Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID)
Funding Opportunity Title	NIAID Clinical Trial Implementation Cooperative Agreement (U01)
Activity Code	U01 Research Project Cooperative Agreements
Announcement Type	Reissue with modifications of PAR-10-186
Related Notices	March 22, 2013 - This PAR has been reissued as PAR-13-151. August 26, 2011 - See Notice NOT-AI-11-053. The purpose of this Notice is to amend and clarify wording.
Funding Opportunity Announcement (FOA) Number	PAR-11-234
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
FOA Purpose	The purpose of this Funding Opportunity Announcement (FOA) issued by the National Institute of Allergy and Infectious Diseases (NIAID) is to invite applications that propose implementation of investigator-initiated high-risk clinical trials. The trials must be hypothesis-driven, related to the research mission of the NIAID and considered a high priority by the Institute. Investigators are encouraged to visit the NIAID website for additional information about the research mission and high-priority research areas of the NIAID http://www3.niaid.nih.gov/about/whoWeAre/planningPriorities/.) Only one clinical trial may be proposed in each NIAID Clinical Trial Implementation (U01) Cooperative Agreement application.

Posted Date	June 16, 2011
Open Date (Earliest Submission Date)	August 13, 2011
Letter of Intent Due Date	Not Applicable.
Application Due Date(s)	September 13, 2011; January 13, 2012; May 14, 2012; September 13, 2012; January 14, 2013, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	December, 2011; April, 2012; August, 2012; December, 2012; April, 2013
Advisory Council Review	January, 2012; May, 2012; October, 2012; January, 2013; May, 2013
Earliest Start Date(s)	March, 2012; July, 2012; November, 2012; March, 2013; July, 2013
Expiration Date	January 15, 2013
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) 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. 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.

Part 1. Overview Information
Part 2. Full Text of the 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

Research Objectives

This Funding Opportunity Announcement (FOA) issued by the National Institute of Allergy and Infectious Diseases (NIAID) invites applications for implementation of investigator-initiated, high-risk clinical trials. A clinical trial is defined by NIH as:

A prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, treatments, devices, or new ways of using known drugs, treatments, or devices). Clinical trials are used to determine whether new biomedical or behavioral interventions are safe, efficacious, and effective .

The proposed trial must be hypothesis-driven, related to the research mission of the NIAID and address a research area considered a high priority by the Institute.

This FOA will utilize the NIH Cooperative Agreement (U01) award mechanism, and will run in parallel with two related FOAs, PAR-10-184 and PAR-10-185, that invite applications for NIAID Clinical Trial Planning (R34) Grants, which support planning activities for investigator-initiated clinical trials, and NIAID Clinical Trial Implementation (R01) Grants, which support implementation of investigator-initiated, non-high-risk clinical trials, respectively.

Background

In FY2009 NIAID funded $1.36 billion in clinical research. A subset of this funding was devoted to clinical trials, which is one research strategy NIAID uses to improve the understanding of the clinical mechanisms of infectious, immunologic, and allergic diseases and to improve prevention, diagnosis, and treatment. For additional information about the mission, strategic plan, and research interests of the NIAID, applicants are encouraged to consult the NIAID web site http://www3.niaid.nih.gov/about/whoWeAre/planningPriorities/.

Clinical Trial Infrastructure

Historically, NIAID has supported a wide variety of clinical research activities through a clinical trial infrastructure funded through cooperative agreements, solicited under NIAID Requests for Applications (RFAs), and contracts, solicited under NIAID Requests for Proposals (RFPs). This infrastructure focuses on high-priority disease research areas. Examples include the HIV/AIDS Clinical Trial Networks supported by the Division of AIDS (http://www3.niaid.nih.gov/about/organization/daids/Networks/daidsnetworks.htm), the Division of Microbiology and Infectious Diseases Clinical Trials Programs and Networks (http://www3.niaid.nih.gov/about/organization/dmid/programs.htm), and the Immune Tolerance Network supported by the Division of Allergy, Immunology and Transplantation (http://www.immunetolerance.org/). NIAID’s clinical research infrastructure includes coordinating centers, statistical units, data centers, central laboratories, clinical centers, and other specialized resources.

Investigator-Initiated Clinical Trials

Although the clinical research infrastructure is crucial to furthering the Institute’s research, NIAID recognizes that additional models of clinical research may be important to advancing its research mission; therefore, NIAID has established the investigator-initiated clinical trial program for clinical trials that cannot or will not be conducted through existing NIAID-supported clinical trial infrastructure. This program consists of support for the NIAID Clinical Trial Planning (R34) Grant, the NIAID Clinical Trial Implementation (R01) Grant and the NIAID Clinical Trial Implementation (U01) Cooperative Agreement.

The NIAID Clinical Trial Implementation (R01) Grant (PAR-10-184) is designed to support non-high-risk clinical trials, while the NIAID Clinical Trial Implementation (U01) Cooperative Agreement (PAR-10-186) is designed to support high-risk clinical trials, as defined by NIAID below and in the associated policy statement (see NOT-AI-10-024). The NIAID Clinical Trial Planning Grant (R34) is available to support planning activities associated with either high- or non-high-risk clinical trials. However, the NIAID Clinical Trial Planning (R34) Grant (PAR-10-185) is not a prerequisite for either NIAID implementation award. If a clinical trial is ready for implementation, and readiness is adequately supported by documentation, submission of an R01or U01 application may occur if prior approval has been provided by NIAID.

For additional information about NIAID s investigator-initiated clinical trial program, see http://funding.niaid.nih.gov/ncn/clinical/iict.htm.

Scope

The NIAID Clinical Trial Implementation (U01) Grant supports implementation of trials that address high priority research related to the mission and goals of NIAID and that are considered high-risk by the NIAID.

A high-risk clinical trial is defined by the NIAID as having one or more of the following attributes:

• provision of a non-routine intervention, that is, an intervention or non-routine use of an intervention that would not otherwise be provided for the condition under study in the local facility where the study is being conducted;
• administration of an unlicensed product; or
• administration of a licensed product for an unapproved indication.

A non-high-risk trial would not have any of the attributes listed above; for example, it would involve provision of a routine intervention and administration of a licensed product for an approved indication. For the purposes of this FOA, examples of routine interventions might include, but would not be limited to: liver biopsy only to measure a research outcome and provision of anti-inflammatory agents and/or immunosuppressants to suppress and prevent transplant rejection, etc.

Implementation support is defined as support for activities related to the conduct of the clinical trial, including, but not limited to:

training of study personnel;

enrollment and recruitment of study subjects;

data collection, management and quality control;

laboratory work and data analyses;

study management and oversight;

establishment of committees to manage the complexity of the trial

preparation of the final study report; and

other related post-enrollment activities.

Each NIAID Clinical Trial Implementation (U01) award will support the implementation of a single clinical trial. Applications that include more than one clinical trial will not be reviewed.

Applicants must propose a time-sensitive, milestone-driven clinical trial and describe the clinical trial stages, criteria for completion of the stages and contingency plans for each stage. Any anticipated impediments that could require a revision in the timeline must be identified and accompanied by a discussion of alternative approaches. The trial must be hypothesis- driven, include a randomized design, and have clear primary and secondary endpoints. A description of the study population, why it is an appropriate group to study the research question(s) posed, subject eligibility, inclusion and exclusion criteria, and a feasible recruitment and enrollment plan must also be included. Statistical methods appropriate for the study design, and adequate plans for data monitoring and safety are required. An overview of the state of the science, current status and relevance of the trial, and discussion of the clinical protocol must be presented in the application.

All clinical trial planning activities must be completed by the time of application submission and investigators must be ready to implement the proposed trial at the time of award.

NIAID reserves the right to specify: 1) whether an IND/IDE application should be submitted to an appropriate regulatory agency; and 2) the entity (NIAID, primary awardee, etc.) who will hold the IND/IDE.

Investigators are referred to NIAID’s Clinical Research Toolkit website (http://www3.niaid.nih.gov/LabsAndResources/resources/toolkit/default.htm ) for protocol templates and guidance, clinical research resources, and links to program divisions. Investigators are strongly encouraged to contact NIAID s program divisions (Section VII. Agency Contacts ) for information regarding division-specific clinical research policies and procedures.

Milestones

Delineation of milestones is a key characteristic of the NIAID Clinical Trial Implementation (U01) Cooperative Agreement. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity.

Applications must include a series of milestones for completion of the clinical trial and provide contingency plans should there be delays in attaining them. The milestones will undergo peer review and will be incorporated into the terms of award.

NIAID U01 clinical trial implementation cooperative agreements will NOT support clinical trial planning tasks such as:

• Development of study design
• Identification of collaborators and enrollment sites
• Development of the clinical protocol and informed consent
• Development of the statistical analysis plan
• Development of the data management plan
• Development of the Investigator’s brochure or equivalent

Investigators seeking support for the planning and design of clinical trials should refer to the NIAID Clinical Trial Planning (R34) Grant FOA (PAR-10-185).

NIAID U01 clinical trial implementation cooperative agreements will NOT support non-high-risk clinical trials. Investigators seeking support for non-high-risk clinical trials should refer to the NIAID Clinical Trial Implementation (R01) Grant FOA (PAR-10-184).

NIAID U01 clinical trial implementation cooperative agreements will NOT provide support for clinical trials that fall outside the mission and high-priority research areas of the NIAID.

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 Resubmission Revision The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.
Award Budget	Application budgets are not limited, but need to reflect actual needs of the proposed project.
Award Project Period	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 NIAID provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds.

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.

Higher Education Institutions:

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

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

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American tribal organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

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

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) 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.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• Grants.gov
• eRA Commons

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.

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 Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

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

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. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Applicants who submitted a new application in response to PAR-05-113 and PAR-10-186 may submit a resubmission application in response to this FOA.

Prior consultation with NIAID staff is strongly encouraged for submission of the NIAID Clinical Trial Implementation (U01) Cooperative Agreement application, including new and resubmission applications. NIAID staff will consider whether the proposed clinical trial meets the goals and mission of the Institute and whether it is appropriate to conduct it as an investigator-initiated clinical trial, but will not evaluate the technical and scientific merit of the proposed trial. Technical and scientific merit will be determined during peer review. Applicants will be informed if the proposed projects do not meet NIAID’s programmatic needs or are not appropriate as investigator-initiated clinical trials. If the NIAID ascertains that substantial staff involvement may not be necessary, for example, because the level of risk has decreased, submission of the application may be considered under the Clinical Trial Implementation (R01) Grant FOA (PAR-10-184), but will not be considered under this FOA. NIAID reserves the right to determine that support for clinical trials may be directed through other available mechanisms supported by NIAID.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) 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.

The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for application submission. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

A Milestone Plan and Complete Clinical Protocol must be included as a single pdf attachment to item #12 of the Other Project Information component of the SF424 application and will not count toward the page limit for the Research Plan. Applications that lack the Milestone Plan and/or the Complete Clinical Protocol will not be reviewed.

Applicants are required to provide detailed project performance and timeline objectives in a section entitled Milestone Plan . This section may not exceed 3 pages and must include:

• a timeline for the following general milestones, as applicable
• completion of regulatory approvals
• enrollment of the first subject
• enrollment of 25%, 50%, 75% and 100% of the projected recruitment time period for all study subjects, including women, minorities and children (as appropriate)
• completion of data collection time period
• completion of primary endpoint and secondary endpoint data analyses time period
• completion of final study report
• detailed protocol-specific performance milestones and timeline; these milestones will be negotiated at the time of the award, if appropriate.

The Complete Clinical Protocol must be included immediately after the Milestone Plan. Investigators are referred to the Trans-NIAID Clinical Research Toolkit website for clinical protocol guidance and templates (http://www3.niaid.nih.gov/LabsAndResources/resources/toolkit/protocol ). Investigators are urged to be succinct.

This FOA uses NIH just-in-time procedures (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm) for some documentation related to readiness to begin clinical trial implementation. If the application is under consideration for funding, the requirement for certification of IRB approval of the proposed use of human subjects, evidence of compliance with the Education in the Protection of Human Research Participants policy, and information on Current Other Support may be deferred until after completion of the peer review and just prior to funding.

Additional information that may be required as part of just-in-time procedures includes:

• training materials and plans for study staff
• Complete Manual of Operations
• evidence that the following requests for approvals have been submitted:

IRB or Ethical Committee approval of the final protocol and the informed consent form (and assent form if applicable)

• other necessary approvals (e.g., Institutional biosafety committee) of the final protocol, as applicable

For additional information about the NIH "just-in-time" concept see Section II. 1. Mechanism of Support, Section VI.1. Award Notices.

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

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

Because all applications must include detailed scientific and operational plans, funding needs for the entire trial and data analysis period must also be included. Investigators must submit a complete, justified, individual budget for each year of support requested. All costs requested and all changes in budgets after the first year should be clearly identified and justified. Separate itemized budgets must be prepared for each subcontract and/or for each collaborating site or core, if multiple sites or cores are proposed. If parts of the costs of the trial are to be borne by sources other than NIH, these contributions must be presented in detail along with supporting letters signed by individuals who have the authority to make fiduciary commitments on behalf of the institution. These outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented either as part of the requested budget or as Estimated Project Funding.

Further information concerning budget preparation may be obtained from the Office of Grants Management contact listed in Section VII. 3. Financial/Grants Management Contact(s).

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

The goals of the trial and the expected outcome(s) should be concisely stated in the Specific Aims section, which is limited to 1 page. The specific objectives of the trial must be clearly and concisely presented, including a specification of the primary and major secondary endpoints to be measured. There should be a clear explanation of the importance of various endpoints.

The following three sections comprise the Research Strategy: Significance, Innovation, and Approach. In addition, the Research Strategy may not exceed 12 pages and must include:

• a discussion of the significance of the problem being studied, the need for the trial, and the potential impact of the results of the trial, as well as how the trial will test the hypothesis(es) proposed;
• a concise description of the overall strategy, methodology and analyses to be used to accomplish the goals and specific aims of the trial;
• a description of and rationale for the proposed study design;
• a description of the intervention to be tested and the protocol to be followed in each arm of the trial, including a discussion of potential biases or challenges in the protocol and how they will be addressed;
• statistical methods that are appropriate for the study design, including sample size and power calculations and the underlying assumptions (and data) used to link these calculations to the endpoints and to the hypothesis(es) being tested;
• a discussion of studies that led to the proposed clinical trial and information or data from preliminary studies which address the need for and the feasibility of the trial; and
• a description of the study organization and administration, including, but not limited to: a description of committee structures needed to manage the complexity of the trial; the role of any internal or external advisory committees; the oversight, responsibilities, and coordination of any sites or cores proposed; and the role of any sub-contractors or service providers for personnel or facilities.
• Milestones

Instructions in the PHS398 Part II Supplemental Instructions for Preparing the Protection of Human Subjects Section of the Research Plan should be closely followed.

The clinical protocol synopsis should be included at the end of the Human Subjects section. Applications that lack the Clinical Protocol Synopsis will not be peer reviewed. The clinical protocol synopsis may not exceed 3 pages and must include the following information:

• a description of the study population, including subject eligibility and inclusion/exclusion criteria;
• sampling, recruitment and enrollment plans, including a discussion of the availability of subjects for the proposed study and the ability of enrollment center(s) to recruit and retain the proposed number of subjects;
• the process to be used for obtaining informed consent and, if applicable, assent;
• approaches to be used for retention, cooperation and follow-up of subjects and to address any anticipated changes in the composition of the study population over the course of the trial;
• methods of assignment of subjects to study groups and of randomization;
• if appropriate to the study, a description and justification for the selection of the dose, frequency and administration of the intervention(s);
• a description of each enrollment site and how data from the site(s) will be obtained, managed, and protected;
• descriptions of all clinical, laboratory, physiological, and/or behavioral tests to enable the research questions to be answered; and
• a description of the data management and quality control plan, including methods for monitoring the quality and consistency of the intervention(s) and data collection; policies and methods for ensuring blinding of study results; and data confidentiality and subject privacy.

A Data and Safety Monitoring (DSM) Plan that is commensurate with the risk level of the proposed clinical research must be included for all clinical trials (see http://grants.nih.gov/grants/guide/notice-files/not98-084.html). All applications or study protocols must include a general description of the monitoring plan, policies, procedures, responsible entities, and approaches to identifying, managing and reporting reportable events (adverse events and unanticipated problems), to the applicable regulatory agencies (e.g., Institutional Review Board (IRB), the NIAID/NIH, the Office of Biotechnology Activities (as appropriate), the Office of Human Research Protections, the Food and Drug Administration, and the Data and Safety Monitoring Board (if one is used). The DSM Plan must address the following areas:

• who will manage and conduct the monitoring
• what will be monitored
• proposed monitoring time points
• where the monitoring will occur
• how the reportable events will be managed and reported
• how sites/centers, and participating facilities (labs, pharmacies) will be monitored

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 SF424 (R&R) Application Guide, with the following modifications:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide, with the following modifications:

The following additional documents must be included in the Appendix material:

• the informed consent form(s) and, if applicable, assent form(s)
• the statistical analysis plan
• identification and qualifications of clinical trial site(s), pharmacies and laboratories
• copies of data collection forms, questionnaires or other relevant materials
• the Investigator’s Brochure or equivalent for the study products(s)
• the Table of Contents of the Manual of Procedures
• a comprehensive Laboratory Plan
• documentation of availability of study agents and support for acquisition and administration of study agent(s)
• the Data Management Plan
• the Site Quality Management Plan
• copies of data collection forms, questionnaires or other relevant materials

Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

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.

Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Applicants may submit a resubmission application, but such an application must include an Introduction addressing the previous peer review critique (Summary Statement). See new NIH policy on resubmission (amended) applications (NOT-OD-09-003, NOT-OD-09-016). Resubmissions from PAR-05-113 (http://grants.nih.gov/grants/guide/pa-files/PAR-05-113.html) are allowed.

Specific Instructions for Applications Requesting $500,000 (direct costs) or More per Year
Applicants requesting $500,000 or more in direct costs for any year (excluding consortium F&A costs) must carry out the following steps:

1) Contact the IC program staff at least 12 weeks before submitting the application, i.e., as plans are being developed for the study;

2) Obtain agreement from the IC staff that the IC will accept the application for consideration for award; and,

3) Include a cover letter with the application that identifies the staff member and IC who agreed to accept assignment of the application.

This policy applies to all new, revision, or resubmission applications. See NOT-OD-02-004.

Letters of Support:

In the Letters of Support section of the Research Plan, provide all appropriate letters of support, including any letters necessary to demonstrate the support of consortium/site participants, cores, laboratories, pharmacies and other collaborators. If co-funding or in-kind support is planned from non-NIH sources, letter(s) outlining details of the commitment (e.g. type, amount and source of support), signed by a business official on organization letterhead, must be included in the Letters of Support section.

Prior consultation with NIAID to discuss programmatic appropriateness is strongly encouraged before submission of an application in response to this FOA. Applicants should contact the applicable NIAID program division (see Section VII. 1. Scientific/Research Contacts) at least 12 weeks before the application due date. A letter that summarizes the discussion may be obtained from the appropriate NIAID Division Director and attached as a pdf file to the PHS398 Cover Letter file.

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

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.

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).

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? If proposed, do the mechanistic studies contribute to the understanding of the disease or treatment? Are the study objectives(s) and hypothesis(es) adequately defined?

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? Do the PD/PIs and key personnel have the necessary expertise in statistics, data management and study coordination to implement the proposed clinical trial and meet milestones and timelines? Are committee structures appropriate to the complexity of the trial? For multicenter trials, does the application identify a core of potential center investigators and staffing for a coordinating center? Is the organizational structure of the multicenter trial 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? Does the application adequately address the following: the intervention, study agent(s), and mode of delivery; availability of the eligible study population; informed consent or assent form, as applicable, statistical hypothesis and analysis; endpoint(s) and data to be collected; sample size, power calculation, duration of the trial; and inclusion/exclusion criteria; ancillary therapies? Does the application provide adequate milestones? Is the plan for acquisition and handling of study agent(s) appropriate? Does the application adequately address differences in the intervention effect due to sex/gender and race/ethnicity? Does the application clearly describe adequate plans for recruitment outreach, enrollment, and retention? Does the application adequately address potential ethical issues? Does the application adequately address Good Clinical Practices (GCP), Good Laboratory Practices (GLP), and Good Manufacturing Practices (GMP) compliance? For multi-center trials, does the application adequately address standardization/quality control of, and adherence to, the clinical protocol and data collection or distribution guidelines?

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? Does the application adequately address plans to add or drop enrollment centers; the availability of the requisite eligible volunteer pool; the availability of children, women and minority individuals as trial participants and specific recruitment and retention plans for their inclusion; plans for recruitment outreach and, as appropriate, follow-up procedures to ensure collection of data at stated intervals? If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

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.

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

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable.

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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.

Applications that are complete will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s)convened by 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:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review), will be discussed and assigned an overall impact/priority score.
• Will receive a written critique.

Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Allergy and Infectious Diseases Council. The following will be considered in making funding decisions:

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

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.

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.

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:

• All aspects of their study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. The awardee agrees to accept close coordination, cooperation, and participation of NIAID staff in those aspects of scientific and technical management of the study as stated in these terms and conditions.
• Meeting NIAID policy requiring 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
• Upon implementation of the protocol, ensuring that each field center, whether a single institution or a consortium of institutions, will follow the procedures required by the protocol regarding study conduct and monitoring, volunteer management, data collection, and quality control.
• Support or other involvement of industry or any other third party in the study--e.g., participation by the third party; involvement of project resources or citing the name of the project or the NIAID support; or special access to project results, data, findings, or resources--may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NIAID.
• Putting all study materials and procedure manuals into the public domain. Awardees are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NIAID/NIH.
• Obtaining prior written approval of the NIAID Grants Management Specialist in consultation with the NIAID Program Officer for any change in any of the key personnel identified in the Notice of Grant Award.

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

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

• Have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, awardees will retain custody of and have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies.
• Provide guidance and support in the development, assembly, and submission of all required regulatory documents, e.g., those regarding the use of investigational drugs, to the Food and Drug Administration.
• Serve as a resource to provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, advising in the selection of sources or resources (e.g., determining where a particular reagent can be found), provision of research resources and reagents available from NIAID grantees and contractors, advising in management and technical performance, or participating in the preparation of publications.
• Provide medical monitoring by an NIAID Medical Officer who will monitor the clinical trials and serve as the Medical Monitor; should a pharmaceutical or biotechnology company sponsoring a clinical trial choose to name its own Medical Monitor, then the NIAID Medical Officer will work with the company-assigned Medical Monitor.
• Oversee the adequacy of adverse event management and reporting, and have regular communications with the PD/PI and study team, which may include attendance at the safety monitoring (or DSMB) and related committee meetings.
• Review the progress of the study, and of each participating facility, through consideration of the annual reports, site visits, volunteer logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting.
• Monitor progress of study milestones; as with any award, continuation, even during the period recommended for support, is contingent upon satisfactory progress. Progress will be monitored by an internal panel with outside consultants as needed and determined by the NIAID. The schedule for these interim reviews will be based upon the duration of the clinical trial period. Continuation of funding will be dependent upon the awardee’s ability to show adequate progress towards milestone accomplishment.
• At each scheduled interim review, compare actual enrollment to the benchmarks and criteria identified in the application and negotiated prior to award; awardees who do not accomplish the negotiated milestones shall submit a milestone report which will include a discussion of why the milestones were not met in the agreed upon timeframe, and propose a corrective recruitment action plan. The corrective recruitment action plan shall include: amended milestones, plans to achieve the amended milestones and any additional items required by NIAID staff. The plan shall be provided to NIAID staff no later than 2 months following the missed milestone.

Studies in which recruitment milestones are not met as per criteria established pre-award, or for which regulatory approval has not been met within one year, and are deemed unlikely to improve sufficiently to bring the study to completion within an acceptable budget or time frame, may be closed for lack of progress following review and consideration by NIAID staff.

If a study is finally determined to lack feasibility and will no longer accrue subjects, awardees are required to submit a close-out plan to NIAID staff in 2 months timeframe of a decision either by NIAID staff or the grantee that an awarded study is no longer feasible. The plan must be approved and signed by the Institutional Official and the PI/PD(s) listed on the award prior to submission.

NIAID reserves the right to terminate or curtail the study (or an individual award) in the event of (a) failure to implement the study protocol, (b) a substantial shortfall in participant recruitment, follow-up, data reporting and dissemination, quality control, or other major breach of the protocol, (c) substantive changes in the agreed-upon protocol with which NIAID does not concur, (d) reaching a major study objective substantially before schedule with persuasive statistical evidence, or (e) human subject ethical issues that may dictate a premature termination.

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

Areas of Joint Responsibility include:

A Steering Committee (SC), composed of the principal investigator, as well as the principal investigators of the various field centers, the Data Coordinating Center and of the specialized core facilities (if any), and one NIAID representative (the Project Scientist ) . The NIAID Project Scientist will have voting membership on the SC and, as appropriate, its subcommittees. The SC will have primary responsibility for facilitating the conduct and monitoring of studies and reporting study results. Awardees will be required to accept and implement the common protocol and procedures approved by the SC. As the components of the SC may be geographically dispersed, the SC should meet with monthly conference calls, supplemented as deemed necessary by face to face meetings.

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.

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 in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

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.

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
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

Ellen Goldmuntz, M.D., Ph.D.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
Room 6807, MSC 6601
6610 Rockledge Drive
Bethesda, MD 20892
Telephone: 301-451-4414
Fax: 301-480-1450
Email: egoldmuntz@niaid.nih.gov

Mr. Martin Gutierrez
Division of Acquired Immunodeficiency Syndrome
National Institute of Allergy and Infectious Diseases
Room 4258, MSC-7620
6700-B Rockledge Drive
Bethesda, MD 20892-7620
Telephone: (301) 451-2703
Fax: (301) 402-1506
Email: mgutierrez@niaid.nih.gov

Ms. Elizabeth Holloman
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room 4504, MSC-6603
6610 Rockledge Drive
Bethesda, MD 20892-6603
Telephone: (301) 402-8339
Fax: (301) 480-0728
Email: hollomone@niaid.nih.gov

Priti Mehrotra, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3138, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
For Express Couriers: 20817-1824
Telephone: (301) 435-9369, (301) 496-2550
Fax: (301) 480-2408
Email: pm158b@nih.gov

Ms. Laura Eisenman
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2120, MSC-7614
6700-B Rockledge Drive
Bethesda, Maryland 20892-7614
Telephone: (301) 402-5541
Fax: (301) 493-0597
Email: le55d@nih.gov

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.

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.