Clinical Trials Addressing Unmet Needs of Rare Neurodegenerative Diseases (R01) Clinical Trials Required

Clinical Trials Addressing Unmet Needs of Rare Neurodegenerative Diseases (R01) Clinical Trials Required is sponsored by U.S. Food and Drug Administration (FDA) - Rare Neurodegenerative Disease Grants Program. This funding opportunity supports clinical trials of products evaluating efficacy and/or safety in support of a new indication or change in labeling to address unmet needs in rare neurodegenerative diseases for children and adults.

Expired RFA-FD-25-001: Clinical Trials Addressing Unmet Needs of Rare Neurodegenerative Diseases (R01) Clinical Trials Required This notice has expired. For NIH, in limited situations, applications may be accepted on a case-by-case basis for a short period after expiration to accommodate NIH late or continuous submission policies . Contact the eRA Service Desk for any submission issues.

Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Participating Organization(s) NOTE: The policies, guidelines, terms, and conditions stated in this Notice of Funding Opportunity (NOFO) may differ from those used by the NIH.

Where this NOFO provides specific written guidance that may differ from the general guidance provided in the grant application form, please follow the instructions given in this NOFO. The FDA does not follow the NIH Page Limitation Guidelines or the NIH Review Criteria.

Applicants are encouraged to consult with FDA Agency Contacts for additional information regarding page limits and the FDA Components of Participating Organizations Office of Orphan Products Development ( OOPD ) Funding Opportunity Title Clinical Trials Addressing Unmet Needs of Rare Neurodegenerative Diseases (R01) Clinical Trials Required March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 04, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 Funding Opportunity Number (FON) Companion Notice of Funding Opportunity See Section III.

3. Additional Information on Funding Opportunity Purpose The purpose of this Notice of Funding Opportunity (NOFO) is to fund clinical trials of products evaluating efficacy and/or safety in support of a new indication or change in labeling to address unmet needs in rare neurodegenerative diseases for children and adults.

Through the support of collaborative, efficient, and/or innovative clinical trials, FDA expects to increase the number of approved treatments for rare neurodegenerative diseases and exert a broad and positive impact on rare disease drug Letter of Intent Due Date(s) October 22, 2024, by 11:59 PM October 21, 2025, by 11:59 PM Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Late applications will not be Required Application Instructions 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 NOFO or in a Notice from the Guide for Grants and Contracts ). Conformance to all requirements (both in the SF424 (R&R) Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the SF424 (R&R) Application Guide as well as any program-specific instructions noted in Section IV . When the program-specific instructions deviate from those in the SF424 (R&R) Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants. gov to the FDA and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. 2. Use Grants.

gov Workspace to prepare and submit your application and eRA Commons to Part 2. Full Text of the Announcement I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information 2. Full Text of Announcement Section I. Notice of Funding The FDA Office of Orphan Products Development (OOPD) was created to identify and promote the development of orphan products.

Orphan products are drugs, biologics, medical devices, and medical foods that are indicated for a rare disease or condition. Through the Orphan Products Grants Program, OOPD has been supporting clinical trial research since 1983, and more than 80 of the funded studies have facilitated the marketing approval of rare disease products.

Access to Critical Therapies for ALS Act" (the ACT for ALS) was enacted on December 23, 2021 which established the FDA Rare Neurodegenerative Disease Grant Program, which is administered by OOPD.

This Act allows the FDA to award grants and contracts to public and private entities to cover costs of research and development of interventions intended to prevent, diagnose, mitigate, treat or cure rare neurodegenerative diseases (including amyotrophic lateral sclerosis (ALS)) in adults and children. Neurodegenerative diseases occur when nerve cells in the brain or peripheral nervous system lose function over time and ultimately die.

In general, they are incurable and debilitating conditions and are progressive. The term rare disease or condition is defined in 21 U.S.C. 360ee.

FDA has funded multiple awards beginning in fiscal year 2022 to help meet the intent of the ACT for ALS Act. FDA sought input from patients, researchers, nonprofit organizations, companies, and other stakeholders on regulatory science research gaps that could advance medical product development ( Docket FDA-2022-N-2544 ).

Specifically, input was sought for development of regulatory science tools or other research and development needs in the preclinical or clinical space. As a result of this feedback, additional biomarker, and clinical outcome assessment studies that help with future product development. FDA continues to build on these important concepts to move therapies along to patients with rare neurodegenerative diseases.

With this new Notice of Funding Opportunity (NOFO), FDA will continue to address unmet funding needs identified for rare neurodegenerative diseases in adults and children.

