PAR-25-064: Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R21 Clinical Trial Optional) is sponsored by National Institute of Mental Health (NIMH) and National Institute on Aging (NIA). Encourages exploratory/developmental research on mechanisms associated with neuropsychiatric symptoms in Alzheimer's disease.

PAR-25-064: Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R21 Clinical Trial Optional) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. 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 ) Funding Opportunity Title Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R21 Clinical Trial Optional) R21 Exploratory/Developmental Research Grant March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose The goal of this Notice of Funding Opportunity (NOFO) 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 NOFO uses the R21 mechanism, while the companion PAR-25-065 uses the R01 grant mechanism.

Investigators proposing high risk/high reward projects that lack preliminary data may be more appropriate for the R21 mechanism, while applicants with preliminary data who seek longer-term funding should apply using the R01 mechanism. Open Date (Earliest Submission Date) The following table includes NIH standard due dates marked with an asterisk.

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. 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 goal of this Notice of Funding Opportunity (NOFO) 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 Psychological 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 NOFO 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 NOFO 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 (e.g., 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 a 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 NOFO, 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 NOFO include, but are not limited to: Improved understanding of the neurobiological and behavioral mechanisms underlying NPS syndromes in AD/ADRD. 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 new or available extensive datasets. Elucidation, refinement and implementation of criteria for distinguishing persons with NPS syndromes that are not resolvable via appropriate attention to their unmet needs.

Examples of studies that are not supported by this NOFO 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: Studies that integrate epidemiologic, genomic and mechanistic research through the application of systems and network biology to understand molecular mechanisms underlying NPS in early and late onset AD/ADRD and inform the selection of novel therapeutic targets and biomarkers of NPS in AD/ADRD.

Of particular interest are studies that examine the molecular mechanisms of NPS in AD/ADRD across populations of diverse ethnic and racial backgrounds and studies focused on understanding the impact of sex differences on the molecular mechanisms of NPS in AD/ADRD.

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

Studies focused on generating multi-omic data using biosamples from existing or legacy clinical trials (pharmacologic or non-pharmacologic) targeting NPS in AD/ADRD and applying 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 for NPS in AD/ADRD including targets identified by the NIA-supported Psych-AD program as well as targets nominated by the Accelerated Medicines Partnership for Alzheimer’s Disease program (AMP-AD) . Research aimed at validation of novel candidate non-pharmacological (environmental, social, interpersonal, behavioral) targets for NPS in AD/ADRD.

Use of digital technologies and/or machine learning techniques to detect, categorize, and/or characterize interpersonal interactions, caregiving activities, and/or environmental contexts which trigger, exacerbate, or mitigate expression of NPS. Such methodologies could include, but are not limited to, active and passive sensing and affective and ubiquitous computing.

Contexts of interest include, but are not limited to, home, community, or formal care settings. Studies leveraging new technologies to collect longitudinal data across time scales, model temporal dynamics of behaviors, and apply within person (or within dyad) analyses to provide insight into the factors in the physical, social, and/or built environment which trigger, exacerbate, or mitigate expression of NPS.

NIA strongly encourages applications that are 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 AD Knowledge Porta l, the NIMH Data Archive , and/or related NIH designated data repositories.

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 NOFO 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 NOFO 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 accepts clinical trials focused on safety, efficacy, and effectiveness under RFA-AG-25-011 .

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.

The NIMH has published updated policies and guidance for investigators regarding human research protection and clinical research data and safety monitoring ( NOT-MH-19-027 ). The application’s PHS Human Subjects and Clinical Trials Information, including the Data and Safety Monitoring Plan, should reflect the policies and guidance in this notice.

Plans for the protection of research participants and data and safety monitoring will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations. See Section VIII. Other Information for award authorities and regulations.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs. 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 Resubmission to PAR-20-159 , PAR-23-208 , or this NOFO Revision to PAR-20-159 , PAR-23-208 , or this NOFO 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 NIH appropriations and the submission of a sufficient number of meritorious applications. The combined budget for direct costs for the two-year project period may not exceed $275,000, and no more than $200,000 may be requested in any single year.

. The maximum project period is 2 years. 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 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) 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 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.

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. 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. 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. 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: Factor 1. Importance of Research Describe how the project has the potential to link mechanisms and/or risk factors to NPS across levels of analysis that may inform novel intervention development.

Clarify the neurobiological and or behavioral mechanisms underlying NPS syndromes in AD/ADRD. Define the current state of the science as a benchmark against which the proposed paradigm, model and/or assay will be measured.

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 NPS. Describe the integration of multiple levels of analysis with regard to understanding the dynamic relationships between NPS symptoms and AD pathogenesis Factor 2.

Rigor and Feasibility Approach: Provide the information below. Provide an appropriate theoretical justification for the proposed approach including the potential to further scientific understanding of the mechanisms of NPS. 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 validated 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 How to Apply- Application Guide.

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions: 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. To advance the goal of advancing research through widespread data sharing among researchers, investigators funded under this Notice of Funding Opportunity (NOFO) are expected to share those data via the National Institute of Mental Health Data Archive (NDA; see NOT-MH-23-100 ).

Established by the NIH, NDA is a secure informatics platform for scientific collaboration and data-sharing that enables the effective communication of detailed research data, tools, and supporting documentation. NDA links data across research projects through its Global Unique Identifier (GUID) and Data Dictionary technology. Investigators funded under this NOFO are expected to use these technologies to submit data to NDA.

To accomplish this objective, it will be important to formulate a) an enrollment strategy that will obtain the information necessary to generate a GUID for each participant, and b) a budget strategy that will cover the costs of data submission.

The NDA website provides two tools to help investigators develop appropriate strategies: 1) the NDA Data Submission Cost Model which offers a customizable Excel worksheet that includes tasks and hours for the Program Director/Principal Investigator and Data Manager to budget for data sharing; and 2) plain language text to be considered in your informed consent available from the NDA's Data Contribution page .

Investigators are expected to certify the quality of all data generated by grants funded under this NOFO prior to submission to NDA and review their data for accuracy after submission.

Submission of descriptive/raw data is expected semi-annually (every January 15 and July 15); submission of all other data is expected at the time of publication, or prior to the end of the grant, whichever occurs first (see NDA Sharing Regimen for more information); Investigators are expected to share results, positive and negative, specific to the cohorts and outcome measures studied.

For more guidance on submitting data to NDA, refer to the NDA Data Sharing Plan on the NDA website . NDA staff will work with investigators to help them submit data types not yet defined in the NDA Data Dictionary . 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. Use of Common Data Elements in NIH-funded Research Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies.

CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records.

NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" ( http://cde. nih.

gov/ ) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection.