Natural History Studies Addressing Unmet Needs in Rare Diseases (R01)

Natural History Studies Addressing Unmet Needs in Rare Diseases (R01) is sponsored by FDA. Supports natural history studies to advance medical product development in rare diseases.

RFA-FD-25-017: Reissue of RFA-FD-22-001 - Efficient and Innovative Natural History Studies Addressing Unmet Needs in Rare Diseases (R01 Clinical Trials Optional) Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) U.S. Food and Drug Administration ( FDA ) 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 Objective Review Process.

Components of Participating Organizations Office of Orphan Products Development ( OOPD ) Funding Opportunity Title Reissue of RFA-FD-22-001 - Efficient and Innovative Natural History Studies Addressing Unmet Needs in Rare Diseases (R01 Clinical Trials Optional) R01 Research Project Grant Funding Opportunity Number (FON) Companion Funding Opportunity See Part 2, Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s) Funding Opportunity Purpose The purpose of this notice of funding opportunity (NOFO) is to support efficient and innovative natural history studies that advance medical product development in rare diseases/conditions with unmet needs.

Through the support of natural history studies with high quality and interpretable data elements, FDA expects to address critical knowledge gaps, remove major barriers to progress in the field, exert a significant and broad impact on a specific rare disease or multiple rare diseases with similar pathophysiology, and facilitate rare disease product development.

Funding Opportunity Goals The goal of this notice of funding opportunity (NOFO) is to support prospective or retrospective, efficient, and innovative natural history studies with a focus on collaborative and standardized approaches to ensure data quality and interpretability. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) February 10, 2026 by 11:59 PM Eastern Time. February 8, 2028 by 11:59 PM Eastern Time.

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. Applicants should be aware that on-time submission means that an application is submitted error free (of both Grants. gov and eRA Commons errors) by 11:59 PM Eastern Time on the application due date.

All applications are due by 11:59 PM Eastern Time. 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. No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

AIDS Application Due Date(s) September 2026; September 2028 Required Application Instructions Conformance to all requirements, both in the the Research (R) Instructions How to Apply - Application Guide and in the NOFO, is required and strictly enforced.

Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV of this NOFO or an applicable related Notice posted to the Guide for Grants and Contracts . When the program-specific instructions deviate from those in the How to Apply - 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 NIH and Department of Health and Human Services partners.

You must use one of these submission options to access the application forms for this opportunity. Use the NIH ASSIST system to prepare, submit and track your application online. 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. Workspace to prepare and submit your application and eRA Commons to track your application.

Part 1. Overview Information Part 2. Full Text of Announcement Section I.

Notice of 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 Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description 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 rare diseases or conditions.

Rare diseases, as generally defined in the US Orphan Drug Act (ODA), are diseases or conditions with a prevalence of fewer than 200,000 persons in the US. Approximately 30 million Americans are affected by more than 10,000 known rare diseases but only a few hundred have approved treatments.

Unlike common diseases, there is little existing knowledge on the initial manifestations, major symptoms and limitations of day-to-day function, which makes drug development challenging. To address this, it is critical to study the natural history of rare diseases.

Per the March 2019 FDA Draft Guidance for Industry and Other Stakeholders entitled, Rare Diseases: Natural History Studies for Drug Development : The natural history of a disease is traditionally defined as the course a disease takes in the absence of intervention in individuals with the disease, from the disease’s onset until either the disease’s resolution or the individual’s death.

A natural history study is a preplanned observational study intended to track the course of the disease. Its purpose is to identify demographic, genetic, environmental, and other variables (e.g., treatment modalities, concomitant medications) that correlate with the disease’s development and outcomes.

Natural history studies are likely to include patients receiving the current standard of care and/or emergent care, which may alter some manifestations of the disease.

Information obtained from a natural history study plays an essential role at every stage of product development, such as identifying the patient population, identifying or developing clinical outcome assessments and biomarkers, and when appropriate, serving as external controls. Natural history studies are observational/non-interventional in nature and may be retrospective or prospective.

To ensure that natural history studies provide optimal support for rare disease product development, it is critical to have standardized approaches to ensure data quality. Natural history studies should have well-defined and documented protocols before study initiation, while potentially incorporating flexible and innovative approaches in study design as the understanding or treatment of the disease evolves.

