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

A. Background

The FDA Office of Orphan Products Development (OOPD) was created to identify and promote the development of orphan products. Orphan products are drugs, biologics, medical devices, and medical foods that are indicated for a rare disease or condition. The term rare disease or condition is defined in 21 U.S.C. 360ee. The "Accelerating Access to Critical Therapies for ALS Act" (ACT for ALS) was enacted on December 23, 2021 which established the FDA Rare Neurodegenerative Disease Grant Program. The FDA Rare Neurodegenerative Disease Grant Program is administered by OOPD. The Act allows the FDA to award grants and contracts to public and private entities to cover costs of research and development of interventions intended to prevent, diagnose, mitigate, treat or cure amyotrophic lateral sclerosis (ALS) and other rare neurodegenerative diseases in adults and children. Such costs include, for example, those incurred with respect to development and critical evaluation of tools, methods, and processes to increase efficiency and productivity of medical product development.

ALS is a neurodegenerative disease that damages and eventually destroys motor nerve cells, leading to a wide range of symptoms. Initially, one of the most common symptoms associated with ALS is muscle weakness, characterized by progressive and impaired muscle function, including those involved in speech. Traditionally, augmentative and alternative communication strategies (AAC) have been utilized by patients with ALS. Brain computer interface (BCI) devices are a type of AAC device that may have the potential to provide improved motor and communication capabilities for ALS patients and have the potential to allow patients to interact with and control their environment. BCIs directly access and interpret neural data from the brain to determine what a patient wants to communicate and provide that information to others. BCI devices may be non-invasive, such as those that use electroencephalogram (EEG) electrodes on the scalp, or invasive that involve implanted electrodes in or near the brain. Communication BCIs (cBCIs) may accomplish their function through computer cursor control and keyboard/text-based interfaces, decoding attempted handwriting, direct speech decoding, or a variety of other digital communication approaches.

Being able to assess the effectiveness of new medical devices such as cBCIs is integral to medical device development and innovation for people living with ALS. Clinical outcome assessments (COAs) describe or reflect how a person feels, functions, or survives and can be reported by a health care provider, a patient, a non-clinical observer (such as a parent), or through performance of an activity or task. COAs may be a single measure or comprised of multiple measures. Measurement examples include:

1. performance outcomes (PerfOs) which are measurements collected when a patient is asked to complete a well-defined, repeatable, and standardized task, such as reading an eye chart or walking as far as possible in 6 minutes

2. patient-reported outcomes (PROs) which are reports of a patient’s health status or functioning provided directly by the patient without interpretation by anyone else and may be collected via scientifically developed and validated surveys, questionnaires, rating scales, or diaries called patient-reported outcome measures (PROMs)

3. clinician-reported outcomes (ClinROs) and observer-reported outcomes (ObsROs) which utilize reports coming from interpretations of signs or observations by health-care professionals and observers such as parents or caregivers, respectively.

Digital health technologies (DHTs) such as wearables may also measure aspects of function, shedding light on patients' daily lives. These COAs, including DHTs, are used to evaluate product effectiveness and inform product development for regulatory decision-making.

There is a need to develop standardized COAs that can be utilized to assess the effectiveness of cBCIs in future clinical trials in ALS patients. COAs such as PerfOs can measure performance characteristics (e.g., comprehension of communication, completion of certain communication tasks) of patients with ALS. However, COAs that measure the functional communication benefits that cBCIs aim to provide are not well-developed. Functional communication refers to the ability to communicate one's feelings, wants, and basic needs effectively. There is a need to identify and develop reliable and valid COAs that assess for cBCIs to enable increased functional communication. This includes the ability to perform activities of daily living (ADLs), to improve patient independence, and to improve subjective quality of life (QOL) for ALS patients and their caregivers. These COAs need to be identified and developed with generalizability and robustness to the home environment so that COAs reflect functional communication in real world settings.

As such, the purpose of this Funding Opportunity Announcement (FOA) is to solicit applications for UH2/UH3 cooperative agreements to support future development of COAs for cBCIs in patients with ALS. The cooperative agreement will consist of two milestone driven phases: (1) the UH2 Phase will include a systematic landscape analysis of the available literature, relevant data sources, and interviews with key opinion leaders (KOLs) to document COAs for cBCIs used clinically and identify gaps between current COAs used in cBCI studies and other outcome measures that could demonstrate functional benefits for ALS patients with severe communication limitations; and (2) the UH3 Phase will consist of patient and caregiver focus groups to collect information about symptoms, functional status, and perceived benefits/risks of cBCIs.

Awards made under this FOA will support the UH2 phase for up to 1 year, and possibly transition after having met the UH2 scientific milestone and feasibility requirements to the UH3 phase for up to 1 additional year. The total award project period will not exceed 2 years. The UH2/UH3 application must be submitted as a single application, and applicants should note specific instructions for each phase in this FOA. The applicant will be required to track short- and long-term goals and objectives and demonstrate how the proposed activities will meet the stated goals. The applicant must demonstrate accessibility to the necessary infrastructure, resources, and collaborations to accomplish the proposed aims. These should be available at the time of application submission. Applicants are encouraged to include diversity (e.g., race, ethnicity, geographic, education, economic status) in their sample populations. It is expected that applicants will include a multi-disciplinary team including clinicians and clinical researchers from relevant fields of neurology, rehabilitation, speech-language pathology, physical and occupational therapy, and neurosurgery among others.

This cooperative agreement will be administered by OOPD in collaboration with the Center for Devices and Radiological Health (CDRH) within the FDA. CDRH assures that patients and providers have timely and continued access to safe, effective, and high-quality medical devices and radiation-emitting products. CDRH facilitates medical device innovation by advancing regulatory science, providing industry with predictable, consistent, transparent, and efficient regulatory pathways, and assuring consumer confidence in devices marketed in the United States.

B. Research Objectives

This project will inform future development of COAs for cBCIs in patients with ALS and will answer the following key research questions:

• What existing measures may be used or adapted to assess the effectiveness of cBCIs?
• What are the strengths and gaps, if any, of existing measures?
• What next steps may be needed to identify and develop COAs for cBCI?

To help answer these questions, this FOA will support a two-phase approach with the following objectives. It is expected that all work product generated through both the UH2 and UH3 phases will be made publicly available by the end of the grant period, at no cost or nominal cost.

UH2 Phase: Landscape Analysis Objectives:

The UH2 Phase will include a systematic landscape analysis of the available literature, relevant data sources, and interviews with key opinion leaders (KOLs). This task is intended to document COAs for cBCIs used clinically and identify gaps between current COAs used in cBCI studies and other outcome measures that could demonstrate functional benefit for ALS patients with severe communication limitations. Support for the UH2 phase may be requested for up to 1 year. UH2 projects that have met the scientific milestones and requirements will be eligible for rapid transition to the UH3 phase, after FDA administrative review. All milestones for the project will be negotiated with FDA and finalized before an award is made.

