It is critical that applicants follow the Research (R) 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

Atopic Dermatitis (AD) is a chronic inflammatory pruritic skin disease that affects 12% of children under 18 years of age in the United States. AD is associated with defective skin barrier function as well as with several cutaneous immune abnormalities including type 2 inflammation, decreased expression of antimicrobial peptides, and low numbers of plasmacytoid dendritic cells. These abnormalities, several of which have been previously identified by the Atopic Dermatitis Research Network (ADRN), appear to translate into cutaneous defense defects as patients with AD are more susceptible to certain viral (e.g., Herpes simplex) and bacterial (e.g., Staphylococcus aureus) infections. A major viral complication in patients with AD is eczema vaccinatum, which is associated with the administration of smallpox vaccine.

The extent of and the mechanisms responsible for the apparent defects in cutaneous host defense, seen in AD patients are not fully defined and therefore, effective therapies to reverse these defects are absent. Beyond its effects on cutaneous defenses, AD is associated with systemic inflammation and appears to be the first step in the development of other atopic conditions including food allergy and asthma.

AD is recognized as a research need by the NIAID Strategic Plan for Biodefense Research. In its 3 iterations, the ADRN has carefully examined various aspects of the cutaneous immune system in patients with atopic dermatitis and healthy individuals and has identified at least 3 instances where a specific AD patient group has diminished host defense compared to another: (a) patients with severe versus moderate or mild atopic dermatitis; (b) patients with atopic dermatitis and a history of eczema herpeticum versus patients with no history of this condition; and (c) individuals with genetic filaggrin-deficiency versus no deficiency in filaggrin. In addition to identifying these groups of atopic dermatitis patients who are at risk for complications from various infectious processes, the ADRN has generated pivotal knowledge on the structure and function of the skin including abnormalities of the skin barrier, the generation of anti-microbial peptides, the skin s lipidomic profile and its susceptibility to Staphylococcus aureus (S. aureus) colonization.

The ADRN aims at further improving our understanding of the defense mechanisms of the skin by focusing on differences in skin structure/function and immune responses between patients with AD and healthy individuals, or disease controls. Specifically, research areas to be pursued by the ADRN-LC investigators may include, but are not limited to:

• Evaluating the immune and skin barrier impairments leading to cutaneous viral (e.g., Herpes simplex) and bacterial (e.g., S. aureus) infections.
• Evaluating the role of the skin microbiome in host defense, including the effects of microbiome perturbations on cutaneous immunity, and the effects of targeted biologic treatments on the skin microbiome.
• Evaluating the role of proteins in both the stratum corneum and the tight junctions, as well as the role of cutaneous lipids in host defense and in the chronic inflammatory aspects of AD.
• Studying the genetic and epigenetic basis of the cutaneous host defense abnormalities and the chronic inflammatory aspects of AD in children and adults.
• Comparing immune responses to cutaneous pathogens in AD versus other chronic or inflammatory skin conditions, such as psoriasis or ichthyosis.
• Developing and validating sample-sparing assays and non-invasive methods to study cutaneous immunity in infancy.
• Characterizing the cutaneous microbiome in infancy.
• Designing and conducting clinical trials to prevent or improve AD and its chronic consequences on skin function and defenses in adults or children, as well as on the progression of atopic diseases in children.
• Designing and conducting observational clinical studies to assess AD phenotypes/endotypes.

The ADRN will consist of two distinct entities that will operate as a single network: the ADRN Leadership Center (ADRN-LC) and the ADRN Clinical Research Centers (ADRN-CRCs).

ADRN-LC

The objectives of the ADRN-LC are to provide scientific strategy and organizational support to the ADRN for the conduct of state-of-the-art clinical research in AD. The ADRN-LC will have the overall responsibility for the funding and organization of the network-wide clinical research projects. Under the leadership of the ADRN-LC, the ADRN-CRCs will conduct the network-wide ADRN clinical research projects. Clinical trial/study participants will only be seen at an ADRN-CRC. The ADRN-LC must propose 3 clinical research projects that include at least 1 clinical trial. The proposed projects should include mechanistic research using biologic samples or other materials derived from the ADRN clinical projects. To accomplish mechanistic research objectives, the ADRN-LC may have responsibilities spread between more than one institution.

Note: It is anticipated that at least two network-wide ADRN clinical projects will be implemented during the course of the awards. At least one project will be a clinical trial, while the second project may be either a clinical trial or a clinical study. The clinical projects to be implemented will be chosen by the ADRN-LC PD(s)/PI(s) from projects proposed by the ADRN-LC or by the ADRN Steering Committee based on scientific advances made during the grant period.

The ADRN will participate in the Systems Biology of Early Atopy Birth Cohort study that is under development by the Consortium for Food Allergy Research (CoFAR). The ADRN-LC PI/PD(s) will participate in the cohort's steering committee. NIAID will inform the ADRN-CRCs after award if they will participate as clinical sites in the cohort study.

Applications proposing any of the following topics will be deemed non-responsive and will not be reviewed.

• Research on HIV/AIDS.
• Phase III, IV or V clinical trials.
• Clinical studies or clinical trials performed at a Foreign site.

Note: Foreign Components may only provide services in support of Clinical Study or Clinical Trial activities (e.g. conduct of laboratory assays). Foreign Components must not conduct Clinical Trials or Clinical Studies.

The following resources will be provided by NIAID to the ADRN-LCs:

NIAID-DAIT Statistical and Clinical Coordinating Center (SACCC): The SACCC will provide a broad range of clinical research support services, including support for the design and organization of every ADRN network-wide protocol, development of protocol-related materials, data collection, management and quality control, clinical site monitoring, safety monitoring and reporting, data analysis and manuscript development.

Clinical Trial Sponsorship: NIAID will be the Sponsor for all network-wide clinical trials and may choose to be the Sponsor for ADRN-CRC clinical trials conducted under Investigational New Drug (IND) Applications.

NIAID-appointed Asthma and Allergy Data and Safety Monitoring Board (DSMB): All ADRN network-wide clinical trials and ADRN-CRC center-specific clinical trials (and clinical studies if deemed necessary) will be reviewed by DSMB provided by NIAID. After study initiation, the DSMB will conduct periodic safety reviews.

Public Access: NIAID will provide for public access, either through ImmPort

or through another NIAID-approved resource. All network-wide clinical trial, clinical study, biomarker and mechanistic data produced by the ADRN and all ADRN-CRC center-specific research projects that will be supported by the SACCC, will be made publicly available by NIAID through the SACCC.

The ADRN Steering Committee will be the forum for the ADRN to discuss network-wide ADRN studies and to advise the ADRN-LC PD(s)/PI(s) on scientific and organizational aspects of the network's activities. The Steering Committee will also receive information and discuss the progress of individual ADRN-CRC center-specific research projects, but it will not be involved in the development or implementation of these projects.

Leadership Center Administration. This section will have the responsibility for the administrative oversight, staffing and fiscal management of the ADRN-LC. In addition, the Leadership Center Administration will be responsible for establishing ADRN-LC governance and maintaining the ADRN-Steering Committee or other committees that the network will establish.

Clinical Operations. This section will have the overall responsibility of organizing, administering and funding the network-wide clinical projects, which includes development, implementation and management. The Clinical Operations will disburse protocol-specific funds to the ADRN-CRCs participating in the network-wide clinical projects. The ADRN-LC will provide a biorepository for all biologic samples collected in the course of the ADRN network-wide clinical projects.

Clinical Research Projects: Each application must propose 3 independent network-wide ADRN clinical research projects that address more than 1 research area. It is anticipated that the network-wide ADRN projects proposed will utilize all of the ADRN-CRC sites.

ADRN Protocol Funds

Additional protocol funds will be disbursed by the ADRN-LC to the ADRN-CRC sites participating in network-wide clinical research projects.

For more information see the NIAID Research Funding site Questions and Answers for RFA-AI-19-014 found at the following:

https://www.niaid.nih.gov/grants-contracts/questions-answers-rfa-ai-19-014

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not 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) 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 to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. 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. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. 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.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Applicants may submit to both the ADRN-LC (RFA-AI-19-014) and ADRN-CRC (RFA-AI-19-015) funding opportunities. However, different clinical projects must be proposed in each of the two applications.

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) 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.

