INCLUDE Project: Clinical Trials Phased Awards for Down syndrome Research (R61/R33 Clinical Trial Required)

INCLUDE Project: Clinical Trials Phased Awards for Down syndrome Research (R61/R33 Clinical Trial Required) is sponsored by National Institutes of Health. Supports phased clinical trials for Down syndrome research.

RFA-OD-27-005: INCLUDE Project: Clinical Trials Phased Awards for Down syndrome Research (R61/R33 Clinical Trial Required) Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations Office of The Director, National Institutes of Health ( OD ) National Heart, Lung, and Blood Institute ( NHLBI ) National Institute of Arthritis and Musculoskeletal and Skin Diseases ( NIAMS ) Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) National Institute on Deafness and Other Communication Disorders ( NIDCD ) National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) National Center for Advancing Translational Sciences ( NCATS ) National Cancer Institute ( NCI ) Office of The Director, National Institutes of Health ( OD ) Funding Opportunity Title INCLUDE Project: Clinical Trials Phased Awards for Down syndrome Research (R61/R33 Clinical Trial Required) R61 / R33 Exploratory/Developmental Phased Award Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3. Additional Information on Eligibility .

Assistance Listing Number(s) 93. 310, 93. 395, 93.

837, 93. 838, 93. 839, 93.

840, 93. 233, 93. 865, 93.

847, 93. 350, 93. 846, 93.

866, 93. 173 Funding Opportunity Purpose The NIH INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project seeks to improve health and quality-of-life for individuals with Down syndrome.

The purpose of this Notice of Funding Opportunity (NOFO) encourages Exploratory/Developmental Phased Innovation (R61/R33) grant applications to support development of clinical trials to treat critical and co-occurring health conditions in individuals with Down syndrome. The proposed research aims should be milestone-driven. The total project period for an application submitted in response to this NOFO may not exceed five years.

This NOFO provides support for up to two years (R61 phase) for preliminary/developmental/planning studies, followed by possible transition to clinical trial support (R33) of up to three years, although the total duration of the award may not exceed five years. This NOFO requires measurable R61 milestones.

Funding Opportunity Goal(s) This listing covers multiple offices in the NIH Office of the Director that offer assistance awards or supplements to assistance awards. Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization.

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.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) 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.

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. Use Grants. gov 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 NIH INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project seeks to improve health and quality-of-life for individuals with Down syndrome. This NOFO requests research grant applications to support development of clinical trials to treat critical and co-occurring health conditions in individuals with Down syndrome.

The overarching emphasis is on the acquisition of knowledge that can be translated into new, enhanced, or tailored therapies for treating Down syndrome and its co-occurring conditions. Applications should focus on delivering better healthcare outcomes and should seek solutions that are effective and deliverable.

This NOFO will support clinical trial research to develop or test new and innovative adaptations of current drugs, interventions, and therapies for the treatment and management of co-occurring conditions in Down syndrome. These therapies should be implementable and sustainable in clinical settings beyond the research environment.

Research applications may address a particular co-occurring condition at a particular stage of development or across the lifespan in people with Down syndrome. Outcomes research and health services research related to Down syndrome are also responsive to this NOFO.

Since some aspects of this research area may be new for the NIH scientific community, there will likely be a need to obtain preliminary data or conduct early-stage clinical trial preparatory activities before moving to a full-scale project. The Exploratory/Developmental Phased Innovation (R61/R33) grant mechanism is appropriate for this purpose.

It provides opportunities for creating, developing, and strengthening new and necessary collaborations, as well as acquisition of preliminary data, and allows for milestone-driven research, supporting a phased research project with a stepped approach for implementation of a clinical trial.

Those that are more basic science focused may be more appropriate for RFA-OD-27-004 INCLUDE Project: Transformative Research Awards for Down syndrome (R01 Clinical Trial Not Allowed). Applications not requiring a phased research approach are encouraged to apply under a different funding mechanism (e.g., investigator-initiated R21 or R01).