Applications must include clearly defined and measurable goals and milestones for the UH2 phase. The goals specified will be used to evaluate the success of the UH2 phase. At the completion of the UH2 planning phase, the applicant will be required to submit a detailed transition request for the UH3 phase. To transition to the UH3 phase, applicants must submit a complete package, including any needed protocols, updated terms for intellectual property considerations, including updated letter(s) of support, summary report of findings, analyses of data, identified concepts, and a revised detailed plan outlining work to be conducted under UH3 phase taking into account considerations learned from the UH2 phase. A UH3 transition request will undergo an administrative review by FDA to determine whether UH2 milestones have been met. It may be the case that funded UH2 projects will not transition to the UH3 phase.

Specific goals of the landscape analysis are to:

• Identify and review current COAs for cBCI technologies;
• Identify important concepts of interest to patients and healthcare providers related to functional communication for ALS patients living with severe communication limitations;
• Evaluate strengths and weaknesses of existing outcome measures and areas for future measurement development.

To meet the specific goals of this landscape analysis, the UH2 phase will include two parts as defined below:

1) Literature Review:

This part of the UH2 activities will include a milestone-driven literature review, analysis, and synthesis of available information (such as peer reviewed research literature, grey literature, professional society guidelines, clinical textbooks) to assess COAs for cBCIs and help address the key research questions of interest in this FOA. Part 1 (Literature Review) should be completed within 6 months of award.

The applicant must submit a draft research protocol for the literature review and analysis of the findings as outlined in the Research Plan section below. The awardee will be required to incorporate FDA’s feedback and collaborate with FDA on protocol revisions until a version acceptable to FDA is achieved. The awardee will not proceed to subsequent tasks until agreement on the protocol has been established with FDA.

2) Key Opinion Leader (KOL) Interviews:

In parallel with the literature review, this part of the UH2 Phase will include interviews with KOLs and qualitative analyses of the findings. The KOLs should include those that have experience treating patients with ALS with severe communication impairment or treating patients with ALS who have cBCIs. Part 2 (KOL Interviews) should be completed within 9 months of award.

The applicant must submit a draft research protocol as outlined in the Research Plan section below, including interview guide(s)/script(s), for FDA review. The awardee is required to incorporate FDA’s feedback and collaborate with FDA to revise the protocol until a version that is acceptable to FDA is achieved. The awardee will not proceed to subsequent tasks until agreement on the protocol has been established with FDA.

UH3 Phase: Patient and Caregiver Interviews Objectives:

Prospective applicants should note that funding of UH2/UH3 Phased cooperative agreement does not guarantee support of the UH3 phase. Transition to the UH3 phase will occur only if an FDA administrative review process recommends that the UH2 activities have been successful and the implementation project (UH3) can proceed with confidence of success, and if funds are available.

The UH3 activities of this FOA will consist of patient and caregiver interviews to collect information about symptoms, functional status, and perceived benefits/risks of cBCIs. These "Concept Elicitation Focus Groups" should identify concepts and domains relating to ALS that are meaningful to patients and caregivers. Support for the UH3 phase may be requested for up to one year.

The applicant must provide a draft research protocol as outlined in the Research Plan section below, that includes the guide(s)/script(s) for FDA review. Additional prompts and topics may be identified from the analyses of the UH2 literature review and interviews with KOLs and subsequently added to the protocol prior to initiating this phase. The awardee will be required to incorporate FDA s feedback and collaborate with FDA to revise the protocol until a version that is acceptable to FDA is achieved. The awardee will not proceed to subsequent tasks until agreement on the protocol has been established with FDA.

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

HHS grants policies as described in the HHS 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 FDA 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)

Local 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)
• 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 HHS 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• 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.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; 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 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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for FDA 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.

Multiple PDs/PIs
The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi.

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

Information for the Contact PD/PI should be entered in item 14 of the SF424 (R&R) form. All other PDs/PIs should be listed in the Research & Related Senior/Key Person Profile and assigned the project role of PD/PI. Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the Credential field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected. All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan
For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan [item 7 of the PHS 398 Research Plan] must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

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

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

Applications Involving Multiple Institutions
When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subaward to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget form. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section R.310 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form.

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

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

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

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 FDA staff to estimate the potential review workload and plan the review. No responsiveness decision will be made based on the letter of intent.

By the date(s) 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 study
• Name(s), email 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 via electronic mail as a PDF file with the FOA Number and the Institution's Name in the message subject heading to:

Shashi Malhotra
Grants Management Specialist
Email: [email protected]

and

Katherine Needleman
Director, Orphan Products Grants Program
Email: [email protected]

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

For this specific FOA, the Research Strategy section is limited to 30 pages.

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.

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:

• Applications requesting multiple years of support must complete and submit a separate detailed budget breakdown and narrative justification for each year of financial support requested.
• If an applicant is requesting indirect costs as part of their budget, a copy of the most recent Federal indirect cost rate or F&A agreement must be provided as part of the application submission. This agreement should be attached to the RESEARCH & RELATED Other Project Information Component as line #12 'Other Attachments'.
• If the applicant organization has never established an indirect cost rate and/or does not have a negotiated Federal indirect cost rate agreement, a de minimis indirect cost rate of 10 percent (10%) of modified total direct costs (MTDC) will be allowed. MTDC means all direct salaries and wages, applicable fringe benefits, materials and supplies, services, travel, and subaward and subcontracts up to the first $25,000 of each subaward or subcontract. MTDC excludes equipment, capital expenditures, charges for patient care, rental costs, tuition remission, scholarships and fellowships, participant support costs and the portion of each subaward and subcontract in excess of $25,000.
• Indirect/F&A costs under grants to foreign and international organizations will be funded at a fixed rate of 8 percent of modified total direct costs (MTDC), exclusive of tuition and related fees, direct expenditures for equipment, and subawards in excess of $25,000. (With the exception of the American University of Beirut and the World Health Organization, which are eligible for full F&A cost reimbursement). Awards to domestic organizations with a foreign or international consortium participant may include 8 percent of MTDC, exclusive of tuition and related fees, direct expenditures for equipment, and subawards in excess of $25,000.

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.

To clearly distinguish between the two UH2/UH3 phases, applicants should specify separate UH2 and UH3 information in each subsection (Specific Aims and Research Strategy) of the PHS398 Research Plan as appropriate.

Research Strategy: The following sections should be included under the Research Strategy following the guidelines in Section V. Application Review Information:

1. Rationale

2. Study Design/Approach

3. Investigator(s)

4. Infrastructure and Resources

5. Ability to Advance the Current Field

Within the Research Strategy, applicants should first describe the UH2 Phase and then the UH3 Phase with a clear demarcation between them. It is not necessary to repeat background information or details of methods in the UH3 portion that were provided in the UH2 portion. The UH2 and UH3 Phases must be described in sufficient detail to permit reviewers to assess the proposed work and the strength of the proposed design and methods.

The "Study Design/Approach" Section of the Research Strategy must also include a subsection with the specific heading Milestones for each of the UH2 and UH3 phases. The application must include clearly specified, well-defined milestones, go/no go decision points, and timelines for assessing progress in both the UH2 and UH3 phases (including specific milestones and timeline for progressing from the UH2 to the UH3 Phase). Milestones and the timeline for each UH2/UH3 phase must be provided in a separate heading at the end of the Study Design/Approach section. Please provide detailed quantitative criteria by which milestone achievement will be assessed and a detailed timeline for the anticipated attainment of each milestone and the overall goal. The "Study Design/Approach" section should identify impediments that could require an addendum to the research strategy, milestones, or timeline with a discussion of alternative approaches.