Further, given the limited number of patients affected by a given rare disease and the potential for patients to be geographically dispersed or considering enrollment in other natural history studies or clinical trials, collaborative and efficient approaches are fundamental.

Development of Biomarkers and COAs in conjunction with Natural history study: The development and/or validation of biomarkers and clinical outcome assessments for rare diseases in conjunction with a prospective natural history study are also essential for clinical trial design and identification of appropriate endpoints.

Biomarkers are a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. Molecular, histologic, radiographic, or physiologic characteristics are types of biomarkers.

A digital biomarker is a characteristic or set of characteristics, collected from digital health technologies, that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. A biomarker is not an assessment of how an individual feels, functions, or survives.

They can be used to diagnose disease or define disease subtypes, determine susceptibility/risk, assess prognosis, monitor disease, predict therapeutic response. FDA encourages applicants to refer to the FDA Resources About Biomarkers and Qualification for biomarker FAQs and guidance . A COA is a measure that describes or reflects how a patient feels, functions, or survives.

Types of COAs include Patient-reported outcome (PRO) measures; Observer-reported outcome (ObsRO) measures; Clinician-reported outcome (ClinRO) measures; and Performance outcome (PerfO) measures. COAs are used to capture data which measure treatment benefit or risk in medical product clinical trials. FDA encourages applicants to refer to FDA Resources About COAs for FAQs and guidance.

This FOA is intended to support prospective or retrospective, efficient, and innovative natural history studies with a focus on collaborative and standardized approaches to ensure data quality and interpretability. FDA encourages consideration of assessment timings that will be used in future clinical trials when planning natural history.

Applicants should refer to " Rare Diseases: Natural History Studies for Drug Development, Guidance for Industry " for guidance on the conduct of a natural history study, considerations to enhance interpretability of study results, and discussion on data collection standards and data quality and integrity.

FDA 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 Guidance Documents for Rare Disease Drug Development for selected guidances relevant to rare disease drug development and information on the Orphan Products Grants Program website before applying for this opportunity. FDA is interested in supporting natural history studies that address unmet needs in rare diseases.

To that end, and based on the criteria outlined below, FDA has identified the following areas of interest for the purpose of this NOFO: 1. Ability to exert a significant impact in the field of rare diseases for future clinical trials. 2.

Inclusion of high quality, interpretable data using well-defined protocols with a rigorous and standardized approach to data collection and analysis, utilization of common data elements, plans for minimization of bias, data sharing across sites, data dissemination and collaborative use of data. 3. Use of existing infrastructure, resources, and collaboration among stakeholders in industry, academia, and patient organizations.

Innovative and Efficient Trial Approaches: FDA is interested in supporting innovative and efficient trial designs supporting the advancement of drug development for rare diseases and will allow for additional funding with justification for applications proposing the use of one or more of the following: Prospective natural history studies collecting longitudinal clinical data in conjunction with the development of drug development tools such as clinical outcome assessments and/or biomarkers.

Natural history studies using machine learning and/or data modeling and simulation to enhance trial population enrichment through a better understanding of such things as susceptibility/risks to disease outcomes, disease progression, and defining disease subtypes. 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 activity. Application Types Allowed The OER Glossary and the How to Apply - Application Guide provide details on these application types.

Only those application types listed here are allowed for this NOFO. Optional: Accepting applications that either propose or do not propose clinical trial(s). Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards The number of awards is contingent upon Congressional appropriations to this FDA grants program 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 up to three (3) additional year(s) contingent upon annual appropriations, availability of funding and satisfactory awardee performance.

See Background for definitions of types of studies ( Section I. 1 ). Prospective Natural History Studies 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) and maximum years of support: Retrospective Natural History Studies See Background for definitions of types of natural history studies ( Section I.

1 ). Applicants may request additional funding over the above listed maximums for certain innovative and efficient trial designs. The additional funding request shall not exceed an additional $200,000 total costs per year (to a maximum total award cost of $600,000 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 IV. 2 ).

The scope of the proposed project should determine the project period. Prospective Natural History Studies The maximum project period is four (4) years, however, the length of the study will depend on the nature of the study. Retrospective Natural History Studies The maximum project period is two (2) years, however, the length of the study will depend on the nature of the study.

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, as 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 Education Private Institutions of Higher Education 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 Businesses) 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 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 Non-domestic (non-U.S.) Entities (Foreign Organizations) Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations 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. NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.

