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

FDA considers the use of patient input an important part of drug development that can foster innovation and the availability of safe and effective drugs. Patient input can help inform the therapeutic context for regulatory review. Patient input also can inform the selection of clinical outcomes, ensure the appropriateness of instruments used to collect trial data, and help ensure that investigations of the effect of treatments are assessing outcomes that are meaningful to patients. If methodologically-sound data collection tools are developed and used within clinical trials of an investigational therapy, patient input can provide a direct source of evidence regarding the benefits and risks of a drug.

As part of FDA's commitments under the 21st Century Cures Act and the sixth authorization of the Prescription Drug User Fee Act, FDA is publishing a series of patient-focused drug development methodological guidance documents intended to provide FDA’s current thinking about methods that could be used to bridge from important early-stage efforts to gain patients narrative perspectives on the therapeutic context to development and use of methodologically-sound data collection tools in clinical trials. A primary component of this guidance series is to provide a patient-focused outcome measurement approach to clinical outcome assessment (COA) selection and/or development for clinical trials.

COAs are often primary, co-primary, or pre-specified secondary endpoints in clinical trials used to support drug approval and labeling claims or other communications regarding clinical benefit. Clinical benefit is defined as a positive clinically meaningful effect of an intervention on how an individual feels, functions, or survives. The demonstration of clinical benefit and how that benefit is measured is an important aspect of drug development. FDA uses COAs to determine whether a drug has been shown to provide clinical benefit to patients. Tolerability of risk and safety can also be measured by COAs. Understanding what is most important to patients can help to develop and/or select tailored COAs to adequately collect meaningful patient input.

The development of a COA that is fit-for-purpose for its intended use in drug development is a lengthy, rigorous, and resource-intensive process. There are different approaches and methods to develop or modify and select COAs.[1] While there are many efforts underway to develop, modify or select COAs, there is little to no external coordination across or even within disease areas. Independent efforts led by different stakeholders (e.g., drug developers, patient groups) result in a wide-range of COAs, which are often proprietary. This current landscape requires repeated significant start-up costs and provides limited opportunities to streamline the work. The siloed efforts also lead to variability in the quality of the COAs, COA development that may be incomplete for a variety of reasons, and a continued learning curve for developers, implementers, end users and regulators.

For long-term sustainability, there is a need for a more collaborative, multi-stakeholder approach to the development, modification and/or selection of COAs within specific disease area(s) that incorporates input from patients and care partners, drug developers, researchers, regulators, payers, and other decision makers.

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications for UG3/UH3 cooperative agreements to support the development of a publicly available standard core set(s) of COAs and their related endpoints for specific disease indications. The standard core set(s) can include different types of COAs (i.e. patient-reported outcome [PRO], clinician-reported outcome [ClinRO], observer-reported outcome [ObsRO], performance outcome [PerfO] instruments) and their related endpoints that assess a minimum list of impacts that matter most to patients, are likely to demonstrate change (including differences in trial arms related to disease burden, treatment burden, and if applicable, physical function) and should be reported in a clinical trial. A standard core set might be relevant across several disease populations or subgroups or be focused on attributes of a specific disease (a disease-specific or generic tool that can adapted and applied more broadly across disease areas or across age groups).

A UG3/UH3 cooperative agreement has two phases: a milestone-driven planning phase (UG3) and an implementation phase (UH3). Awards made under this FOA will initially support a milestone-driven planning phase (UG3) for up to 2 years, with possible transition to an implementation phase of up to four years (UH3).

Only UG3 projects that have met the scientific milestones and feasibility requirements necessary for UH3, may transition to the UH3 implementation phase. An administrative review will determine whether the milestones and requirements have been met for a project to transition to the UH3 implementation phase. It may be the case that not all funded UG3 projects will transition to the UH3 phase. The number of awards is dependent on the availability of funds. The UG3/UH3 application must be submitted as a single application, and applicants should note specific instructions for each phase in this FOA. The total award project period will not exceed 5 years.

Under the UG3/UH3 phases, applicants will conduct a well-managed, transparent, and methodologically-sound process following a core set development strategy and protocol. FDA is interested in the identification of modifiable disease and treatment impacts that matter most to people living with a disease or condition. To minimize ambiguity and uncertainty for both regulatory decision makers and drug developers, FDA is not only interested in the high-level concepts related to those impacts but also in the set of specific instruments, tools, and endpoints for a given disease or condition.

The core set development work pursued under the cooperative agreement should be informed by FDA guidance documents (e.g., patient-focused drug development methodological guidances), the COA compendium, drug development tools qualification guidelines, a review of the literature (including a gap analysis to evaluate the use of existing tools), and current knowledge of the disease area.

To ensure the development of coordinated and quality core set(s) in or across disease states, existing publicly available COAs and available outcome sets can be leveraged to pursue development of a core set. A core set could include publicly available COAs that have already been evaluated against standards outlined in the FDA Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims and related documents and undergone sufficient psychometric testing to provide evidence that demonstrates they are fit-for-purpose for regulatory use. For disease areas such as rare diseases, where there may not be existing COAs, de novo instrument development or testing available COAs in new populations may be necessary. Given this understanding, proposed activities in both phases will depend on the specific condition of interest and research strategy proposed by the applicant (e.g., proposed outcomes of interest, type of COA, expressed aim).