UH2 Phase Part 1: Literature Review:

• Provide an overall plan for identifying, reviewing, analyzing, and synthesizing available information (such as peer-reviewed research literature, grey literature, professional society guidances, clinical textbooks) to assess COAs for cBCIs and help address the key research questions of interest in this FOA. It would be expected that through this review, the grantee will provide key information for all identified COAs that may be relevant to cBCI technologies for ALS patients (e.g., constructs covered, the contexts in which the COAs have been used, scoring and performance thresholds, applicability for use in various settings, appropriateness for different ALS populations, whether and how measures have been previously used with ALS patients, evidence of the measure s psychometric properties including reliability, sensitivity to change, and validity).
• The applicant must submit a draft research protocol for the literature review and analysis of the findings as an appendix. The protocol should include the following details: research questions to be answered, list of targeted databases that will be used, time period the review will encompass with rationale, search elements such as search terms/strategy for each question adapted for each target database, inclusion/exclusion criteria, screening criteria, quality assessment tool, outcome measures, timelines, and plans for article selection, data extraction and result compilation.
• Note, the awardee will be required to incorporate FDA s feedback and collaborate with FDA to revise the protocol until a version that is acceptable to FDA is achieved. The awardee will not proceed to subsequent tasks until agreement on the protocol has been established with the FDA.
• Part 1 (Literature Review) should be completed within 6 months of award. Timelines must be provided to exhibit how this will be accomplished.

UH2 Phase Part 2: KOL Interviews:

• Provide an overall plan for conducting interviews with qualified KOLs to learn of gaps between cBCI COAs and demonstration of functional benefits for ALS patients with severe communication limitations, evaluate strengths of existing measures, and inform areas for future measurement development.
• The applicant must submit a draft research protocol, including interview guide(s)/script(s), for the KOL interviews and qualitative analysis as an appendix with the following details:

1. Details about the conduct of the interviews including but not limited to: the number of participants, number of interviews, length of each interview, format and recording of the interview (virtual), and plan for de-identification of transcripts prior to analyses to ensure no personal information is included in any transcripts or submitted documents. The applicant will be required to provide transcripts and recordings to FDA as part of the final report.

2. Screening criteria (inclusion and exclusion criteria) taking into account the makeup of the KOL group ensuring diverse representation of expertise and backgrounds in relation to care of ALS patients, including those with cBCIs.

3. Participant recruitment plan, which should include methods by which eligible participants will be identified, how participants will be contacted (e.g., via phone, electronic communications), and how the research team will be cognizant of any conflicts of interest (COI), such as involvement in the development or testing of medical products under the jurisdiction of FDA.

4. Description of any payment or reimbursement for the KOLs, informed consent, data management, privacy and confidentiality.

5. Qualitative analysis plan for results of the interviews, which shall include but is not limited to coding methodology and analysis software to be used, and method for assessing concept saturation (the point at which no additional relevant concepts are elicited, suggesting that all relevant concepts have been elicited).

6. Experience of interviewers, qualitative methods experts, and data analysis experts.

• Summary of results from the KOL interviews and associated transcript review will be submitted as a report upon completion of this phase. These findings should include a description of the information outlined in the protocol and summary of results including cBCI outcomes and assessments and recommendations for the patient and caregiver interview protocol based on these findings.
• A draft manuscript (suitable for submitting to a peer-reviewed journal) and final report on the results will be expected following completion of the UH2 phase. This report should address common quality criteria for reporting qualitative research and include recommendations on which of the existing outcome measures identified in the literature review are best supported by the evidence to detect changes in patient functioning. If no COAs are adequate assessments of patient functioning, the report should detail the reasons for this determination.
• Note, the awardee will be required to incorporate FDA s feedback and collaborate with FDA to revise the protocol until a version acceptable to FDA is achieved. The awardee will not proceed to subsequent tasks until agreement on the protocol has been established with the FDA.
• Part 2 (KOL Interviews) should be completed within 9 months of the start of the award. Timelines must be provided to demonstrate how this will be accomplished.

UH3 Patient and Caregiver Interviews:

• Provide a plan for patient and caregiver interviews. These "Concept Elicitation Focus Groups" should identify concepts and domains relating to ALS that are meaningful to patients and caregivers. The plan should ensure participant feedback about the symptoms they experience and describe their affects with respect to communication and function. The focus group discussions should collect information about symptoms, functional status, quality of life, and perceived benefits/risks of cBCIs.
• The applicant must submit a draft research protocol, including a semi-structured interview script, as an appendix of the application with the following details:

1. Details about the conduct of the interviews including but not limited to: the number of participants, focus groups, and sites, length of each interview, format of the interview (virtual), how the video or audio will be recorded, and plan for de-identification of the transcripts prior to analyses to ensure no personal information is included in any transcripts or submitted documents. The applicant will be required to provide transcripts and recordings to FDA as part of the final report. It is encouraged that the focus groups should be conducted at least two sites and a total of up to ten (10) focus groups should be planned in order to include a total of at least 30 participants and up to 50 participants.

2. Screening criteria (inclusion and exclusion) taking into account the demographics of the ALS patient community to determine the appropriate demographic make-up of the sample regarding age, gender, socioeconomic status, geographic diversity, race, and ethnicity that will be representative of the U.S. patient population with ALS.

3. Participant recruitment plan, which should include the method by which eligible participants will be identified and how the eligible participants will be contacted (e.g., via phone or electronic communication). The plan should also describe how patients with advanced ALS will be identified and how patients and their caregivers will be included as participants, when necessary, and whether patients with previous or existing cBCI will be recruited. Description of how the research team will be cognizant of other protocols in which participants might be enrolled and actions to be taken if they are enrolled in another protocol should be included.

4. Description of any payment or reimbursement to the participants, informed consent, data management, privacy and confidentiality.

5. Qualitative analysis plan for results of the interviews, which shall include but is not limited to coding methodology, analysis software to be used, and method for assessing concept saturation (the point at which no additional relevant concepts are elicited, suggesting that all relevant concepts have been elicited).

6. Experience of moderators, interviewers, qualitative methods experts, and data analysis experts.

• A draft manuscript (suitable for submitting to a peer-reviewed journal) and final report on the results will be expected following completion of this phase. This report should address common criteria for reporting qualitative research, analyze responses by patients and caregiver status, and provide recommendations for future outcome assessments.
• In addition, a comprehensive final report should describe the background, methodology, all findings from this study (both phases), and a detailed proposal for next steps. The report shall include a full discussion of the scan of available information, interviews with KOLs, focus groups discussions with patients and caregivers, the qualitative analyses, and final recommendations for outcome measures. Full de-identified transcripts from the interviews and focus groups shall be included.
• Note: Additional prompts and topics may be identified and need to be included following the analyses of the UH2 literature review and interviews with KOLs.
• Note: The awardee of the cooperative agreement will be required to incorporate FDA’s feedback and work with FDA to revise the protocol until a version that is acceptable to FDA is achieved. The awardee should not begin the study until agreement on the protocol has been established with the FDA.
• Phase 2 (Patient and Caregiver Interviews) should be completed within 12 months of the start of the phase following adequate completion of Phase 1. Timelines must be provided to demonstrate how this will be accomplished.

