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

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

Announcement Type
This is a reissue of RFA-AI-08-057.

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

Request For Applications (RFA) Number:  RFA-AI-10-006

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

Key Dates
Release Date: July 30, 2010
Letters of Intent Receipt Date: October 15, 2010
Application Receipt Date: November 17, 2010
Peer Review Date: March, 2011
Council Review Date: May, 2011
Earliest Anticipated Start Date: July, 2011
Additional Information To Be Available Date (Url Activation Date): http://www.niaid.nih.gov/ncn/qa/revniaid.htm  
Expiration Date:  November 18, 2010

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, Review and Anticipated Start Dates
         1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
    D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
3. Anticipated Announcement and Award Dates

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

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

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

Purpose

The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH) invite applications from single institutions and consortia of institutions to participate in the Integrated Preclinical/Clinical Program for HIV Topical Microbicides (IPCP-HTM) for the advancement of novel single and combination safe, effective and acceptable microbicides and microbicide strategies to prevent sexual transmission of HIV.  The overarching goal of the IPCP-HTM is to advance the field of microbicides and facilitate the transition of microbicide candidates from preclinical development to clinical evaluation.  The IPCP-HTM FOA is specifically designed to serve as a platform for microbicide development by supporting integrated and iterative research projects and activities that may include but are not limited to addressing critical research questions central to the development of a safe, effective microbicide candidate, preclinical virologic and toxicologic assessments of lead candidates; development and validation of Good Laboratory Practice (GLP)-compliant analytical assays; GLP toxicology studies (pharmacokinetics, pharmacodynamics and safety) and Good Manufacturing Practice (GMP)-manufacturing activities in support of IND-filing and exploratory small scale “pre-Phase I” clinical trials. Applications may also include research that is designed to advance microbicide science or the field by addressing critical research questions central to the development of a safe, effective and acceptable microbicide.  Applications may include any combination of these activities.  The proposed research is not required to include a pre-Phase I clinical trial or provide comprehensive coverage for all activities that might be required to develop a specific microbicide candidate or strategy from the preclinical phase to pre-Phase I clinical trials.

NOTE: While pre-Phase I clinical trials may be supported under the IPCP-HTM, the proposed research is not required to include a pre-Phase I clinical trial.  Further, this FOA will NOT support Phase I, II, or III clinical trials.

Background

With current global HIV infection estimates exceeding 42 million people, the development of a safe, effective, and acceptable topical microbicide to prevent the sexual transmission of HIV could play a major role in world-wide reduction of the over 7,000 new HIV infections per day, potentially saving millions of lives.  Topical microbicides are agents which when applied to the penis, vagina and/or the lower gastrointestinal tract (GI) tract via the rectum can result in inhibition of the transmission of HIV during sexual exposure. Microbicides may also inhibit sexually transmitted infections (STIs) that may alter susceptibility to HIV infection and/or act as co-factors in HIV transmission.

The IPCP-HTM Program has been integral in supporting the transition of topical microbicide candidates from early discovery to initial clinical testing. The IPCP-HTM Program currently supports a wide range of microbicide candidates including small chemically-defined molecules, peptides and proteins targeting a wide range of microbicide-relevant targets.  Other microbicide strategies such as siRNA and bioengineered Lactobacilli are also being supported.  In addition to iterative development of candidates, the IPCP-HTM FOA supports programs designed to advance our understanding of the mechanism(s) of sexual transmission of HIV and new technologies and approaches for assessing the safety, efficacy and acceptability of microbicide candidates.

The IPCP-HTM through its support of iterative microbicide studies has provided a platform for the evolution of microbicide science to meet the many challenges that have arisen in the rapidly changing fields of topical microbicides and HIV prevention.  Some of the current challenges the field faces that are compatible with this IPCP-HTM FOA, are:

Milestones

Milestones are critical for measuring the progress of individual projects and scientific/administrative cores within the IPCP-HTM Program.  For applications incorporating an IND-enabling critical path project, milestones will also be used to facilitate subsequent years of project funding by providing objective measures of project success.

Milestones should identify research outcomes by providing quantifiable measures of success within a specific timeline.  In addition to providing a quantifiable measurement of research/development outcome, it is expected that milestones will also be used by the IPCP-HTM team and the Scientific Advisory Panel (SAP) to track the successes and failures of individual activities.  Assigned NIAID staff, through the Cooperative Agreement 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 that are supported by strong scientific rationale.

Industry Partnerships

A key component of this FOA is partnering with industry.  For the purposes of this FOA, “industry” is defined as for-profit or not-for-profit pharmaceutical, biotechnology, bioengineering, or chemical companies that are large or small, domestic or foreign in origin. The applicant PI may be affiliated with industry, an academic institution and/or a non-profit organization. 

Industrial partners are expected to contribute in a positive and significant way to the overall scientific agenda of the IPCP-HTM.  Industry partners should participate as significant collaborators in the application, fulfilling roles such as application PD/PI (note this includes PD/PI designation on a multi PD/PI application), Project or Core Leader, or act as key personnel with commensurate time commitments to a Project or Core  IPCP-HTM applications may be derived solely from an industry source, and although industry applicants are not required to involve collaborators from academic and/or non-profit research organizations, they are encouraged to include members of these organizations when appropriate to the scope and focus of the application.  Incorporation of Contract Research Organizations (CROs) into IPCP-HTM applications solely for the purpose of providing fee-for-service resources without a demonstrable level of scientific involvement in the IPCP-HTM development process DOES NOT meet this requirement.

