Part I Overview Information

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Department of Health and Human Services

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

Components of Participating Organizations
National Institute of Allergy and Infectious Disease (NIAID) ( http://www.niaid.nih.gov)
National Institute of Mental Health (NIMH) (http://www.nimh.nih.gov/ )
Office of Research on Women’s Health (ORWH) (http://orwh.od.nih.gov/)

Title: Microbicide Innovation Program (MIP III) (R21/R33)

Announcement Type
This is a reissue of RFA-AI-06-005 and RFA-AI-06-042, which were previously released November 22, 2005 and September 12, 2006, respectively.

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

• April 15, 2009 - This RFA has been reissued as (RFA-AI-09-021) .
• April 16, 2008 - This RFA has been reissued as (RFA-AI-08-016).

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.

Request For Applications (RFA) Number: RFA-AI-07-034

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

Key Dates
Release/Posted Date: August 17, 2007
Opening Date: October 19, 2007(Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): October 19, 2007
NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Submission/Receipt Date(s): November 20, 2007
Peer Review Date(s): March 2008
Council Review Date(s): May 2008
Earliest Anticipated Start Date(s): July 1, 2008
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: November 21, 2007

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

• Purpose. The Microbicide Innovation Program (MIP III) solicits applications in the field of topical microbicides to advance:
  • Development of new microbicide approaches and targets through preclinical and basic research;
  • Discovery and exploration of microbicides (singly or in combinations) directed against HIV, or STIs (Sexually Transmitted Infections) linked to HIV acquisition;
  • Emerging technologies or models that contribute to the development of new and/or more efficient ways of assessing microbicide safety, efficacy and acceptability; and
  • Exploration of complex prevention strategies that incorporate vaginal, rectal, and/or penile applied microbicides in the context of mucosally active vaccines.
  • Mechanism of Support. This Funding Opportunity Announcement (FOA) will utilize the NIH R21/R33 Phased Innovation Award to support innovative exploratory and developmental research. Under the R21 phase, research is initiated and carried out through a milestone-driven process to establish the feasibility of new microbicides, microbicide strategies and support technologies. The R33 phase then provides the support required to translate the innovation discoveries into the preclinical/clinical development pipeline.
• Funds Available and Anticipated Number of Awards. The NIAID intends to commit approximately $2,000,000 in FY 2008 to fund 10 to 15 grants. Funding will be based on scientific and technical merit, program priorities, and availability of funds. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary.
• Budget and Project Period: The total project period for an application submitted in response to this funding opportunity may not exceed 5 years. Awards will support milestone-driven exploratory/feasibility proof-of-concept studies (2-year R21 phase), with possible rapid transition to expanded development (3-year R33 phase). Direct costs are limited to $275,000 over the R21 two-year period, with a maximum of $200,000 in direct costs allowed in any single year. The R33 award phase will be limited to $300,000 in direct costs per annum. The NIAID anticipates that a maximum of fifty percent (50%) of the funded R21 phase awards will progress to the R33 award.
• Eligible Institutions/Organizations: Public/State Controlled Institution of Higher Education; Private Institution of Higher Education; Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education); Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education); Small Business; For-Profit Organization (Other than Small Business); State Government; U.S. Territory or Possession; Indian/Native American Tribal Government (Federally Recognized); Indian/Native American Tribal Government (Other than Federally Recognized); Indian/Native American Tribally Designated Organization; Non-domestic (non-U.S.) Entity (Foreign Organization); Hispanic-serving Institution; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); Alaska Native and Native Hawaiian Serving Institutions; Regional Organization; Eligible agencies of the Federal government; Faith-based or community based organizations.
• Eligible Project Directors/Principal Investigators (PDs/PIs): Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
• Number of Applications. Applicants may submit more than one application, provided each application is scientifically distinct.
• Renewals and Resubmissions. Applications for R21 support alone are not accepted under this FOA. Up to two resubmissions (formerly revisions/amendments ) of a previously reviewed MIP I (in response to RFA-AI-06-005) or MIP II (in response to RFA-AI-06-042) exploratory/developmental grant application may be submitted. The Phased Innovation Award (R21/R33) is not renewable and competing renewal (formally competing continuation ) applications will not be accepted.
• Number of PDs/PIs: More than one PD/PI, or multiple PIs/PIs, may be designated on the application.
• Application Materials. See Section IV.1 for application materials.
• General Information. For general information on SF424 (R&R) Application and Electronic Submission, see these the following Web sites:
  • SF424 (R&R) Application and Electronic Submission Information: http://grants.nih.gov/grants/funding/424/index.htm
  • General information on Electronic Submission of Grant Applications: http://era.nih.gov/ElectronicReceipt/
• Hearing Impaired. Telecommunications for the hearing impaired is available at: TTY 301-451-5936.

Table of Contents

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Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

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

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

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

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting

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

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

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Section I. Funding Opportunity Description

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1. Research Objectives

Purpose

The purpose of the Microbicide Innovation Program (MIP III) is to support novel and under-explored strategies in the field of topical microbicides. This broadly based program will support research and development of microbicides with the ultimate goal of facilitating technology or methodology design and development that can advance the field as a whole.

Objectives and Scope

The development of a safe, effective acceptable topical microbicide to prevent the sexual transmission of HIV could play a major role in world-wide reduction of the over 14,000 new HIV infections per day, and potentially save millions of lives. Topical microbicides are agents that when applied vaginally, rectally or on the penis can result in inhibition of the transmission of HIV and/or other sexually transmitted infections (STI), which may be co-factors in HIV transmission and acquisition. Recent study results demonstrate that combinations of microbicides can protect against SHIV infection in a non-human primates (http://www3.niaid.nih.gov/news/newsreleases/2005/monkeymicrob.htm). Although no licensed microbicide is currently available, large-scale effectiveness trials of three candidate microbicides are under way, including an NIAID-sponsored trial that opened in February 2005. That trial is described at http://www.hptn.org/research_studies/hptn035.asp.

The MIP III program is designed to foster the introduction of novel scientific ideas, model systems, tools, agents, targets, and technologies that have the potential to substantially advance microbicide science. Aims may include identification and development of new approaches and antiviral targets for microbicides that may entail high-risk research. Efforts can also include the identification of new lead microbicide candidates or targets through incremental and iterative optimization of the microbicide candidate/target. This may be done by demonstrating: (1) establishment of new pathways to microbicide-related science, (2) in vitro demonstration of efficacy with minimal or no toxicity for newly discovered leads, (3) activity (single dose) or lack of toxicity (multiple dose) in relevant animal models, or (4) preliminary data that establish a strong rationale for the use of the vaginal, rectal and/or penile microbicide or strategy.

Applications that propose technological/methodological advancement must be directly applicable to microbicide discovery and development. Advancement includes approaches designed to substantially improve existing method(s) for safety, effectiveness or acceptability assessment. Applications may incorporate development of unique approaches to product development and/or discovery of new molecular entities or targets applicable to the microbicide prevention problem that may be deployed as single, combination or multi-component microbicide products. Proposed projects could assess novel areas of investigation or new experimental systems that have the potential to enhance microbicide-related research.

The Microbicide Innovation Program (MIP III) will support five areas:

(1) Development of microbicides through preclinical and basic research that will lead to new opportunities for microbicide development.

(2) Discovery and exploration of microbicides (singly or in combination) directed against HIV and/or STIs that potentially contribute to HIV transmission and acquisition. These include, but are not limited to Herpes Simplex virus, Trichomonas vaginalis, Treponena pallidum, human Papillomavirus, Haemophilus ducreyi, Neisseria gonorrhoeae, Chylamydia trachomatis and Bacterial Vaginosis.

(3) Emerging technologies or models that contribute to new and/or more efficient mechanisms for (i) assessing microbicide safety, efficacy and acceptability, (ii) discovery and exploration of new microbicide candidates, (iii) formulation and delivery of microbicide products, and (iv) validation of surrogate markers for safety and/or efficacy.

(4) Complex prevention strategies incorporating vaginally, rectally and/or penile applied microbicides.

(5) Development of behavioral and social tools that address product acceptability, initiation, and potential for sustained use. Tools must be designed to integrate with microbicide preclinical development and allow iterative improvements in the product or strategy employed. Success of these tools will hinge on behavioral, cultural, and contextual factors (e.g., product characteristics, perceived risk of infection, partner cooperation, etc.).

Examples of the types of studies that are considered responsive to this FOA and could be supported under this program include but not limited to:

• Discovery, development and validation of new agents that interact with specific steps in the viral replication cycle and the pathways involved in HIV transmission leading to new avenues for microbicide development.
• Exploration, development and/or improvement of new and existing in vivo safety and efficacy models. Model development may also include the development and validation of co-infection models with STIs that are associated with increased HIV susceptibility.
• Discovery of new antimicrobial chemical substances. Applications proposing large screening efforts must provide a defined decision algorithm intended to select a microbicide lead for further development during the R33 phase. Applicants are encouraged to incorporate the physical and in silico tools of medicinal chemistry and rational drug design. Selection and optimization of the candidate should be performed in an iterative hypothesis-driven manner to select the best microbicide. Screening efforts not closely tied to target identification will be considered non-responsive to this FOA.
• Performance of in vitro assays to establish the feasibility of a lead microbicide such as those specified under the FDA (U.S. Food and Drug Administration) guidance for Preclinical development of an antiviral product (http://www.fda.gov/OHRMS/DOCKETS/98fr/05d-0183-gdl0002-01.pdf). Projects could include determination of the mechanism of action, range of antiviral action, toxicity on multiple cell types, effect of relevant body fluids on antiviral activity and toxicity, effect in combination with other potential candidates under development, and the potential to engender microbicide resistance. Analyses should be performed in an iterative fashion to provide the scientific rationale for the feasibility of a single or combination formulated or unformulated microbicide.
• Exploration of unique delivery systems or formulations. This could include optimization of existing microbicide formulations or delivery methods that incorporate novel approaches or unique formulary agents to accomplish a significant improvement over existing formulations and/or create coitally-independent delivery approaches. Applicants are encouraged to demonstrate feasibility through the appropriate in vitro and in vivo safety assessments.
• Identification and exploration of new or alternate technologies for determining microbicide safety and efficacy. These technologies may include identification and validation of specific surrogate markers for adaptive and innate immunity; creation and development of new in vivo models to assess microbicide efficacy, safety and pharmacokinetics; or adaptation/engineering of hardware or software for microbicide applications. Investigators are encouraged to link their technology development with microbicide assessment to validate any proposed approaches.
• Strategies to link induction or modification of adaptive and/or innate immune responses in the vagina or gastrointestinal tract to susceptibility to transmission. If a vaccination strategy is used to modify immunity, the primary mode of prevention must be the microbicide strategy and not the development of a new mucosal vaccine, vector or delivery system.
• Assessments of product application on innate and adaptive immune responses, as correlates of product safety, efficacy or feasibility of a microbicide strategy.
• Programs designed to identify and provide validation of a defined panel of surrogate safety and/or efficacy markers using genomic or proteomic technologies to advance microbicide science.
• Exploration of combination microbicides with activities against HIV or to another relevant STI if the combination also has activity against HIV. Combination strategies may integrate mucosally active vaccine(s) or coital-disassociated use of products as part of the overall microbicide-focused prevention approach.
• Assessments of baseline behavioral and social parameters that could directly affect microbicide adherence or acceptability. This may include development of specific tools or measures designed to identify acceptability of formulated microbicides or delivery strategies. It may also include preliminary assessments of baseline conditions or practices within specific microbicide target populations that could directly inform the biophysical properties of a microbicide product or strategy. In this latter case it is essential for the applicant to demonstrate the relevance and need of the studies to the proposed microbicide strategy.

Applications proposing research in the following areas will NOT be considered responsive to this FOA and will be returned to the applicant without review:

• Proposed development or an incremental modification of a detergent, surfactant or non-specific membrane active agent, such as reactive oxygen, metal ions or oxidizing/reducing agents, as a single or combination microbicide agent.
• Combination microbicides derived solely from detergents, surfactants or non-specific membrane active agents. Incorporation of these agents into combinations with other microbicides active against other relevant microbicide targets may be considered responsive to this FOA when accompanied by sufficient preliminary safety data to demonstrate lack of toxicity.
• Further development of over-the-counter products (OTC) or non-specific vaginal and/or female/male rectal health products to prevent HIV transmission as a microbicide. It is acceptable to use OTC or health products as a delivery vehicle for a specific microbicide strategy, where the constituents of the formulary are addressed for safety and potential efficacy.
• Development of N-9 (Nonoxynol-9).
• Applications proposing microbicides without activity to HIV, or that show activity to STIs with no concomitant activity to HIV, or to STIs that do not increase the risk of HIV transmission when present as a co-infection. This includes solely spermicidal products
• Random or bulk screening of chemical or natural product libraries or collections that do not identify a specific lead microbicide candidate through use of appropriate efficacy and safety assessments.
• Proposed development of an uncharacterized natural product, such as lime or lemon juice. Applications proposing development of an uncharacterized or standardized natural product may be considered responsive to this FOA if the application describes plans to deconstruct the natural product, identify microbicidal components, and provide a rational basis for standardization or improvement of the initial product.
• Development of sulfonated polysaccharides or other large molecular weight charged polyanions as a single microbicide product. However, microbicide strategies using these entities in combination with other microbicide candidates will be considered responsive to this FOA.
• Basic behavioral research to develop measures of sustained microbicide use, or general behavioral parameters relevant to the epidemic.
• Phase I, II or III clinical trials proposed specifically to advance an IND for a microbicide or microbicide strategy or first-time-in human studies will NOT be supported. However, clinical research that uses clinical specimens or uses collection of behavioral or social data and/or phase 0 studies as defined by the FDA http://www.fda.gov/cder/guidance/7086fnl.htm, may be supported under this FOA. Applicants are strongly urged to discuss any proposal containing clinical elements with Program prior to submission.

Note: When clinical studies or trials are a component of the research proposed, NIAID policy requires that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. AN UPDATED NIAID policy was published in the NIH Guide on July 8, 2002 and is available at: http://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html. The full policy, including terms and conditions of award, is available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf.

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

Section II. Award Information

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1. Mechanism of Support

This Funding Opportunity Announcement (FOA) will use the NIH Phased Innovation Award (R21/R33) that couples the Phase I (R21) and Phase II (R33) Exploratory/Developmental Research Grant award mechanisms. The applicant will be solely responsible for planning, directing, and executing the proposed project.

The combined R21/R33 application offers two advantages over the regular application process: (1) single submission and evaluation of both the R21 component and the R33 component as one application; and (2) minimal or no funding gap between the R21 and R33 phases.

Transition of the R21 to the R33 phase will be expedited and is dependent on the completion of negotiated milestones. Milestones will be evaluated in the peer review process and negotiated with NIAID or NIMH program staff prior to award of the R21 phase. Once they are achieved, the R33 phase will be considered.

Although applicants are solely responsible for planning, directing, and executing the proposed project, the transition from the R21 feasibility phase, and eligibility for award of the R33 development phase, will be determined by NIAID or NIMH program staff in the context of the peer review recommendations and based on successful completion of negotiated scientific milestones, program priorities, and availability of funds.

The R21 phase provides up to two years of funding for innovative hypothesis-driven projects supported by limited or no preliminary data to allow investigators to demonstrate feasibility of the proposed microbicide-related innovation or developed technology using Milestones. Although preliminary data are not required, applicants are urged to supply preliminary data when possible, and in lieu of preliminary supporting data are urged to provide sufficient information to allow assessment of the rationale of the proposed hypothesis or concept. The R33 award provides a second phase for the support of additional innovative exploratory research initiated under the R21 mechanism for a period of up to three years, for a total period of support of five years. It is strongly recommended that applicants contact institute staff at an early stage in application development to discuss programmatic responsiveness of the proposed project. Refer to the INQUIRIES section of this FOA for institute staff contacts.

This FOA uses Just-in-Time information concepts. For both the R21 and the R33 phases, applicants must complete and submit detailed budget requests using the SF424 Research and Related (R&R) Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 4.7, R&R Budget Component of the Application Guide). Modular budgets are not permitted for this funding opportunity.

Under this FOA applicants may only submit for the combined R21/R33 (Phased Innovation Award). Applications for R21 support alone are not accepted under this FOA. Investigators seeking support solely through the R21 mechanism are encouraged to apply for the NIH-wide R21 Exploratory/Developmental Research Grant Program (see http://grants2.nih.gov/grants/guide/pa-files/PA-06-181.html, or other announcements).

Up to two resubmissions (formerly revisions/amendments ) of a previously reviewed exploratory/developmental grant application in response to RFA-AI-06-005 or RFA-AI-06-042 may be submitted. See NOT-OD-03-041, May 7, 2003, http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-041.html.

The Phased Innovation Award (R21/R33) is not renewable and competing renewal (formally competing continuation ) applications will not be accepted.

2. Funds Available

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

Funding for the total project period for an application submitted in response to this FOA cannot exceed five years. Support for the R21 feasibility phase cannot exceed two years and is limited to $275,000 direct costs over the two year award period with no more than $200,000 in direct costs allowed in any single year. Budgetary support for the R33 phase is limited to $300,000 per annum in direct costs and cannot exceed three years.

The funding components anticipates a maximum of fifty percent (50%) of the initially funded applications will eventually progress to the R33 phase. Funding of the R33 phase will be based on program priorities, the availability of funds, and successful completion of negotiated scientific milestones within the R21 phase, as determined by NIAID or NIMH Program staff in the context of peer review recommendations.

The NIAID anticipates committing approximately $2,000,000 in fiscal year 2008 to support 10-15 applications in response to this FOA.

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.

F&A costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004, November 2, 2004.

Section III. Eligibility Information

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1. Eligible Applicants

1.A. Eligible Institutions

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

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

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the Project 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.

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

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

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Applicants may submit more than one application, provided each application is scientifically distinct.

Section IV. Application and Submission Information

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To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

• Grants.gov (http://www.grants.gov/GetStarted) and
• eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm)

PDs/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.

Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Started

• Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants.gov registration process.
• If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration.
• The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days.
• Direct questions regarding Grants.gov registration to:
  Grants.gov Customer Support
  Contact Center Phone: 800-518-4726
  Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
  Email support@grants.gov

2) Organizational/Institutional Registration in the eRA Commons

• To find out if an organization is already Commons-registered, see the "List of Grantee Organizations Registered in NIH eRA Commons.
• Direct questions regarding the Commons registration to:
  eRA Commons Help Desk
  Phone: 301-402-7469 or 866-504-9552 (Toll Free)
  TTY: 301-451-5939
  Business hours M-F 7:00 a.m. 8:00 p.m. Eastern Time
  Email commons@od.nih.gov

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

• The individual(s) designated as PDs/PIs on the application must also be registered in the NIH eRA Commons. In the case of multiple PDs/PIs, all PDs/PIs must be registered and be assigned the PI role in the eRA Commons prior to the submission of the application.
• Each PD/PI must hold a PD/PI account in the Commons. Applicants should not share a Commons account for both an Authorized Organization Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a PD/PI role and an Internet Assisted Review (IAR) role, both roles should exist under one Commons account.
• When multiple PDs/PIs are proposed, all PDs/PIs at the applicant organization must be affiliated with that organization. PDs/PIs located at another institution need not be affiliated with the applicant organization, but must be affiliated with their own organization to be able to access the Commons.
• This registration/affiliation must be done by the AOR/SO or their designee who is already registered in the Commons.

Both the PD/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo: Telephone 301-710-0267, Email: GrantsInfo@nih.gov.

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

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide for this FOA through Grants.gov/APPLY.

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY will include all applicable components, required and optional. A completed application in response to this FOA will include the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
Research & Related Budget
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist

Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

Note: While both budget components are included in the SF424 (R&R) forms package, the NIH R21/R33 uses ONLY the Research & Related Budget. (Do not use the PHS398 Modular Budget.)

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

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

Applications from foreign organizations must:

• Request budgets in U.S. dollars.
• Prepare detailed budgets for all applications (that is, complete the Research & Related Budget component of the SF424 (R&R) application forms not the PHS398 Modular Budget component). See NOT-OD-06-096, August 23, 2006.
• Charge back of customs and import fees is not allowed.
• U.S. Government grants cannot pay taxes in foreign countries, including VAT tax.
• Format: Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8.5 x 11 within each PDF.
• Funds for up to 8% administrative costs (excluding equipment) may be requested. See NOT-OD-01-028, March 29, 2001.
• Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards.
• Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., Administrative and National Policy Requirements.

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

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in item 15 of the SF424(R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of PD/PI. Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the Credential field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership of the project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan (Section 14 of the Research Plan Component in the SF424 (R&R)), must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

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

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form.

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Submission, Review, and Anticipated Start Dates
Opening Date: September 19, 2007 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): October 19, 2007
NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Submission/Receipt Date(s): November 20, 2007
Peer Review Date(s): March 2008
Council Review Date(s): May 2008
Earliest Anticipated Start Date(s): July 1, 2008

3.A.1. Letter of Intent

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

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

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

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Edward W. Schroder, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3116, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (For express couriers: 20817-7616)
Phone: 301-435-8537
Fax: 301-480-2310
Email: eschroder@mail.nih.gov

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow steps 1-4. Note: Applications must only be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image.

• If everything is acceptable, no further action is necessary. The application will automatically move forward for processing by the Division of Receipt and Referral, Center for Scientific Review, NIH, after two business days.
• Prior to the submission deadline, the AOR/SO can Reject the assembled application and submit a changed/corrected application within the two-day viewing window. This option should be used if the AOR/SO determines that warnings should be addressed. Reminder: warnings do not stop further application processing. If an application submission results in warnings (but no errors) it will automatically move forward after two business days if no action is taken. Please remember that some warnings may not be applicable or may need to be addressed after application submission.
• If the two-day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants.gov system issue, the application does not correctly reflect the submitted application package (e.g., some part of the application was lost or didn t transfer correctly during the submission process). The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.
• If the AOR/SO chooses to Reject the image after the submission deadline for a reason other than an eRA Commons or Grants.gov system failure, a changed/corrected application still can be submitted, but it will be subject to the NIH late policy guidelines and may not be accepted. The reason for this delay should be explained in the cover letter attachment.
• Both the AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves forward in the process after two days.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status in the Commons.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review unless the applicant withdraws the pending application.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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

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

6. Other Submission Requirements

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD/PI to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Registration FAQs Important Tips -- Electronic Submission of Grant Applications.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

PHS398 Research Plan Component Sections

While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporating "Just-in-Time" information concepts, and with the following requirements for R21/R33 applications:

• The NIH modular budget concept is not to be used. Even though the budget for the R21 phase is limited, applications must present the detailed SF424 (R&R) Budget forms for all years. In the budget justification, it must be indicated whether the budget year is for the R21 or the R33 phase. The SF424 (R&R) application submitted in response to this FOA cannot be accepted with a modular budget for the R21 phase and a detailed budget for the R33 phase.
• Although preliminary data are not required for an R21/R33 application, they may be included. Applicants are strongly urged to include any preliminary data, if available, that will support or justify the development of the proposed hypothesis and rationale.
• Introduction (required for a resubmission application) is limited to 3 pages
• Items 2-5 of the Research Plan of the R21/R33 application may not exceed 25 pages, including tables, graphs, figures, diagrams, and charts.
• There should be a single Research Plan. Within the individual sections, describe both the R21 and R33 phases, as appropriate. Item 2 (Specific Aims) must provide separate sets of aims for the R21 and R33 phases. Item 5 (Research Design and Methods) must provide separate descriptions for the R21 and R33 phases, but it is not necessary to repeat background information or details of methods in the R33 section that were provided in the R21.
• Milestones for the R21 phase MUST be included, and should be placed at the end of the Research Design and Methods section and are included in the 25 page limit.
• The Milestone section must propose milestones for completion of the R21 part of the application, a discussion of the suitability of the proposed milestones for assessing success in the R21 phase, and a discussion of the implications of successful completion of these milestones for the proposed R33 study. Milestones should be specific, quantifiable and scientifically justified; they should not be simply a restatement of the R21 specific aims. Milestones may be provided for the R33 phase at the discretion of the applicant.
• In preparing the R21/R33 application investigators should consider that the application will be assigned a single priority score. Thus, clarity and completeness of the application with regard to specific goals and the feasibility of each phase and the Milestones are critical. Milestones that are not sufficiently scientifically rigorous to be valid for assessing progress in the R21 phase will reflect poorly on the scientific merit of the application as a whole.

Appendix Materials

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

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the relevant policies and procedures may be delayed in the review process.

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

• Indicate how the proposed project has specific relevance to the mission and objectives of the IC and has the potential for significantly advancing the health sciences in the United States.

Plan for Sharing Research Data

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

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

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

Sharing Research Resources

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

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

Section V. Application Review Information

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1. Criteria

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

2. Review and Selection Process

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

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

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

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:

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

In addition, decisions for funding the R33 portion of award for years 3 to 5 will be based on:

• Successful completion of the milestones proposed.
• Availability of funds.
• Relevance to program priorities.

The NIH Phased Innovation Award (R21/R33) mechanism supports novel scientific ideas, new model systems, tools, or technologies that have the potential to significantly advance our knowledge or the status of health-related research. An exploratory/developmental grant application need not have extensive background material or preliminary information as one might normally expect in a Research Project Grant (R01) application. Accordingly, reviewers will be asked to focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding.

Reviewers will be asked to place less emphasis on methodological details and certain indicators traditionally used in evaluating the scientific merit of R01 applications, including supportive preliminary data. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application.

• Significance
• Approach
• Innovation
• Investigator
• Environment

Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

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

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? For applications designating multiple PDs/PIs, does the Leadership Plan ensure that there will be sufficient coordination and communication among the PDs/PIs? Are the administrative plans for the management of the research project appropriate, including plans for resolving conflicts?

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

Investigators: Are the PD/PIs and other key personnel appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the PD/PI(s) and investigative team bring complementary and integrated expertise to the project (if applicable)?

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

Milestones: Are the proposed Milestones well-defined with quantifiable measures that are appropriate for assessing the success in the R21 phase of the application? Do the milestones have specific quantifiable criteria that will enable clear decisions about their attainment? Is it clear how the R33 phase of the study will develop and expand once the R21 Milestones are achieved?

2.A. Additional Review Criteria:

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

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

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. See the Human Subjects Sections of the PHS398 Research Plan component of the SF424 (R&R).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated. See the Human Subjects Sections of the PHS398 Research Plan component of the SF424 (R&R).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the adequacy of the plans for their care and use will be assessed. See the Other Research Plan Sections of the PHS398 Research Plan component of the SF424 (R&R).

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

2.B. Additional Review Considerations

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

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

2.C. Sharing Research Data

T he reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

2.D. Sharing Research Resources

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

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

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

Model Organism Sharing Plan: Reviewers are asked to assess the sharing plan in an administrative note. The sharing plan itself should be discussed after the application is scored. Whether a sharing plan is reasonable can be determined by the reviewers on a case-by-case basis, taking into consideration the organism, the timeline, the applicant's decision to distribute the resource or deposit it in a repository, and other relevant considerations. For the R21/R33 mechanism, the presence or adequacy of a plan should not enter into the scoring of the application.

3. Anticipated Announcement and Award Dates

Not Applicable.

Section VI. Award Administration Information

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1. Award Notices

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

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

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

2. Administrative and National Policy Requirements

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

3. Reporting

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

Section VII. Agency Contacts

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

1. Scientific/Research Contacts:

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

Andrew D. Forsyth, Ph.D.
Center for Mental Health Research on AIDS
National Institute of Mental Health
Room 6201, MSC-9619
6001 Executive Boulevard
Bethesda, MD 20892-9619
Telephone: (301) 443-8403
Fax: (301) 443-9719
Email: aforsyth@mail.nih.gov

2. Peer Review Contacts:

Edward W. Schroder, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3116, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (For express couriers: 20817-7616)
Phone: 301-435-8537
Fax: 301-480-2310
Email: eschroder@mail.nih.gov

3. Financial or Grants Management Contacts:

Mary Ledford
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2129, MSC-7614
6700B Rockledge Drive
Bethesda, MD 20892-7614
Telephone: (301) 402-6446
Fax: (301) 493-0597
Email: mledford@mail.nih.gov

Section VIII. Other Information

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Required Federal Citations

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

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

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

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

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

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

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

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

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

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

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

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

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

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

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

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

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

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

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ in the following areas: 93.855, 93.856, 93.242, and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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

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