Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R01 Clinical Trial Optional)

Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R01 Clinical Trial Optional) is sponsored by National Institute on Aging (NIA) - NIH. This program supports research into novel mechanisms underlying neuropsychiatric symptoms in Alzheimer's dementia, which can be highly relevant to understanding and treating delirium in this population.

Expired PAR-20-157: Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R01 Clinical Trial Optional) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Mental Health ( NIMH ) National Institute on Aging ( NIA ) Funding Opportunity Title Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R01 Clinical Trial Optional) R01 Research Project Grant June 14, 2023 - This PAR has been reissued as PAR-23-207 NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022 October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available.

See Notice NOT-OD-22-018 . September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022.

See Notice NOT-OD-21-169 . August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170 April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel.

See Notice NOT-OD-21-109 April 10, 2020 - Notice of NIA Participation in PAR-20-157 . See Notice NOT-AG-20-027 . July 26, 2019- Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research.

See Notice NOT-OD-19-128 August 23, 2019- Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-137 Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity PAR-20-159 , R21 Exploratory/Developmental Grant See Section III. 3.

Additional Information on Eligibility . Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose The goal of this Funding Opportunity Announcement (FOA) is to encourage applications for studies that will enhance knowledge of mechanisms associated with neuropsychiatric symptoms (NPS) in persons with Alzheimer's disease (AD) or Alzheimer's disease-related dementias (ADRD).

The findings are expected to advance mechanistic understanding of both biobehavioral and neurobiological pathways leading to NPS. Findings may also provide insight into novel therapeutic targets that can be advanced into interventions to treat and prevent the development of NPS in AD and/or ADRD. This FOA uses the R01 mechanism, while the companion announcement PAR-20-159 uses the R21 mechanism.

High risk/high payoff projects that lack preliminary data or utilize existing data may be most appropriate for the R21 mechanism. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) The first standard due date for this FOA is June 5, 2020 All applications are due by 5:00 PM local time of applicant organization.

All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s). 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.

AIDS Application Due Date(s) Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide ,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced.

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

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

Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Part 2. Full Text of Announcement Section I.

Funding Opportunity Description The goal of this Funding Opportunity Announcement (FOA) is to encourage biomedical, behavioral and social sciences research that will enhance knowledge of mechanisms underlying neuropsychiatric symptoms (NPS) in persons with Alzheimer's disease (AD) or Alzheimer's disease-related dementias (ADRD) so as to enable novel treatment development.

NPS, or Behavioral and Psycholgical Symptoms of Dementia (BPSD), include (but are not limited to) aggression, psychosis, anxiety, apathy, depression, agitation, sleep disturbances and wandering, and can be significant challenges to the care and treatment of people with dementia. These symptoms lead to accelerated declines in both functional abilities and may lead to earlier nursing home placement.

Currently, few pharmacological treatments are available. In addition, there is a need to understand behavioral and environmental targets to further refine and develop promising behavioral treatments for these disorders. The demand for novel treatment approaches highlights the importance of identifying and dealing with the underlying causes of these symptoms among older adults with dementia.

There is an urgent need to advance the mechanistic understanding of these problems to identify new treatment targets. The National Plan to Address Alzheimer's Disease specifically calls for the development of better treatments for the behavioral and psychiatric complications due to the disease.

This FOA is intended to support research designed to identify the neurobiological, behavioral, and social mechanisms underlying NPS in AD/ADRD in order to deepen our understanding of the pathways and contextual factors involved.

Research that assesses NPS dimensionally, integrating across multiple levels of analysis and employing cutting-edge methodology from fields such as cognitive and affective neuroscience, including neuroimaging, neurophysiology, gene expression and epigenetics, and behavioral intervention research, is encouraged.

Both basic neuroscience work examining models of NPS and translational approaches to understanding neural circuits involved in the expression of NPS are encouraged. Research that seeks to clarify mechanism of action of evidence-based treatments or proposes to examine potential biomarkers of treatment response is encouraged and will be accepted if it fits under the NIH mechanistic clinical trials framework.

The research supported under this FOA is expected to advance mechanistic understanding of neuropsychiatric syndromes in AD/ADRD and underlying neurobiology that will advance the field. Such findings may identify modifiable targets for further intervention development in this area.

Some portion of NPS stem from problems in recognizing and rendering appropriate care for treatable issues in persons with limited cognitive and communicative abilities. Issues, such as medical comorbidities, physical pain/discomfort, hydration, boredom/socialization, etc., can become "unmet needs" that find expression in the form of NPS if not recognized and properly addressed.

