, will be deemed unresponsive by NIAID Program staff and will not be reviewed. NIAID defines substantially different as the pursuit of new molecular entities, mechanisms/targets of action or strategies. Development of a combination microbicide or complex strategy that incorporates a molecule from a previous award may be considered responsive. Interaction with the Program contact, listed in Section VII. Agency Contacts, will be crucial in determining whether the new application is sufficiently different to be responsive.

Resubmissions (formerly revisions/amendments") of a previously reviewed IPCP-HTM grant application may be submitted.

PIs, Project Leaders, and Administrative and Scientific Core Leaders are requested to commit substantial time and effort to ensure success of the complex IPCP-HTM Program. It is recommended that these individuals devote a minimum of 2.4 calendar months per year effort to the Program. This level of commitment can be all in one project/scientific core or a total effort across several projects/scientific cores within a single application. However, if the effort is derived from multiple scientific cores and/or individual research projects, the level of effort is expected to be commensurate with the direct involvement necessary to ensure successful implementation and management.

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected].

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

Foreign Organizations

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from foreign organizations must:

Request budgets in U.S. dollars.
Contain detailed budgets. See NOT-OD-06-096.

In addition, for applications from foreign organizations:

Charge back of customs and import fees is not allowed.
Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8.5 x 11 within each PDF.
Funds for up to 8% Facilities and Administrative (F&A) costs (excluding equipment) may be requested. See NOT-OD-01-028, March 29, 2001.
Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards.
Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., Administrative and National Policy Requirements

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

SUPPLEMENTAL INSTRUCTIONS FOR THE PREPARATION OF MULTI-PROJECT APPLICATIONS

The following section supplements the instructions found in Form PHS 398 for preparing the multi-project grant application. Additional instructions are required because the Form PHS 398 is designed primarily for individual, free-standing research grant (R01) applications, and has no specific instructions for multi-project applications consisting of research projects interrelated by a common theme.

The supplemental instructions below are divided as follows:

A. General Instructions addresses collaborative efforts among research projects, the administrative and organizational structure as well as the overall facilities and environment, and the overall budget.

B. Specific Instructions for Individual Projects describes modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the project.

C. Specific Instructions for Core Units scientific cores must provide services or resources to support at least two research projects. Instructions describe modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the project.

D. Specific Instructions for Resubmissions - describes the requirements for resubmission.

A. GENERAL INSTRUCTIONS

All applications must be submitted on Form PHS 398. The multi-project grant application should be assembled and paginated as one complete document.

1. Face Page

Items 1 - 15: complete these items as instructed. This should be the first page of the entire application and all succeeding pages should be numbered consecutively.

2. Form Page 2

Using Page 2 of Form 398, provide a succinct but accurate description (abstract) of the OVERALL multi-project application addressing the major, common theme of the program. Do not exceed the space provided.

List the performance sites where the research will be conducted.

Under "Key Personnel", list the Principal Investigator of the multi-project application, followed by the Project Leaders of the component research projects and cores, and then by other key personnel.

3. Form Page 3 - Table of Contents

Do not use Form Page 3 of the PHS 398; a more comprehensive table of contents is needed for a multi-project application.

Bearing in mind that the application will be scientifically reviewed project by project and core by core, prepare a detailed Table of Contents that will enable reviewers to readily locate specific information pertinent to the overall application as well as to each component research project and core. A page reference should be included for the budget for each project and each core. Further, each research project should be identified by number (e.g. Project 1), title, and responsible Project Leader, and each Core should be identified by letter (e.g. Core A), title, and responsible Core Leader. The page location of a COMPOSITE BUDGET should be indicated in the "Table of Contents."

4. Composite Budget

Do not use Form Page 4 of PHS Form 398. Instead, using the suggested format presented below, prepare a Composite Budget For All Proposed Years of Support. (Justification for budget elements should not be presented here but in the individual budgets of the projects and cores.)

SAMPLE: Consolidated Direct Cost Budget for All Proposed Years of Support

Component	Year 1	Year 2	Year 3	Year 4	Year 5	All Years
Project 1. Invest.	125,000	130,000	135,200	140,608	146,232	677,040
Project 2. Study	125,000	130,000	135,200	140,608	146,232	677,040
Project 3. Develop.	100,000	104,000	108,160	112,486	116,985	541,631
Core A. Admin. Core.	50,000	52,000	54,080	56,243	58,493	270,816
Core B. DNA	25,000	50,000	52,000	54,080	56,243	237,323
Totals	425,000	466,000	484,640	504,025	524,185	2,403,850

5. Form Page 5

Complete the Total Direct Cost line entries for all requested budget periods (years) and the Total Direct Cost for Entire Period of Support entry.

6. Biographical Sketch Format Page

Biographical sketches of all professional personnel for all components should be placed at the end of the application with the Principal Investigator first, followed by those of other key personnel in alphabetical order.

7. Other Support Format Page

Do not complete. (Any required information will be requested from successful applicants prior to grant award.)

8. Resources Format Page

Do not complete. Essential information is to be presented in the individual research project and core sections of the application.

9. Program Overview (Research Objectives and Strategic Plan)

This narrative section summarizes the overall research plan for the multi-project application and is limited to 25 pages. The multi-project application should be viewed as a confederation of interrelated research projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program by giving a statement of the general problem area and by laying out a broad strategy for attacking the problems. As the strategy develops, each project and core should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique.

10. Appendix

IMPORTANT NOTE: NIH has published new limitations on grant application appendix materials to encourage applications to be as concise as possible while containing the information needed for expert scientific review. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html.

B. SPECIFIC INSTRUCTIONS FOR INDIVIDUAL RESEARCH PROJECTS

1. Cover Page

The Face Page of the 398 Form should not be used as a cover page for individual research projects within a multi-project application. Instead, a "Cover Page" containing selected data about each individual research project should be prepared. A Cover Page should contain the following information items (these are a subset of the information provided on a PHS 398 Face Page):

Project Number and Title: (e.g., 1. Preclinical Evaluation of HIV Rectal Microbicides)

Name of Project Leader: (e.g., Jones, Roberta A.)

Human Subjects: (Yes or No)
If Yes, exemption number:
(or)
IRB Approval Date: (e.g., 12/13/2006,or "Pending")
(and)
Federalwide Assurance (FWA) number:

Vertebrate Animals: (Yes or No)
If Yes, IACUC Approval Date: (e.g., 11/17/2006, or Pending)
(and)
Animal welfare assurance number:

Proposed Period of Support:
From: (mmddyy - e.g., 07/01/2007)
To: (mmddyy - e.g., 06/30/2112)

Costs Requested for Initial Budget Period: (e.g. 07/01/2007-06/30/2008)
Direct Costs: (e.g., $ 150,000)
Total Costs: (e.g., $162,000)

Costs Requested for the Entire Budget Period: (e.g., 07/01/2007-06/30/2112)
Direct Costs: $700,000

Applicant Organization:
(full address)

2. Form Page 2

Provide a Description (abstract) of the research proposed in the project according to the instructions on Form Page 2 of PHS Form 398. In addition, the abstract should contain a brief description of how the research project will contribute towards attainment of the multi-project program objectives.

For all other items in the individual project application, follow the usual PHS 398 instructions.

C. SPECIFIC INSTRUCTIONS FOR CORES

1. All Cores

Cover Page. The Face Page of the 398 Form should not be used as a cover page for cores within a multi-project application. Instead, use the 398 continuation page to create a "Cover Page" containing selected data about each individual core should be prepared. This cover page will demarcate each core. A Cover Page should contain the following information items (which are a subset of the information provided on a Face Page - see PHS 398):

Core Letter and Core Title
(e.g., A. Monoclonal Antibody Production Core)

Name of Core Leader
(e.g., Smith, Robert A.)

Human Subjects (Yes or No)
If Yes, Exemption Number
(or)
IRB Approval Date (e.g., 5/14/02, or Pending)
(and)
Federalwide Assurance (FWA) number

Vertebrate Animals (Yes or No)
If Yes, IACUC Approval Date (e.g., 4/15/07, or Pending)
(and) Animal welfare assurance number

Proposed Period of Support
From: (mmddyy, e.g., 07/01/2007)
To: (mmddyy, e.g., 06/30/2012)

Costs Requested for Initial Budget Period
(e.g., Direct Costs: $50,000)
(e.g., Total Costs: $70,000)

Costs Requested for the Entire Budget Period
(e.g., Direct Costs: $212,323*)
(e.g., Total Costs: $297,252*)

Applicant Organization
(ABC University
111 Main Street
Anywhere, Else 99999)

The following are specific instructions for sections of the PHS 398 application form that are to be completed differently than usual. For all other items in the core application, follow the usual PHS 398 instructions.