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

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

gov Applicants must have an active SAM registration in order to complete the Grants. gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account.

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

Eligible Individuals (Program Director/Principal Investigator) 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 their organization to develop an application for 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 How to Apply - Application Guide .

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below.

More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants. nih.

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

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

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

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

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

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

Applications Involving a Single Institution When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide. Applications Involving Multiple Institutions When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subaward to be administered by the prime institution.

When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget form. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section R.

310 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form. This NOFO does not require cost sharing as defined in the HHS Grants Policy Statement . 3.

Additional Information on Eligibility 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, per 2. 3.

7. 4 Submission of Resubmission Application . 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. An application that has substantial overlap with another application pending appeal of initial peer review (see 2. 3.

9. 4 Similar, Essentially Identical, or Identical Applications ). Section 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.

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows FDA staff to estimate the potential review workload and plan the review. No responsiveness decision will be made based on the letter of intent.

By the date(s) listed in Part 1.

Overview Information , prospective applicants are asked to submit a letter of intent that includes the following information: Descriptive title of proposed 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 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: 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 limited to 12 pages.

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 How to Apply - Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply - Application Guide must be followed. Applicable only to Resubmission, Renewal, and Revision Applications: For field 4. 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 1U01FD007777-01). For field 8.

TYPE OF APPLICATION - select one of the following: Resubmission - Check this option when submitting a revised (altered or corrected) or amended application. Please see additional Resubmission requirements under the Research Strategy. Renewal - 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 . Revision - Check this option for competing revisions and non-competing administrative supplements. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information All instructions in the How to Apply - Application Guide must be followed. SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply - Application Guide must be followed. All instructions in the How to Apply - 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.

Applications requesting additional funding (up to $200,000 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. Description of any additional funds expected to be contributed by other sources (including the applicant) to the study prior to FDA grant funding and those to be used during the proposed funding period should be included and described in the budget justification section separate from FDA request justification.

Details should be provided on total amounts, location of sources, and confirmation if these funds have been secured. If an applicant is requesting indirect costs as part of their budget, a copy of the most recent Federal indirect cost rate or F&A agreement must be provided as part of the application submission.

This agreement should be attached to the RESEARCH & RELATED Other Project Information Component as line #12 ‘Other Attachments’ If the applicant organization has never established an indirect cost rate and/or does not have a negotiated Federal indirect cost rate agreement, a de minimis indirect cost rate of 10 percent (10%) of modified total direct costs (MTDC) will be allowed.

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

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

Awards to domestic organizations with a foreign or international consortium participant may include 8 percent of MTDC, exclusive of tuition and related fees, direct expenditures for equipment, and subawards in excess of $25,000. All instructions in the How to Apply - Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the How to Apply - Application Guide must be followed.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions: Research Strategy: The following sections should be included under the Research Strategy following the guidelines in Section V. Application Review Information: 3. Inclusion of Patient Input 4.

Investigator(s), Infrastructure and Financial Resources 5. Ability to Advance the Current Field The Rationale Section of the Research Strategy should also include a subsection with the specific heading “Rare Disease Prevalence. ” This subsection should include documentation to support that the estimated prevalence of the orphan disease or condition in the United States is 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.

For studies proposing assessing multiple rare diseases, supportive prevalence data for each rare disease is required. Additional information may be required upon request, for example, regarding population estimate and rationale. 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 announcement.

Support of Product Development: The Rationale Section of the Research Strategy should also include a subsection with the heading “Support of Product Development.

” This subsection should include an explanation of how the proposed study will address critical knowledge gaps, to remove major barrier(s) to progress in the field, exert a significant and broad impact on a specific rare disease or multiple rare diseases with similar pathophysiology, and meet data standards to inform rare disease product development.

If the proposal is for multiple products or multiple rare diseases, a plan as to how the applicant intends to proceed with product development in collaboration with multiple sponsors should be provided in the grant application. FDA will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application.

However, the FDA will accept a resubmission application addressing the criteria in this announcement. A resubmission application must include an Introduction Section of the Research Strategy (1 page maximum) addressing the most recent objective review critique (Summary Statement). The Summary Statement issued from OOPD 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. The Study Design/Data Quality and Interpretability Section of the Research Strategy should include a further subsection with the heading "Study Monitoring Plan."

This subsection should include a proposed plan for monitoring. This subsection should include a proposed plan for monitoring. The specific