Since the UG3/UH3 cooperative agreement is a phased approach, FDA understands that, depending on the proposal, the information generated early in the UG3 phase may be at an early proof-of concept stage. However, it is expected that all work products, including de novo or modified COAs and additional COA supportive evidence generated through both the UG3 and UH3 phases of this FOA are currently or will be publicly available by the end of the grant period, at no cost or nominal cost. In addition, it will be important to ensure that identified concepts, COAs, and endpoints reflect what is most important and relevant in stakeholder decision making. To facilitate this, stakeholders including patients, care partners, FDA reviewers, drug developers, as well as other government and academic researchers, health care providers, health technology assessors and health payers, will ideally be engaged at key milestones via public meetings. The scope of this cooperative agreement will cover all aspects of planning (e.g., protocol development, literature review, gap analysis), implementation (e.g., execution of plan, active stakeholder engagement, development of work products) and other tasks necessary to support the objectives specified.

For this cooperative agreement, development of a standard core set(s) of instruments, tools and their related endpoints may either focus on a specified disease area or a disease impact that may span multiple disease areas. FDA encourages using the following criteria to identify a disease area or disease impact for the development of standard core set(s) under this FOA:

• Disease areas that are chronic, symptomatic, or affect functioning and activities of daily living
• Disease areas that represent a broad range in terms of size of the affected population, including common conditions experienced by large numbers of patients and rare diseases that affect much smaller patient populations
• Disease impacts that are relevant to patients' experience across a range of disease areas

FDA is interested in supporting the development of standard core sets for disease areas or disease impacts that are representative of the disease conditions encountered in regulatory decision making, relevant to other regulators, health technology assessors and payers, and expected to support efficient regulatory review and decision-making. Moreover, FDA is interested in the development of standard core sets of COA and related endpoints, not only for use in adults but also those for use in pediatric trials. To that end, and based on the criteria outlined above, FDA has identified the following areas of interest for the purpose of this FOA:

• COAs and endpoints for use in trials in gastrointestinal diseases/conditions, specifically for use across gastrointestinal diseases/conditions with overlapping signs and symptoms. These include, but are not limited to, abdominal pain, nausea, vomiting, bloating, postprandial fullness, and bowel symptoms (e.g., constipation, diarrhea) COAs and endpoints to assess physical/functional status including, but not limited to, standardized assessment of activities of daily living dependent on gross and fine motor function (including upper and lower limb function) across a range of diseases and populations; COAs and endpoints should incorporate any use of assistive devices
• COAs and endpoints for use in migraine trials, including functional impact or disability from migraine
• COAs and endpoints for use in trials of opioid sparing drugs intended to treat acute pain
• COAs and endpoints for use in schizophrenia trials, including but not limited to, shortened versions of current instruments, as appropriate

FDA is also interested in applications for disease areas or disease impacts that are not represented on this list. When proposing an alternative disease area or disease impact for consideration, applicants should describe how they applied the above criteria to identify the alternative disease area or disease impact for standard core set development.

For awards made under this FOA the projects will be funded as phased awards. Contingent on continued availability of funds, this would include one to two years in the planning phase (UG3) and three to four years in the implementation phase (UH3). Funds will be awarded to applicants pursuing development of a single core set for a disease area and/or multiple core sets. Applicants must clearly specify in the application whether they will be pursuing development of a single or multiple core set(s) for a disease area. Outlined below are activities that should generally be included in each phase.

Applications must include clearly defined and measurable goals and milestones for the UG3 phase of the research. The goals specified will be used to evaluate the success of the UG3 phase.

A UG3 cooperative agreement may include a review of the literature and current work, including a gap analysis, to determine if there are instruments which assess outcomes of importance to patients and meet FDA evidentiary standards. It may also propose what additional work would be necessary to conduct during the UH3 period to ensure the instruments meet FDA evidentiary standards.

During the UG3 or planning phase activities will generally include, but are not limited to:

- Develop detailed protocol to describe how core set development will be conducted (study objective(s), design, methodology, operational considerations) and make it publicly available to ensure stakeholder awareness as well as FDA agreement on protocol content.

- Develop plan to ensure successful development of affordable, publicly available standard core set(s) of COAs and endpoints are developed and successfully eliminate or minimize users' cost burden.

- Develop detailed plan to understand the disease(s) or condition(s) from direct report of patient experience, including by newly collecting patient input on disease and treatment burden and outcomes that matter most to them.

- Identify concepts, and methods to measure the identified concepts, for a given disease area based on the collected patient input.

- Evaluate existing instruments and/or tools for potential inclusion in a minimum core set(s) of COAs and endpoints by conducting gap analysis, and literature review, and applying other existing methodologies, and approaches.

- Develop detailed approach to modify existing instruments for the intended context of use, if applicable.

- If instruments and tools are not available, develop approach for de novo instrument development.

- Demonstrate the ability to successfully convene and engage with multiple stakeholders.