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:

Louis Rosenthal, Ph.D.
Telephone: 240-669-5070
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the additional following instructions:

The Research Strategy must consist of the following sub-sections with the indicated page limits:

Subsection A: ADRN Overview-one required-12 pages

Subsection B: ADRN Leadership Center Administration- one required-12 pages

Subsection C: ADRN Clinical Operations-one required-12 pages

Subsection D: ADRN Clinical Research Projects- three required-12 pages each

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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:

• Provide a PDF file with the name Staffing Plan . This section should contain a staffing plan for the network-wide clinical projects that are proposed by the LC and executed by the CRCs. The staffing plan should indicate the qualifications and expertise in the field of AD research that will be required for each position. Positions may include: coordinators for network-wide activities such as day-to-day administration, central IRB activities, project specific training for staff or laboratory support of mechanistic research studies. Do not name individuals or sites.

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

• If applicable, in the bio-sketch describe the experience and ability of the investigator and key personnel to prepare an IND/IDE application.

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

Include funds for the following:

• For single PD/PI applications, the PD/PI must commit an overall minimum of 3 person-months for ADRN-LC activities. For multi-PD/PI applications, one of the PD(s)/PI(s) must commit a minimum of 3 person-months for ADRN-LC activities.
• Clinical Operations personnel, single IRB costs, biorepository costs and Leadership Center administration personnel and operating costs.
• Travel and other expenses for ADRN-LC Senior/Key Personnel to attend two (2) one and a half (1.5) day ADRN Steering Committee meetings per year in the Rockville, Maryland area
• Funds for the support of ADRN's participation in the Systems Biology of Early Atopy Birth Cohort study ($500K).
• Additional funds as needed for specific network-wide clinical research projects.
• Funds for the purchase of the pharmacologic, biologic or device-based intervention in a clinical trial (if applicable).
• Budget justification to support Protocol Funds for the 4 ADRN-CRCs to conduct 2 network-wide clinical research projects. Protocol funds include (but are not limited to) the following protocol specific expenses.
• Salary for additional staff beyond core staff at CRC.
• Protocol-specific participant screening and recruitment.
• Study participant retention.
• Protocol required tests and evaluations.
• Study participant reimbursement.
• Equipment and supplies necessary to conduct the clinical trials or clinical study.
• Shipping costs for biosamples from the ADRN-CRC sites to the ADRN biorepository and from the biorepository to mechanistic laboratories.
• Funds for mechanistic research associated with every network-wide clinical research project.

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:

Specific Aims: List the overarching long-range goals and objectives of the ADRN including the administration and operations as well as of the proposed network-wide clinical projects.

Research Strategy: The Research Strategy consists of the following subsections:

Subsection A: ADRN Overview

Provide an overview of the proposed scientific strategy and vision of ADRN.

• Describe and discuss the scientific goals of the network in the context of recent studies, current knowledge in the field of AD, and the objectives of this FOA. Present a strategy that either builds on previous research in the field or stems from novel, but well justified concepts.
• Include data pertinent to the development of the overall research agenda and scientific goals.
• Discuss the rationale of each proposed network-wide clinical project as it relates to the ADRN overall research agenda and how each clinical project might inform future studies.
• Discuss concepts for potential future studies that may emerge as a result of the findings of each of the proposed clinical projects. Emphasize innovative elements included in the proposed projects, both in terms of novel interventions, as well as novel study designs (for example, with incorporation of adaptive designs).
• Provide a table or graphic representation of an overall, combined timeline including at least 2 of the proposed network-wide clinical projects. Note for specific studies, a Study Timeline is included as part of the Study Record: PHS Human Subjects and Clinical Trials Information.
• Discuss policies and procedures for the operation of the ADRN.