Down syndrome is the most common genetic cause of intellectual disability, the most common autosomal trisomy, and one of the most visible and universally recognized genetic syndromes. Each year there are approximately 5300 babies born in the United States with Down syndrome. Within the past 25 years, the average lifespan for a person with Down syndrome has doubled, from 30 to 60 years.

Despite this increase in lifespan, individuals with Down syndrome and their families face significant and changing health challenges with age, and they have often been excluded from participation in research that could improve their health outcomes and quality of life.

While all people with Down syndrome are connected by the common feature of a complete or partial copy of chromosome 21 (trisomy 21), there are significant physical and cognitive differences among them, indicating that inter-individual variability exists. Down syndrome is associated with an increased prevalence of autism and epilepsy.

The lifetime risk of Alzheimer's dementia is over 90% in individuals with Down syndrome with symptom onset a decade or two earlier than typical Alzheimer’s disease.

Individuals with Down syndrome also have high rates of hearing loss, eye abnormalities, congenital heart defects, sleep apnea, pulmonary hypertension, gastrointestinal malformations, thyroid disease, leukemia, and other autoimmune or immune dysregulation disorders including celiac disease.

However, people with Down syndrome infrequently develop solid tumors such as breast or prostate cancer, and despite multiple risk factors for coronary artery disease and high rates of obesity, sleep apnea, and type 1 diabetes, they rarely develop atherosclerosis or have myocardial infarctions.

Understanding this unique combination of risk and resiliencies will inform medical advances for individuals with Down syndrome, and for individuals who do not have Down syndrome but share these co-occurring conditions.

This NOFO is one of several trans-NIH research initiatives created in response to Omnibus Appropriations Reports starting in 2018, which encourage NIH to expand its current efforts on Down syndrome and common co-occurring conditions also seen in the general population, while increasing the pipeline of Down syndrome investigators.

Together, the initiatives are called the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Information about projects that were funded in prior years, as well as the NIH INCLUDE Down Syndrome Research Plan, are available on the INCLUDE Project website at https://www. nih.

gov/include-project . The INCLUDE Project has three components: Component 1: Conduct targeted, high-risk, high-reward basic science studies on chromosome 21 Component 2: Assemble a large study population of individuals with Down syndrome Component 3: Conduct clinical trials research inclusive of individuals with Down syndrome This NOFO addresses Component 3 of the INCLUDE project.

Specifically, it is designed to encourage research and increase infrastructure support of clinical trials for co-occurring conditions in individuals with Down syndrome.

This includes research on the development of technologies (e.g., wearables to monitor biomarkers of health), screening (e.g., effectiveness in typical primary care settings), access and management through new delivery systems (e.g., telehealth), system barriers (e.g., availability of services) as well as behavioral research at the individual patient level (e.g., patient outcomes).

Research is needed to develop or test new and innovative adaptations of current drugs, interventions, and therapies, for the treatment and management of co-occurring conditions in Down syndrome. Solutions should be implementable and sustainable in settings beyond the research environment and should have the potential to address disparities in health care for individuals with Down syndrome.

Infrastructure support may include the creation of research partnerships among interested organizations (e.g., academia, practice-based research networks, community-based health care organizations, industry, and professional and patient organizations).

It may also include support for creating pooled clinical data sets across institutions, agencies, or health care systems to analyze characteristics of patient populations, provider or health care settings and patient outcomes. Clinical trials researchers may focus on repurposing of existing therapies as well as developing new ones for the unique needs of the Down syndrome population.

Approaches could include: (1) obtaining de-identified clinical data, and working with the investigators of prior failed clinical trials to determine “lessons learned,” with a particular focus on inter-individual variation; (2) testing existing therapies for conditions that occur in both the general population and in people with Down syndrome, since their responses to therapy may not be the same as a result of differences in metabolism (for example, standard treatments for leukemia cause exaggerated toxicity in infants with Down syndrome); or (3) testing new therapies that may arise as a result of the basic science studies performed under the auspices of Component 1, building on the biobanked specimens and the participant data from Component 2.

Responsive R61/R33 applications must be milestone-driven and may include, but are not limited to, the following questions and research needs: Augment inclusion of cohorts of individuals with Down syndrome in clinical trials aimed at common neurological symptoms and syndromes (e.g., infantile spasms, cognitive decline, sleep apnea, cervical spinal cord dysfunction) and stratification of analyses to enable discernment of differences in response to therapy between individuals with and without Down syndrome.

Use existing clinical trials infrastructure (e.g., NeuroNEXT, NIA’s Alzheimer’s Clinical Trial Consortium, and NCATS-linked institutional networks) to bring agents proposed for use in Alzheimer’s disease that show promise in cognitive improvement in animal models of Down syndrome and related Alzheimer’s dementia to clinical trial in individuals with Down syndrome.

Use existing networks to explore epilepsy, including dementia-related epilepsy, in aging individuals with Down syndrome, given the peak of epilepsy in adulthood in this group. Studies could range from limited natural history studies in the planning phase to treatment trials in the R33 phase.

Since more than 50% of individuals with Down syndrome have sleep apnea, a study could provide robust evidence for treatment options, including surgical (e.g., mandibular advancement, tonsillectomy/adenoidectomy), and mechanical (continuous positive airway pressure (CPAP)). Clinical trials could compare individual strategies, or combinations of strategies.

In addition to improving hypoxia and sleep, an important question to answer in children is whether effective treatment of obstructive sleep apnea has an influence on future neurocognitive development. Computational modeling of airway flow using data from MRI could help identify optimal trial interventions.

Exploration of the use of immunosuppression to treat the neuroinflammation and abnormal immune responses in the brains of individuals with Down syndrome or general immune suppression targeted to the dysregulated immune system in those with Down syndrome.

The clinical trial preparatory and/or piloting portion of the research occurs during the R61 phase of the research plan, and implementation and/or clinical trial occurs within the R33 phase. Transition from the R61 phase to the R33 phase is contingent on successful completion of milestones delineated in the application and is subsequently approved by NIH staff (see Section IV. 6).

At the end of a successful R61/R33, it is expected that there will be measurable and documented advances to address critical health needs related to co-occurring conditions for individuals with Down syndrome. As an example, in the R61 portion of the application the PD/PI may propose pilot work in which investigators pilot delivery of a hearing intervention to individuals with Down syndrome and hearing loss using a new delivery system.

Upon proof of the feasibility of such an approach, the R33 phase would provide funds to perform a clinical trial on a larger population. A second example might be one in which a new technology is developed or refined. Upon completion of the technology development and readiness (R61 phase), the R33 phase would evaluate the utilization of this tool in a larger clinical population.

A third example may be one in which in the R61 phase, questionnaires are developed and piloted addressing relevant outcomes for those with Down syndrome and hearing loss. Upon completion, the R33 phase would utilize the questionnaire in a clinical trial.

Studies may include research focused on development or testing new and innovative adaptations of current drugs, interventions, and therapies, for the treatment and management of co-occurring conditions in Down syndrome. Innovative designs such as platform trials, adaptive, including real-time adaptive methods, seamless Phase I/II designs, and Bayesian designs are encouraged.

Decentralized trial elements, including remote informed consent, remote study visits, and wearable or at-home based data collection are also encouraged, as applicable and consistent with the FDA’s Final Guidance on Decentralized Clinicals. Investigators are strongly encouraged to contact NIH program staff to ensure that their applications are responsive.

Applications are assigned to participating Institutes and Centers (ICs) based on receipt and referral guidelines, and applications may be assigned to multiple participating ICs with related research interests. Applicants are encouraged to identify a participating IC that supports their area of research and to contact Scientific/Research staff from relevant ICs to inquire about their interest in supporting the proposed research project.

IC-specific funding priorities are listed on the INCLUDE website . Questions about the suitability of applications can also be addressed to the scientific/research (program) contact listed in the "Agency Contacts" section of this NOFO. Projects that propose to recruit subjects with Down syndrome are encouraged to promote enrollment of research subjects in the Down syndrome patient registry supported by NIH, DS-Connect® .

For biospecimens collected from human genetic or non-genetic studies, awardees are encouraged to use biorepositories designated by INCLUDE staff that meet requirements for broad sharing. An NIH resource describing Common Data Elements may be helpful during the planning phases of a project when considering ways to optimize data collection in order to facilitate broad data sharing.