Specifically, FDA will support clinical trials to facilitate drug development in safe and efficient means by encouraging the use of established infrastructure and resources (e.g., clinical trial networks and data standardization, analytics, and sharing platforms), collaborative efforts between stakeholders (e.g., industry/academia/patient organizations), and early and ongoing patient engagement in trial design (e.g., study feasibility, assessment of important clinical outcomes).

Additionally, applications are encouraged to propose innovative clinical trial designs as applicable (i.e., seamless, adaptive, basket, umbrella, platform trials) or innovative methods (i.e., data modeling and simulations). These designs will be eligible for additional funding (see Section II below).

These approaches are vital in expediting drug development and have the potential to make a broad and positive impact for rare diseases in general. This NOFO is intended to support clinical trials in all phases of product development (phase 1, 2 and/or 3) for rare neurodegenerative diseases with unmet needs.

These clinical trials should evaluate safety and/or efficacy of medical products in support of a new indication or a change in labeling. Depending on the phase of development, these trials may need to include an appropriate comparator, such as a concurrent control or a historical control.

OOPD encourages applicants to refer to " Rare Diseases: Considerations for the Development of Drugs and Biological Products " for guidance on conducting more efficient and successful drug development programs. Applicants are also encouraged to refer to information on the Orphan Products Grants Program website before applying for this opportunity.

To facilitate efficient product development, the use of shared, established infrastructure and resources and collaborative efforts between stakeholders in industry, academia, and patient organizations are highly encouraged under this NOFO.

Additionally, patients living with a rare neurodegenerative disease, or their caregivers have experiences and knowledge that contribute to important considerations in product development, such as with trial feasibility, thus early and ongoing patient engagement is Innovative and Efficient Trial Approaches: is interested in supporting innovative and efficient trial designs and will allow for additional funding with justification for applications proposing the use of one or more of the following: Innovative trial designs such as seamless and adaptive trial designs, which compress the phases of a trial into one continuous trial, as well as basket, umbrella and platform trials, which allow for testing of multiple drugs and/or multiple diseases using a common Innovative methods using data simulations and modeling toward the study of safety and efficacy of a product.

These approaches may hold significant promise for the advancement of therapeutic treatments for rare diseases through all phases of product development. Early engagement with FDA review divisions to discuss the use of these innovative approaches is highly recommended prior to submitting a grant application (e.g., preIND, INTERACT, other meetings). See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or Application Types Allowed SF424 (R&R) Application Guide provide details on these application types.

Only those application types listed here are allowed for this NOFO. Required: Only accepting applications that propose help determining whether you are doing a clinical trial? Anticipated Number of Awards The number of awards is contingent upon FDA appropriations and the submission of a sufficient number of meritorious applications.

Award(s) will provide one (1) year of support and include future recommended support for an additional three (3) years contingent upon annual appropriations, availability of funding, and satisfactory recipient performance.

Application budgets need to reflect the actual needs of the proposed project and should not exceed the following in maximum total costs (direct and indirect costs) and maximum Application budgets need to reflect the actual needs of the proposed project and should not exceed the following in maximum total costs (direct and indirect costs) and maximum years of support.

Applicants may request additional funding over the above listed maximums for innovative and efficient trial approaches. The additional funding request shall not exceed an additional $250,000 total costs per year (to a maximum total award cost of $900,000 per year) for up to 4 years. Justification for the additional funding request must be reflected in the budget request and will be reviewed annually by the program.

See Appendix Section below for definitions of types of studies eligible for additional funding ( Section proposed project should determine the project period.

The maximum project period is four (4) years; however, the length of support will depend on the For those studies with an expected duration of more than 1 year, a second, third, or fourth year of noncompetitive continuation of support will depend on the following factors: (1) Performance during the preceding year; (2) compliance with regulatory requirements of IND/investigational device exemption (IDE), if applicable; and (3) availability of Federal funds.

HHS grants policies as described in the HHS Grants Policy Statement will apply to the applications submitted and awards made from this NOFO. Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Private Institutions of Higher Education The following types of Higher Education Institutions are always encouraged to apply for FDA support as Public or Private Institutions of Higher Education: Hispanic-serving Institutions Historically Black Colleges and Universities Tribally Controlled Colleges and Universities Alaska Native and Native Hawaiian Serving 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 (Other than Small City or Township Governments Special District Governments Indian/Native American Tribal Governments Indian/Native American Tribal Governments (Other than Federally Recognized) U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Organizations) Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible 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. organizations must complete and maintain the following registrations as described in the How to Apply - 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, please reference the HHS Grants Policy Statement for additional information. 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 organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to Entity Identifier (UEI)- A UEI is issued as part of the SAM.

gov registration process. The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.

gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants.

gov Applicants must have an active SAM registration in order to complete the Grants. gov registration. Directors/Principal Investigators (PD(s)/PI(s)) 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 Eligible Individuals (Program Director/Principal 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 their organization to develop an application for 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 The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project.

Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD/PI model.

Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants. nih. gov/grants/multi_pi .

When multiple PDs/PIs are proposed, FDA requires one PD/PI to be designated as the "Contact PI, who will be responsible for all communication between the PDs/PIs and the FDA, for assembling the application materials outlined below, and for coordinating progress reports for the project.

The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above. Information for the Contact PD/PI should be entered in item 14 of the SF424 Research & Related (R&R) form. All other PDs/PIs should be listed in the (R&R) Senior/Key Person Profile and assigned the project role of PD/PI.

Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the Credential field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

All projects proposing multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project. For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan [item 7 of the PHS 398 Research Plan], must be included. A rationale for choosing a multiple PD/PI approach should be described.

The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award Involving a Single Institution When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget form.

All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section G.

310 of the SF424 (R&R) Application Guide for further instruction regarding the use of the This NOFO does not require cost sharing as defined in the HHS Information on Eligibility Applicant organizations may submit more than one application, provided that each application is The FDA will not accept duplicate or highly overlapping applications under review at the same time.

This means that the FDA will not 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 IV. Application and Submission Information 1.

Requesting an Application Package 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 NOFO. 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 notice of funding opportunity to do otherwise.

Conformance to the requirements in the SF424 (R&R) Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted helpful, though it is not required, is not binding, and does not enter into the review of a subsequent application. The information that it contains allows FDA staff to estimate the potential review workload and plan the review.

No responsiveness decisions will be made based on the letter of intent. By the date listed in Part 1.

Overview Information , prospective applicants are asked to submit a letter of intent that includes the following Descriptive title of the Main Proposed Clinical Name(s), address(es), and telephone number(s) of Names of other key personnel Participating institution(s) Number and title of this funding opportunity The letter of intent should be sent via electronic mail as a PDF file with the NOFO Number and the Institution's Name in the message subject heading to: Grants Management Specialist Director, Orphan Products Grants Program All page limitations described in the How to Apply Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements: For this specific NOFO, the Research Strategy section is A resubmission application must include an Introduction Section of the Research Strategy (1 page maximum) addressing the most recent objective review critique (Summary Statement).

Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this NOFO. SF424 (R&R) Application Guide must be followed, with the following additional instructions: only to Resubmission, Renewal, and Revision Applications: a. Federal Identifier - The Federal Identifier is required.

Include only the IC and serial number of the previously assigned award number (e.g., use FD007777 from TYPE OF APPLICATION - select one of the following: Check this option when submitting a revised (altered or corrected) or amended application. Please see additional Resubmission requirements under the Research - Check this option if you are requesting additional funding for a period subsequent to that provided by a current award.

Please see additional Renewal requirements under the Research Strategy . Check this option for competing revisions and non-competing administrative Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed. Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed.

Senior/Key Person Profile 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 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.

requesting additional funding (up to $250,000 total costs per year) for innovative and efficient trial approaches must submit a clear description and justification as to how they have met the requirements as outlined in the Appendix Section below (limited to 3 pages). This description and justification must be included as an appendix to the application. Applications not meeting these requirements may be requested to reduce their budget.

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 If the applicant organization has never established an indirect cost rate and/or does not have a negotiated Federal indirect cost rate agreement, a de minimis indirect cost rate of 10 percent (10%) of modified total direct costs (MTDC) will be allowed.

MTDC means all direct salaries and wages, applicable fringe benefits, materials and supplies, services, travel, and subaward and subcontracts up to the first $25,000 of each subaward or subcontract. MTDC excludes equipment, capital expenditures, charges for patient care, rental costs, tuition remission, scholarships and fellowships, participant support costs and the portion of each subaward and subcontract in excess of $25,000.

Indirect/F&A costs under grants to foreign and international organizations will be funded at a fixed rate of 8 percent of modified total direct costs (MTDC), exclusive of tuition and related fees, direct expenditures for equipment, and subawards in excess of $25,000. (With the exception of the American University of Beirut and the World Health Organization, which are eligible for full F&A cost reimbursement).

Awards to domestic organizations with a foreign or international consortium participant may include 8 percent of MTDC, exclusive of tuition and related fees, direct expenditures for equipment, and subawards in excess of $25,000. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional following sections should be included under the Research Strategy following the guidelines in Section V.

Application Review Information: Inclusion of Patient Input Investigator(s), Infrastructure, and Financial Resources Ability to Advance the Current Field The Rationale Section of the Research Strategy should also include a subsection with the specific heading Rare Neurodegenerative Disease Population/Prevalence. This subsection must include documentation that the disease or condition to be studied is a rare neurodegenerative disease.