Research Objectives and Scope

The scientific and microbicide development objectives of the IPCP-HTM are to:

1.    Stimulate a strong and diverse base in preclinical discovery and development of novel single and combination strategies for vaginal, rectal/GI and/or penile use

2.    Support translation of novel microbicides and microbicide strategies from preclinical studies to pre-Phase I clinical trials

3.    Facilitate entry of new methods and expertise into the microbicide field such as:

The scope of work eligible for support includes strategies developed around a novel single microbicide and/or combination microbicide that prevents HIV transmission through interaction with well described anti-HIV (gp120, gp41, RT, etc.) or cellular targets, (CD4, CCR5, etc) or via novel cellular or viral target(s) that is compatible with the concept of a microbicide that can prevent transmission of HIV.  Additionally, inhibition of HIV transmission may be achieved by modulating innate and adaptive immunity or through the creation of inhibitory strategies employing one or more modes of biomedical prevention in addition to a topical microbicide.  In this latter case, the strategy should focus on the development of the topical microbicide and use the additional non-microbicide biomedical prevention approach to enhance and/or complement the activity provided by the microbicide.  Finally, the scope of the IPCP-HTM supports development of microbicides to STIs associated with HIV acquisition, where inhibition of the STI enhances the potency and/or safety of the anti-HIV microbicide.

An innovative approach is critical for enabling microbicide development within the context of an IPCP-HTM Program.  However, unlike basic research programs where innovation is derived from scientific investigation of a basic science-derived hypothesis, innovation in microbicide development may be realized through incremental advancement of the microbicide or strategy.  Innovation may also be achieved through the overall contribution of the IPCP-HTM to advancement of the microbicide field and/or a specific microbicide strategy.  Additionally, the innovation of individual projects and/or scientific cores may be a function of their positive impact on the IPCP-HTM Program and/or contribution to the microbicide field.

Research Project: When submitting a multi project (U19) application, at least two research projects must be proposed for the application to be considered responsive.

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

1. Microbicide Development: Although the overarching goal of the IPCP-HTM is to advance novel microbicides toward clinical studies, hypothesis–driven projects with a potential impact broader than a specific microbicide strategy can also play an important role in an IPCP-HTM Program.  These projects may be designed to address hypotheses that are central to understanding and development of the IPCP-HTM-supported microbicide or strategy, with the knowledge gained adding significantly to the microbicide field.  All microbicide development projects must be carried out in the context of an identifiable microbicide candidate(s) or strategy(ies) and the outcomes of the research should directly support the advancement of the microbicide or strategy forming the thematic basis of the application.  Examples of responsive microbicide development projects include the role of: the vaginal/rectal microenvironment, biofilms, age and hormonal changes, vaginal fluid factors, semen/seminal plasma, adaptive and/or innate immune systems in promotion and/or inhibition of HIV acquisition and the affect these factors may have on microbicide safety, efficacy and acceptability.  Microbicide development projects may also include the development and validation of new technologies, i.e. novel formulation strategies, optical imaging techniques and novel safety techniques.

Investigators are cautioned that microbicide development projects should be focused on advancing a specific candidate.  Studies focusing solely on the basic research of HIV transmission and/or basic/general microbicide candidate discovery are more appropriate for the Microbicide Innovation Program (MIP) (R21/R33) (RFA-AI-10-011) and other funding sources.

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).

For the purposes of this FOA, feasibility of a microbicide candidate is defined as the demonstration of one or more attributes compatible with:

Preclinical studies are expected to be incremental and iterative in nature, resulting in down selection and/or optimization of the microbicide candidate.  The proposed studies should be developed such that a strong scientific rationale can be established for use of the candidate as either a vaginal, rectal/GI, and/or penile microbicide.  Applicants are encouraged to include preliminary studies, that may not meet the rigorous requirements of GLP IND-enabling critical path studies, but may provide initial assessments of toxicity (acute and/or chronic vaginal, rectal and/or penile), immunogenicity of protein and peptide microbicides, potential toxic effects on the immune system (Immunotoxicity), compatibility, stability and release from proposed delivery systems (formulations and devices), and pharmacokinetic and pharmacodynamic studies. Projects should work toward a defined set of milestones that specify the predicted range and magnitude of toxicity, potency and/or antiviral activity for the microbicide and/or strategy under development.

3. IND-enabling Critical Path projects: This type of project is new to the IPCP-HTM FOA and focuses on enabling clinical testing of the microbicide candidates, either through proposed pre-phase I trial(s) within the IPCP-HTM Program or by preparation and submission of an Investigational New Drug (IND) application for a future phase I clinical trial.  This type of development is not strongly hypothesis–driven, is costly to perform, and is highly structured with its objectives and milestones derived from the federal code of regulations governing clinical testing.  The types of studies performed and their design may also rely on direct consultations with the FDA.  Proposed projects to address these requirements within an IPCP-HTM application must be specifically designed to address the FDA-requirements for filing an IND application.  Projects designed to meet other regulatory requirements to advance a microbicide or microbicide strategy into clinical use, such as other regulatory agencies, e.g. European Medicines Agency (EMEA) and Investigational Device Evaluation (IDE) and/or New Device Exception (NDE) applications are also considered appropriate.  Proposed studies should directly address GLP, GMP and any other FDA requirements and/or International Conference on Harmonization (ICH) guidelines for drug development and testing.  The microbicide testing, production and delivery approaches proposed within the IND-enabling critical path project may require iterative testing, and may include assessments of acute and chronic toxicology in rodent and non-rodent models, pharmacokinetic [absorption, distribution, metabolism and excretion (ADME)] and pharmacodynamic studies, development of a clinical dosage form (formulation), reproductive toxicology, genotoxicity, analytical method development/validation and studies to address Chemistry, Manufacturing and Control (CMC) requirements for a proposed active pharmaceutical ingredient (API) and its delivery vehicle.  Limited GMP manufacturing and packaging of a clinical dosage form (provision of investigational product for a proposed pre-Phase I clinical trial(s)) may also be included.  Applicants are encouraged to include knowledgeable and experienced regulatory experts and/or consultants as members of their project teams, and to conduct consultations with the FDA, as applicable.  The overarching goal of the IND-enabling critical path project should be to (1) determine whether a proposed candidate can meet the regulatory requirements to enable clinical testing and (2) produce a regulatory package that will enable Phase I clinical safety testing under other funding mechanisms. 