Research is needed to establish underlying causes for NPS symptoms resulting from these "unmet needs" in order to develop and implement effective methods for screening and handling such issues across the spectrum of typical care settings.

The use of constructs from NIMH's Research Domain Criteria (RDoC) initiative , or of RDoC-compatible approaches, in assessing NPS or associated factors, such as emotion processing, other component aspects of mental disorders, and/or related domains of brain function, is encouraged. RDoC has defined a set of dimensional constructs that may be useful in this research.

Applicants may propose to examine dimensional constructs that do not appear in the NIMH RDoC matrices as long as there is strong theoretical support for their relevance to a mechanistic understanding of NPS.

Applicants should cite substantial evidence for the validity of such constructs and indicate strong theoretical support that the construct maps onto a specific biological system, such as a brain circuit or physiological pathway thought to be involved in specific aspects of NPS.

With respect to assessing psychopathology or mental disorder, an RDoC approach encourages taking a dimensional perspective that is, concentrating on aspects of behavior and brain function that span a range from intact to gradations of impairment, independent of diagnosis.

Thus, in such an approach, recruitment and eligibility of study participants need not be determined on the basis of traditional diagnostic categories, but should instead be based on criteria that result in a sample that is optimized to study the clinical phenomena of interest over their full range of variability.

Such an emphasis on understanding the full dimensionality of neurobehavioral functioning generally precludes simple, dichotomous designs comparing patients versus controls.

Under this FOA, if an RDoC or other dimensional construct is proposed to serve as the primary variable representing psychopathology (as opposed to using a diagnostic characterization), the study design and sampling plan must be such as to assure that an adequate number of individuals assessed as falling within the more severely impaired ranges of that dimension will be included in the study.

Areas of research interest for this FOA include, but are not limited to: Improved understanding of the neurobiological and behavioral mechanisms underlying NPS syndromes in AD and related dementias; Assessments of neural circuits involved in apathy or other NPS in AD/ADRD, as compared to other neuropsychiatric diseases; Examination of circadian rhythm disruptions as related to the manifestation of agitation and other disruptive behaviors; Defining and clarifying specific irregularities of perception, cognition, emotion processing or other basic psychological functions, and their neurobiological correlates, that are associated with particular forms of NPS in persons with AD/ADRD; Evaluation of differences in the brain circuits or cortical areas recruited during emotional challenge or cognitive task performance in individuals with MCI or AD/ADRD, and whether such differences predict vulnerability to or resilience against onset of NPS; Examination of the role of prior psychiatric disorder or other historical factors as influences on the development or expression of NPS syndromes in AD/ADRD; Utility of passive sensing technology to more precisely and comprehensively characterize the behavioral patterns, circadian and other neurophysiological fluctuations, environmental exposures, and like factors associated with NPS in persons with AD/ADRD; Identification and regulation of clinically relevant brain circuits and/or neurobiological systems that may be targets for treatment development or mechanisms of NPS pathophysiology; Development of outcome measures that are clinically meaningful to AD/ADRD patients and caregivers; Development of clinically useful biomarkers to predict NPS onset and/or treatment outcome; Utility of computational approaches to identify predictive and/or explanatory patterns of factors associated with NPS in available extensive datasets; Elucidation, refinement and implementation of criteria for distinguishing subjects with NPS syndromes that are not resolvable via appropriate attention to their unmet needs.

Examples of studies that are not supported by this FOA include the following: Applications that assess potential NPS mechanisms at only a single level of observation and analysis (i.e., without combining multiple levels/methods such as genetic, cellular, brain circuit, physiological, behavioral, self-report); Areas of research of high programmatic relevance to the National Institute on Aging (NIA): In addition to the research areas listed above, NIA is interested in the following lines of investigation: Research that integrates epidemiologic, genomic and mechanistic research through the application of systems and network biology to understand the dynamic relationship between NPS and AD/ADRD pathogenesis across diverse populations.

Systems-based approaches aiming to examine the role of the gut-brain axis and the microbiome in the emergence of NPS in AD and as a mediator of the efficacy of interventions targeting NPS.

Research that aims to generate multi-omic data using biosamples from existing or legacy clinical trials targeting NPS in AD/ADRD (with pharmacologic and non-pharmacologic interventions) and apply a variety of computational approaches to interrogate disease mechanisms and to identify the molecular determinants of responsiveness to treatment.

Research aimed at preclinical validation of novel candidate targets nominated by the Accelerated Medicines Partnership for Alzheimer’s Disease program (AMP-AD), to test their utility as therapeutic targets for NPS in AD/ADRD. A list of nominated targets along with the associated data and druggabillity information can be accessed through the NIA-supported AGORA platform.