Letters of support: Letters of support should not be included as part of the Research Strategy and instead should be uploaded to line 9 on the PHS 398 Research Plan Form.

Letters of support should be included for the following areas:

1) Study Sites and Key Personnel: The leader(s) of the existing clinical research institutions that will conduct the study should describe their site support, including relevant resources and study infrastructure. Letters of support should include any support of additional institutions that will be performing the research. If the proposed key personnel are not current employees of the awarded institution, then a signed commitment letter should be included from such individuals that reflects their intention and willingness to perform in the event the grant is funded.

2) Intellectual Property: (if applicable): Provide a plan for resolving intellectual and material property issues among participating organizations and how data will be shared and managed across institutions. Information can be found in Code of Federal Regulations, Title 2, Part 200.315 (2 CFR 200.315), Intangible Property.

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.

Appendix:

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

Do not use the Appendix to circumvent page limits.

The Appendices should include the following, as appropriate for the proposed study:

• Protocols and Interview Guides: Draft protocols for each phase as described in the Research Strategy section. Draft interview guides/scripts should also be included with the protocol.
• Informed Consents: Consent forms, assent forms, and any other information given to a participant must be provided and must comply with all elements of Human Subject Research per 21 CFR 50.25.

When involving 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.

Study Record: PHS Human Subjects and Clinical Trials Information

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

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

Foreign (non-U.S.) institutions must follow policies described in the HHS Grants Policy Statement, and procedures for foreign institutions.

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.

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, FDA’s electronic system for grants administration. eRA Commons 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. Late applications will not be accepted for this FOA.

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 FDA awards are subject to the terms and conditions, cost principles, and other considerations described in the HHS Grants Policy Statement and 45 CFR 75, currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

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

Additional funding restrictions may be part of the Notice of Award.

Protection of Human Research Subjects

All institutions engaged in human subject research financially supported by HHS must file an assurance of protection for human subjects with the Office of Human Research Protections (OHRP) (45 CFR part 46). See Office of Human Research Protections for guidance on human subject protection issues. Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained.

The requirement to file an assurance applies to both awardee and collaborating performance site institutions. Awardee institutions are automatically considered to be engaged in human subject research whenever they receive a direct HHS award to support such research, even where all activities involving human subjects are carried out by a subcontractor or collaborator. In such cases, the awardee institution bears the responsibility for protecting human subjects under the award.

The awardee institution is also responsible for, among other things, ensuring that all collaborating performance site institutions engaged in the research hold an approved assurance prior to their initiation of the research. No awardee or performance site institution may spend funds on human subject research or enroll subjects without the approved and applicable assurance(s) on file with OHRP. An awardee institution must, therefore, have its own IRB of record and assurance. The IRB of record may be an IRB already being used by one of the performance sites, but it must specifically be registered as the IRB of record with OHRP.

For further information, applicants should review the section on human subjects in the application instructions as posted on the Grants.gov application Web site. The clinical protocol should comply with ICHE6 Good Clinical Practice Consolidated Guidance which sets an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects. All human subject research regulated by FDA is also subject to FDA's regulations regarding the protection of human subjects (21 CFR part 50 and 21 CFR part 56 and Guidance for Institutional Review Boards and Clinical Investigators). Applicants are encouraged to review the regulations, guidance, and information sheets on human subject protection and good clinical practice available at FDA's site on Clinical Trials and Human Subject Protection.

Key Personnel and Human Subject Protection Education

The awardee institution is responsible for ensuring that all key personnel receive appropriate training in their human subject protection responsibilities. Key personnel include all principal investigators, co-investigators, and performance site investigators responsible for the design and conduct of the study. HHS, FDA, and OOPD do not prescribe or endorse any specific education programs. Many institutions have already developed educational programs on the protection of research subjects and have made participation in such programs a requirement for their investigators. Other sources of appropriate instruction might include the online tutorials offered by the Office of Human Subjects Research, NIH at http://ohsr.od.nih.gov/ and by OHRP at https://www.hhs.gov/ohrp/education-and-outreach/index.html.

Within 30 days of the award, the principal investigator should provide a letter to FDA's grants management office that includes the names of the key personnel, the title of the human subjects protection education program completed for each key personnel, and a one-sentence description of the program. This letter should be signed by the principal investigator and cosigned by an institution official and sent to the Grants Management Specialist whose name appears on the official Notice of Grant Award (NGA).

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. 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 form. 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 FDA. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier 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 assigned Grants Management Specialist and responsiveness by components of participating organizations, FDA. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post-submission materials are those submitted after submission of the grant application but prior to objective review. They are not intended to correct oversights or errors discovered after submission of the application. FDA accepts limited information between the time of initial submission of the application and the time of objective review. Applicants must contact the assigned Grants Management Specialist to receive approval, prior to submitting any post submission materials. Acceptance and/or rejection of any post submission materials is at the sole discretion of the FDA. Any inquiries regarding post submission materials should be directed to the assigned Grants Management Specialist.

In unusual circumstances, additional information may be considered, on a case by case basis, for

inclusion in the objective expert panel review, however, the FDA cannot assure inclusion of any

information after the receipt date other than evidence of final IRB approval and FWA or assurance.

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

FDA grants management and program staff will review all applications sent in response to this funding opportunity announcement. To be responsive, an application must be submitted in accordance with the requirements of this notice. Applications found to be non-responsive will receive notice that the application will not be reviewed.

Program Responsiveness Review Criteria

The following criteria will be used to decide whether or not an application is responsive to this RFA.

1. Applications must propose a systematic review including a landscape analysis of the available literature, relevant data sources, and interviews with key opinion leaders (KOLs) and interviews with patient and caregiver focus groups to review current cBCI technologies and identify commonly used COAs in patients with amyotrophic lateral sclerosis (UH2/UH3 cooperative agreement).

2. The requested time must not exceed 2 years.

3. Appropriate documentation is needed including the protocols, interview guides/scripts, and informed consent forms. These should be submitted as appendices to the application.

4. Letters of support regarding study sites and intellectual property are also required.

5. Page limits, font size and margins should comply with the Application Guide, Electronic Submission of Grant Applications. (https://grants.nih.gov/grants/how-to-apply-application-guide.html), with the exceptions noted in the Page Limitations section above for Resubmissions.

6. Additional information may be required upon request after submission of an application to determine responsiveness.

Applicants are strongly encouraged to contact FDA to resolve any questions about criteria before submitting their application. Please direct all questions of a technical or scientific nature to the OOPD program staff and all questions of an administrative or financial nature to the grants management staff (see Agency Contacts in Section VII of this document).