- Develop a detailed plan for multi-stakeholder engagement (e.g., patient disease advocacy community, FDA reviewers, drug developers, government and academic researchers, health care providers, health technology assessors and health payers) to ensure participation and involvement.

- Establish an external technical advisory committee to oversee and monitor the specific projects.

- Identify milestones for all work products (interim and final) to be made publicly available to ensure transparency and allow stakeholders to review, comment or utilize work products.

- To ensure effective stakeholder engagement, identify and plan for activities such as a public meeting or workshop, webinar, publication, or white paper. Some activities may be in conjunction with planned face-to face meetings with the Program Steering Committee.

- Develop a maintenance plan or lifecycle management plan to demonstrate the ability to perform appropriate maintenance and lifecycle activities to ensure core set development reflects current state of the science and patient community needs beyond the grant period.

- Develop an updated detailed budget for conduct and completion on the core outcome set project, including maintenance and lifecycle considerations.

The objective of the three-to-four-year UH3 implementation phase is to conduct standard core set(s) development, in accordance with activities planned in UG3 phase. In addition to proposing a well-defined set of milestones for the UG3 planning phase, an application must also propose key milestones for the UH3 implementation phase. It is understood that the proposed milestones for the UH3 phase may be revised as activities start during the UG3 planning phase. In the event of an award, FDA staff will negotiate a list of milestones and planned activities (e.g., public workshops) for each year of support.

At the completion of the UG3 planning phase, the applicant will be required to submit a detailed transition request for the UH3 implementation phase. To transition to the UH3 implementation phase, applicants must submit a complete package, including any needed protocols, updated terms for intellectual property considerations including updated letter(s) of support, statistical analysis plans (SAPs), analysis data, identified concepts, sample size information, stakeholder engagement plan, and a detailed plan outlining work to be conducted under UH3. A UH3 transition request will undergo an administrative review to determine whether the milestones have been met. It may be the case that not all funded UG3 projects will transition to the UH3 phase.

Prospective applicants should note that funding of UG3/UH3 Phased cooperative agreement does not guarantee support of the UH3 implementation phase. Transition to the UH3 phase of the project will occur only if an administrative review process recommends that the UG3 activities have been successful and the implementation project (UH3) can proceed with confidence of success, and if funds are available.

Implementation activities will depend on the disease area /disease area impact being addressed, but in general the following goals should be achieved:

- Successful completion of planned activities to develop standard core set(s) of COAs and their related endpoints, following the research protocol that is in line with FDA evidentiary framework and guidances.

- Demonstration of development of a standard core set that can be utilized by regulators and may also be usable by other healthcare decision makers (e.g. health technology assessors and payers).

- Availability of all work products including de novo or modified COAs and additional COA supportive evidence generated through both the UG3 and UH3 phases of this FOA are currently or will be publicly available by the end of the grant period in the public domain at nominal or no cost

- Minimization of overall reporting burden for patients living with that disease for data collection.

Sharing Research Resources: Rights in Data

The ultimate goal of this funding award is to support the development of a publicly available core set(s) of COA and their related endpoints for specific disease indications. Recipients of awards are encouraged to identify and foster relationships with potential licensing and commercialization partners early in the COA tool development process, to identify any potential issues that may impact the public availability of any resulting COA tools. The PD/PI(s) are expected to work closely with technology transfer officials at their institution to ensure that royalty agreements, patent filings, and all other necessary intellectual property arrangements are completed in a timely manner and that plans are developed and updated over the course of the project. 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.

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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• 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.

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

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for 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.

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.

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

• Descriptive title of proposed activity
• Name(s), 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
• Any questions pertaining to this FOA that should be answered at the technical session (please see below)

The letter of intent should be sent to:

Shashi Malhotra
Telephone: 240-402-7592
Email: [email protected]

A technical session will be held for prospective applicants in April 2019. The conference call information will be provided to prospective applicants that submit a letter of intent. The technical session will provide an overview of the submission requirements and allow FDA to provide responses to the questions received regarding the application process. Prospective applicants will participate in the technical session in listening mode only. All questions must be submitted as part of the letter of intent. Participation in the technical session is optional, but strongly encouraged.

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, with the following additional requirements:

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.
• Application budgets must include a minimum effort for the PD/PI of 25% annually (3.0 calendar months) to the project. If a project includes multiple PDs/PIs, the total annual PD/PI effort must be at least 20% (2.4 calendar months) for each individual.
• Application must be an appropriate mix of time allocated for senior and junior scientists to ensure the successful conduct of the project. Budgeted effort of other personnel must be appropriate to the needs of the project.
• The budget must include cost estimates for personnel with the range of expertise relevant to the project.
• Cost estimations must also include a sufficient travel budget for key personnel (at a minimum the project PD/PI(s), program/project manager[s]/coordinator[s]) to attend three separate two to three-day Program Steering Committee meetings (kick-off, mid-year and end of year) in Silver Spring, Maryland area during the first year (UG3 Phase). In the subsequent years during the UG3 and UH3 phase, applicants must estimate a travel budget for key personnel to attend two separate two to three-day steering committee meetings (mid-year and end of year) in Silver Spring, Maryland area each year, for the duration of the project. Based on the project needs, routine teleconferences with FDA (e.g., at least monthly) should be anticipated. Steering committee meetings and other planned workshops will be conducted in consultation with FDA. Awards also can cover payments and travel related to the External Technical Advisory Committee. Travel for additional meeting(s) in the Planning Phase may also be required.