Proposed IND-enabling critical path projects must meet the following requirements:

4.    Pre-Phase I Exploratory Clinical Development: Inclusion of pre-Phase I clinical trials allow the pursuit of microbicide-derived clinical hypotheses that are critical to the advancement of a specific microbicide and/or are broadly applicable to microbicide development.  Proposed trials should follow the FDA Guidance for Exploratory IND Studies found at:  www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM078933.pdf .  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 objectives.  It is not the intent of pre-Phase I clinical trials to provide powered statistical assessments of the proposed hypothesis of a microbicide candidate or strategy, but rather to be an initial determination of whether additional (more adequately powered) trials are warranted.  It is intended that the Phase I, II or III trials be performed outside the framework of the IPCP-HTM.  Examples of responsive clinical projects include but are not limited to:

Studies may include HIV positive cohorts or specific at-risk populations including, but not limited to intravenous drug users (IDUs) and alcohol users and abusers when scientifically appropriate and within the scope of an exploratory clinical development program.

Clinical projects may start, i.e. initiate enrollment, as early as year 1, but no later than the end of year 4 of the project period.  Applicants should not propose or depend upon the NIAID DAIDS-supported clinical trial networks to perform the proposed clinical activity, but are encouraged to coordinate with clinical trial sites affiliated with the NIAID HIV/AIDS Clinical Trials Networks, whenever possible (http://www.niaid.nih.gov/news/newsreleases/2006/pages/leadership.aspx).  All interactions with the NIAID HIV/AIDS Clinical Trials Networks should be collaborative in nature, with the IPCP-HTM Program assuming responsibility for conducting the proposed trial.

5. Additional Animal Study Support: Applicants may request additional funds when proposing humanized mouse and nonhuman primate (NHP) studies for safety and/or efficacy (see Section II. Award Information). For the purposes of this FOA, NHP studies are divided into two categories.  The first are studies that address the basic and developmental science issues of virus transmission within the context of microbicides.  Examples are assessments of environmental and physiological factors resulting from or in addition to microbicide exposure that might alter susceptibility, acquisition and dissemination of virus at mucosal tissues, such as hormonal state, pregnancy, age and immune status.  The second category is the use of NHP for screening/testing candidates with the intent of selecting potential clinical candidates.  There are no additional restrictions or suggestions for use of the additional funding when NHP are used for basic and developmental science purposes.  However, because of the recent trends of (1) investigator use of NHP studies as “gateways” for clinical selection in the absence of a requirement for demonstration of efficacy by the FDA for Phase I clinical testing, (2) the cost of using these resources as “screening tools”, and (3) limited availability of NHP, NIAID strongly encourages investigators proposing the use of NHP in this manner to design robust experiments for testing.  Robust experiments are defined as studies where: (1) superiority assessments (selecting best candidate or more potent candidate) include appropriate placebo and no-treatment control arms, (2) use of a sufficient number of NHP  in all groups to allow for endpoint statistical analysis, and (3) the studies use a formulated product.  The formulated product used for NHP testing does not need to be in clinical dosage form, but should have undergone sufficient preformulation and formulation development to establish product stability and release from the dosing vehicle.  Studies in which unformulated microbicides or microbicides mixed in vehicles without establishing stability or release from the vehicle are strongly discouraged in this FOA.  The proposed NHP studies, wherever possible, are encouraged to include additional study endpoints such as pharmacokinetic and pharmacodynamic analysis and safety measurements (colposcopy, histology, vaginal pH. microflora and/or adaptive/innate immune markers).

Responsive Areas of Research

All examples of responsive criteria assume that the identified activities are being conducted in the context of advancing the thematic IPCP-HTM microbicide or microbicide strategy.  Responsive criteria include, but are not limited to:

Non-responsive Areas of Research

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

Applicants are strongly encouraged to discuss applications with Program staff to determine if the approach, concept or strategy meets the stated responsive and/or nonresponsive criteria.

Administrative Core: Each application must include an administrative core headed by the contact PD/PI.  An administrative core is a resource to the multi-project grant, providing for the overall management, coordination and supervision of the Program.  As part of the administrative core, provide an administrative plan that includes an outline for the short- and long-term management of the program.  The Administrative Core should specifically address communications, group meetings and teleconferences, presentation and publication of data, resource and model sharing and transmission of information and reagents, awareness of development, progress and outcomes of other projects within the program, the identification and resolution of problems, and engagement of the SAP and NIAID as appropriate.  Since IPCP-HTM Programs involve potentially complex interactions among multiple investigators and institutions, the Administrative Core should demonstrate its potential for leadership by describing 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.

Funding for the overall administrative efforts, including secretarial, and/or other administrative services, expenses for publications demonstrating collaborative efforts, and communication expenses, should be requested here.  Applications should include travel funds for the PI, Project Leaders, Scientific Core Leaders, other key IPCP-HTM personnel, and SAP members to attend one annual IPCP-HTM meeting to be hosted at a site chosen by the awardee, ideally at one of the IPCP-HTM project or scientific/administrative core sites, with the concurrence of the assigned NIH Project Scientist.  Applicants proposing pre-Phase I clinical trials where travel is required to coordinate activities among clinical sites, additional travel funds may be requested for coordination with the clinical trial sites.  However, all such travel requests should be well justified.  Requests for additional travel to visit subcontractor or consortium sites for discussion and planning involved in supplying specific assays or services, such as GLP/GMP services in support of a IND-enabling critical path project or animal testing must be specifically justified.  Applicants should provide a justification for why the meeting needs to be face-to-face and cannot be adequately conducted via tele- or web conference.