Form Page 2. Provide a Description (abstract) of the Core activities and services according to the instructions on Form Page 2 of PHS Form 398. In addition, the abstract should contain a brief description of how the core services will contribute towards attainment of the multi-project program objectives.

Form Page 3. Prepare a Table of Contents for the core using page 3 of Form PHS 398. Since the biographical sketches of all participating investigators will be located at the end of the overall application (and therefore should be referenced in the Overall Table of Contents), it is not necessary to repeat these pages.

CORE RESEARCH PLAN (Items 2-5 cannot exceed 25 pages)

Item 2 - Specific Aims: List in priority order the broad, long-range objectives of the proposed core. In addition, state the core's relationship to the multi-project program goals and how it relates to the research projects or other cores in the application.
Item 3 - Background and Significance: Use this section to describe how the proposed core activities will contribute to meeting the goals and objectives and explain the rationale for the selection of the general methods and approaches proposed to accomplish the specific aims. In addition, this section should indicate the relevance of the core to the primary theme of the multi-project grant.

For all other items in the individual core section of the application, follow the usual PHS 398 instructions.

1. Administrative Core

Each application must provide for an Administrative Core headed by the Principal Investigator or other senior investigator and responsible for the overall management, coordination and supervision of the IPCP-HTM. Provide an administrative plan that includes a discussion of the structure and roles of administrative staff, including the training and experience of proposed staff and the functions to be performed; how fiscal and other resources will be prioritized, allocated and managed; how communications will be facilitated; and how research related travel and training will be budgeted.

Funding for the overall administrative efforts, including secretarial, and/or other administrative services, expenses for publications demonstrating collaborative efforts, communication expenses, etc., should be requested here.

2. Scientific Cores

A scientific core is a resource to the multi-project grant as a whole and must support at least two of the proposed research projects. The application must indicate the specific projects to be served by the Scientific Core(s). This section of the application should present a clear picture of the facilities, techniques, and skills that the core will provide and describe the role of the Scientific Core Leader and each of the key participants. The apportionment of dollars, or percentage of dollars, that will be required to support each component research project which will utilize each scientific core should also be presented

D. INSTRUCTIONS FOR RESUBMISSIONS

The resubmission must include an Introduction of not more than three pages that summarizes the substantial additions, deletions, and changes for the overall application and for each project and core resubmitted. The Introduction for the overall application should summarize and address significant changes in the proposed IPCP-HTM, i.e. Projects or Cores eliminated or significantly modified. The Introduction to Projects and Cores should address the specific criticisms of the component and how the changes improve the overall integration of the Project or Core in the overall IPCP-HTM. The Introduction must also include responses to the criticisms and issues raised in the Summary Statement. Insert the Introduction just before the very beginning of the Research Plan.

A resubmission application must include substantial changes in the Research plan. Identify the changes in the Research Plan clearly by bracketing, indenting, or changing typography, unless the changes are so extensive as to include most of the text. This exception should be explained in the Introduction. Do not underline or shade changes.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date: June 17, 2008
Application Receipt Date: July 17, 2008
Peer Review Date: November, 2008
Council Review Date: January 2009
Earliest Anticipated Start Date: March 2009

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed research
Name, address, and telephone number of the Principal Investigator
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Peter R. Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3133, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)

Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: (301) 496-8426
FAX: (301) 480-2310
Email: [email protected]

3.B. Sending an Application to the NIH

Applications must be prepared using the research grant applications found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Peter R. Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3133, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)

Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: (301) 496-8426
FAX: (301) 480-2310
Email: [email protected]

3.C. Application Processing

Applications must be received on or before the application receipt date described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by NIAID. Incomplete and non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application However, the NIH will accept a resubmission application, but such application must include an Introduction addressing the critique from the previous review.

Resubmissions (formerly revisions/amendments") of a previously reviewed IPCP-HTM grant application may be submitted.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

6. Other Submission Requirements and Information

Special requirements of this FOA include:

A minimum of two individual research projects and an Administrative Core;
Milestones and timelines (presented on Gantt charts, timelines or equivalent) for the overall proposed IPCP-HTM, the individual research projects, and all proposed scientific cores; and
At least one component, individual research project or scientific core, from industry.