Responsive applications will be reviewed and evaluated for scientific and technical merit by a panel of experts in rare neurodegenerative diseases/regulatory/device development. Consultation with experts in the subject field, including FDA experts, may also occur during this phase of the review. This will help to determine whether the proposed study will provide acceptable data that could contribute to future product development or have a regulatory impact in the field. Funding decisions will be made by the Commissioner of Food and Drugs or his designee. By submitting an application in response to this RFA, applicants understand and agree that members of the objective review panel of experts may be provided access to non-public information contained in the grant application, as necessary for application evaluation and subject to necessary restrictions on the further information disclosure.

A score will be assigned to each application based on the scientific/technical review criteria. The review panel will advise program staff proposal alignment with the goals of this FDA grant program.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to identify existing measures, and strengths and gaps of these measures to assess the effectiveness of cBCIs and inform future development of COAs for cBCI. Consideration of the following review criteria and additional review criteria (as applicable for the project proposed) will be used to assess the application.

Reviewers will consider each of the review criteria below in the determination of scientific merit.

An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, an application with moderate correctable weaknesses in a criterion may still receive a high overall impact score because one or more of the other review criteria are critically important to the research and have significant strengths. The relative importance of strengths and weaknesses, not simply the number of strengths and weaknesses, are considered in developing the overall impact score.

The soundness of rationale in relation to the current understanding of ALS, cBCI, and COAs, and the likelihood the proposal will facilitate future COA and cBCI development for ALS patients.

• Description of the state of existing knowledge.
• Explanation of knowledge gap(s) and critical facilitators and barrier(s) to progress the field that the proposed project will address.
• Explanation of how the proposed study will provide essential data for systematic review and evaluation of COAs for cBCIs for future development in patients with ALS.

The quality and appropriateness of the study design, research methodology, data collection, and data analyses to accomplish the specific aims of the proposed study and its potential to inform future cBCI development for ALS.

• Description of the study including study aims, study design, and how data will be collected, analyzed, and interpreted.
• Description of plans for ensuring data quality including, but not limited, to standardized data collection and analysis, minimization of bias, data entry, data access, data monitoring, data sharing and data dissemination.
• Description of clearly-defined, feasible, and quantifiable milestones with regards to specific goals and accomplishments.
• Description of plans for protecting the rights, safety, and welfare of study participants in compliance with federal law and how data will be collected according to Good Clinical Practice Guidelines.
• Discussion of challenges, potential problems, alternative strategies, and benchmarks for success anticipated to achieve the aims within a stated timeframe.
• Description of the criteria and milestones provided for the UH2 phase that will be utilized in determining milestone completion before proceeding to the UH3 phase.

The qualifications of the Principal Investigator(s) (PIs), collaborators, and other support staff.

• Description of the competence of the PI(s), collaborators, and other support staff in conducting the proposed research, including their academic qualifications, research experiences, productivity, and any special attributes that demonstrates ability to perform, oversee and carry out this project with respect to relevant technical areas.
• Description of the leadership structure, decision-making processes, and planned communication, coordination, and outreach process among research team members.
• If applicable, description of the rationale, leadership approach, governance, and organizational structure for a multi-PD/PI project.

The probability of success of the proposed project given the environment in which the work will be done.

• Description of the study timelines, taking into account start up activities, the applicant's ability to recruit and complete the proposed study within budget, stated milestones, and time limits, including a detailed research and recruitment plan and timeline for implementation of the project upon funding.
• Description of plans and infrastructure to: submit necessary documents for review by FDA prior to proceeding with the protocol/project, meet milestones, and submit progress reports/results at the completion of the grant.
• Description of institutional support, equipment, and other resources, such as with existing research networks, industry, academia and/or patient organizations and resource sharing plans as appropriate.
• Description of any additional funds expected to be contributed by other sources (including by the applicant) to the study prior to FDA grant funding and those to be used during the proposed funding period.

The ability of the project to advance current research towards future COA and cBCI development and foster public availability of any Intellectual Property and data sharing.

• Explanation of how the project will address critical barriers in the field and support future development of COAs in cBCIs for ALS.
• Explanation of plans for data sharing and dissemination following completion of the project. Considerations include innovative methods for data collection and data dissemination for use in further phases of development.
• Explanation of strategy for communication of project goals including publications and presentations.

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

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 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.

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.

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.

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 Objective Review Committee using the stated review criteria.

As part of the objective review, all applications:

• Will receive a written critique.

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

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

• Scientific and technical merit of the proposed project as determined by objective review.
• Availability of funds.
• Ability to start study.
• Relevance of the proposed project to program priorities.

Successful applicants will be notified of additional information that may be required or other actions leading to an award. The decision not to award a grant, or to award a grant at a particular funding level, is discretionary and is not subject to appeal to any FDA or HHS official or board.

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 recipient’s business official.

Recipients must comply with any funding restrictions described in Section IV.5. Funding Restrictions and in the Notice of Award. 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 in the HHS Grants Policy Statement, this FOA, and Notice of Award.

Institutional Review Board or Independent Ethics Committee Approval: For projects that involve Human Subjects and/or Clinical Trials Research, Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in FDA-funded studies, the recipient must provide FDA copies of documents related to all major changes in the status of ongoing protocols.

All FDA grant and cooperative agreement awards include the HHS Grants Policy Statement as part of the NoA.

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

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 FDA grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about FDA's commitment to supporting a safe and respectful work environment, and what FDA's expectations are for institutions and the individuals supported on FDA-funded awards, please see https://www.fda.gov/science-research/about-science-research-fda/fda-sexual-harassment-policy-concerning-extramural-research.
• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/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.

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), FDA 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 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all FDA grants and cooperative agreements.

FDA considers the sharing of research resources developed through FDA-sponsored research an important means to enhance the value and further the advancement of research. When research resources have been developed with FDA funds and the associated research findings published, those findings must be made readily available to the scientific community.

Upon acceptance for publication, scientific researchers must submit the author’s final manuscript of the peer-reviewed scientific publication resulting from research supported in whole or in part with FDA funds to the NIH National Library of Medicine's (NLM) PubMed Central (PMC). FDA defines the author's final manuscript as the final version accepted for journal publication, which includes all modifications from the publishing peer review process. The PMC archive is the designated repository for these manuscripts for use by the public, health care providers, educators, scientists, and FDA. Please see the FDA Public Access Policy.

Termination provisions in 2 CFR 200.340 (a) (1-4) are applicable to awards issued under this Notice of Funding Opportunity.

Additional terms and conditions regarding FDA regulatory and OC programmatic requirements may be part of the Notice of Award.

Reporting Requirements:

All FDA grants require both Financial and Performance reporting.

Financial Reporting:

A. Financial Expenditure Reports

A required Federal Financial Report (FFR) must be submitted annually. All annual FFRs must be submitted electronically using the Payment Management System (PMS). This includes all initial FFRs being prepared for submission and any revised FFRs being submitted or re-submitted to FDA. Paper expenditure/FFR reports will not accepted.

Annual FFRs must be submitted for each budget period no later than 90 days after the end of the calendar quarter in which the budget period ended. The reporting period for an annual FFR will be that of the budget period for the particular grant; however, the actual submission date is based on the calendar quarter. If a grant is under expanded authorities, the grantee must indicate the carryover amount in Section 12. Remarks of the annual FFR.