Subsection B: ADRN Leadership Center Administration

• Describe the administrative structure of the ADRN-LC as it pertains to communications among its investigators and between its investigators and staff, and the handling of its finances. Also describe the management of ADRN governance and the ADRN Steering Committee.
• Present a concise organizational chart of the administrative structure of the ADRN Leadership Center Administration. Identify the types of staff associated with each operation.
• Provide a detailed plan of the interactions among investigators and between investigators and the Leadership Center Administrative staff with reference to meetings, teleconferences and other communications. Explain the role of those interactions in the overall functionality of the ADRN.
• Describe the process of establishing consortium agreements.
• Describe plans and procedures for establishing and maintaining the functions of committees responsible for the ADRN governance and management, including the ADRN Steering Committee. In discussing the functions of those committees, propose additional activities such as:
• Developing and implementing policies to ensure the efficient operation and effective management of the functions of the ADRN, including resolution of disputes and differences of opinion within the Steering Committee.
• Developing and implementing policies and procedures for the identification, disclosure, reporting and management of potential and actual conflicts of interest for members of the ADRN-LC, ADRN-CRCs and SACCC.
• Developing and implementing policies and procedures for planning, authorship, preparation, review and final approval of manuscripts resulting from ADRN-supported studies and for submission of manuscripts for publication in peer-reviewed journals.
• Developing and implementing policies and procedures for publicizing the accomplishments and the data resulting from ADRN studies to the scientific and lay communities and other relevant audiences. This includes policies for presentations at scientific meetings and for communications with the press.
• Provide a brief plan for leadership succession if the PD/PI is, for any reason, unable to continue as the leader of the program.

Subsection C: ADRN Clinical Operations

Describe the personnel and the procedures and processes that the ADRN-LC will use for the implementation and management of the proposed clinical projects.

• Present a concise organizational chart of Clinical Operations that the ADRN-LC will conduct.
• Identify the types of staff associated with each operation and describe their respective roles and responsibilities.
• Describe plans and procedures (not the scientific rationale) for clinical protocol and other clinical document development and how the ADRN-LC will interact with the ADRN-CRCs and the SACCC.
• Describe the process through which the ADRN-LC will choose appropriate CRCs to conduct a particular network-wide clinical project.
• Discuss in detail plans for management and administration of funds including protocol specific funds and their need, distribution and monitoring. Describe the timing and processes through which the ADRN-LC will disburse protocol specific funds to the ADRN-CRCs and how the use of those funds will be monitored by the ADRN-LC.
• Define the role of the ADRN-LC in the organization and implementation of the network-wide clinical projects including:
• Plans for the development of and adherence to protocol-specific milestones and performance guidelines.
• Professional development plans of ADRN-CRC investigators and staff in accordance with Federal regulatory requirements, Good Clinical Practice (GCP) guidelines and International Conference on Harmonization (IHC) standards. Include professional development plans on: clinical protocol participant screening, recruitment, enrollment and retention; informed consent; assessment and reporting of Adverse Events and Serious Adverse Events; collection of protocol-specific biologic specimens; receipt, storage, packaging, labeling and management of study products; collection, quality control and management of study data; data entry, and creation, maintenance and storage of research records, including Case Report Forms (CRFs), standard operating procedures, manuals of operation, source documents, regulatory files, and subject identification information.

Biorepository:

• Describe the biorepository for the biosamples to be collected during network-wide clinical projects and indicate the rationale for this selection.
• Describe the processes and procedures that the ADRN-LC will use to ensure that collected samples will be forwarded to the biorepository in a safe and expeditious manner.
• Describe the biorepository cataloguing and storing systems and its ability and timeline to provide samples for analysis to mechanistic investigators, at the request of the ADRN-LC.

Subsection D: ADRN Clinical Research Projects

• Discuss the rationale and approach to the selection of the proposed network wide research projects aimed at furthering the understanding of the defense mechanisms of the skin, focusing on differences in skin structure/function and immune responses between patients with AD and healthy individuals, or disease controls.
• Propose three clinical research projects, including at least 1 clinical trial, and discuss the overall significance of the problems being studied, their role in the overall research strategy of the ADRN and the potential impact of the proposed work. For a clinical trial, indicate how the trial will improve the clinical outcome of patients with AD. Describe earlier studies that led to the proposed clinical trial or clinical study and provide the rationale and pertinent information or data from preliminary studies which address the need for and the feasibility of the project. Outline the hypothesis, objective and how the proposed outcomes will adequately address the hypothesis. Concisely describe the design of the proposed network-wide clinical project, include rationale and process for the selection of the patient population, choice of intervention (if applicable), duration and schedule of events. As applicable for research studies include approaches to statistical methodology. Note: Specific details for trials and studies will be captured using the PHS Human Subjects and Clinical Trials Information Form. Do not duplicate information requested under the PHS Human Subjects and Clinical Trials Information.
• Per each project provide a management plan that includes description of the types of personnel involved in conducting the research, personnel involved in data entry and management, pharmacy personnel involved in handling investigational products and personnel involved in processing and handling of biosamples.
• For proposed mechanistic studies, which are required for each of the proposed Clinical Research Projects, describe the rationale and overall thought process for laboratory and biosample selection.