All applications must include:

1. IPCP-HTM PROGRAM OVERVIEW

An overview of the proposed IPCP-HTM is required and should be placed ahead of the discussion of individual research projects, the Administrative Core and any proposed scientific cores. It should be labeled IPCP-HTM Program Overview . The overview will address the entire IPCP-HTM application and include:

Specific aims or objectives of the overall IPCP-HTM program
Background and significance of the IPCP-HTM program
Preliminary Studies
Research Design and Methods
Milestones and timelines/Gantt charts
IPCP-HTM Scientific Advisory Panel (SAP)

The IPCP-HTM Program Overview must not exceed 25 pages. The Research Design and Methods section of the Program Overview should address the overall design of the IPCP-HTM program, and how it will accomplish its stated objectives. The Program Overview also should address integration of the individual research projects and scientific cores, and outline the processes and procedures to be developed or already in place to administer the IPCP-HTM.

In preparing the IPCP-HTM application, investigators should consider the fact that the application as a whole will be assigned a single priority score that reflects the integration of the individually identified research projects, the scientific cores and the Administrative Core and their perceived ability to advance the identified microbicide candidate(s) or strategy. Thus, clarity and completeness of the application’s combined components with regard to specific goals, proposed feasibility and measurable milestones and timelines are critical. Scientific milestones should be sufficiently rigorous to be valid for assessing progress and outcomes.

IPCP-HTM Scientific Advisory Panel (SAP)

Applications should describe the proposed expertise to be represented on the SAP and how this expertise will be utilized to guide the IPCP-HTM research projects, including procedures and approaches for obtaining SAP input via teleconferences, meetings, review of written materials/data, etc. If a pre-Phase I clinical trial is proposed, at least one of the SAP members should have clinical trial experience. This section should also include a discussion of the role of the SAP and its integration into the operations of the IPCP-HTM.

NOTE: Applicants must not name proposed SAP members in their applications or contact potential SAP members prior to application submission and completion of peer review.

2. MILESTONES FOR INDIVIDUAL RESEARCH PROJECTS AND SCIENTIFIC CORES

For each individual research project and each scientific core, applicants must provide well-described, quantifiable, and scientifically justified milestones that are not simply a restatement of specific aims. Milestones should be presented via a Gantt chart or equivalent, with associated timelines and identified outcomes. Milestones must specify the outcome(s) for each activity, i.e., synthesize n compounds or initiate pre Phase I clinical trial. It is recognized that milestones associated with more basic science-oriented projects may be difficult to quantify; however, in those cases, applicants should develop quantifiable outcomes such as minimal toxicity, marker selection, range of action, etc. Milestones should be integrated with the overall goals of the proposed IPCP-HTM program. Applicants should include plans for periodically revisiting and revising milestones and timelines, if needed, as new information becomes available, challenges to the proposed development path are encountered, and research outside the IPCP-HTM modifies the science of microbicides.

Milestones and timelines should be placed at the end of the Research Plan section for each individual research project and scientific core and fall within the 25 page limit.

3. APPLICATIONS PROPOSING PRE-PHASE I CLINICAL TRIALS

Applications proposing pre-Phase I clinical trials must address the following:

Outline of the hypothesis to be tested and the trial design to be used to address the hypothesis. This includes identification of primary, secondary and tertiary trial objectives.
Contribution to advancement of the microbicide candidate and/or microbicide field achieved by the clinical trial within the context of the overall proposed research program
Inclusion and exclusion criteria
Plans for the recruitment and retention of study participants
Safety and data monitoring plan
Statistical design and analysis plans
Storage and acquisition of product.
If a product requires current Good Manufacturing Practices (cGMP) production, a description of the facilities and processes should be provided.
Processes and procedures for ensuring compliance with Good Laboratory Practices (GLP) and cGMP requirements for clinical trial processes and analytical assays.
Contingency plans to address unexpected delays in achieving scientific, administrative or regulatory requirements prerequisite to initiating the trial.

4. APPLICATIONS PROPOSING CLINICAL STUDIES INVOLVING THE USE OF HUMAN SAMPLES

For applications proposing a clinical study involving the use of human samples, such samples may be derived from clinical studies or clinical trials that are planned, ongoing or completed and sponsored by any source of support. Applications must include:

Documentation of the ability to acquire human samples, including written agreements between the Principal Investigator and the applicant institution, the clinical trial sponsor(s), including drug companies, if applicable, and the IND sponsor, if not one of the above, for the conduct of the proposed studies proposed in the application
The complete clinical protocol and informed consent form(s) for the associated clinical study/trial from which samples will be obtained (to be provided as an appendix). NIH will treat as confidential any scientific, pre-clinical, clinical, or formulation data and information that the sponsor of the associated clinical trial deems to be proprietary and confidential.
A draft consent form, where necessary, to obtain human samples not provided for in the associated clinical trial/study
A detailed description of the proposed clinical study, including: hypothesis, study objectives, study population, relevance of the proposed study to clinical disease/patient outcome, statistical design and analysis plan, plan for management and quality control of data, and plan for receipt and storage of human samples.

5. ADMINISTRATIVE CORE

Applications should outline an Administrative Core for the short- and long-term management of the program. The Administrative Core should specifically address communications, group meetings and teleconferences, presentation and publication of data, resource and model sharing and transmission of information and reagents, awareness of development, progress and outcomes of other projects within the program, the identification and resolution of problems, and engagement of the SAP and NIAID as appropriate. Since IPCP-HTM programs involve potentially complex interactions among multiple investigators and institutions, the Administrative Core will be required to demonstrate its potential for leadership by providing processes and procedures that address routine activities, as well as discuss its preparedness to deal with unexpected outcomes such as delays in the finalization of inter-institutional agreements.

Applications should include travel funds for the PI, Project Leaders and Scientific Core Leaders to attend one annual scientific conference each year to be held in the Washington, D.C. area, and for the PI, Project Leaders, Scientific Core Leaders, other key IPCP-HTM personnel, and SAP members to attend one annual IPCP-HTM meeting to be hosted at a site chosen by the awardee, ideally at one of the IPCP-HTM project or scientific core sites, with the concurrence of the assigned NIH Project Scientist. Applicants proposing pre-Phase I clinical trials where travel is required to coordinate activities among clinical sites, additional travel funds may be requested for coordination with the clinical trial sites. However, all such travel requests should be well justified. Requests for additional travel to visit subcontractor or consortium sites for discussion and planning involved in supplying specific assays or services, such as GLP analytical services or animal testing must be specifically justified. Applicants should provide a justification for why the meeting needs to be face-to-face and cannot be adequately conducted via tele- or web conference. ,

No additional travel funds will be provided for any members of the IPCP-HTM to attend other domestic or foreign meetings.

Applications lacking the information described here, as determined by NIAID staff, will be designated as non-responsive to the RFA and will not be reviewed.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIAID in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

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

The following will be considered in making funding decisions:

Scientific merit of the proposed project as determined by peer review
Availability of funds
Relevance of the proposed project to program priorities

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria 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 in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, AN INVESTIGATOR MAY PROPOSE TO CARRY OUT IMPORTANT WORK THAT BY ITS NATURE IS NOT INNOVATIVE BUT IS ESSENTIAL TO MOVE A FIELD FORWARD.

1. REVIEW CRITERIA FOR THE OVERALL IPCP-HTM APPLICATION

The following items will be considered in the determination of overall scientific merit and priority score for the entire IPCP-HTM application:

Overall score: A single numerical priority score will be assigned to the whole application after consideration of all of the elements. The overall score for the application will be based primarily on the scientific merit of the individual components, with additional consideration of the overall synergy and integration of the components, the overall program organization, and the capabilities of the associated personnel. If peer reviewers deem that fewer than the required two research projects have substantial and significant merit, the application will be recommended for no further consideration .

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Is the program as a whole, as well as that of the individual research projects and scientific cores, scientifically meritorious?
Are the overall program goals significant and appropriate?
Will combining the component projects into a multi-project program result in scientific gain beyond that which is achievable if each project were to be pursued independently?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

Is the overall program cohesive?
Are the multi-disciplinary scope of the program and the coordination and interrelationships for all individual research projects and scientific core(s) appropriate and focused on the common theme?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators: Are the investigators 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? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

Does the PI possess the leadership skills and scientific ability to develop a program of integrated research projects with a well-defined central research focus?
Has the PI devoted adequate time and effort to the program?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

Overall Program Milestones: Are the overarching program milestones applicable to the overall program, feasible within the proposed time frames, and integrated with the milestones for individual research projects and scientific cores? Do they provide quantifiable measures for the achievement of intended outcomes for the program as a whole?

2. REVIEW CRITERIA FOR IPCP-HTM INDIVIDUAL RESEARCH PROJECTS

What is the potential biomedical significance of the proposed program and will it advance the microbicide field by providing new technologies, single or combination microbicides or microbicide strategies?
For applications proposing pre-Phase I clinical trials, have the applicants provided sufficient information to demonstrate that the proposed trial(s) has the potential to advance the field of microbicides?

Is there a sound scientific rationale and basis for the candidate microbicide/strategy, and does the strength of the existing data support product feasibility, safety and potential efficacy?
Is there a sound scientific rationale and basis for the development of the proposed new microbicide-associated technology or model, and does it advance efforts to determine microbicide product feasibility, safety and potential efficacy?
Are the proposed projects appropriate for the stage of development of the candidate microbicide/strategy?
Are the pre-Phase I clinical trials appropriately designed, and if iterative pre-phase I clinical trials are proposed, how do the outcomes relate to the objectives of the project, and to the overall program?
Is the private sector (industrial) component well integrated into the proposed IPCP-HTM program? Does the private sector involvement provide access to expertise, activities, other resources and processes that would not otherwise be available to the investigators?

Has innovation been established in the context of the global need for a microbicide to prevent HIV transmission and is the innovation realized through incremental development and advancement of the microbicide or strategy where the value added to the field is produced through iterative interactions of the individual projects and cores? Does the integration of the overall program establish an innovative approach to the developmental problem(s) of creating a topical microbicide candidate or strategy?

Are the time commitments of the PI, Project Leaders and Scientific Core Leaders to the program appropriate?

In cases where subcontracts are proposed for carrying out specific tasks, i.e. animal toxicology, are the quality/appropriateness of the personnel, facilities and procedures (laboratory methods, work plan and/or QA/QC procedures) adequate?

Milestones for Individual Research Projects: Are the milestones appropriate, adequately described, feasible, quantifiable and achievable within the proposed time frame? Are the individual research project milestones integrated into the overarching IPCP-HTM program milestones and are they applicable to the overall program?

3. REVIEW CRITERIA FOR IPCP-HTM CORES

Administrative Core

Is the administrative and organizational structure appropriate to facilitate attainment of the objective(s) of the proposed IPCP-HTM?
Does the management plan provide for fiscal accountability and ongoing communications within the IPCP-HTM?
Are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the IPCP-HTM adequate?
Are the proposed plans to manage subcontracts and fee-for-service activities adequate to assess the quality/appropriateness of the facilities, methods and other resources to be used?

Scientific Research Cores

Are the core facilities appropriate and adequate to support at least two of the individual research projects?
Is the relationship of each core to the central focus of the overall IPCP-HTM established and well justified?
Are the criteria for prioritization and usage of core facilities or services (including procedures, techniques, and quality control) appropriate?

Milestones for Individual Research Cores: Are the milestones appropriate, adequately described, feasible, quantifiable and achievable within the proposed time frame? Are the individual research core milestones integrated into the overarching IPCP-HTM program milestones and are they applicable to the overall program?

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Resubmission Applications (formerly revised/amended applications): Are the responses to comments from the previous scientific review group adequate? Are the improvements in the resubmission application appropriate?

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Resource Sharing Plan(s)

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score, unless noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing.

Data Sharing Plan. [http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm]
Sharing Model Organisms. [http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html]
Genome Wide Association Studies (GWAS). [http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html]

3. Anticipated Announcement and Award Dates

Not applicable.

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

Effective January 1, 2008, NIH will no longer provide paper notification of the Notice of Award (NoA) letters. Instead, NoAs will be sent solely via e-mail to grantee organizations and will be accessible in the eRA Commons through the Status module. All award recipients are required to be e-mail enabled to allow for the electronic transmission of the NoA. Institutions registered in the Commons should verify the e-mail address on file is correct, or add the appropriate e-mail address. For more information regarding this requirement, please read the NIH Guide Notice, NOT-OD-08-002, http://grants1.nih.gov/grants/guide/notice-files/NOT-OD-08-002.html.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Section IV.5., Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities.

The following terms and conditions will be incorporated into the NoA and will be provided to the PD/PI and the appropriate institutional official at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement (U19), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

2.A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for: defining the research objectives, approaches and details of the projects and scientific cores within the guidelines of the FOA. Specifically, awardees have primary responsibility as described below.

The Principal Investigator retains primary responsibility for the performance of the scientific activity, and agrees to accept close assistance, coordination, cooperation and participation of NIAID staff in scientific and technical management of the project, as described below. The responsibility for planning, direction, and execution of the proposed project will be solely that of the Principal Investigator.

Annual IPCP-HTM Meetings

All awardees are required to host an annual meeting attended by Project Leaders, Scientific Core Leaders, SAP members, other key IPCP-HTM staff and NIAID staff. The PI and other IPCP-HTM members shall present: (1) an update on the results achieved for each research project and scientific core; (2) a review of progress in achieving established milestones within the specified timelines, any modifications in milestones or timelines that are proposed or have been implemented and their rationale, and a discussion of scientific, technical and other problems and obstacles, including performance, encountered and methods/approaches proposed or implemented to overcome and/or resolve obstacles and problems; and (3) future plans for achieving remaining milestones, any identified or potential problems that may impede or slow progress, and proposed methods/approaches to dealing with such problems, including contingency plans for delays, acceleration of timelines, and/or recommended modifications to established milestones and timelines.

Annual Scientific Conference

All awardees (Project Leaders and Scientific Core Leaders) will attend a scientific conference of NIAID Topical Microbicide Program Investigators or the Annual Alliance for Microbicide Development Meeting organized yearly in the Washington D.C. area. Awardees will be informed by NIAID staff which scientific conference to attend.

IPCP-HTM Awards Involving Clinical Trials

Applicants are encouraged to familiarize themselves with Division of AIDS Clinical Research Policies, which specify requirements for conducting clinical research under Division of AIDS sponsorship (http://www3.niaid.nih.gov/research/resources/DAIDSClinRsrch/). Protocols for clinical trials must be reviewed and approved by the Division of AIDS Prevention Sciences Review Committee (PSRC) prior to implementation. In addition, awardees engaged in the conduct of clinical trials will be required to adhere to the NIAID Clinical Terms of Award (http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf).

Monitoring Clinical Studies and Pre-Phase I Clinical Trials

When clinical studies or pre-phase I trials are a component of the research conducted, NIAID policy requires that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. AN UPDATED NIAID policy was published in the NIH Guide on July 8, 2002 and is available at: http://grants.nih.gov/grants/guide/notice-files/NOT-AI-02 -032.html.

The full policy, including terms and conditions of award, is available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf. All clinical research activities performed outside of the U.S. must, in addition to U.S. Federal regulations, comply with the host country regulations for human subjects.

Intellectual Property

The successful development of high priority products as microbicide candidates will require substantial investment and support by private sector industries, and may involve collaborations with other organizations such as academic and/or non-profit research institutions not directly involved in the IPCP-HTM. It is the intent of this initiative to encourage the formation of the appropriate public-private partnerships that are essential to meet these urgent public health needs. NIAID recognizes that intellectual property rights are likely to play an important role in achieving the goals of this program. To this end, all awardees shall understand and acknowledge the following:

The awardee is solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed for the applicant to perform the project.
Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the awardee any proprietary rights, including intellectual property rights, or any materials needed by the awardee to perform the project.
The awardee is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 202 (Bayh-Dole Act).

Awardees are expected to make new information and materials known to the research community in a timely manner through publications, web announcements, reports to the NIAID, and other mechanisms.

Data

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

Publications

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

2.A.2. NIH Responsibilities

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

During performance of the IPCP-HTM award, the NIH Project Scientist will provide appropriate assistance, advice, and guidance by: participating in scheduled meetings and teleconferences that may include, but are not limited to, Steering Committee meetings and teleconferences to discuss program coordination and/or progress; participating in annual meetings and SAP deliberations; participating in the design of the activities; facilitating collaboration with other NIAID-supported research resources; and advising in project management and technical performance. However, the role of the NIH Project Scientist will be to facilitate and not to direct the activities. It is anticipated that the NIH Project Scientist, and other NIAID staff identified by the Principal Investigator, the Steering Committee and/or the NIH Project Scientist as having relevant expertise, may be given the opportunity to offer advisory input. The NIH Project Scientist will facilitate liaison activities for partnerships, and provide assistance with access to NIAID-supported resources and services.

Other appropriate NIH program staff assistance will be coordinated by the NIH Project Scientist, which may include Medical Officer(s), clinical operations and regulatory staff and other expertise as required. The NIH Project Scientist, with support of the appropriate staff and expertise, will provide coordination and assistance to the awardee to meet the Division of AIDS requirements for clinical protocol content, PSRC review and pre-Phase l clinical trial initiation and conduct. For awardees conducting pre-Phase l clinical trials, the NIAID reserves the right to terminate or curtail a clinical trial in the event of (a) substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breach of the protocol, (b) substantive changes in the consensus protocol to which the NIAID does not agree, (c) reaching a major study endpoint substantially before schedule with persuasive statistical significance, or (d) human subject ethical issues that may dictate a premature termination.

The Government, via the NIH Project Scientist, will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, awardees will retain custody of and have primary rights to all data developed under these awards.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

2.A.3. Collaborative Responsibilities

Steering Committee

Within two months of award, a Steering Committee will be established and chaired by the Principal Investigator. The Steering Committee will consist of the designated leaders for each Project and Core, the NIH Project Scientist, other NIH scientists as identified by the Principal Investigator and/or Steering Committee, and any other key personnel identified by the Principal Investigator. The NIH Project Scientist will act in an advisory capacity and be a non-voting member of the Steering Committee. The Steering Committee may add additional members by majority vote. Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

The Steering Committee will serve as the main governing board of the IPCP-HTM Program. The Steering Committee will:

Assist the Principal Investigator in achieving the goals of the IPCP-HTM Program
Create subcommittees and request input from the SAP as needed
Evaluate progress of the IPCP-HTM and make recommendations for achieving Project, Core and IPCP-HTM milestones. This may include recommending alterations in the level of effort for specific Projects and/or Cores and/or modification of milestones.
Be responsible for identifying policies and procedures to be implemented by the Principal Investigator to support IPCP-HTM operations and scientific progress, including development of guidelines for publication of the results of collaborative projects
Assist the Principal Investigator, as required, in preparing formal reports summarizing IPCP-HTM activities and/or progress, such as the Annual Progress Report
Advise the NIH Project Scientist on scientific opportunities, emerging needs and impediments
Assist in protocol development for clinical studies and evaluate human subjects issues as needs arise
Ensure timely release of data to NIH-supported and/or public databases

The NIH Project Scientist will participate in the activities of the Steering Committee as required, providing verbal or written responses to the Steering Committee or its designated subcommittees upon request.

Milestones and Timelines

The specific milestones and timelines agreed to by the Principal Investigator and the NIAID shall be included in the terms and conditions of award. It is recognized that milestones and timelines may require revision and renegotiation during the project period. The Principal Investigator and NIAID must agree to all such revisions.

IPCP-HTM Scientific Advisory Panel (SAP)

Each IPCP-HTM program will establish a SAP of 3-5 investigators not affiliated with any of the institutions participating in the IPCP-HTM research program. SAP membership will be determined in consultation with the NIH Project Scientist. The SAP should be constituted no later than 12 months following award. The members of the SAP are expected to attend one or more of the IPCP-HTM annual meetings during the award period. The complete SAP membership is not required to attend all annual meetings, but at least 1 member of the SAP must attend each annual meeting. When the complete SAP is in attendance, it will assist in review of the IPCP-HTM activities and evaluate progress toward achieving milestones, adherence to the original time frames, and the continued relevance of each project and scientific core to the overall goals of the research program. The Panel will recommend new directions as appropriate and will provide the PI with a comprehensive written evaluation of the IPCP-HTM activities and recommendations after the annual meeting. For awards involving a pre-Phase I clinical trial, the Panel may, at the discretion of NIAID, also be called upon to evaluate the feasibility of initiating a clinical study per the final goals and milestones. When the complete SAP is in attendance the SAP will provide the PI and the NIH Project Scientist with a comprehensive written evaluation of the SAP’s activities and recommendations within 30 days of each meeting.

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts

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

1. Scientific/Research Contacts:

Jim A. Turpin, Ph.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases
Room 5114, MSC-7620
6700B Rockledge Drive
Bethesda, MD 20892-7620
Telephone: (301) 451-2732
Fax: (301) 496-8530
Email: [email protected]

Roberta Black, Ph.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases
Room 5135, MSC-7620
6700B Rockledge Drive
Bethesda, MD 20892-7620
Telephone: (301)-496-8199
FAX: (301)-402-3684
Email: [email protected]

2. Peer Review Contacts:

Peter R. Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases

Room 3133, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)

Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: (301) 496-8426
FAX: (301) 480-2310
Email: [email protected]

3. Financial or Grants Management Contacts:

Quadira Huff
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2231, MSC-7614
6700 B Rockledge Drive
Bethesda, MD 20892-7614
Telephone: (301) 451-2696
FAX: 301-493-0591
Email: [email protected]

Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

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

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

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Policy for Genome-Wide Association Studies (GWAS):

NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh-Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

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 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 funding opportunity 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.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

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 (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

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

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy, investigators funded by the NIH must submit or have submitted for them to the National Library of Medicine’s PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication. The NIH Public Access Policy is available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html). For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

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

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

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 FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.