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)

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

Announcement Type
This is a re-issuance with modifications, as a Request for Applications, of a previous Program Announcement, PAR-03-137, last released on June 9, 2003.

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

Request For Applications (RFA) Number: RFA-AI-07-001

Catalog of Federal Domestic Assistance Number(s)
93.855, Immunology, Allergy, and Transplantation Research
93.856, Microbiology and Infectious Diseases Research

Key Dates
Release Date: September 29, 2006
Letters of Intent Receipt Date(s): February 26, 2007
Application Receipt Date(s): March 26, 2007
Peer Review Date(s):  June, 2007
Council Review Date(s):  September, 2007
Earliest Anticipated Start Date:  January, 2008
Additional Information To Be Available Date (Url Activation Date):  http://www.niaid.nih.gov/ncn/budget/qa/
Expiration Date:  March 27, 2007

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

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

Section V. Application Review Information
  1. Criteria
  2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Sharing Research Data
    D. Sharing Research Resources
  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) invites 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 the of 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 toxicoclogic assessment of lead candidates; development and validation of Good Laboratory Practice (GLP)-compliant analytical assays; 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 will be supported under the IPCP-HTM, this RFA 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 14,000 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 (PAR-03-137, http://grants.nih.gov/grants/guide/pa-files/PAR-03-137.html ) and its predecessor, the Microbicide Preclinical Development Program (HD-00-018, http://grants.nih.gov/grants/guide/rfa-files/RFA-HD-00-018.html ), were  released (June 9, 2006 and November 7, 2000, respectively, the microbicide field still faces significant challenges in the following areas:

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 nine IPCP-HTM awards and the National Institute of Child Health and Development (NICHD) is supporting two, for a total of eleven awards. Current IPCP-HTM awards are supporting 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.  Microbicide candidates supported include small chemically-defined molecules, peptides, proteins, 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.

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 outcomes, it is expected that milestones will allow 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 backed 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 and small, domestic or foreign, pharmaceutical, biotechnology, bioengineering, and chemical companies.  Since academic organizations are often the source of new candidate products, this RFA will also support a partnership between industry and collaborators from academic and non-profit research organization as necessary.  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:

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

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

(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 must support at least two 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, and (2) be composed of complex strategies incorporating other modes of prevention in support of the microbicide component (single or combination), such as the use of a mucosal vaccine to establish a level of protection that may be enhanced by coital use of the microbicide.

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, an integrated basic science program 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:

Preclinical studies are expected to be incremental and iterative in nature, resulting in the optimization of the microbicide candidate and establishing a strong scientific rationale 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), genotoxicity and/or systemic absorption in animal models.  In all cases, responsive 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 a Pre-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 drug 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 allows the pursuit of microbicide-derived clinical hypotheses that are critical to the advancement of a specific microbicide and/or 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, 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 RFA.  Examples of responsive clinical projects include:

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 DAIDS clinical trial networks when possible (http://www3.niaid.nih.gov/news/newsreleases/2006/leadership.htm).

Examples of the types of research projects that could be incorporated into a responsive IPCP-HTM Program include:

Applications focusing on the following areas will not be considered responsive and will be returned to the applicant without review:

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 already available and/or cannot be funded through other means for the purposes proposed. 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.

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

IPCP-HTM Scientific Advisory Panel

Each IPCP-HTM awardee will 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 with a comprehensive written evaluation of the group’s activities and the Panel’s recommendations following each annual meeting.

NOTE:  The SAP may not be constituted prior to award and recommendations for potential SAP members are NOT to be provided in the application.

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 will use the U19 award mechanism. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

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".

2. Funds Available

The NIAID intends to commit approximately $3 million dollars in FY 2008 to fund 2 to 3 new applications in response to this RFA.  An applicant may request a project period of up to 4 years for applications without clinical trials, and up to 5 years for applications with clinical trials.

Annual direct costs for current IPCP-HTM awards involving basic and preclinical research range from $0.5 million to $0.9 million; annual direct costs for current IPCI-HTM awards involving clinical trials range from $1.0 million to $1.4 million.  The anticipated start date is February 2008.

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) 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

You may submit (an) application(s) if your organization has any of the following characteristics:

1.B. Eligible Individuals

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

2. Cost Sharing or Matching

No cost sharing is required.

The most current Grants Policy Statement can be found at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing

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.

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 the previous award will not be considered different from the previous award and, therefore, will be deemed unresponsive and will be returned to the applicant without review.  NIAID defines substantially different as in 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 the previous award will satisfy this criterion.  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.

Competing continuation grants in response to this RFA or competitive supplements to existing IPCP-HTM awards will not be accepted.

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 20% 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) 435-0714, Email: GrantsInfo@nih.gov.

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.

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.

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

The Appendix is limited to a total of ten (10) documents or one hundred (100) total pages, whichever is less. All pages in reprints and other documents count as one page.

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 A-D cannot exceed 25 pages)

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

2.  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

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

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.