Letter(s) of Support: If investigational drug(s) or device(s) are to be provided by the manufacturer at no cost, provide letter(s) of commitment.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans 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. The PD/PI is expected to make the biological samples, diagnostic products, and other research tools, methods, data, and materials that they develop under ADRN-LC award available to the research community per policies established by the ADRN-Steering Committee. Therefore, the Data Sharing plan should include a summary of how the applicant will achieve this.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

Describe actions to be taken to address problems with recruitment or retention of study participants.

Section 3 - Protection and Monitoring Plans

3.1 Protection of Human Subjects

1 Risks to Human Subjects

a Human Subjects Involvement, Characteristics, and Design

Additional Instructions

For studies involving the use of identifiable human biospecimens collected from independently funded clinical research, applicants should include both historical and current study information that is clearly distinguishable within the same study record when providing the information requested.

b Study Procedures, Materials and Potential Risks

Additional Instructions

For applications proposing to use samples from ongoing or completed clinical research, provide a timeline for the request, transportation and arrival of the biological samples, and the timeline associated with the preparation and use of the biological samples.

• For all research projects provide the following information on:
• Description the type(s) of biosamples to be used
• Description the handling and processing of biosamples at the collection site (collection, processing, storage, transportation and quality control measures to ensure sample integrity)
• List the research laboratory(ies) to be used and describe the selection rationale and qualifications
• Description the laboratory methodology(ies) to be used for each proposed assay/test and provide evidence of assay feasibility

Section 4 - Protocol Synopsis (only available for a study record that proposes a clinical trial)

4.2 Study Design

4.2.a Narrative Study Description

Additional instructions

For multi-visit studies, provide a description of the study design including the procedures and activities that can occur at each visit (schedule of events).)

Section 5.1 - Other Clinical Trial-related Attachments

Describe the plan to obtain required investigational agent(s).

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. 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. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

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 and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

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.

• Awards issued under this FOA will be incrementally funded awards for project periods of up to seven years. Multi-year funded grants will not be awarded.
• Grants awarded under this FOA will be excluded from automatic carryover all carryover requests must be approved.
• Grants awarded under this FOA will not be provided the authority to automatically extend the final budget period one time for up to 12 months beyond the original expiration date shown in the Notice of Award all extensions, including the first extension, will require approval.
• Progress and financial reporting will be required and reviewed annually.
• All funds must be expended within the approved project period.

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 How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

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.

See more tips for avoiding common errors.

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

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

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

Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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). While each application will be evaluated in its entirety based on one overall impact score per application, the ADRN Clinical Research Project within each application will also each receive a separate impact score.

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.

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? 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?

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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?

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, 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 a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Does the application adequately address the following, if applicable?

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Specific to this FOA:

ADRN Overview

• Are the scientific goals of the network presented and justified in the context of recent studies, current knowledge in the field of AD, and the objectives of this FOA?
• Is an overall strategy presented that either builds on previous research in the field or stems from novel, but well justified concepts?
• Are data pertinent to the development of the overall research agenda and the scientific goals of the ADRN presented and of adequate quality?
• Is the rationale of each proposed network-wide clinical project as it relates to the ADRN overall research agenda and how each clinical project might inform future studies sound?
• Are concepts for potential future studies that may emerge as a result of the findings of each of the proposed clinical projects appropriately presented?
• Do the presented policies and procedures for the operation of the ADRN provide assurances that the network can operate efficiently and can conduct its proposed studies?