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

Scientific Core(s):  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 that will utilize each scientific core should also be presented.

The activities of Scientific Cores should not overlap with those of a proposed project, e.g. antiviral screening for candidate selection.  Scientific cores should be designed to provide broad-based support for routine activities that individual projects may need to facilitate their development activities.  If an activity is being performed in a project and other projects may need access to that activity, then applicants should consider: removing the activity from the project and creating a core, making the project a core or developing a plan for access to the project resources rather than creating a core that duplicates the project’s activities.  Examples of scientific cores include performance of in vitro and in vivo screening/testing algorithms, and statistical, data management, and regulatory support for IND-enabling critical path projects and pre-Phase I clinical trials. Scientific cores may conduct activities that are typically associated with the IND-enabling process, i.e. manufacturing, performance of GLP and GMP activities.  However, these cores are not eligible for the IND-enabling critical path project funds and should only be proposed when IND-enabling critical path projects are NOT included in the IPCP-HTM application.  Scientific cores should not be solely concerned with coordinating contractual activities to support preclinical development of a microbicide, such as those associated with fee-for-service support, i.e. GLP toxicology, GMP manufacturing, etc. 

NOTE: Pre-Phase I clinical trial(s) may only be conducted as a research project.  Applications proposing clinical trials as part of a scientific core will not be reviewed.

Scientific Advisory Panel

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

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

Section II. Award Information


1. Mechanism of Support

This funding opportunity will use the U19 award mechanism(s). The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses “Just-in-Time” information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). 

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

2. Funds Available

NIAID intends to commit approximately $5.5 million dollars in FY 2011 to fund 1-3 new applications in response to this FOA.

An applicant may request a project period of up to 4 years for an application that does not include a pre-Phase I clinical trial, and up to 5 years for an application that includes a pre-Phase I clinical trial.

The IPCP-HTM Program application must consist of 2 projects and an administrative core to support the preclinical development of a single or combination microbicide candidate at a total direct cost limit of $0.8 million (range $0.5 to $0.8 million).  Applications may request additional funding to support research in any or all of the following areas of interest:

The total direct cost requested for the IPCP-HTM application (base plus combination of 1-4 above) may not exceed $2.8 million.

With Program Officer approval applicants may propose to exceed the individual direct cost cap within the research areas listed above. However, the total direct cost request cannot exceed the sum of the direct cost of all the elements selected for inclusion in the application.

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.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

1.B. Eligible Individuals

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

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application.  Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

Applicants may not serve as the overall PI for more than 1 IPCP-HTM application or award at any time.  However, a PI may serve as a Project Leader and/or Scientific Core Leader on one or more other applications provided the total effort does not exceed 12 calendar months and there is no scientific overlap.

PIs, Project Leaders, and Administrative and Scientific Core Leaders are requested to commit substantial time and effort to ensure success of the complex IPCP-HTM Program.  It is recommended that these individuals devote a minimum of 2.4 calendar months per year effort to the Program.  This level of commitment can be all in one project/scientific core or a total effort across several projects/scientific cores within a single application.  If effort is devoted to 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 of each project and/or core.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Number of Applications.  Applicants may submit more than one application, provided they are scientifically distinct.  An investigator may be a PI on only one application, but may serve as a Project Leader and/or Scientific Core Leader on one or more other applications, provided there is no scientific overlap with the application submitted by the PI.

Resubmissions.  Resubmissions are not permitted in response to this FOA. 

Renewals. Renewal applications are not permitted in response to this FOA.  

Section IV. Application and Submission Information


1. Address to Request Application Information

The current 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

Prepare all applications using the PHS 398 application forms and in accordance with the PHS 398 Application Guide (http://grants.nih.gov/grants/funding/phs398/phs398.html).

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 in item (box) 2 only of the face page of the application form and the YES box must be checked.

The exceptions from the PHS 398 instructions and detailed information on the application structure and components are provided in Section IV.6 “Other Submission Requirements”.  All applicants must follow the specific instructions in that section.

Foreign Organizations (Non-domestic (non-U.S.) Entity)

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

Applications from foreign organizations must:

In addition, for applications from 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.

Applications with Multiple PDs/PIs

When multiple PD/PIs are proposed, use the Face Page-Continued page to provide items 3a – 3h for all PD/PIs. NIH requires one PD/PI be designated as the “contact PD/PI” for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the “Contact PD/PI, et. al.” The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, the section of the Research Plan entitled, “Multiple PD/PI Leadership Plan”, must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators. 

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Additional information is available in the PHS 398 grant application instructions.

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: October 15, 2010
Application Receipt Dates: November 17, 2010
Peer Review Date: March, 2011
Council Review Date: May, 2011
Earliest Anticipated Start Date: July, 2011

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 in Section IV.3.A.

The letter of intent should be sent to:

Brenda Lange-Gustafson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3122, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
(express courier ZIP: 20817-7616)
Phone: (301) 451-3684
Fax:  (301) 480-2408
E-mail: bgustafson@niaid.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the forms 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:

Brenda Lange-Gustafson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3122, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
(express courier ZIP: 20817-7616)
Phone: (301) 451-3684
Fax:  (301) 480-2408
E-mail: bgustafson@niaid.nih.gov

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, the application may be delayed in the review process or not reviewed.  Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute. Incomplete and/or non-responsive applications will not be reviewed.