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:

To clearly distinguish between the two phases, applicants should specify separate UG3 and UH3 information in each subsection (Specific Aims and Research Strategy) of the PHS398 Research Plan as appropriate.

In preparing the application, investigators should consider the fact that the applications will be assigned a single impact score for both UG3 and UH3 phases.

Specific Aims: Each submitted application should address one specified disease or disease impact area. If applicants are submitting more than one application, each application should be scientifically distinct. Applicants should include separate aims for each phase (UG3/UH3) and delineate the planned work to be conducted during the funding period, separately for each phase (UG3/UH3). All information should be summarized within the designated page limit.

Research Strategy:

Within the Research Strategy, applicants should first describe the UG3 Phase and then the UH3 Phase with a clear demarcation of the UG3 and UH3 phases of the application. It is not necessary to repeat background information or details of methods in the UH3 portion that were provided in the UG3 portion. The UG3 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. An application should identify key decision elements for core set(s) development for the targeted disease or disease impact area. The application should describe details about the proposed core set development plan and how each plan component is suitable for the development of COAs for regulatory purposes. The application should also describe how the standard core set COAs and endpoints development process will accommodate variability across geographic regions/countries, subpopulations, cultures, and regional technology and infrastructure.

The application should describe the approach to ensure key stakeholder (multiple authorities and decision makers) engagement at key milestones in the core set development. The application must provide a description of the infrastructure and the expertise available to develop core set(s) COAs and endpoints. The application should also describe the approach to ensure the core set and the supportive information to aid use in regulated environments are publicly available for minimal or no cost.

Applicants must describe their willingness to comply with policies, guidelines, and practices developed by the PD/PI(s), and to work with FDA, Science Policy Board, and the Program Steering Committee in providing relevant information and materials when needed.

Applicants must not propose work that duplicates efforts already funded or underway. Although novel theoretical approaches and methodologies may be needed and de novo development may be necessary, when possible applicants should leverage existing instruments and tools and/or modify existing instruments and tools.

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

1. Rationale

2. Infrastructure and Resources

3. Investigator(s)

4. Approach

5. Significance

Rationale:

The Rationale section of the Research Strategy should be framed within context, detailing how the proposed project fits within more current knowledge of the disease and measurement area(s) and the likelihood that the forthcoming standard core set(s) of COAs and endpoints will facilitate drug development to address an unmet medical need in a disease and measurement area(s) or substantially contribute to market approval of product(s). This subsection should include:

• Description of the state of existing knowledge (e.g., literature citations and summaries of relevant preliminary or ongoing studies.
• Explanation of current knowledge gap(s) and critical barrier(s) to progress in the field.
• Explanation of how the proposed project will help fill the aforementioned gaps and help support drug development and approval.

Research Team and Member's Roles/Responsibilities (without duplicating information already requested/provided in the bio sketches):

The Investigator section of the Research strategy should also include a subsection with the heading, "Research Team and Member Roles/Responsibility." This subsection should reflect the research strategy and approach outlined by the applicant and include the following:

• Description of the relevant qualifications and expertise of proposed team members to conduct that work (including biographies; credentials should be supported by appended CVs for key team members). Relevant expertise includes but is not limited to experience in any of the following content areas: clinical trial design, literature reviews, qualitative study methodology (e.g., concept elicitation interviewing or focus groups, cognitive debriefing), item generation, quantitative study methodology (e.g., psychometrics), biostatistics, data analysis, eCOA development, translation and cultural adaptation and the broader application of these methods in drug development. Other expertise may include clinical expertise in the therapeutic area of interest and experience with patient and other stakeholder outreach and engagement as part of COA development or revision and refinement. Team members with legal expertise (i.e. contracting), senior level project management, library science, data management and scientific writing should also be included, where appropriate. Each team member should be sufficiently trained in study conduct and good clinical practice.
• Description of the leadership structure, decision-making processes, and planned communication, coordination, and outreach process among research team members.
• Description of the composition of the External Technical Advisory Committee to be established by the awardee. The External Technical Advisory Committee will include the FDA program officer and scientific officer and may include disease specific experts, COA experts, biostatisticians, or other technical experts as appropriate (see Additional Information below).
• Describe the research team member's past collaborations

Milestones:

Both the UG3 and UH3 phases of the Research Strategy must have a section of proposed milestones, which should be well described, quantifiable, and scientifically justified to allow an assessment of progress. For UG3 milestones, applications should delineate what they propose to achieve in order to proceed to the UH3 phase. The milestones should also include a timeline, a discussion of the suitability of the milestones assessing success in the UG3 phase, and a discussion of the implications of successful completion of these milestones for the proposed UH3 phase. The application should also identify key milestones for periodic engagement with external stakeholders. Annual milestone for the UH3 phase should also be included in the application, although it is understood that timelines and milestones for implementation in the UH3 phase that are proposed in the application will evolve as activities in the UG3 phase progress, if an Award is made.