ADRN Leadership Center Administration

• Does the administrative structure of the ADRN-LC as it pertains to communications among its investigators and between its investigators and staff provide assurances for an efficient operation?
• Are the plans for the handling of the ADRN-LC finances in support of sound management?
• Does the organizational chart of the administrative structure of the ADRN-LC administration identify the types of staff associated with each operation and does it support sound operations?
• Is a detailed plan of the interactions among investigators and between investigators and the ADRN-LC administrative staff described with reference to meetings, teleconferences and other communications? Is the role of those interactions in the overall functionality of the ADRN adequately explained and does it support efficiency for the function of the network?
• Is the process of establishing consortium agreements acceptable?
• Do the plans and procedures for establishing and maintaining the functions of committees responsible for the ADRN governance and management, including the ADRN Steering Committee, support sound and efficient network operations?
• Is the plan for development of policies and procedures for resolution of disputes and differences of opinion within the Steering Committee acceptable?
• Is the plan for development of policies and procedures for the identification, disclosure, reporting and management of potential and actual conflicts of interest for members of the ADRN-LC, ADRN-CRCs and SACCC acceptable?
• Is the plan for development of policies and procedures for planning, authorship, preparation, review and final approval of manuscripts resulting from ADRN-supported studies and for submission of manuscripts for publication in peer-reviewed journals acceptable?
• Is the plan for development of policies and procedures for publicizing the accomplishments and the data resulting from ADRN studies to the scientific and lay communities and other relevant audiences acceptable?
• Is the plan for leadership succession if the PD/PI is, for any reason, unable to continue as the leader of the program acceptable?

ADRN Clinical Operations

• Is the organizational chart of Clinical Operations chart well-thought and appropriate for the function of the network?
• Are the types of staff associated with each operation and their respective roles and responsibilities well described and is the staffing appropriate with respect to expertise and time commitment?
• Are plans and procedures for clinical protocol and other clinical document development well described and will they contribute to an expeditious process for ADRN study implementation?
• Are plans and procedures on how the ADRN-LC will interact with the ADRN-CRCs and the SACCC well described and are they appropriate for an effective network function?
• Is the process through which the ADRN-LC will choose appropriate CRCs to conduct a particular network-wide clinical project appropriate?
• Are the processes through which the ADRN-LC will determine protocol-specific funds and how those funds will be distributed and monitored appropriate?
• Is the role of the ADRN-LC in the organization and implementation of the network-wide clinical projects that the ADRN will conduct adequately discussed and does the application include appropriate description of:
• The development of and adherence to protocol-specific milestones and performance guidelines?
• Professional development plans for ADRN-CRC investigators and staff in accordance with Federal regulatory requirements, Good Clinical Practice (GCP) guidelines and International Conference on Harmonization (IHC) standards?
• Actions to be taken to address problems with recruitment or retention of study participants?
• How problems with study conduct and compliance with Federal regulatory requirements and ICH E6 (R2) guidelines will be addressed?
• Has a biorepository for the biosamples to be collected during network-wide clinical projects been adequately described and is the rationale for this selection sound?
• Are processes and procedures to ensure that biosamples will be collected, shipped and stored in a manner that will ensure suitability and availability for the mechanistic studies appropriate?

ADRN Clinical Research Projects

• For studies focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this study needed to advance scientific understanding in the field of atopic dermatitis?
• Does the application adequately discuss the overall significance of the problems being studied, their role in the overall research strategy of the ADRN and the potential impact of the proposed work?
• For a clinical trial, does the application adequately discuss how the trial will improve the clinical outcome of patients with AD?
• For each clinical project, do earlier studies that led to the proposed project or data from preliminary studies adequately provide rationale and pertinent information to address the need for and the feasibility of the project?
• For each clinical project, is the hypothesis appropriately outlined and do the proposed outcomes adequately address the hypothesis?
• For each clinical project, are the rationale and process for the selection of the patient population, the choice of intervention (if applicable), and the study duration adequately justified?
• Are management plans provided that include adequate description of the types of personnel involved in conducting the research, personnel involved in data entry and management, pharmacy personnel involved in handling investigational products and personnel involved in processing and handling of biosamples?
• For proposed mechanistic studies, within each clinical research project, is the rationale appropriate and will the mechanistic study contribute to the value of the clinical project?
• Are the proposed mechanistic study assays established and feasible, considering the multi-center nature of the network-wide clinical research projects?
• Is there a clear description of the source and quantity of biosamples to be obtained, and potential safety and ethical issues in obtaining such samples (for example, blood drawing volume limitations)?
• For each clinical project, is the summary of the statistical analysis plan and of sample size calculations with description of statistical power adequate and the sample size justified?
• For each clinical project, if applicable, is there a plan to obtain required study agent(s) including evidence of commitment by a manufacturer to provide an investigational drug if part of the plan?
• For each clinical project, does the application discuss anticipated problems and propose approaches to overcome or minimize such problems?

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.

Study Timeline

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

For research that involves human subjects but does not involve one of the 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 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 Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Not Applicable

Not Applicable

Not Applicable

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.

Not Applicable

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).

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) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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 Infection 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.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned 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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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’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 terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 Part 75, 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:

Determining and coordinating the scientific and administrative activities of the network-wide clinical research projects; setting project goals and timelines; accepting and implementing common guidelines proposed by the Steering Committee.

The PD(s)/PI(s) working within the ADRN-LC structure and with other ADRN-LC staff will carry out the following functions:

• Developing, implementing and managing a process for allocating ADRN-LC resources for approved studies, including a plan to recommend reallocation of funds to achieve the scientific goals of the ADRN.
• Establishing and operating the ADRN Steering Committee.
• Establishing and implementing ADRN policies and procedures.

Protocol Development, Review and Approval

• The ADRN-LC PD(s)/PI(s) will provide all clinical research protocols to NIAID for review and will not implement a protocol until all NIAID approvals are obtained and a NIAID DAIT study initiation notification has been provided.

Data Sharing Responsibilities

• Awardees are expected to make the biological samples, diagnostic products, and other research tools, methods, data, and materials that they develop under ADRN-LC award available to the research community, per policies established by the ADRN-Steering Committee and consistent with achieving the goals of the program. Informed consent/assent forms utilized in ADRN-LC supported clinical trials or studies should reflect this commitment.
• To promote rapid public access to ADRN-supported data, all ADRN-LC investigators are expected to share their ADRN-supported data publicly through ImmPort (https://immport.niaid.nih.gov) or other public portals designated by NIAID and consistent with achieving the goals of the program. The privacy of participants will be safeguarded, and confidential and proprietary information will be protected. The PDs/PIs are responsible for developing data sharing plans to be presented to the NIAID Program Official assigned to the grant for approval. Sharing plans represent a commitment by the awardees to support and abide by the plan. The PD(s)/PI(s) will establish procedures to ensure that all members of ADRN-LC and associated scientists conform to the data-sharing plan.

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

NIAID Project Scientists will provide guidance and support in the design of research activities, will serve as a resource for protocol design and development, will provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, will advise in the selection of sources or resources, and will advise in management and technical performance. In ADRN-LC network-wide clinical research projects that include clinical trials and, in some cases, clinical studies, an NIAID-assigned Project Scientist will also have Medical Monitor responsibilities.

Two NIAID Project Scientists will be non-voting members of the Steering Committee and participate in all Steering Committee activities, including conference calls, subcommittees and special committees. It is anticipated that decisions in all activities will be reached by consensus and that the NIAID Project Scientists will participate in this process.

Protocol Review and Approval

All clinical research protocols will be reviewed by NIAID and, depending on their level of complexity and risk, will be further reviewed by the NIAID DAIT Clinical Research Committee and by the NIAID DAIT Data and Safety Monitoring Board (DSMB) or another monitoring body.

IND/IDE

NIAID will serve as the IND/IDE sponsor for all ADRN network-wide clinical trials requiring an IND/IDE. As part of NIAID’s IND/IDE sponsor responsibilities, the NIAID Medical Monitor will obtain, through the SACCC, regular reports on adverse events and protocol deviations and will review all serious adverse events. NIAID will be responsible for reporting safety information in accordance with FDA requirements. Also, NIAID, in cooperation with the SACCC, will prepare and submit the final study reports to the FDA. This role may be delegated by NIAID to another entity (e.g., a collaborating pharmaceutical company).

Clinical Trial Monitoring

NIAID will monitor compliance with good clinical practices, regulatory compliance, accurate protocol implementation, internal quality assurance, and test agent accountability at the ADRN-CRCs. At NIAID s discretion, the NIAID Medical Monitor may request that the DSMB convenes ad hoc to review a serious adverse event or a cluster of adverse events or serious adverse events. The NIAID Medical Monitor may request that the SACCC conduct for-cause monitoring visits to an ADRN-CRC. Depending on the seriousness of the problem, such visits may be conducted by the NIAID Medical Monitor and/or NIAID staff. The PD/PI of the ADRN-LC may be asked to participate in those visits.

Study Termination

NIAID reserves the right to terminate or curtail a clinical study or clinical trial for any of the following reasons:

• risk to subject safety;
• occurrence of unforeseen safety issues or emerging data indicating a presence of unanticipated toxicity;
• risks that cannot be adequately quantified;
• the scientific question is no longer relevant, or the objectives will not be met;
• failure to comply with cGCP, federal regulations, or Terms and Conditions of Award;
• failure to remedy deficiencies identified through site monitoring;
• substandard data;
• inadequate progress in fulfilling the research agenda;
• slow accrual;
• reaching a major study endpoint substantially before schedule with persuasive statistical significance

Access to Data

The NIAID Project Scientist or designee will have access to all data generated under this cooperative agreement and may review the data as recorded on the case report forms or in a database. Data must be available for external checking against the original source documentation. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the study.

Coordination with Outside Entities

In the occasion a company provides investigational materials for an ADRN study, NIAID will be responsible for entering into Clinical Trial Agreements with that company.

External Scientific Advisory Group (ESAG)

NIAID will establish an ESAG composed of clinical and basic science investigators. Members of the ESAG will review and offer input on ADRN network-wide clinical projects, both during protocol development and during the analysis of results. ESAG members may be invited to attend some ADRN Steering Committee meetings. The ESAG will submit its recommendations to the NIAID Project Scientists, who will then inform the ADRN-LC PD(s)/PI(s). Recommendations by the ESAG are advisory.

Areas of Joint Responsibility include:

Research Plans

Implementing, monitoring, and updating the clinical research agenda for ADRN to ensure consistency and relevance with the NIAID scientific priorities.

Protocol Development

The ADRN-LC PD(s)/PI(s) will fully develop the clinical research protocols for the projects supported by this FOA with the participation of the ADRN Steering Committee, SACCC and the NIAID Division of Allergy, Immunology, and Transplantation (DAIT) staff. ADRN-LC protocols will utilize the protocol templates provided by NIAID.

Research Activities

Reviewing the ADRN-LC's research activities and goals on an agreed upon schedule (but no less than once every year). Promoting, evaluating and executing opportunities to collaborate with other federal or non-federal research sponsors.

ADRN Steering Committee

The purpose of this committee is to advise the ADRN-LC PD(s)/PI(s) on the network-wide clinical projects to be conducted, approve the final clinical trial and study protocols and modify or add protocols as scientifically indicated. The overall ADRN scientific plan will be reviewed and updated yearly. In addition, the Steering Committee will develop and implement policies and procedures for publicizing the accomplishments and the data resulting from ADRN studies to the scientific and lay communities and other relevant audiences. The ADRN Steering Committee will include the PD(s)/PI(s) of the ADRN-LC (who will also serve as the Chairperson), a PD/PI from each of the ADRN-CRCs the designated Project Leader of the SACCC, and 2 NIAID Project Scientists. All members of the Steering Committee are voting members with the exception of the NIAID Project Scientists. If one individual is the same PD/PI for both an ADRN-CRC and the ADRN-LC, s/he will have only one vote.

Network-wide Clinical Study Implementation and Management

• The PD(s)/PI(s) of the ADRN-LC will work in coordination with the SACCC, through NIAID, to execute the following tasks related to network-wide ADRN clinical research projects:
• Establish and implement policies and procedures for study management and continuous oversight to ensure adequate rates of human subject recruitment, timely and accurate data collection, and completion of all studies. This will include compliance with clinical site and study monitoring functions carried out by the SACCC for: (i) site initiation visits; (ii) routine monitoring visits to the clinical study sites and the mechanistic sites on a protocol-specific basis; and (iii) specialized site visits, when deemed necessary (e.g., research pharmacy and laboratory operations and compliance with protocol-specific requirements, for cause or remedial site visits). This will also include PD(s)/PI(s) compliance with the NIAID-designated Medical Monitor-approved corrective/remedial actions resulting from clinical site and study monitoring activities.
• Establish and implement policies and procedures for the preparation and submission of AE and SAE Reports to the SACCC for initial review and assessment, followed by final assessment and classification by the NIAID-designated Medical Monitor.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, 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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Michael Minnicozzi, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3532
Email: [email protected]

Louis Rosenthal, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5070
Email: [email protected]

Jordan A. Kindbom
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2983
Email: [email protected]

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 Part 75.