Performance Progress Reporting:

When multiple years (more than one budget period) are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually as required in the Notice of Award. Annual RPPRs must be submitted using the RPPR module in eRA Commons. The annual RPPR must include a detailed budget. Annual RPPRs are due no later than 60 days prior to the start of the next budget period.

Failure to submit timely reports may affect future funding. Additional Financial and Performance Progress reports may be required for this award. Any additional reporting requirements will be listed under Section IV Special Terms and Condition of the Notice of Award.

Salary Caps:

None of the funds in this award shall be used to pay the salary of an individual at a rate in excess

of the current Executive Level II of the Federal Executive Pay Scale.

Certificates of Confidentiality 42 U.S.C. 241(d)

Awardees are responsible for complying with all requirements to protect the confidentiality of identifiable, sensitive information that is collected or used in biomedical, behavioral, clinical, or other research (including research on mental health and research on the use and effect of alcohol and other psychoactive drugs) funded wholly or in part by the Federal Government. See 42 U.S.C. 241(d). All research funded by FDA, in whole or in part, that is within the scope of these requirements is deemed to be issued a Certificate of Confidentiality through these Terms and Conditions. Certificates issued in this manner will not be issued as a separate document.

Awardees are expected to ensure that any investigator or institution not funded by FDA who receives a copy of identifiable, sensitive information protected by these requirements, understand they are also subject to the requirements of 42 U.S.C. 241(d). Awardees are also responsible for ensuring that any subrecipient that receives funds to carry out part of the FDA award involving a copy of identifiable, sensitive information protected by these requirements understand they are also subject to subsection 42 U.S.C. 241(d).

Acknowledgment of Federal Support:

When issuing statements, press releases, publications, requests for proposal, bid solicitations and other documents --such as tool-kits, resource guides, websites, and presentations (hereafter statements )--describing the projects or programs funded in whole or in part with FDA federal funds, the recipient must clearly state:

1. the percentage and dollar amount of the total costs of the program or project funded with federal money; and,

2. the percentage and dollar amount of the total costs of the project or program funded by non-governmental sources.

When issuing statements resulting from activities supported by FDA financial assistance, the recipient entity must include an acknowledgement of federal assistance using one of the following statements.

If the FDA Grant or Cooperative Agreement is NOT funded with other non-governmental sources:

This [project/publication/program/website, etc.] [is/was] supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award [FAIN] totaling $XX with 100 percent funded by FDA]/HHS. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government.

If the FDA Grant or Cooperative Agreement IS partially funded with other nongovernmental sources:

This [project/publication/program/website, etc.] [is/was] supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award [FAIN] totaling $XX with XX percentage funded by FDA/HHS and $XX amount and XX percentage funded by non-government source(s). The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government.

The federal award total must reflect total costs (direct and indirect) for all authorized funds (including supplements and carryover) for the total competitive segment up to the time of the public statement. Any amendments by the recipient to the acknowledgement statement must be coordinated with FDA. If the recipient plans to issue a press release concerning the outcome of activities supported by FDA financial assistance, it should notify FDA in advance to allow for coordination.

Additional prior approval requirements pertaining to Acknowledgement of Federal Support, publications, press statements, etc. may be required, and if applicable, will be listed under Section IV Special Terms and Condition of the Notice of Award.

Prior Approval:

All prior approval requests must be submitted using the Prior Approval module in eRA Commons. Any requests involving budgetary issues must include a new proposed budget and a narrative justification of the requested changes. If there are any questions regarding the need or requirement for prior approval for any activity or cost, the grantee is to contact the assigned Grants Management Specialist prior to expenditure of funds.

For grant awards not covered under Expanded Authorities, Carryover and No Cost Extension (NCE) requests will require prior approval. All Carryover and NCE requests should be submitted using the Prior Approval module in eRA Commons. ****Please review the section on Expanded Authorities to determine if this award is covered/not covered under Expanded Authorities and whether prior approval is needed for carryover and no cost extension requests.****

The following activities require prior approval from FDA on all awards:

1. Change in Grantee Organization

2. Significant Rebudgeting

3. Change in Scope or Objectives

4. Deviation from Terms and Conditions of Award

5. Change in Key Personnel which includes replacement of the PD/PI or other key personnel as specified on the NoA.

6. Disengagement from the project for more than three months, or a 25 percent reduction in time devoted to the project, by the approved PD/PI. No individual may be committed to more than 100% professional time and effort. In the event that an individual's commitment exceeds 100%, the grantee must make adjustments to reduce effort. For FDA-sponsored projects, significant reductions in effort (i.e., in excess of 25% of the originally proposed level of effort) for the PD/PI and key personnel named on named on this Notice of Award must receive written prior approval from FDA.

Additional prior approval requirements may be required for this award, and if applicable, will be listed under Section IV Special Terms and Condition of the Notice of Award.

Audits and Monitoring:

Audit Requirements:

1. Recipients of Federal funds are subject to annual audit requirements as specified in 45 CFR 75.501 (https://www.ecfr.gov/cgi-bin/retrieveECFR?gp=1&SID=8040c4036b962cc9d75c3638dedce240&ty=HTML&h=L&r=PART&n=pt45.1.75#se45.1.75_1501). Grantees should refer to this regulation for the current annual Federal fund expenditure threshold level which requires audit.

2. Foreign recipients are subject to the same audit requirements as for-profit organizations (specified in 45 CFR 75.501(h) through 75.501(k).

3. For-profit and foreign entities can email their audit reports to [email protected] or mail them to the following address:

U.S. Department of Health and Human Services
Audit Resolution Division, Room 549D
Attention: Robin Aldridge, Director
200 Independence Avenue, SW
Washington, DC 20201

Monitoring:

Recipients are responsible for managing the day-to-day operations of grant-supported activities using their established controls and policies, as long as they are consistent with Federal, DHHS and FDA requirements. However, to fulfill their role in regard to the stewardship of Federal funds, FDA monitors our grants to identify potential problems and areas where technical assistance might be necessary. This active monitoring is accomplished through review of reports and correspondence from the recipient, audit reports, site visits, and other information available to FDA.

1. Desk review: FDA grants monitoring specialists will periodically reach out to recipients to request information for the completion of desk reviews. Requested information may include:

• Policies and procedures
• List of grant expenditures
• Accounting records
• Supporting documents (e.g., invoices, receipts, paystubs, timesheets, contracts, etc.)
• Financial statements
• Audit reports
• Other related documentation

2. Site visits: FDA will conduct site visits when necessary and will notify the recipient with reasonable advance notice of any such visit(s).

3. Foreign entities: All Foreign entities are subject to the same monitoring requirements as domestic entities. Foreign entities covered under immunity Executive Orders will provide supporting documents for monitoring requirements unless such an action is a violation of the Executive Orders. Recipients may discuss with the FDA to come up with an alternate approach to satisfy the award monitoring requirements.

All recipients will make reasonable efforts to resolve issues found, including audit findings. Successful resolutions to issues are important as they are part of the grant performance review. All recipients are responsible for submitting all requested information in an expeditious manner. Failure to submit timely reports and/or respond to inquiries from FDA may affect future funding or enforcement actions, including withholding, or conversion to a reimbursement payment method.