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 NIH Grants Policy Statement.

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 award if such costs: 1) are necessary to conduct the project, and 2) 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 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

The following section supplements the instructions found in Form PHS 398 for preparing a multi-project grant application U19.  Additional instructions are required because the Form PHS 398 is designed primarily for individual, free-standing research project grant applications, and has no specific instructions for multi-project applications consisting of research projects interrelated by a common theme. 

The supplemental instructions for multi-project applications 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.

C. Specific Instructions for Core Units – Describes modifications to PHS Form 398 instructions on selected.

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. Form Page 1 - Face Page

Items 1 - 14: complete these items as instructed. This should be the first page of the entire application and all succeeding pages should be numbered consecutively.

When multiple PDs/PIs are proposed, use the Face Page-Continued page to provide items 3a-3h for all PDs/PIs.  The Contact PI should be listed on block 3 of Form Page 1-Face Page, with additional PDs/PIs listed on the Face Page-Continued.

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 PD(s)/PI(s) of the multi-project application, followed by the Project and Core Leaders of the component research projects and cores, and other key personnel and then other significant contributors.

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. Detailed budgets are required within the descriptions of each project and core (see below).  If the FOA allows for budget requests beyond 5 years, use a second Form Page 5 to reflect the additional budget years requested. 

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 PI(s)/PD(s) first, followed by those of other key personnel in alphabetical order.

7. Resources Format Page

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

8. Program Overview (Research Objectives and Strategic Plan)

This narrative section summarizes the overall research plan for the multi-project application and is limited to (12)
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.

9.  Leadership Plan for Multiple PDs/PIs (required if applicable)

Applications designating multiple PDs/PIs for the overall Program must include a new section, entitled “Multiple PD/PI Leadership Plan”, as part of the Program Overview.  This Plan must describe: a rationale for choosing a multiple PD/PI approach; the governance and organizational structure of the leadership team and the research projects and cores; communication plans, processes for making decisions on scientific direction, and procedures for resolving conflicts; the administrative, technical, and scientific roles and responsibilities for the PDs/PIs and other collaborators.  If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should also be delineated.  In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Please note: A separate leadership plan is not required within individual project(s) and core(s) that designate multiple Project/Core Leaders.

10. Checklist

One Checklist, placed at the end of the application, is to be submitted for the entire application.

11. Appendix Materials

Refer to Section IV.6. “Appendix Materials” below, for instructions on submitting appendix materials.

For each project or core in the multi-project application, 3 publications plus other approved material are allowed.  

B. Specific Instructions for Individual Research Projects

Except for the requirements below, follow the PHS 398 Specific Instructions found at http://grants1.nih.gov/grants/funding/phs398/phs398.doc#_Toc130797900 in preparing each research project.

For each individual Research Project, include:

Cover page (see special instructions, below)

Description & Key personnel (PHS 398 Form Page 2)

Table of Contents (PHS 398 Form Page 3)

Budget Pages (PHS 398 Form Pages 4 and 5); with budget justifications

Research Strategy

Resources  

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, use the PHS 398 continuation page to create a "Cover Page" containing selected data about each individual research project.  This Cover Page will demarcate each individual research project and 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 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: (e.g., $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.

List the performance sites where the research will be conducted.

Under "Key Personnel", list the Project Leader, followed by other key project personnel, and then other significant contributors.

3. Form Page 3

Prepare a Table of Contents for the research project using Form Page 3 of the PHS 398.

4. Budget Pages (PHS 398 Form Pages 4 and 5)

Prepare a detailed budget and justification for the research project using Form Pages 4 and 5 of the PHS 398.

5. Research Plan

Introduction

New applications and cores should not include an Introduction. 

Specific Aims (Limited to 1 page.)

List in priority order, the broad, long-range objectives and goals of the proposed project. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the project's relationship to the multi-project program goals and how it relates to other projects or cores.

Research Strategy (Limited to 12 pages.)

Use this section to describe how the proposed research will contribute to meeting the program's goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the project's relevance to the primary theme of the application.

Organize the Research Strategy in the specified order as stated in the PHS 398 Instructions, Section 5.5.  Make sure to start each section with the appropriate section heading in order, Significance, Innovation, Approach, and include the appropriate information.  Experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy.  Preliminary Studies for new projects and progress reports for renewal and revision projects as part of a renewal or revision application must be included as part of the approach section.

Select Agent Research (if applicable)

Provide a description of all facilities where the Select Agent(s) will be used in the project.  Describe the procedures that will be used to monitor possession, use and transfer of the Select Agent(s).  Describe plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).  Describe the biocontainment resources available at all performance sites.

6. Resources

Provide information on resources available for the project.  Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport.)  For Early Stage Investigators, describe institutional investment in the success of the investigator.  If there are multiple performance sites, describe the resources available at each site.  Describe any special facilities used for working with biohazards or other potentially dangerous substances.

7. Biographical Sketches

Do not repeat the biographical sketches of participating investigators since this information will be included at the end of the overall application (and therefore will be referenced in the Overall Table of Contents). 

C. Specific Instructions for Core(s)

Except for the requirements below, follow the PHS 398 Specific Instructions found at http://grants1.nih.gov/grants/funding/phs398/phs398.doc#_Toc130797900 in preparing each proposed core.

For each individual Core, include:

Cover page (see special instructions, below)

Description & Key personnel (PHS 398 Form Page 2)

Table of Contents (PHS 398 Form Page 3)

Budget Pages (PHS 398 Form Pages 4 and 5); with budget justifications

Research Plan

Resources Format Page

1. 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.  This Cover Page will demarcate each core and 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., 5/14/06, 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

Direct Costs (e.g. $50,000)

Total Costs (e.g. $70,000)

Costs Requested for the Entire Budget Period

Direct Costs (e.g. $212,323)

Total Costs (e.g. $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.