Letters of support: Applicants should include a letter of support from consultants, contractors, and collaborators.

• If applying from an academic institution, include a letter of support from the technology transfer official who will be managing intellectual property associated with this project.
• If research will be performed at more than one institution, include a letter of support from each institution clarifying how intellectual property will be shared or otherwise managed across the institutions.
• If collaborating with a private entity, state if they are agreeing to provide the device or technology, if there is any limit on the studies that can be performed with that device or technology, limitations on sharing of data, and whether licensing agreements are in place

Additional Information:

Governance: The awards funded under this FOA will be cooperative agreements (See Section VI.

Cooperative Agreement Terms and Conditions). Close interactions between the FDA and the awardee will be required to accomplish the goals of this program. The governance of this award will include programmatic insight and oversight by a Program Steering Committee and Scientific Policy Board. The Scientific Policy Board may include US regulatory and health authorities, other government regulatory staff, and other key stakeholders as deemed necessary by FDA for the specific project of interest.

The Program Steering Committee will include one voting representative from each award, the FDA Scientific Officer and representatives appointed by the FDA Program Officer to facilitate appropriate oversight and guidance to ensure the project goals remained aligned with the program aims. The combined vote of FDA members of the Program Steering Committee will not exceed half of total votes of the Program Steering Committee. All members are expected to actively participate in all Steering Committee activities.

It is expected each awardee PD/PI will establish an External Technical Advisory Committee specific to their award with external experts to advise and assist with facilitating the overall goals of this program and implementing the guidance and insight provided via the Scientific Policy Board and Scientific Program Steering Committee.

Data Sharing Plan: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan https://www.fda.gov/ScienceResearch/AboutScienceResearchatFDA/ucm433459.htm .

Individuals are required to provide primary data to FDA for regulatory review similar to the level of data expected to be submitted to support FDA pre-market review of a New Drug Application or Biologics Licensing Application. This includes person level data, transcripts, interview guides, and other documents similar to what is submitted as part of the submission to the FDA COA DDT qualification program.

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. Applicants must provide a description of the resources that will be made broadly available including protocols, methods, SAP, policies, interim work products, study data, interview guides, search algorithms for literature reviews, to facilitate collaboration, reuse, and utilization of the instruments, tools and endpoints. Applications should provide descriptions of how privacy and confidentiality will be maintained. The plan must include a description of how data will be shared to show for transparency and reproducibility of research findings.

Appendix:

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

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

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

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.

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.

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 Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to FDA. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the 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.

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA:

Is the need for a core set of COAs and endpoints and area of unmet need in the proposed disease/impact area clearly defined? Is the need for a core set of COA(s) and endpoints in the proposed disease/impact area well supported by information presented in the application (e.g., evidence from the literature, review of previous trials, etc.)? Does the applicant outline efforts that will strategically build on previous work in the current space and add a unique contribution to the field, above and beyond what is currently available? Does the application demonstrate that a core set(s) of analysis-ready clinical trial endpoints (not only outcome measurement instruments) will be developed for a given disease area or condition? Will the UG3 and UH3 activities and resulting core set(s) of COAs advance the science, development and utilization of core set(s) of COAs and endpoints for in the proposed disease/impact area?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA:

Do the PD/PIs have the expertise, operational management skills, and training needed for core set development as demonstrated in their biographical sketches and CVs? Do the PD/PI(s) and other key personnel (e.g., project management team) have sufficient content area expertise in the disease and/or condition, including knowledge and experience with the specific population and/or subpopulation of interest? Do the PD/PI(s) and key personnel have expertise in qualitative and quantitative methods necessary for core set COA development (e.g., qualitative and quantitative methods required for de novo instrument development, modification of existing instruments; this also includes expertise necessary for the psychometric evaluation of COAs)? Do the PD/PI(s) and key personnel have expertise in data standards related to the core set COAs to aid regulatory submission? Do the PD/PI(s) have extensive experience in performing proposed UG3 phase activities? Do they have expertise in study coordination, data management, and statistics? What is the likelihood that all PD/PI(s) will be able to collaboratively work together to complete the proposed work?

Does the application represent sound approaches or methodologies, instrumentation, or interventions for core set development? Are the concepts, approaches or methodologies, instrumentation, or interventions in relation to enhancing the current understanding of a specific disease or disease impact supported by this application? Is there a critical barrier or important knowledge gap in the current drug development paradigm this proposed project will address? Does the proposed project provide essential data needed for drug development? For a given context of disease and subpopulation, does the project address specific limitations in patient population which may impact core set development?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

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

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

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

Specific to this FOA:

Does the application identify key decision points and milestones for core set development? Does the approach ensure key stakeholder engagement (e.g., with multiple authorities and decision makers, patients, and key opinion leaders in the core set(s) development? Does the project include innovative approaches to overcoming barriers and challenges? Does the plan propose work that complements (in part or whole) efforts already funded or underway? What differentiates the proposed work from what has already been done? Does the application provide an adequate plan to leverage existing instruments and tools? Is the plan to develop/modify instruments reasonable, and could the proposed instruments and trial endpoints be developed for use in regulatory decision-making using the plan that is described? Is there an adequate plan to test the validity, reliability, and responsiveness to change of the instruments and endpoints? Is there an adequate plan to evaluate the feasibility of using the COAs and endpoints in clinical trials? Does the project ensure the inclusion of input from patients and other key stakeholders as part of the core set development strategy? Does the proposed approach incorporate steps to reduce respondent (patient and other informant's) burden? Is there an adequate plan to minimize users' cost burden? Is there an adequate plan to determine the applicability of core set(s) developed in one region/country to patient populations in other countries/regions of the world? Does the approach adequately discuss sustainability beyond the proposed timeline? Will proposed UG3 activities and proposed milestones allow for implementing UH3 activities? Is the proposed approach for maintenance and minimal cost accessibility reasonable? Will the approach allow FDA to receive documents and data that will be necessary for the instruments and endpoints in the core set(s) to be evaluated by FDA reviewers as part of a regulatory review process to inform regulatory decision making?

In addition, for applications proposing clinical trials:

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed? Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate? If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial? If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Will the organizational infrastructure in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the organization infrastructure and resources, subject populations, or collaborative arrangements?

Specific to this FOA:

If proposal includes multiple PD/PI, what specific resources or infrastructure elements does each provide to facilitate success of the project? What capabilities are available to support maintenance and lifecycle considerations of the project? What capabilities are available to support the availability of the core set(s) in the public domain? If IT application or systems will be used, is support available organizationally to ensure the needs for patient engagement, training and/or testing of software are met appropriately? How will applicability and operability across regions, subpopulation differences, variations in culture, and regional technology and infrastructure differences will be accounted for in the development of the core set? If proposal includes use of existing tools for inclusion within a core set(s) of COAs, are infrastructure and resources available to support intellectual property, licensing, or technology transfer concerns which may arise with the existing tools or measures of interest? Does the letter of support address technology transfer, intellectual property concerns, and collaborations with private entities?

As applicable for the project proposed, reviewers will evaluate the following additional items but will not give separate scores for these items, and should not consider them in providing an overall score.

Milestones

Are the steps and milestones clearly defined? Are the proposed milestones well described, feasible, and quantifiable with regards to specific goals and accomplishments? Are adequate criteria provided for the UG3 phase that will be utilized in determining milestone completion before proceeding to the next phase of the project? Are UH3 milestones appropriate for the next phase of the project?

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Ability to Foster Public Availability of Core Set Development Efforts:

The reviewers will comment on the appropriateness and adequacy of the proposed approach to manage intellectual property, data sharing, and software sharing as applicable amongst multiple entities with the aim of ensuring core set development aligns with the overall aim of being publicly available.

Does the proposed approach ensure public availability of preliminary and final project research deliverables? Is there an appropriate mechanism to incorporate feedback from the Program Steering Committee and other key stakeholders during development? Does the proposed software and/or data sharing aspects of the project approach ensure public availability?

Ability to Advance the Current Field

The reviewers will comment on the ability of the project to advance current research paradigms towards future drug development and to exert a significant influence on drug development. The reviewers will evaluate the following:

• Explanation of how the proposed study will exert a sustainable influence on the research field and drug overall. Considerations include core set(s) that have the potential to have a broad impact on advancing drug development.
• Explanation of novel or innovative concepts or methodologies to be developed or used to facilitate efficient regulatory review.
• Description of plans for sharing/dissemination of data and data products following completion of study. Considerations include innovative methods for data collection as well as data dissemination which can serve as a model for future studies.
• Explanation of sustainability plans beyond the proposed funding period and for acquiring alternative/additional funding if needed.

Study Timeline

Specific to applications proposing clinical trials:

• Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g. practice-based research networks, electronic medical records, administrative database) to increase the efficiency of participant enrollment and data collection, as appropriate?
• Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)? Does the clinical trial design support the ability to enhance drug development? Does the clinical trial structure support public availability of results and/or preliminary findings?

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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

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

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

Not Applicable

Not Applicable

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.

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.
• 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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found in the HHS Grants Policy Statement.

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

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

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

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), 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 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.

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).

Additional terms and conditions regarding FDA regulatory and FDA Center for Drug Evaluation and Research/ Office of the Center Director programmatic requirements may be part of the Notice of Award.

All references to the Program Steering Committee and Scientific Policy Board are in accordance as defined below.

Program Steering Committee: The Program Steering Committee will function as the main governing board of all grants awarded under this RFA. The Program Steering Committee will include one voting representative from each award and will include FDA Scientific and Program Officer(s) (no more than 49% of total votes). 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.

Scientific Policy Board: The scientific policy board will consist of representatives from US regulatory and health authorities (e.g., FDA, NIH) and representatives from other regulatory and health authorities (e.g., European Commission/European Medicines Agency, Health Canada, Japanese Ministry of Health, Labour and Welfare/Pharmaceuticals and Medical Devices Agency) to facilitate the program goals and objectives. Other stakeholders may be identified and included as needed. The Scientific Policy Board will be appointed by the FDA. The Scientific Policy Board will meet at least twice each year in conjunction with the Program Steering Committee. A schedule for subsequent meetings will be discussed and prepared during the project kick-off meeting. Other FDA staff may be invited to attend Scientific Policy Board meetings when their expertise is required for a specific discussion.