Financial Conflict of Interest (FCOI):

This award is subject to the Financial Conflict of Interest (FCOI) regulation at 42 CFR Part 50 Subpart F.

Closeout Requirements (when applicable):

A Final Research Performance Progress Report (FRPPR), Final Invention Statement HHS-568 (if applicable), Tangible Personal Property Report SF-428 (if applicable), and Statement of Disposition of Equipment (if applicable) must be submitted within 120 days after the expiration date of the project period. All closeout documents must be submitted electronically in eRA Commons.

The Final Federal Financial Report (FFR SF-425), must be submitted in PMS and indicate the exact balance of unobligated funds and may not reflect unliquidated obligations. There must be no discrepancies between the Final FFR expenditure data and FFR cash transaction data in the Payment Management System (PMS). The expended funds reported on the Final FFR must exactly match the disbursements and the charge advances in PMS. It is the recipient's responsibility to reconcile reports submitted to PMS and to the FDA.

Program Income:

The grantee is required to report any Program Income generated during the Project Period of this grant. Except for royalty income generated from patents and inventions, the amount and disposition of Program Income must be identified on lines 10 (l), (m), (n), and (o) of the grantee s Federal Financial Report (FFR) SF-425.

Examples of Program Income include (but are not limited to): fees for services performed during the grant or sub-grant period, proceeds from sale of tangible personal or real property, usage or rental fees, patent or copyright royalties, and proceeds from the sale of products and technology developed under the grant.

Any Program Income generated during the Project Period of this grant by the grantee or sub-grantee will be treated as identified below.

Treatment of Program Income:

Prohibition on certain telecommunications and video surveillance services or equipment:

(a) As described in 2 CFR 200.216, recipients and subrecipients are prohibited to obligate or spend grant funds (to include direct and indirect expenditures as well as cost share and program) to:

(1) Procure or obtain,

(2) Extend or renew a contract to procure or obtain; or

(3) Enter into contract (or extend or renew contract) to procure or obtain equipment, services, or systems that use covered telecommunications equipment or services as a substantial or essential component of any system, or as critical technology as part of any system. As described in Pub. L. 115-232, section 889, covered telecommunications equipment is telecommunications equipment produced by Huawei Technologies Company or ZTE Corporation (or any subsidiary or affiliate of such entities).

i. For the purpose of public safety, security of government facilities, physical security surveillance of critical infrastructure, and other national security purposes, video surveillance and telecommunications equipment produced by Hytera Communications Corporation, Hangzhou Hikvision Digital Technology Company, or Dahua Technology Company (or any subsidiary or affiliate of such entities).

ii. Telecommunications or video surveillance services provided by such entities or using such equipment.

iii. Telecommunications or video surveillance equipment or services produced or provided by an entity that the Secretary of Defense, in consultation with the Director of the National Intelligence or the Director of the Federal Bureau of Investigation, reasonably believes to be an entity owned or controlled by, or otherwise, connected to the government of a covered foreign country.

Other:

This award is subject to the requirements of 2 CFR Part 25 for institutions to maintain an active registration in the System of Award Management (SAM). Should a consortium/subaward be issued under this award, a requirement for active registration in SAM must be included.

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 with cumulative total value greater than $10,000,000 must report and maintain information 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 the Federal Awardee Performance and Integrity Information System (FAPIIS)). Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75.

You must administer your project in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes taking reasonable steps to provide meaningful access to persons with limited English proficiency and providing programs that are accessible to and usable by persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/providerobligations/index.html and https://www.hhs.gov/civil-rights/forindividuals/nondiscrimination/index.html.

• You must take reasonable steps to ensure that your project provides meaningful access to persons with limited English proficiency. For guidance on meeting your legal obligation to take reasonable steps to ensure meaningful access to your programs or activities by limited English proficient individuals, see https://www.hhs.gov/civilrights/for-individuals/special-topics/limited-english-proficiency/fact-sheetguidance/index.html and https://www.lep.gov.
• For information on your specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and taking appropriate steps to provide effective communication, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sexdiscrimination/index.html.
• For guidance on administering your project in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws, see https://www.hhs.gov/conscience/conscienceprotections/index.html and https://www.hhs.gov/conscience/religiousfreedom/index.html.

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 (HHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and FDA 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 FDA programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, FDA's 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and FDA as defined below.

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

Program Steering Committee:

The Program Steering Committee will function as the advisory board for the cooperative agreement. The Program Steering Committee will include one representative from the award and will include FDA Scientific and Program Officer(s). Additional people relevant to the program aims and goals may be invited to attend meetings and participate in working groups by action of the Program Steering Committee or FDA. The Program Steering Committee will meet throughout the entire period of project performance.

Principal Investigator Responsibilities:

The PD(s)/PI(s) will have the primary responsibility for the scientific, technical, or programmatic aspects of the cooperative agreement and for day-to-day management of the project or program. The PD(s)/PI(s) will maintain general oversight for ensuring compliance with the financial and administrative aspects of the award, as well as ensuring that all staff have sufficient clearance and/or background checks to work on this project or program. This individual will work closely with designated officials within the recipient organization to create and maintain necessary documentation, including both technical and administrative reports; prepare justifications; appropriately acknowledge Federal support in publications, announcements, news programs, and other media; and ensure compliance with other Federal and organizational requirements.

Additionally, PD/PIs will:

1. Comply with all special terms and conditions of the grant, including those which state that future funding of the study will depend on recommendations from the OOPD program official. The scope of the recommendations will consider the following: (1) progress based on specific circumstances of the study; and (2) compliance with applicable FDA and HHS regulatory requirements for the trial.

2. Participate in milestone meetings (virtual) and submit meeting summaries and periodic milestone progress reports to FDA program staff in a standard form as agreed upon at the initiation, and by provide additional information as needed.

3. Submit a detailed transition request for the UH3 implementation phase 60 days prior to the year one budget end date, outlining UH2 progress, how negotiated UH2 Milestones have been met, as well as detailed plans, budget and annual milestones for the UH3 implementation phase. Note that, funding of the UH2 phase cooperative agreement does not guarantee support of the UH3 implementation phase.

4. Ensure that the products and materials resulting from FDA’s support are free to the public or made available to the public at nominal cost. PIs should make data publicly available through speaking engagements and publications, presentations at scientific symposia and seminars, while ensuring that confidentiality and privacy of the data is protected. Follow FDA requirements as noted in #8 below.

5. Participate in site visits or grant evaluations (in person or virtual) or attend meetings as requested by the FDA. Make the resources available for grant evaluation or site visits or inspections (in person or virtual) during and/or after the study if requested by FDA.