2. Form Page 2.  Provide a Description (abstract) of the core activities and services according to the instructions on Form Page 2 of the PHS 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.

List the performance sites where the core activities and services will be conducted.

Under "Key Personnel", list the Core Leader, followed by other key core personnel, and then other significant contributors.

3. Form Page 3.  Prepare a Table of Contents for the core using page 3 of Form PHS 398. 

4. Budget Pages (PHS 398 Form Pages 4 and 5)

Prepare a detailed budget and justification for the core using Form Pages 4 and 5 of the PHS 398.

5. Research Plan

Introduction

New applications and cores should not include an Introduction. 

Specific Aims (Limited to 1 page.)

List in priority order, the broad, long-range objectives and goals of the proposed core. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the core’s relationship to the multi-project program goals and how it relates to the research projects or other cores in the application.

Core Research Strategy (Limited to 6 pages.)

Use this section to describe how the proposed core activities will contribute to meeting the program's goals and objectives and explain the rationale for selection of the general methods and approaches proposed to accomplish the specific aims.  In addition, this section should indicate the relevance of the core to the primary theme of the multi-project application.

Organize the Research Strategy in the specified order as stated in the PHS 398 Instructions, Section 5.5.  Make sure to start each section with the appropriate section heading in order, Significance, Innovation, Approach, and include the appropriate information.  Experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy.  Preliminary Studies for new cores and progress reports for renewal and revision cores in a renewal or revision application must be included as part of the approach section.

Select Agent Research (if applicable)

Provide a description of all facilities where the Select Agent(s) will be used with respect to the core.  Describe the procedures that will be used to monitor possession, use and transfer of the Select Agent(s).  Describe plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).  Describe the biocontainment resources available at all performance sites.

6. Resources

Provide information on resources available for the core.  Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport.)  For Early Stage Investigators, describe institutional investment in the success of the investigator.  If there are multiple performance sites, describe the resources available at each site.  Describe any special facilities used for working with biohazards or other potentially dangerous substances.

7. Biographical Sketches

Do not repeat the biographical sketches of participating investigators since this information will be included at the end of the overall application (and therefore will be referenced in the Overall Table of Contents).

Additional Requirements

A minimum of two individual research projects and an Administrative Core.

Milestones and timelines (presented on Gantt charts or equivalent) for the overall IPCP-HTM application, the individual research projects, and all scientific cores.

The inclusion of at least one applicant component from industry on an individual research project or scientific core.

If an IND-enabling critical path project is proposed, specific go/no-go criteria in addition to milestones and times lines should be provided to track progress over a  project duration not to exceed 3 years.

Milestones

A. INDIVIDUAL RESEARCH PROJECTS, SCIENTIFIC AND ADMINISTRATIVE CORES.  Applicants must provide well-described, quantifiable, and scientifically justified milestones that are not simply a restatement of specific aims for each individual research project, scientific, and administrative core.  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 specific criteria, benchmarks or outcomes to be met that can be used to quantify progress.  All proposed milestones should be integrated with the overall goals of the proposed IPCP-HTM Program.  Applicants should include plans for periodically revisiting and revising milestones and timelines, if needed, as new information becomes available, challenges to the proposed development path are encountered, and research outside the IPCP-HTM modifies the science of microbicides.

B. IND-ENABLING CRITICAL PATH PROJECTS.  For applications requesting funds to support an IND-enabling critical path project, applicants must provide quantifiable milestones and interim go/no-go decision points for all years of the project.  Milestones and decision points must also be provided for individual elements of the IND-enabling critical path project, i.e. preformulation, formulation, analytical assay development, acute/chronic toxicology, etc.  The milestones and go/no-go criteria should be presented in Gantt charts with proposed timelines to clearly identify specific outcomes for each activity at each stage of the project.  For example an overarching milestone may indicate completion of specific preformulation/formulation studies, while interim milestones and go/no-go criteria may identify completion of excipient compatibility and stability studies. The milestones for this project will be used by Program to measure progress and will be critical for determining whether the next funding increment will be awarded for this project.

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

IPCP-HTM Scientific Advisory Panel (SAP)

As part of the Administrative Core (counts towards the 6 page limit), applications should describe the proposed expertise to be represented on the SAP and how this expertise will be utilized to guide the IPCP-HTM research projects, including procedures and approaches for obtaining SAP input via teleconferences, meetings, review of written materials/data, etc.  If a pre-Phase I clinical trial is proposed, at least one of the SAP members should have clinical trial experience.  It is recommended that if an IND-enabling critical path project is included that appropriate expertise be included on the SAP.  This section should also include a discussion of the role of the SAP and its integration into the operations of the IPCP-HTM.

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

See Section IV.2, “Content and Form of Application Submission” and additional text above for page limitations associated with multi-project applications.

PHS398 Research Plan Sections

All application instructions outlined in the PHS398 Application Instructions are to be followed, with the following additional requirements: ·          

Budget

This FOA uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). 

All foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096.

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CDs only. Include five identical CDs in the same package with the application. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.

Do not use the Appendix to circumvent the page limitations. An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

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

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

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

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

Specific Instructions for Foreign Applications

All foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096.

Section V. Application Review Information


1. Criteria

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

2. Review and Selection Process

Review Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by National Institute of Allergy and Infectious Diseases and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability.  As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system. 

REVIEW CRITERIA FOR THE OVERALL MULTI-PROJECT APPLICATION

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the program project as a whole to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five scored review criteria, and additional review criteria (as applicable for the program proposed).