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 awardees 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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and FDA as defined below.

2.A.1. Principal Investigator Rights and 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.

Sharing Research Resources: Rights in Data

The ultimate goal of this funding award is to support the development of a publicly available core set(s) of COA and their related endpoints for specific disease indications. Recipients of awards are encouraged to identify and foster relationships with potential licensing and commercialization partners early in the COA tool development process, to identify any potential issues that may impact the public availability of any resulting COA tools. The PD/PI(s) are expected to work closely with technology transfer officials at their institution to ensure that royalty agreements, patent filings, and all other necessary intellectual property arrangements are completed in a timely manner and that plans are developed and updated over the course of the project. 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.

Additionally, PD/PIs will:

1. Participate in site visits or attend meetings as requested by the FDA. A portion of the budget should be reserved for such travel.

2. FDA may also request data be made available through speaking engagements and publications, presentations at scientific symposia and seminars, while making sure that confidentiality and privacy of the data is protected.

3. The awardees will provide FDA any data obtained from investigations if requested by FDA.

4. Any publication or oral presentation of regarding outcomes of this grant must undergo FDA Office of Research and Center review and approval process. This process can take 30-90 days.

The PD(s)/PI(s) will have the responsibilities for:

• Convening an external technical advisory committee for their award to provide advice and facilitate the overall goals of this program and implementing the guidance and insight provided via the Scientific Policy Board and Program Steering Committee.
• Overseeing the overall budget, activities and performance of the project. The PD/PI must devote a minimum level of effort 25% annually (3.0 calendar months) to the project. If a project includes multiple PDs/PIs, the total annual PD/PI effort must be at least 20% (2.4 calendar months) for each individual.
• Adhering to FDA guidance documents (e.g., patient-focused drug development methodological guidances), the COA compendium, drug development tool and related statutes and regulations, applicable FDA Code of Federal Regulations (CFR) sections and rules, and current knowledge of the disease area and measurement science.
• Leading the development and implementation of a plan to ensure successful development of an affordable, publicly-available standard core set of COAs and endpoints for a given disease area or disease impact.
• Leading the development of patient-focused outcome measurement approach to COA selection and/or development for clinical trials in the proposed disease area/impact. This would include developing and implementing a methodologically-sound plan to collect comprehensive and representative patient input on what matters most to patients and identifying important impacts and concepts from patients to develop or modify potential study instruments.
• Leading the evaluation of existing COAs for inclusion in a standard core set of COAs and endpoints for the given disease area or disease impact.
• Leading the development of a de novo instrument and/or modifying existing COAs as needed to develop a standard core set of COAs and endpoints for the given disease area or disease impact. This would include developing and implementing a plan to test the validity, reliability, and responsiveness to change of the COAs.
• Evaluating the feasibility of using the standard core set of COAs and endpoints in drug development.
• Publishing reports or preliminary findings conducted under this award.
• Serving as members of the Program Steering Committee.
• Participating in in-person meetings at least 2-4 times a year expected to be held in the Silver Spring, Maryland area, and weekly/monthly teleconferences.
• Submitting periodic milestone progress reports to FDA program staff in a standard form as agreed upon at the initiation, and by providing additional information as needed.
• Participating in teleconferences with FDA program staff, as needed.
• Assuring 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).
• Ensuring compliance with the applicable mandatory regulations (including protection of human subjects) as required by specific research activities.
• Submitting a detailed transition request for the UH3 implementation phase, outlining UG3 progress, how negotiated UG3 Milestones have been met, as well as detailed plans, budget and annual milestones for the UH3 implementation phase. Note that, funding of the UG3 planning phase cooperative agreement does not guarantee support of the UH3 implementation phase.
• Assuming responsibility and accountability to the applicant organization for the performance and proper conduct of the research in accordance with the terms and conditions of the award.
• Accepting and implementing the goals, priorities, procedures, and policies agreed upon by the Scientific Policy Board and Program Steering Committee to the extent consistent with grant regulations.
• Overseeing the implementation of the approved data and sharing plans.
• The PD(s)/PI(s) and their awardee institutions will be accountable for implementing the approved research resource sharing plan.
• All institutions/organizations will be expected to share publicly their analytical approaches and the knowledge gained from these activities.

2. A.2. FDA Responsibilities

An FDA Project Officer (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; 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.

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

FDA will provide technical monitoring and/or direction of the work, including monitoring of data analysis, interpretation of analytical findings and their significance.

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

In addition to the FDA responsibilities described above, FDA staff have substantial programmatic involvement that is above and beyond normal stewardship in awards, as described below: One or more designated FDA program staff will have substantial involvement in the Standard Core Clinical Outcomes Assessments and Endpoints Program as part of the Scientific Policy Board and Program Steering Committee.