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(s): February 26, 2007
Application Receipt Date(s): March 26, 2007
Peer Review Date(s):  June, 2007
Council Review Date(s):  September, 2007
Earliest Anticipated Start Date:  January, 2008

3.A.1. Letter of Intent

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

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:

Eugene Baizman, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3125, MSC 7616
6700 B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) 402-1464
FAX: (301-480-2408)
Email: ebaizman@niaid.nih.gov

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:

Eugene Baizman , Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3125, MSC 7616
6700 B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) 402-1464
FAX: (301-480-2408)
Email: ebaizman@niaid.nih.gov

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

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. If the application is not responsive to the RFA, NIH staff may contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next appropriate NIH review cycle.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

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

Special requirements of this RFA include:

All applications must include:

1. Program Overview (Research Objectives and Strategic Plan)

An introduction to the proposed IPCP-HTM is required and should be placed ahead of the discussion of individual research projects, the Administrative Core and scientific cores.  The introduction will address the entire IPCP-HTM application and include:

(1) Specific aims or objectives of the overall IPCP-HTM program;

(2) Background and significance of the IPCP-HTM program;

(3) Preliminary Studies;

(4) Research Design and Methods;

(5) Milestones and timelines/Gantt charts;

(6) IPCP-HTM Scientific Advisory Panel (SAP). 

The IPCP-HTM program introduction must not exceed 25 pages.  Pages in excess of this number will be removed and will not be reviewed.  The Research Design and Methods section should address the overall design of the IPCP-HTM program, and how it will accomplish its stated objectives.  The introduction 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.

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 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 completion of application 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.

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

3. Applications Proposing Pre-Phase I Clinical Trials

For applications proposing pre-Phase I clinical trials, the following must be addressed:

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:

(1)     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;

(2)     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 deems to be proprietary and confidential;

(3)     A draft consent form, where necessary, to obtain human samples not provided for in the associated clinical trial/study; and

(4)     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 sharing and transmission of information and reagents, awareness of development 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 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 between clinical sites, institutions and/or scientific projects may request additional travel funds for coordination with the clinical trial unit.  However, these requests should be well justified.  Travel to subcontractor or consortium sites for discussion and planning involved in supplying specific assays or services, such as GLP analytical services or animal testing, will not be supported.

No additional travel funds will be provided 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 be returned to the applicant without review.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information


1. Criteria

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

The following will be considered in making funding decisions:

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:

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.

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 is recommended for “no further consideration.”

Review criteria for the overall application:

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 preventive interventions that drive this field?

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?

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)?

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, integrated with the individual research projects and scientific core milestones, and have quantifiable outcomes that are appropriate to the proposed program?

Review Criteria for IPCP-HTM Individual Research Projects

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?

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?

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)?

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?

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

Review Criteria for IPCP-HTM Cores

Administrative Core

Scientific Research Cores

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:

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. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy. The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data.  Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not analytic tools also will be provided, whether or not a data-sharing agreement will be required, and if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave).  Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement.  References to data sharing may also be appropriate in other sections of the application.  All applicants must include a plan for sharing research data in their application.  The NIH data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing.  All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

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).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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 Also 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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to 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 RFA.  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.

Within two months of award the Principal Investigator will establish and chair a steering committee to assist in managing the overall research program, reviewing progress, developing and implementing policies and procedures, and making ongoing recommendations on scientific coordination and administrative activities.  The Project Leaders and Scientific Core Leaders as well as other scientific staff of the program shall serve as members of the steering committee and shall participate in all steering committee meetings and teleconferences.   The NIH Project Scientist may participate in steering committee activities in an advisory capacity.

Annual IPCP-HTM Meetings

All awardees are required to host an annual meeting of 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 have been implemented and the rationale, and a discussion of scientific, technical and other problems and obstacles, including performance, encountered and methods/approaches implemented to overcome and/or resolve obstacles and problems; (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 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

Protocols for clinical trials must be reviewed and approved by the DAIDS 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

When clinical studies or trials are a component of the research proposed, NIAID policy requires that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study.  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:

Awardees are expected to make new information and materials known to the research community in a timely manner through publications, web announcements, and reports to the NIAID, or 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 part or in total 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 scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond normal program stewardship for grants, 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  teleconferences that may include, but are not limited to Steering Committee 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, Steering Committee and/or the NIH Project Scientist as having relevant expertise, may be given the opportunity to offer advisory input into this process. The NIH Project Scientist will facilitate liaison activity 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 expertise. 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 awards 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

A Steering Committee will be established and chaired by the Principal Investigator.  The NIH Project Scientist will act as described above in an advisory capacity and be a non-voting member of the Steering Committee.

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.  Additionally the Steering Committee, may add additional members by majority vote.  The Steering Committee will serve as the main advisory and governing board of the IPCP-HTM Program.  The Steering Committee will:

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

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 SAP is expected to attend one or more of the IPCP-HTM annual meetings during the award period.  The SAP is not required to attend all annual meetings. When the SAP is in attendance, it will assist in review of the group's activities, and evaluate progress towards achieving milestones, adherence to the original time frame of activities, and the continued relevance of each project and scientific core to the group's overall goals.  The Panel will recommend new directions as appropriate and will provide the PI with a comprehensive written evaluation of the 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.  The IPCP-HTM Project Lead may request a written summary of the SAPs recommendations, which will be provided to him and the NIH Project Scientist 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 Principal Investigator  one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two.. 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

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) 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: jturpin@niaid.nih.gov

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: rblack@niaid.nih.gov

2. Peer Review Contacts:

Eugene Baizman , Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3125, MSC-7616
6700 B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) 402-1464
FAX: (301-480-2408)
Email: ebaizman@niaid.nih.gov

3. Financial or Grants Management Contacts:

Quadira R. 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) 493-0597
Email: huffq@niaid.nih.gov  

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.

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:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov/ and view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_manual.htm).

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) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.


Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA 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/, in the following citations: 93.855, Immunology, Allergy, and Transplantation Research and 93.856, Microbiology and Infectious Diseases Research,
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 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 NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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.


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