For those applications that generate clinical data, it is expected that the data sharing plan will include the INCLUDE Data Coordinating Center (DCC) . Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs. 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. Required: Only accepting applications that propose clinical trial(s).

Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards NIH intends to commit an estimated $3,000,000 to fund up to 4 awards per year in FY2027, FY2028, and FY2029. The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Future year amounts will depend on annual appropriations. Application budgets for the R61 phase and the R33 phase are not limited but need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period.

The maximum period of the combined R61 and R33 phases is 5 years, with up to 2 years for the R61 phase and up to 3 years for the R33 phase. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO. Section III.

Eligibility Information Higher Education Institutions - Includes all types 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).

Eligible Agencies of the Federal Government 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) Foreign Organizations/International Collaborations 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. NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts.

All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16. 8 Collaborative International Research Awards .

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding.

This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components , funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

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 NIH Grants Policy Statement Section 2. 3. 9.

2 Electronically Submitted Applications 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. Foreign organizations must obtain a NATO Commercial and Government Entity (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.

All PD(s)/PI(s) must be registered with ORCID . The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help .

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. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 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 (in this NOFO, in a policy notice , or other notice from NIH Guide for Grants and Contracts ). 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. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. 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. 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.

Budgets should include all costs associated with Data Safety and Monitoring Board (DSMB) activities, including preparing reports for the DSMB, assessing DSMB member conflict of interest, meeting reimbursement for DSMB members, and support for at least one DSMB meeting per year. 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: The Research Strategy should contain separate subsections that describe the R61 and the R33 phases: The clinical trial preparatory and/or piloting portion of the research occurs during the R61 phase.

This subsection should describe the need for conducting the trial preparatory and/or piloting study activities. Applicants should describe the clinical trial needs (e.g., biomarker or clinical outcomes validation or qualification, feasibility studies, cohort development, etc.) that will be addressed by the R61 phase. The implementation and/or clinical trial occurs within the R33 phase.

This subsection should describe the clinical trial that will be initiated following successful completion of the milestones delineated in the R61 phase. Milestones and R61/R33 Transition The application must include milestones the researchers expect to achieve by the end of the R61 phase, as well as milestones for the R33 phase.

Milestones should be specific, quantifiable, and scientifically justified; they should not be a restatement of the specific aims for the R61 phase. It is recommended that PD(s)/PI(s) include a section labeled "milestones" describing milestones to be achieved during the R61 phase to qualify for the transition to the R33.

It is understood that the proposed milestones for the R33 phase may be revised based on activities during the R61 phase. In the event of an award, the PD(s)/PI(s) and NIH staff will negotiate the list of milestones for each award phase. Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide .

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions: A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page .

The DMS Plan must address the elements in the structured format should not exceed two (2) pages. Where the DMS Plan Format Page requires a “Yes or No” response, no additional narrative is allowed. Appendix: Only limited Appendix materials are allowed.

Follow all instructions for the Appendix as described in the How to Apply - Application Guide . No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- 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 How to Apply - Application Guide must be followed.

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 How to Apply- Application Guide must be followed. PHS Assignment Request Form All instructions in the How to Apply- Application Guide must be followed.

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement , and procedures for foreign organizations described throughout the How to Apply- Application Guide. 3. Unique Entity Identifier and System for Award Management (SAM) See Part 2.

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 4.

Submission Dates and Times Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day. Organizations must submit applications to Grants. gov (the online portal to find and apply for grants across all Federal agencies).

Applicants must then complete the submission process by tracking the status of the application in the eRA Commons , NIH’s electronic system for grants administration. NIH and Grants. gov systems check the application against many of the application instructions upon submission.

Errors must be corrected and a changed/corrected application must be submitted to Grants. gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2. 3. 9.

2 Electronically Submitted Applications . 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 How to Apply-Application Guide .

5. Intergovernmental Review (E. O.

12372) This initiative is not subject to intergovernmental review. All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement . Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.

9. 1 Selected Items of Cost. 7.

Other Submission Requirements