OVERALL IMPACT

Is the program as a whole scientifically compelling? Are there coordination and synergy of the individual research projects and cores toward the achievement of the central objectives of the program?  Are the overall program goals significant and focused on studies that meet the objectives of the FOA? Will the integration of the individual projects into a single program be more beneficial than pursuing each project independently? Will combining the component projects into a multi-project program result in scientific gain beyond that which is achievable if each project were to be pursued independently?  Are the administrative plans for the management of projects, including plans for resolving conflicts, appropriate? Are the program milestones applicable to the overall program, feasible within the proposed time frames, and integrated with the milestones for individual research projects and scientific cores? 

Scored Review Criteria 

Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each.  An application does not need to be strong in all categories to be judged likely to have major scientific impact.  For example, a program that by its nature is not innovative may be essential to advance a field.

Significance. If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced?  What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Is the program as a whole, as well as that of the individual research projects and scientific cores, scientifically meritorious?  Are the overall program goals significant and appropriate?

Investigators. Does the Program Director have the leadership and scientific ability to develop an integrated and focused research program?  Will the Program Director and other Project/Core Leaders devote adequate time and effort to the program?  Does the investigative team bring complementary and integrated expertise to the Program? For applications designated multiple PDs/PIs, is the Leadership Plan both adequate and appropriate to ensure that there will be sufficient coordination and communication among the PDs/PIs?   

Innovation.  Is the program original and innovative?  For example: Does the program challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field?  Does the program develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?  Has innovation been established in the context of the global need for a microbicide to prevent HIV transmission?  Is the innovation of the IPCP-HTM Program realized through iterative development and advancement of the microbicide/microbicide strategy, where the value added to the field is achieved through the interactions of the individual projects and cores?  Does the integration of the overall program establish an innovative approach to the developmental problem(s) of creating a topical microbicide candidate or strategy?  

Approach. Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the program?  Does the applicant acknowledge potential problem areas and consider alternative tactics? Are the multi-disciplinary scope of the program and the coordination and interrelationships for all individual research projects and scientific core(s) appropriate and focused on the common theme?  Does the private sector involvement provide access to expertise, activities, other resources and processes that would not otherwise be available to the investigators?  Is the private sector (industrial) component well integrated into the proposed IPCP-HTM Program?  Are the program milestones applicable to the overall program, feasible within the proposed time frames, and integrated with the milestones for individual research projects and scientific cores?  Do they provide quantifiable measures for the achievement of intended outcomes for the program as a whole in a timely manner? Are the administrative plans for the management of projects, including plans for resolving conflicts, appropriate?

Environment. Do the scientific environments 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?  Do they provide quantifiable measures for the achievement of intended outcomes for the program as a whole in a timely manner?

REVIEW CRITERIA FOR INDIVIDUAL RESEARCH PROJECTS WITHIN THE MULTI-PROJECT APPLICATION

Overall Evaluation

Reviewers will provide an overall score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five scored review criteria, and additional review criteria (as applicable for the project proposed).

Scored Review Criteria 

Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit. A project does not need to be strong in all categories to be judged likely to have major scientific impact.  For example, a project that by its nature is not innovative may be essential to advance a field.

Significance.  Does the project address an important problem or a critical barrier to progress in the field?  If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved?  How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  What is the potential biomedical significance of the proposed project and will it advance the microbicide field by providing new technologies, single or combination microbicides or microbicide strategies? For applications proposing pre-Phase I clinical trial projects, have the applicants provided sufficient information to demonstrate that the proposed trial(s) has the potential to advance the field of microbicides?

Investigator(s).  Are the PD/PIs, collaborators, and other researchers well suited to the project?  If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training?  If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?  If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Are the time commitments of the PI and Project Leaders to the program appropriate?

Innovation.  Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions?  Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense?  Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach.  Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?  Are potential problems, alternative strategies, and benchmarks for success presented?   If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?  Are there a sound scientific rationale and basis for the candidate microbicide/strategy, and does the strength of the existing data support product feasibility, safety and potential efficacy?  Are there a sound scientific rationale and basis for the development of the proposed new microbicide-associated technology or model, and does it contribute to the advancement of the IPCP-HTM microbicide candidate(s)?  Is the proposed project(sappropriate for the stage of development of the candidate microbicide/strategy?  Is the pre-Phase I clinical trial(s) appropriately designed, and if iterative pre-phase I clinical trials are proposed, how do the outcomes relate to the objectives of the project, and to the overall program?  Is the IND-enabling clinical path project adequately described, and are its outcomes adequately justified and timed in terms of the information it may supply to other projects and cores to assist in the overall IPCP-HTM-driven advancement of the microbicide?  Does the proposed private sector involvement provide access to expertise, activities, other resources and processes that would not otherwise be available to the investigators?  Are the milestones appropriate, adequately described, feasible, quantifiable and achievable within the proposed time frame?  Do milestones provided for the IND-enabling critical projects incorporate Go/No-Go criteria appropriate for the described testing?

Environment.  Will the scientific environment in which the work will be done contribute to the probability of success?  Is there adequate evidence of sufficient institutional support for the Program Director in terms of laboratory space, equipment and other resources?  Are the institutional support, equipment and other physical resources available to the other investigators adequate for the project proposed?  Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? In cases where subcontracts are proposed for carrying out specific tasks, are the quality/appropriateness of the personnel, facilities and procedures (laboratory methods, work plan and/or QA/QC procedures) adequate?

REVIEW CRITERIA FOR INIDIVUDAL CORES WITHIN THE MULTI-PROJECT APPLICATION

Reviewers will consider each of the criteria below in the determination of scientific and technical merit:

Administrative Core: Is the administrative and organizational structure appropriate and adequate to the attainment of the objective(s) of the proposed program?  Is the management plan for fiscal accountability and communication within the Center appropriate?  Are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the program appropriate?  Are the experience, level of commitment, and availability of the Administrative Core Leader and administrative staff adequate to manage the program?  Is the administrative and organizational structure appropriate to facilitate attainment of the objective(s) of the proposed IPCP-HTM?  Does the management plan provide for fiscal accountability and ongoing communications within the IPCP-HTM?  Are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the IPCP-HTM adequate?  Has an administrative structure been proposed that allows for decisions to be made in the absence of the IPCP-HTM Program leaders or to replace him/her if the need arises?  Are the proposed plans to manage subcontracts and fee-for-service activities adequate to assess the quality/appropriateness of the facilities, methods and other resources to be used?

Scientific Cores (if applicable):  Reviewers will consider each of the criteria below in the determination of scientific and technical merit. Is provision of resources and core services for the individual Research Projects critical and justified? Is the relationship of a scientific core to the central focus of the overall program strong?  Is the quality of the relevant facilities or services provided and criteria for prioritization and usage appropriate?  Are the qualifications, competence, and commitment of the Core Leader and key personnel appropriate?  Are the core facilities appropriate and adequate to support at least two of the individual research projects?  Is the relationship of each core to the central focus of the overall IPCP-HTM established and well justified?  Are the criteria for prioritization and usage of core facilities or services (including procedures, techniques, and quality control) appropriate? Are the milestones appropriate, adequately described, feasible, quantifiable and achievable within the proposed time frame?  Are the individual research core milestones integrated into the overarching IPCP-HTM Program milestones, and are they applicable to the overall program?  Do the milestones provided for the administrative core identify critical activities with a time line that the core has to achieve to adequately oversee and administer the IPCP-HTM Program?

Additional Review Criteria

As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

Protections for Human Subjects.  For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects  and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children.  When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals.  The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information, see http://grants.nih.gov/grants/olaw/VASchecklist.pdf.

Biohazards.  Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmission Applications.   Resubmission applications are not applicable to this FOA.

Renewal Applications.   Renewal applications are not applicable to this FOA.

Revision Applications.   Revision applications are not applicable to this FOA.

Additional Review Considerations

As applicable for the project proposed, reviewers will address each of the following items, but will not give scores for these items and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations.  Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agents Research. Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans.  Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable:  1) Data Sharing Plan (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

Budget and Period Support.  Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Selection Process

The following will be considered in making funding decisions:

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.

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.

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

2. A.1. Principal Investigator Rights and Responsibilities

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

The Principal Investigator retains primary responsibility for the performance of the scientific activity, and understands the role of the Program Officer in the Cooperative Agreement award mechanism as described below.

The Principal Investigator will be solely responsible for:

Annual IPCP-HTM Meetings

All awardees are required to host an annual meeting attended by Project Leaders, Scientific Core Leaders, SAP members, other key IPCP-HTM staff and NIAID staff.  The PI and other IPCP-HTM members shall present: (1) an update on the results achieved for each research project and scientific core, (2) a review of progress in achieving established milestones within the specified timelines, any modifications in milestones or timelines that are proposed or have been implemented and their rationale, (3) discussion of scientific, technical and other problems and obstacles encountered and the methods/approaches proposed or implemented to overcome and/or resolve obstacles and problems, and (4) future plans for achieving remaining milestones, addressing 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.

IPCP-HTM Awards Involving Clinical Trials

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

Monitoring Clinical Studies and Pre-Phase I Clinical Trials

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

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

The Investigator is responsible for providing information to the IND holder for required FDA annual IND reports and for preparing Clinical Study Reports after the completion of the Pre-phase 1 trials for regulatory submission.

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 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, reports to the NIAID, and other mechanisms.

Data

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

Publications

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

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.

2. A.2. NIH Responsibilities

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

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

Other appropriate NIH program staff assistance will be coordinated by the NIH Project Scientist and may include Medical Officer(s), clinical operations and regulatory staff and other expertise as required.  The NIH Project Scientist, with the support of 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 I clinical trial initiation and conduct.  For awardees conducting pre-Phase I 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.

The assigned program director may also serve as an NIH Project Scientist.

2.A.3. Collaborative Responsibilities

Steering Committee

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

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

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

Milestones and Timelines

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

IPCP-HTM Scientific Advisory Panel (SAP)

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

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

2.A.4. Dispute Resolution 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 Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution 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 Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

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-7628
6700B Rockledge Drive
Bethesda, MD 20892-7628
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 5117, MSC-7628
6700B Rockledge Drive
Bethesda, MD 20892-7628
Telephone: (301)-496-8199
FAX: (301)-402-3684
Email: rblack@niaid.nih.gov

Andrew D. Forsyth, Ph.D.
Center for Mental Health Research on AIDS
National Institute of Mental Health
Room 6204, MSC-9619
6001 Executive Boulevard
Bethesda, MD 20892-9619
Telephone: (301) 443-8403
Fax: (301) 443-9719
Email: aforsyth@mail.nih.gov

2. Peer Review Contacts:

Brenda Lange-Gustafson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3122, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
(express courier ZIP: 20817-7616)
Phone: (301) 451-3684
Fax:  (301) 480-2408
E-mail: bgustafson@niaid.nih.gov

3. Financial or Grants Management Contacts:

Mollie Shea
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2234, MSC-7614
6700B Rockledge Drive
Bethesda, Maryland 20892-7614
Telephone: (301) 402-6576
FAX: (301-493-0597
Email: mshea@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.

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

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-09-116.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.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award.  For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

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

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

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) 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 FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations: This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. 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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