The specific roles of the involved FDA program staff members include the following activities:

• Working with the PD/PI(s) and the Program Steering Committee to ensure the objectives of the program are being met. 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.
• Interacting with the PD/PI(s) on a regular basis to monitor progress. Monitoring may include: regular communications with the PD/PI(s) and key personnel, fiscal reviews, and other relevant stewardship activities.
• Providing scientific input on the development of a patient-focused outcome measurement approach to clinical outcome assessment (COA) selection and/or development for clinical trials in the proposed disease area/impact.
• Convening Science Policy Board to facilitate the program goals and objectives.
• Serving as members on the Program Steering Committee.
• Participating in in-person scientific/milestone meetings 2-4 times a year, and any working group and committee calls on an as-needed basis.
• Acting as a resource and facilitator for activities of the awardee with key stakeholders.
• Assisting the awardees as a liaison in stimulating their broader interactions with other FDA programs to disseminate results and outcomes from the program and effectively leveraging existing FDA resources and infrastructures.
• Contributing, as appropriate, to scientific manuscripts and other scientific and scholarly activities (e.g., oral presentations, poster presentations) resulting from the program.
• Evaluating the adherence of awardees to the approved data sharing plans and intellectual property plans.
• Monitoring the operations of the UG3/UH3 research projects, and making recommendations on overall project directions and allocations of project funds.
• Reviewing the individual progress of the UG3/UH3 research projects, as well as the progress of awardees.
• Conducting administrative review of the 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 UG3 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.
• FDA reserves the right to terminate or curtail the award (or an individual component of the award) in the event of inadequate progress.
• Additionally, a Program Official (PO) will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the Notice of Award.

The institution/organization specific program oversight committee will make decisions on project continuation with input from FDA staff 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

2.A.3. Areas of Joint Responsibility:

Areas of joint responsibility will occur within the Program Steering Committee. FDA staff will assist the Program Steering Committee in developing and drafting operating policies and policies for dealing with recurring situations that require coordinated action(s).

2.A.4. 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 voting, 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.

Financial Reporting:

A. Cash Transaction Reports

The Federal Financial Report (FFR) has a dedicated section to report Federal cash receipts and disbursements. For recipients this information must be submitted quarterly directly to the Payment Management System (PMS) using the web-based tool. Quarterly reports are due 30 days following the end of each calendar quarter. The reporting period for this report continues to be based on the calendar quarter. Questions concerning the requirements for this quarterly financial report should be directed to the PMS.

B. Financial Expenditure Reports

A required Federal Financial Report (FFR) must be submitted annually. FDA now requires all annual financial expenditure reports to be submitted electronically using the Federal Financial Report (FFR) system located in the eRA Commons. This includes all initial FFRs being prepared for submission and any revised FSR/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. Failure to submit timely reports may affect future funding.

Performance Progress Reporting:

1. Annual progress reports are required. The Annual Progress Report will be due as part of the Research Performance Progress Report (RPPR).

2. Grants with Multiple Years: When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR).

Information regarding submitting the RPPR is available at https://era.nih.gov/erahelp/commons/default.htm#cshid=1020

PROGRAM INCOME:

1. 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.

2. 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.

3. Any Program Income generated during the Project Period of this grant by the grantee or sub-grantee is subject to the Addition Alternative for Program Income and, therefore, must only be used to further the goals of the project for which this grant was awarded.

PRIOR APPROVAL:

All requests that require prior approval must include the award number and bear the signature of an authorized official of the grantee business office as well as that of the PI/PD. Any requests involving funding issues must include a new proposed budget and a narrative justification of the requested changes. If a grantee questions whether prior approval is required for an activity or cost, they should contact the assigned Grants Management Specialist prior to expenditure of funds for clarification. Below are activities that require prior approval from FDA:

CHANGE IN SCOPE OR OBJECTIVES

CHANGE IN KEY PERSONNEL

CHANGE IN GRANTEE ORGANIZATION

DEVIATION FROM TERMS AND CONDITIONS OF THE AWARD

CARRYOVER OF UNOBLIGATED BALANCES

NO COST EXTENSIONS

SIGNIFICANT REBUDGETING

ACKNOWLEDGEMENT OF FEDERAL SUPPORT:

When issuing statements, press releases, publications and other documents describing projects or programs funded in whole or in part with Federal money, all awardees receiving Federal funds, including and not limited to State and local governments and recipients of Federal research grants, shall clearly state:

*Funding for this statement, publication, press release, etc. was made possible, in part, by the Food and Drug Administration through grant (ENTER GRANT NUMBER). Views expressed in written materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organization imply endorsement by the United States Government. *

FAILURE TO COMPLY WITH THE ABOVE STATED TERMS AND CONDITIONS COULD RESULT IN THE SUSPENSION OR TERMINATION OF THIS COOPERATIVE AGREEMENT.

All formal correspondence/reports regarding the grant should be signed by an authorized institutional official and the Principal Investigator and should be sent to the attention of the grants management specialist, unless otherwise directed.

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

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable 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 $25,000.

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

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

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

Pujita Vaidya
Center for Drug Evaluation and Research (CDER)
Telephone: 301-796-0684
Email: [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.

Awards are made under the authorization of Section 301 of the Public Health Service Act as amended (42 USC 241) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.