Specifically, neurodegenerative diseases occur when nerve cells in the brain or peripheral nervous system lose function over time and ultimately die. In general, they are incurable and debilitating conditions and are progressive. In addition to being neurodegenerative, the disease must also be rare.

The term rare disease or condition is defined in 21 U.S.C. 360ee. Generally, FDA considers drugs, devices, and medical foods potentially eligible for grants under this grant program if they are indicated for a disease or condition that has a prevalence of fewer than 200,000 people in the United States or in the case of an acute disease (i.e., less than 1 year duration), an annual incidence of less than 200,000 per year.

(Please Note: Applications may be considered for the use of a product in an orphan subset of a non-rare disease or condition when the applicant can explain based on a characteristic or feature of the product (e.g., mechanism of action, toxicity profile, prior clinical experience) why the product will be limited to use in the subset of question.

An orphan subset is not based on an unmet need, or how a sponsor may wish to study or indicate a product. The explanation for the orphan subset must make it clear to OOPD that the product would not be appropriate in the disease or condition outside of the subset, including pediatric subpopulations).

For studies proposing assessing multiple rare neurodegenerative diseases, supportive prevalence data for each rare neurodegenerative disease is required. information may be required upon request, for example, regarding population This additional information may be required, in part, to assure that human clinical trials of drugs are eligible to receive funding under the OOPD Grants Program. 21 U.S.C.

360ee(b)(1)(A). See Section VIII, Other Information - Required Federal Citations , for policies related to this Section of the Research Strategy should also include a subsection with the specific heading Support of Product Development. This subsection should include an explanation of how the proposed study will either help support product approval or provide essential data needed for product development.

If the proposal is for multiple products or multiple rare neurodegenerative diseases, a plan as to how the applicant intends to proceed with product development (potentially in collaboration with multiple sponsors) should be provided in the grant application. any application in response to this NOFO that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application.

However, FDA will accept a resubmission application addressing the criteria in this announcement. A resubmission application must include an Introduction Section of the Research page maximum) addressing the most recent objective review critique (Summary Statement). The Summary Statement issued from the Office of Orphan Products Development must be included as an Appendix in the resubmission application.

A resubmission application must otherwise also be complete and stand-alone from previous versions. Resubmissions are intended for those applications that were previously submitted to OOPD, reviewed and received a score on the application.

Note: Only previously submitted applications to the FDA Rare Neurodegenerative Disease Grants program that received a numeric score will be accepted as a resubmission to this The Study Design Section of the Research Strategy should include a subsection with the specific heading "Study Monitoring Plan." This subsection should include a proposed plan for monitoring.

The specific approach to monitoring will depend on features of the clinical trial to be conducted e.g., several levels of monitoring: Data and Safety Monitoring Board (DSMB), Study Monitoring Committee (SMC), and Independent Medical Monitor (IMM). Monitoring activities should be appropriate to the study, study phase, population, research environment, and degree of risk involved. Guidance is available at: https://www.

fda. gov/media/116754/download . This section will detail the parties responsible for monitoring, what will be monitored, and the frequency (which will depend on such factors as the study design, interventions and anticipated recruitment rate).

The plan will specify individual and study "stopping guidelines" and other criteria for the monitors to follow. Guidance on these topics is available at: http://www. fda.

gov/downloads/RegulatoryInformation/Guidances/UCM127073. pdf For Renewal applications, the Research Strategy should include a brief Progress Report that summarizes Progress to Date and accomplishments achieved during the current funding period.

The Progress Report should include a summary of the specific aims of the previous project period and the importance of the findings, progress made towards achievements, explanation on any significant changes to the specific aims and any new of support should not be included as part of the Research Strategy and instead should be uploaded to line 9 on the PHS 398 Research Plan Form.

Letters of support should be included for the following Study Sites: The leader(s) of the existing clinical research institutions that will conduct the study should describe their site support, including relevant resources and study infrastructure and an estimate of the number of patients with the target rare disease(s) who would be eligible for the study; There must be evidence that the product(s) to be studied is available to the applicant in the form and quantity needed for the clinical trial proposed.

A current letter(s) from the supplier as an appendix will be acceptable. If negotiations regarding the supply of the study product(s) are underway but have not been finalized at the time of application, please provide a letter indicating such in the application.

Verification of adequate supply of study product(s) will be necessary before an award is made; Patient Engagement: There must be evidence that patient input has been obtained in a meaningful way. A current letter(s) from patient(s)/caregiver(s)/patient organizations describing early and ongoing engagement in trial design should be provided.

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: applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Only limited Appendix materials are allowed.

Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide , with the following additional requirements: Do not use the Appendix section to circumvent page limits. The Appendices must include the following, as appropriate The full final protocol (IND/IDE submitted protocol) must be provided. 2.

Informed Consent: Consent forms, assent