6. Submit data for quality assessment and/or validation in any manner if requested by FDA.

7. Serve as member of the Program Steering Committee.

8. Note that any publication or oral presentation regarding outcomes of this grant must undergo FDA/OC review and approval process. This process can take 30-90 days. Prior to submission of a manuscript, presentation, or abstract with FDA co-author(s) describing the results for publication, the PI should forward to the FDA a copy of the manuscript, presentation, or abstract to be submitted to review for any potential language that might reference, imply or infer any FDA endorsement of regulatory and/or policy changes related to the project. For publications without an FDA co-author but using FDA funds to support the grant, a courtesy review of the publication should be shared with FDA to ensure that any potential language that might reference, imply, or infer any FDA endorsement of regulatory and/or policy changes related to the project is not stated. Publications or oral presentations of work performed under this cooperative agreement will require appropriate acknowledgement of FDA support. See Section VI (Acknowledgement of Federal Support) for language that needs to be used for this acknowledgement.

9. Assure that appropriate administrative and logistical support is provided to coordinate the project (including but not limited to facilitating the formation of working groups, scheduling and coordinating logistics of teleconferences and in-person meetings, and approval and tracking of research projects).

10. Oversee the implementation of the approved data and sharing plans.

11. Ensure compliance with the applicable mandatory regulations (including protection of human subjects) as required by specific research activities.

FDA Responsibilities:

1. An FDA Program Official (PO) will have substantial programmatic involvement as described below. The PO is the official responsible for the programmatic, scientific, and/or technical aspects of assigned applications and grants. The PO’s responsibilities include, but are not limited to, post-award monitoring of project/program performance, including review of progress reports and making site visits or grant evaluations; and other activities complementary to those of the Grants Management Officer (GMO). The PO and the GMO work as a team in many of these activities. The PO and GMO will be named in the Notice of Award.

2. One or more designated FDA program staff will have substantial involvement in the Program Steering Committee to ensure the objectives of the program are being met within milestones and participate in scientific/milestone meetings. The primary responsibility for the program resides with the awardee, although specific tasks and activities will be shared among the awardee and the FDA program staff.

3. FDA will provide periodic technical monitoring and/or direction of the work, including final approval of protocols, monitoring of data analysis, interpretation of analytical findings and their significance. The oversight may be in the form of telephone conversations, e-mails, or written correspondence between the PO/grants management officer or specialist and the PI. Information including, but not limited to, information regarding study progress, enrollment, problems, changes in protocol, study monitoring activities, new collaborations, publications, financial and data leveraging, and changes in clinical guidelines based on the project will be requested. Periodic grant evaluations (teleconference or on-site) with officials of the grantee organization may also occur. OOPD may request information related to the impact of this study on future regulatory development and other outcomes such as publications or data leveraging. The results of these monitoring activities will be recorded in the official grant file and will be available to the grantee upon request consistent with applicable disclosure statutes and with FDA disclosure regulations.

4. FDA will assist and approve (as deemed appropriate) the substance of publications, co-authorship of publications and data release.

5. Evaluate the adherence of awardees to the approved data sharing plans and intellectual property plans.

6. Monitor the operations and progress of the project and make recommendations on overall project directions and allocations of project funds. FDA will make recommendations on overall project directions and allocations of project funds and will review the UH2/UH3 transition request to determine whether the project will transition to UH3 funding and be implemented. Criteria for transition to the UH3 phase used in the FDA administrative review include: successful achievement of UH2 milestones, potential for successfully meeting the UH3 implementation phase plans and milestones, demonstrated ability of the team to work and make progress, and the availability of funds.

7. Decide on project continuation with input from the PI and/or any established committee, based on:

• Successful achievement of milestones
• The overall feasibility of project advancement, considering data that may not have been captured in milestones
• Program priorities
• Availability of funds

FDA reserves the right to terminate or curtail the award (or an individual component of the award) in the event of inadequate progress.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the FDA 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 Program Steering Committee chosen without FDA staff input, one FDA 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.

Data Access, Sharing, and Rights

FDA considers the sharing of research resources developed through FDA-sponsored research an important means to enhance the value and further the advancement of research. FDA seeks to ensure that the products and materials resulting from FDA’s support, are free to the public or made available to the public at nominal cost. When research resources have been developed with FDA funds and the associated research findings published, those findings must be made readily available to the scientific community. Upon acceptance for publication, scientific researchers must submit the author's final manuscript of the peer-reviewed scientific publication resulting from research supported in whole or in part with FDA funds to the NIH National Library of Medicine's (NLM) PubMed Central (PMC). FDA defines the author's final manuscript as the final version accepted for journal publication, which includes all modifications from the publishing peer review process. The PMC archive is the designated repository for these manuscripts for use by the public, health care providers, educators, scientists, and FDA. Please see the FDA Public Access Policy.

In all cases, whether FDA funded all or part of the project or program resulting in the data or other copyrightable work, FDA must be given a royalty-free, nonexclusive, and irrevocable license for the Federal government to reproduce, publish, or otherwise use the material and to authorize others to do so for Federal purposes.

The awardee is responsible for timely publication, public release and dissemination of results of data (as defined in the HHS Grants Policy Statement). This plan should be concordant with an approved plan for making Data and materials available to the scientific community and FDA.

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the Notice of Award.

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 terms and conditions of award and the HHS Grants Policy Statement. FDA FOAs outline intended goals and objectives. Post award, FDA will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable FDA grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Monitoring Activities

The guidelines are intended to provide information for principal investigators who are conducting clinical trials. The procedures outlined herein are in addition to (and not in lieu of) Institutional Review Board (IRB), Office for Human Research Protections (OHRP), other Food and Drug Administration (FDA), and Good Clinical Practices requirements.

Oversight Activities

Documentation of assurances with the Office of Human Research Protection (OHRP) (see Section IV.5.A of this document) must be on file with the FDA grants management office before an award is made. Any institution receiving Federal funds must have an institutional review board (IRB) of record even if that institution is overseeing research conducted at other performance sites. To avoid funding studies that may not receive or may experience a delay in receiving IRB approval, documentation of IRB approval and Federal Wide Assurance (FWA) for the IRB of record for all performance sites must be on file with the FDA grants management office before an award to fund the study will be made.

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: https://grants.nih.gov/support/index.html(preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

Katherine Needleman
Office of Orphan Products Development
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
Phone: 301-796-8660
E-mail: [email protected]

Shashi Malhotra
Office of Acquisitions & Grants Services (OAGS)
Food and Drug Administration
Telephone: 240-402-7592
Email: [email protected]

Shashi Malhotra
Office of Acquisitions & Grants Services (OAGS)
Food and Drug Administration
Telephone: 240-402-7592
Email: [email protected]

All awards are subject to the terms and conditions, cost principles, and other considerations described in the HHS Grants Policy Statement, Notice of Award, and 45 CFR 75, currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions .

Awards are made under the authorization of Section 301 of the Public Health Service Act (42 USC 241), 21 U.S.C. 360ee, and under Federal Regulations 42 CFR Part 52, 45 CFR Part 75, and 2 CFR Part 200. All grant awards are subject to applicable requirements for clinical investigations imposed by sections 505, 512, and 515 of the act (21 U.S.C. 355, 360b, and 360e) or safety, purity, and potency for licensing under section 351 of the Public Health Service Act (42 U.S.C. 262), including regulations issued under any of these sections.

The applicant is referred to HHS regulations at 45 CFR 46.116 and 21 CFR 50.25 for details regarding the required elements of informed consent.