NIA strongly encourages applications that developed through academic-industry collaborations. Applicants are also encouraged to integrate across in silico and experimental approaches and across human, cell-based, and animal model studies.

In keeping with NIA's and NIMH's goals to enhance transparency of reporting and enable reproducible and translatable discovery research, applicants are expected to make all data, analytical methods and outputs, and research tools available to the broad scientific community prior to publication via the NIA-supported AMP-AD Knowledge Portal, the NIMH Data Archive, and/or related NIH designated data repositories.

Applications to the NIMH should have a Resource sharing plan as described in NOT-MH-19-033. Applicants should include appropriate support for annotation and curation of the molecular and clinical data types used and/or generated on the project to maximize the usability of the data by the broader research community for various types of meta-analyses and systems biology research.

This FOA will support mechanistic clinical trials, defined by the NIH to include studies designed to understand a biological or behavioral process, or the pathophysiology of a disease process, through a manipulation of that process, or to understand the mechanism of action of an intervention) see NOT-OD-15 -015.

This FOA will not support studies whose purpose is to evaluate safety; clinical efficacy, effectiveness, and management; and/or implementation of new interventions. See the NIMH Clinical Trials website for further details about submission of mechanistic clinical trials to NIMH. NIA supports clinical trials focused on safety, efficacy, and effectiveness under PAR-18-877 and PAR-18-878 .

If the proposed research involves neuroimaging methods, applicants are encouraged to incorporate use of protocols from the Human Connectome Project , assuming that the research addresses constructs that have been previously examined in the Human Connectome Project and that such protocols are available to the investigator. See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed Resubmission from RFA-MH-19-510 or this FOA The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Only those application types listed here are allowed for this FOA. 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 NIH appropriations and the submission of a sufficient number of meritorious applications.

Application budgets 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 project period is 5 years.

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

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education: Hispanic-serving Institutions Historically Black Colleges and Universities (HBCUs) Tribally Controlled Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Institutions Asian American Native American Pacific Islander Serving Institutions (AANAPISIs) Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (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 Institutions) Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.

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

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

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

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 his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement. 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. 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 NOT-OD-11-101 ) 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 FOA. 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 SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review.

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed Instructions for Application Submission Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages.

For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages. The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA. All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) 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. All instructions in the SF424 (R&R) Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide must be followed.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.

All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Significance : Applicants should describe how the project has the potential to link mechanisms and/or risk factors to neuropsychiatric symptoms across levels of analysis that may inform novel intervention development.

Applicants should clarify the neurobiological and or behavioral mechanisms underlying NPS syndromes in AD and related dementias. Innovation: Applicants should define the current state of the science as a benchmark against which the proposed paradigm, model and/or assay will be measured.

Applicants should describe how and to what extent the resulting paradigm, model and/or assay has the potential to result in a significant improvement in terms of advancing scientific knowledge toward linking mechanisms and/or risk factors to neuropsychiatric symptoms.

Applications should also integrate multiple levels of analysis with regard to understanding the dynamic relationships between NPS symptoms and AD pathogenesis Approach: Applicants should provide the information below. Provide an appropriate theoretical justification for the proposed approach including the potential to further scientific understanding of the mechanisms of neuropsychiatric symptoms.

For imaging studies, an examination of neural circuits involved in NPS in AD/ADRD as compared to other neuropsychiatric diseases. For animal studies, well validated models of the circuitry involved in the NPS model proposed, with corresponding validates behavioral assays that target those circuits.

Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide. The following modifications also apply: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

In order to advance the goal of furthering research by widespread data sharing among researchers, investigators funded under this FOA are expected to share those data via the NIMH Data Archive (NDA) ( https://grants. nih. gov/grants/guide/notice-files/NOT-MH-19-033.

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

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-definedclinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions: If you answered Yes to the question Are Human Subjects Involved?

on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the SF424 (R&R) Application Guide must be followed.

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed. PHS Assignment Request Form All instructions in the SF424 (R&R) Application Guide must be followed.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement , and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide. 3. Unique Entity Identifier and System for Award Management (SAM) See Part 1.

Section III. 1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants. gov 4.

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

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 Policy on Late Application Submission. Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission. Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

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 .

7. Other Submission Requirements and Information Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide . If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance . For assistance with application submission, contact the Application Submission Contacts in Section VII .

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Requests of $500,000 or more for direct costs in any year Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy . Any instructions provided here are in addition to the instructions in the policy. Section V.

Application Review Information Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review. Only the review criteria described below will be considered in the review process.

Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system. In addition, for applications involving clinical trials: A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs.

Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted