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 Grant (R01)
Activity Code	R01 Research Project Grant
Announcement Type	Reissue of PAR-10-184
Related Notices	May 18, 2016 - This PA has been reissued as PAR-16-269. December 11, 2015 - Notice of Change in Key Dates for PAR-13-149. See Notice NOT-AI-16-014. June 3, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same. August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications. May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.
Funding Opportunity Announcement (FOA) Number	PAR-13-149
Companion Funding Opportunity	PAR-13-151, U01 Research Project Cooperative Agreements PAR-13-150, R34 Clinical Trial Planning Grant Program
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.855; 93.856
Funding Opportunity Purpose	This Funding Opportunity Announcement (FOA) issued by the National Institute of Allergy and Infectious Diseases (NIAID) invites applications for implementation of investigator-initiated, non-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 (R01) Grant application.

Posted Date	March 22, 2013
Open Date (Earliest Submission Date)	May 4, 2013
Letter of Intent Due Date(s)	30 days before the application due date
Application Due Date(s)	June 4, 2013; September 11, 2013; January 13, 2014; May 13, 2014; September 11, 2014; January 13, 2015; May 13, 2015; September 11, 2015; January 13, 2016, and May 13, 2016 by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	June 4, 2013; September 11, 2013; January 13, 2014; May 13, 2014; September 11, 2014; January 13, 2015; May 13, 2015; September 11, 2015; January 13, 2016, and May 13, 2016 by 5:00 PM local time of applicant organization.
Scientific Merit Review	September 2013; January 2014; May 2014; September 2014; January 2015; May 2015; September 2015; January 2016; May 2016; and September 2016
Advisory Council Review	October, 2013, January 2014; May 2014; October 2014; January 2015; May 2015; October 2015; January 2016; May 2016; and October 2016
Earliest Start Date	March 2014; August 2014; December 2014; March 2015; July 2015; December 2015; March 2016; July 2016; December 2016; and March 2017
Expiration Date	New Date May 14, 2016 per issuance of NOT-AI-16-014. (Original Expiration Date: January 14, 2016)
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (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

This Funding Opportunity Announcement (FOA) issued by the National Institute of Allergy and Infectious Diseases (NIAID) invites applications for implementation of investigator-initiated, non-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. For AIDS-related clinical trials, the Institute encourages investigator-initiated studies that include but are not limited to biobehavioral trials and equally as important, trials and studies that also explore disease pathogenesis.

This FOA will utilize the NIAID Clinical Trial Implementation (R01) Grants, which support implementation of investigator-initiated, non-high-risk clinical trials, and will run in parallel with two related FOAs, PAR-13-151 and PAR-13-150, that invite applications for NIAID Clinical Trial Planning (R34) Grants, which support planning activities for investigator-initiated clinical trials, and the NIAID Clinical Trial Cooperative Agreement (U01) award mechanism, which support implementation of high-risk clinical trials, respectively.

Over the past three years, NIAID committed over $2 billion to clinical research, of which $1.5 billion was devoted to clinical trials. Clinical trials are one research strategy NIAID uses to improve the understanding of the clinical mechanisms of infectious, immunologic, and allergic diseases or 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/.

Historically, NIAID has supported a wide variety of clinical research activities through a clinical trial infrastructure funded through cooperative agreements, solicited under NIAID Funding Opportunity Announcements (FOAs), 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://www.niaid.nih.gov/about/organization/daids/Networks/Pages/daidsnetworks.aspx ), 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. For additional information on DMID supported clinical trials refer to the DMID Good Clinical Practice Resource Guide http://www.niaid.nih.gov/labsandresources/resources/dmidclinrsrch/Pages/clinhandbook.aspx

Although 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-13-149) FOA is designed to support non-high-risk clinical trials, while the NIAID Clinical Trial Implementation (U01) Cooperative Agreement (PAR-13-151) FOA 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-13-150) FOA is not a prerequisite for either NIAID implementation award. If a clinical trial is ready for implementation, and readiness is adequately supported by appropriate documentation, the R01 or U01 application may be submitted to the appropriate FOA.

For additional information about NIAID s investigator-initiated clinical trial program, see http://www.niaid.nih.gov/researchfunding/sci/human/pages/iict.aspx

The NIAID Clinical Trial Implementation (R01) Grant supports implementation of non-high-risk clinical trials that address research areas that are well matched with the mission and goals of 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. Applicants are strongly encouraged to contact NIAID staff listed in Section VII. Agency Contacts for questions concerning the classification of the proposed clinical trial.

