Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Mental Health (NIMH)

Funding Opportunity Title

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

Activity Code

U19 Research Program – Cooperative Agreements

Announcement Type

Reissue of RFA-AI-10-006

Related Notices

Funding Opportunity Announcement (FOA) Number

RFA-AI-11-031

Companion FOA

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.855; 93.856, 93.242 

FOA 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 this Funding Opportunity Announcement (FOA), Integrated Preclinical/Clinical Program for HIV Topical Microbicides (IPCP-HTM). The purpose of this FOA is to support integrated and iterative multi-project, multi-disciplinary preclinical and exploratory clinical studies with the goal of advancing a safe, effective and acceptable single or combination topical microbicide for the prevention of the sexual transmission of HIV. A minimum of two research projects and an Administrative Core must be proposed. At least one component (research project or scientific core) must be from a private sector for-profit or not-for-profit company.

Key Dates
Posted Date

June 9, 2011

Letter of Intent Due Date

October 7, 2011

Application Due Date(s)

November 8, 2011   

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

March, 2012   

Advisory Council Review

May, 2012 

Earliest Start Date(s)

July, 2012 

Expiration Date

November 9, 2011 

Due Dates for E.O. 12372

Not Applicable.

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

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.  Activities may include, but are not limited to, 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, as defined below, 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 clinical trials that do not meet the definition of a pre-Phase I clinical trial (below) or traditional Phase I, II, or III clinical trial.

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 (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 potential of a topical microbicide to have an impact not only on HIV acquisition, but also on the acquisition of other STIs (HSV) was recently provided by the CAPRISA 004 trial (Karim et al. Science 2010 329:1168) wherein a 1% tenofovir gel applied twice in a 24 h period (once 12 h before and once within 12h of intercourse, a strategy called BAT 24) provided 39% protection from HIV infection and 51% from HSV infection. The potential of antiretrovirals to interrupt HIV transmission was further supported by the results of the iPrEx trial (Grant et al. N Engl J Med 2010), wherein oral Truvada® decreased acquisition of HIV infection by 43%. In both trials there were correlations between drug level and protection and indications that adherence to product use was a major factor in overall efficacy. The results of these 2 trials provide proof-of-concept that HIV infection can be prevented by pharmacological intervention, and highlight the need for supportive pharmacokinetic determinations of drug level in the relevant tissues and secretions, and methods to more accurately access and enhance product adherence, such as sustained release dosage forms.

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 have also been 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, acceptability and adherence to 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 this IPCP-HTM FOA addresses, 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 PD/PI to adjust or modify established milestones as needed to adapt to changes that are supported by a strong scientific rationale.

Industry Partnerships

A key component and requirement to be responsive to this FOA is partnering with and inclusion of an industry partner as a significant contributor to the proposed IPCP-HTM. 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 PD/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 and/or Core Leader, or act as key personnel with commensurate time commitments to a Project and/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 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). The candidate’s proposed mechanism of action must be compatible with the concept of a microbicide that can prevent transmission of HIV. Strategies employing modulation of innate and adaptive immunity as a microbicide strategy alone or in combination with a microbicide targeting a cellular or viral target, and 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 are also responsive.

Creation of inhibitory strategies employing one or more modes of biomedical prevention in addition to a topical microbicide is also considered within the scope of the IPCP-HTM. The strategy should focus on the combination of a topical microbicide with another biomedical prevention approach, for example pre-exposure prophylaxis (PrEP) or vaccine (HIV, HSV and/or HPV), to enhance and/or complement the activity provided by the microbicide. It is envisioned that the final outcome of this effort will be a proof-of-concept for the multi-prevention strategy developed. Multi-prevention strategies employing condoms or other barrier devices without modification of the device to deliver an active anti-HIV agent are considered non-responsive.

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 advance 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: Multi-project (U19) applications will only be considered responsive if they include at least two research projects.

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 a proposed IPCP-HTM Program. These projects may be designed to address hypotheses that are central to understanding and development of the IPCP-HTM-supported microbicide, 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, mucus, 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, acceptability and adherence. Microbicide development projects may also include the development and validation of new technologies, i.e. novel sustained release formulation strategies, electronic monitoring of adherence, optical imaging techniques and novel safety assessment 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 to alternative funding resources.

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 and predefined product characteristics (Targeted Product Profile [TPP]) that specifies the predicted range and magnitude of toxicity, potency and/or antiviral activity for the microbicide and/or strategy under development.  At this stage of development, although applicants are encouraged to consider potential cost of a licensed product, it is not required that potential cost be considered a major factor in advancement.

3. IND-enabling Critical Path projects: These types of projects focus 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 to be conducted outside the current IPCP-HTM proposal. 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 (pharmacokinetics(PK) and pharmacodynamics, (PD)), 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. Applicants are encouraged to acknowledge considerations of cost of goods and feasibility of GMP production in the context of advancement of the microbicide strategy to future clinical testing and licensure. The overarching goals 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, PK and PD 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 safety 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, specific populations, such as adolescents and post menopausal women and/or specific at-risk populations including, but not limited to specific ethnicities, 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 IPCP-HTM clinical activity. Applicants may collaborate with NIAID DAIDS-supported clinical trial networks to achieve clinical objectives.  However, the IPCP-HTM Program will assume primary responsibility for the cost, planning, and conduct of the proposed trial(s).

At the completion of the clinical trial an International Conference on Harmonization E3 report (Structure and Content of Clinical Study Reports, must be submitted to the appropriate regulatory agency(s) and the NIAID Program Officer.

5. Additional Animal Study Support: Applicants may request additional funds when proposing humanized mouse and/or 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 and establishment of biological plausibility in the absence of a requirement for demonstration of animal model efficacy by the FDA, (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) studies that 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 identity, 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, etc.).

Responsive Areas of Research

All examples of responsive areas assume that the identified activities are being conducted in the context of advancing the thematic IPCP-HTM microbicide or microbicide strategy.  Responsive areas 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:

Administrative Core (required):  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.   The administrative core administers the plan provided in the application to address 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 Scientific Advisory Panel (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 PD/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, may request additional travel funds 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 an 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) (optional):  A scientific core is a resource to the multi-project grant and inclusion of Scientific Cores is at the discretion of the applicant. Scientific Cores 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. 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 their scientific expertise should be 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 upon request the PD/PI and NIH Project Scientist with a comprehensive written evaluation of the group’s activities and the Panel’s recommendations following the annual meeting. See Section VI. Award Administration Information.

See Section VIII. Other Information, for policies related to this announcement

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New

The OER Glossary and the PHS398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NIAID intends to commit $6.0 million dollars in FY 2012for 1-3 awards.

Award Budget

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 base 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:

  • An additional $0.3 million (range $0.2 to $0.3 million) may be requested for applications using non-human primates and/or humanized mouse models for assessment of in vivo safety and/or efficacy of a microbicide candidate or strategy.
  • Up to $0.6 million (range $0.2 to $0.6 million) may be requested for applications incorporating an exploratory pre-Phase I clinical trial(s).
  • Up to $0.3 million (range $0.2 to $0.3 million) may be requested for applications incorporating behavioral studies of microbicide acceptability, adherence and use as either a standalone project or for incorporating these studies into a proposed pre-phase I clinical trial(s).
  • Support for a total of 3 years during the 4 or 5 year duration of award may be requested for an IND-enabling critical path project with a maximum direct cost per year of $0.8 million (range $0.4 to $0.8 million).  The monies identified for support of this activity may not be used for these types of activities when they are incorporated into another project or core.

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 allowed total direct cost still remains $2.8.

Award Project Period

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.

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
 
Eligible Organizations

Higher Education Institutions:

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

Nonprofits Other Than Institutions of Higher Education

For profit Organizations

Governments

Other

Foreign (non-U.S.) components of U.S. Organizations are allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Eligible Individuals (Program Director/Principal Investigator)

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

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple PD/PI Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.

An investigator may not serve as the overall PD/PI for more than one (1) IPCP-HTM application or award at any time. However, a PD/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 person months and there is no scientific overlap.

PDs/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 person 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

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.    

Section IV. Application and Submission Information

1. Address to Request Application Package

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the PHS398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed research
Name, address, and telephone number of the PD(s)/PI(s)
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

The letter of intent should be sent to:

Peter R. Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3133, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
FedEx Zip: 20817-7616
Telephone:  (301) 496-8426
FAX:  (301) 480-2310
Email:  PJackson@mail.nih.gov

Application Submission

Applications must be prepared using the PHS 398 research grant application forms and 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)

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

Peter R. Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3133, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
FedEx Zip: 20817-7616
Phone:  301.496.8426
FAX:  301.480.2310
Email:  PJackson@mail.nih.gov

Page Limitations

All page limitations described in the PHS398 Application Guide and the Table of Page Limits must be followed, with the following requirements:

Research Plan

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

The following section supplements the instructions found in Form PHS 398 for preparing a multi-project grant application. 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 Research Projects – describes modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the Project.

C. Specific Instructions for Cores – Describes modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the Core.

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.

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/PI 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.)

EXAMPLE: 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/PD 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)

Specific Aims (Limited to 1 page.)

List in priority order, the broad, long-range objectives and goals of the proposed Program. Concisely and realistically describe the hypothesis or hypotheses to be tested.

Research Objectives and Strategic Plan (Limited to 12 pages)

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 individual research 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.  Preliminary studies and/or progress reports must be contained within the page limits of the Research Strategy section.

9 Checklist

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

10. 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 Plan

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 individual research 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 individual research project will contribute towards attainment of the multi-project 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. Individual Research Project Research Plan (a minimum of two individual research projects are required for the IPCP-HTM

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 individual research project's relationship to the 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 must be included as part of the approach section, and must be contained within the page limits of the Research Strategy section.

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 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. Core Research Plan (required minimum core: Administrative Core

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 goals and how it relates to the individual research projects or other cores in the application.

Research Strategy (Limited to 6 pages.)

Use this section to describe how the proposed core activities will contribute to meeting the  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 Center 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 must be included as part of the approach section and must be contained within the page limits of the Research Strategy section.

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.

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

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 the overall application, 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 Strategy section for each individual research project and scientific core and fall within the page limits.

Milestones are a term of award (TOA) for all IPCP-HTM cooperative agreements.

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

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS398 Application Guide, with the following modifications:

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide

Foreign Organizations

Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the PHS398 Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 

Information on the process of receipt and determining if your application is considered “on-time” is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

4. Intergovernmental Review (E.O. 12372)

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.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

6. Other Submission Requirements and Information

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.  

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact - Overall

Reviewers will provide an overall impact/priority 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 review criteria and additional review criteria (as applicable for the project proposed).

Significance: Is the program as a whole, as well as that of the individual research projects and scientific cores, scientifically meritorious?  Are the overall program goals significant and appropriate? Will 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?

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?

Innovation: 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? 

Approach: Does the integration of the overall program establish an innovative approach to the developmental problem(s) of creating a topical microbicide candidate or strategy? Are the 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 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?

Environment: Are the administrative plans for the management of projects, including plans for resolving conflicts, appropriate?

Scored Review Criteria - Individual Research Projects

Reviewers will consider each of the review criteria below in the determination of scientific 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 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 PD/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 (appropriate 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? Are the institutional support, equipment and other physical resources available to the 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? 

 Scored Review Criteria – Cores

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

Review Criteria for Administrative Core

Are the 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? Are the proposed core facilities appropriate and adequate to support at least two of the individual research projects? 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? Is the administrative and organizational structure appropriate to facilitate attainment of the objective(s) of the proposed IPCP-HTM? Are the experience, level of commitment, and availability of the Administrative Core Leader and administrative staff adequate to manage the program? Are the qualifications, competence, and commitment of the Core Leader(s) and key personnel appropriate? Is the relationship of the core to the central focus of the overall IPCP-HTM established and is it appropriately justified as supporting the innovation of the research projects? Are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the IPCP-HTM adequate, and is the administrative and organizational structure proposed appropriate and adequate to the attainment of the objective(s) of the proposed program?  Is the management plan for Program coordination, problem identification and resolution, establishment of a strong collaborative environment, fiscal accountability and communication appropriate? Does the management plan provide for ongoing formal and informal communications within the IPCP-HTM? 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? 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? Is the quality of the relevant facilities or services provided and criteria for prioritization and usage appropriate?

Review Criteria for 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 Scientific core milestones integrated into the overarching IPCP-HTM Program milestones, and are they applicable to the overall program?   

Additional Review Criteria Projects and Cores

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

Milestones

Given the critical nature of the milestones for to measure the success of the IPCP-HTM program and microbicide development, are the proposed Milestones well-defined with quantifiable measures that are appropriate for assessing the success of the individual cores and projects and overall Program activities of the IPCP-HTM application? Do the Milestones have specific quantifiable criteria that will enable clear decisions about their attainment? Is it clear how the IPCP-HTM Program and its scientific and operational objectives will evolve as milestones are achieved? Given the potential benefits of the proposed research, do the milestones support the potential for the overall program to advance the proposed microbicide strategy? 

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. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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 on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Resubmissions

Not applicable.  

Renewals

Not applicable.

Revisions

Not applicable.

Additional Review Considerations - Overall

As applicable for the project proposed, reviewers will consider 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 Agent 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; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIAID, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

Applications will be assigned to the appropriate NIH Institute or Center and will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropraite Institute Council. The following will be considered in making funding decisions:

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. 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.      

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

2. Administrative and National Policy Requirements

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) 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.

The PD(s)/PI(s) will have the primary responsibility for:

The PD/PI 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.

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 PD/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.

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).

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 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:

PD/PIs 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.

The PD/PI 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 PD/PI 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 PD/PI and appropriate Project Leaders and will require appropriate acknowledgement of NIAID support.  Timely publication of major findings is encouraged.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

Areas of Joint Responsibility include:

Within two months of award, a Steering Committee will be established and chaired by the PD/PI.  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 PD/PI and/or Steering Committee, and any other key personnel identified by the PD/PI.  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.

1.  Assist the PD/PI in achieving the goals of the IPCP-HTM Program

2.  Create subcommittees and request input from the SAP as needed

3.  Evaluate progress of the IPCP-HTM and make recommendations for achieving Project, Core and IPCP-HTM milestones.  This may include recommending alterations in the level of effort for specific Projects and/or Cores and/or modification of milestones.

4.  Be responsible for identifying policies and procedures to be implemented by the PD/PI to support IPCP-HTM operations and scientific progress, including development of guidelines for publication of the results of collaborative projects

5.  Assist the PD/PI, as required, in preparing formal reports summarizing IPCP-HTM activities and/or progress, such as the Annual Progress Report

6.  Advise the NIH Project Scientist on scientific opportunities, emerging needs and impediments

7.  Assist in protocol development for clinical studies and evaluate human subject's issues as needs arise

8.  Ensure timely release of data to NIH-supported and/or public databases

The specific milestones and timelines agreed to by the PD/PI 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 PD/PI and NIAID must agree to all such revisions.

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 a majority of the 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 a majority of the 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.

Dispute Resolution:

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 does not alter the awardees’ right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

When multiple years are involved, 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 the expenditure data portion of the Federal Financial Report are required for closeout of  an award as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement. 

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

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  

Application Submission Contacts

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Jim A. Turpin, Ph.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases (NIAID)
Room 5114, MSC-7628
6700B Rockledge Drive
Bethesda, MD 20892-7628
Telephone: (301) 451-2732
Email: jturpin@niaid.nih.gov

Roberta Black, Ph.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases (NIAID)
Room 5117, MSC-7628
6700B Rockledge Drive
Bethesda, MD 20892-7628
Telephone: (301) 496-8199
Email: rblack@niaid.nih.gov

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

Peer Review Contact(s)

Peter R. Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3133, MSC 7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
FedEx Zip: 20817-7616
Telephone:  (301) 496.8426
FAX:  (301) 480-2310
Email:  PJackson@mail.nih.gov

Financial/Grants Management Contact(s)

Mollie Shea
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
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

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.


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