For the purposes of this FOA, 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; and
• preparation of the final study report; and other related post-enrollment activities.

Each NIAID Clinical Trial Implementation (R01) award will support the implementation of a single clinical trial; applications that include more than one clinical trial will not be reviewed. 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. 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, 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. 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 (Investigational New Drug)/IDE (Investigational Device Exemption) application should be submitted to an appropriate regulatory agency; 2) the entity (NIAID, primary awardee, etc.) who will hold the IND/IDE; and 3) the requirements for the establishment of a DSMB(Data Safety Monitoring Board)/SMC (Safety Monitoring Committee).

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

Delineation of milestones is a key characteristic of the NIAID Clinical Trial Implementation (R01) Grant. 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 R01 clinical trial implementation grants 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

Applications that propose to conduct planning activities are not responsive to this FOA and will not be reviewed. Investigators seeking support for the planning and design of clinical trials should refer to the NIAID Clinical Trial Planning (R34) Grant FOA (PAR-13-150).

NIAID R01 clinical trial implementation grants will NOT support high-risk clinical trials. Investigators seeking support for high-risk clinical trials should refer to the NIAID Clinical Trial Implementation Cooperative Agreement (U01) Grant FOA (PAR-13-151).

NIAID R01 clinical trial research project grants will NOT provide support for clinical trials that fall outside the mission and high-priority research areas of the NIAID and will not support more than one clinical trial in a single application.

Funding Instrument	Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed	New Resubmission Revision The OER Glossary and the SF424 (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	The scope of the proposed project should determine the project period. The maximum period is 5 years.

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
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

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 Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) 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 SF424 (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 that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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

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

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

The letter of intent should be sent to:

Priti Mehrotra, M.Sc, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3G40, MSC 9823
5601 Fishers Lane
Rockville, MD 20892-9823
(For Express Couriers: 20852-9823)
Telephone: 240-669-5066
Email: pm158b@nih.gov

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

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

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

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

Other Attachments: Provide the following information:

1. Clinical Protocol Synopsis

The filename "Clinical Protocol Synopsis.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.

The clinical protocol synopsis 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.

Applications that lack the Clinical Protocol Synopsis are nonresponsive and will not be peer reviewed.

2. Statistical Analysis Plan

The filename "Statistical Analysis Plan.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.

This plan is critical to knowing whether applicants have selected the correct cohort size based on proper power calculations and/or are using the most appropriate methods to analyze the resulting data and make correct conclusions at the end of the study. The ability to make conclusions of primary outcomes other than safety will be particularly important in small studies.

Applications that lack the Statistical Analysis Plan are nonresponsive and will not be peer reviewed.

3. Data and Safety Monitoring (DSM) Plan

The filename "Data and Safety Monitoring Plan.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.

The DSM plan should be commensurate with the risk level of the proposed clinical research ND 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 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; and
• How sites/centers, and participating facilities (labs, pharmacies) will be monitored.

Applications that lack the DSM Plan are nonresponsive and will not be peer reviewed.

4. Milestone Plan and Complete Clinical Protocol

The filename Milestone Plan and Complete Clinical Protocol.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.

Applicants are required to provide detailed project performance and timeline objectives in a section entitled Milestone Plan . This section 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; and
• 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.

Applications that lack the Milestone Plan and/or the Complete Clinical Protocol are nonresponsive and will not be reviewed.

All instructions in the SF424 (R&R) Application Guide must be followed.

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

This FOA uses non-modular budget formats described in the SF 424 Application Guide.

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, 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 (see Letters of Support in the PHS 398 Research Plan below). 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 Financial/Grants Management Contact(s) listed in Section VII. Agency Contacts.

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

A letter that summarizes the discussion during prior consultation with NIAID may be obtained from the appropriate NIAID Division Director and attached as a .pdf file to the PHS398 Cover Letter file.

All instructions in the SF424 (R&R) Application Guide must be followed.

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

Specific Aims: The goals of the trial and the expected outcome(s) should be concisely stated in the Specific Aims section. 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.

Research Strategy: The following three sections comprise the Research Strategy: Significance, Innovation, and Approach.

The Research Strategy 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.
• A description of the plans to implement and monitor Good Clinical Practices (GCP), Good Laboratory Practices (GLP) and Good Manufacturing Practices (GMP), as appropriate.

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.

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 modification:

• 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.

The following additional documents must be included in the Appendix material in the order listed below. Place all documents in a single .pdf file:

• the informed consent form(s) and, if applicable, assent form(s)
• 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 Operations
• a comprehensive Laboratory Plan
• documentation of availability of study agents as well as plans and support for acquisition and administration of study agent(s)
• documentation of cofounding of clinical trials from partners, as appropriate

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

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to 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. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applicants are responsible for viewing their application before the due date 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 SF424 (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(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(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. See Section III of this FOA for information on registration requirements.

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 System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

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

Responsive applications include: an appropriate Clinical Protocol Synopsis, Statistical Analysis Plan, Data Safety and Monitoring Plan, Milestone Plan and Complete Clinical Protocol, Informed consent, and if applicable, assent forms, Comprehensive laboratory plan and Table of Contents for the Manual of Operations. Applications that omit any of these components will be considered non-responsive and will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 10 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Consultation with NIAID staff at least 10 weeks prior to the application due date is strongly encouraged for submission of the NIAID Clinical Trial Implementation (U01) Cooperative Agreement application, including new and resubmission applications. If requested, NIAID staff will consider whether the proposed clinical trial meets the goals and mission of the Institute, whether it addresses one or more high priority research areas, and whether it is appropriate to conduct as an investigator-initiated clinical trial. NIAID staff will not evaluate the technical and scientific merit of the proposed trial; technical and scientific merit will be determined during peer review using the review criteria indicated in this FOA. NIAID staff members are also available to work with potential applicants to determine the risk level of the proposed trial and delineate all documentation that will be needed at the time of application submission. During the consultation phase, if the proposed trial does not meet NIAID’s programmatic needs or is not appropriate as an investigator-initiated clinical trial, applicants will be strongly encouraged to consider other Funding Opportunities. NIAID reserves the right to provide support for clinical trials through other available mechanisms supported by NIAID. If NIAID ascertains that substantial additional planning may be necessary, or that substantial staff involvement may not be necessary, the applicant will be encouraged to consider funding applying for under the Clinical Trial Planning Grant (R34) (PAR-13-150) or the Clinical Trial Implementation Cooperative Agreement (U01) FOA (PAR-13-151), respectively.

A letter that summarizes the discussion during prior consultation 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-13-030.

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 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(s)/PI(s), 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 expertise and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For multicenter trials, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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? If applicable, does the proposed multi-disciplinary trial leverage accelerated vaccine, adjuvant, therapeutic, immunotherapeutic, or diagnostics product development, innovatively?

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? Does the application adequately address the following: the intervention, study agent(s), mode of delivery; ancillary therapies and plans for acquisition and handling of study agent(s)? Does the application adequately address all aspects of proposed clinical trial, e.g., the study population, inclusion/exclusion criteria, plans for recruitment outreach, enrollment, retention, informed consent or assent form, differences in the intervention effect due to sex/gender and race/ethnicity as applicable and primary and secondary endpoints? Are potential ethical issues adequately addressed? Are proposed mechanistic studies feasible and would they contribute to the understanding of the disease or treatment? Does the application adequately address the statistical hypothesis and analysis including sample size and power calculation? Are the proposed milestones and timelines appropriate? 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?

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?

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, as needed? Is there an available pool of the eligible volunteers as trial participants? 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 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 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 will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Allergy and Infectious Diseases in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group 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 score.
• Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the 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. 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; IRB or Ethical Committee approval of the final protocol and the informed consent form (and assent form if applicable); and other necessary approvals (e.g., Institutional biosafety committee) of the final protocol, as applicable.

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’s 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, SAM 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

Not Applicable

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) 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.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Phone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
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

Ellen Goldmuntz, M.D., Ph.D.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: (240) 627-3502
Email: egoldmuntz@niaid.nih.gov

Mr. Martin Gutierrez
Division of Acquired Immunodeficiency Syndrome
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: (240) 292-4844
Email: mgutierrez@niaid.nih.gov

Shy Shorer, M.D.
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: (240) 627-3371
E-mail: ss932c@nih.gov

Priti Mehrotra, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5066
Email: pm158b@nih.gov

Ms. Laura Eisenman
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2962
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.