Mood and Psychosis Symptoms during the Menopause Transition (R01 Clinical Trial Optional)

Mood and Psychosis Symptoms during the Menopause Transition (R01 Clinical Trial Optional) is sponsored by National Institutes of Health (NIH). Encourages research on the onset and worsening of mood and psychotic disorders during the menopausal transition, aiming to identify novel targets for future mental health interventions.

PAR-25-281: Mood and Psychosis Symptoms during the Menopause Transition (R01 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 ) All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Research on Women's Health ( ORWH ) Funding Opportunity Title Mood and Psychosis Symptoms during the Menopause Transition (R01 Clinical Trial Optional) R01 Research Project Grant Notices of Special Interest associated with this funding opportunity 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 Exploratory/Developmental Grants See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose The purpose of this Notice of Funding Opportunity (NOFO) is to encourage applications that will advance mechanistic and translational research on the onset and worsening of mood and psychotic disorders during the menopausal transition (or perimenopause).

In particular, NIMH seeks research that will advance understanding of the underlying neurobiological and behavioral mechanisms of mood disruption, emotion dysregulation, and psychosis during the menopausal transition and that will identify novel targets for future mental health interventions or prevention efforts This NOFO uses the R01 grant mechanism, while the companion NOFO PAR-25-282 uses the R21 mechanism.

Investigators proposing high risk/high reward projects, projects that lack preliminary data, or studies that utilize existing data may wish to apply using the R21 mechanism, while applicants with preliminary data who seek longer-term funding may wish to apply using the R01 mechanism.

Funding Opportunity Goal(s) The mission of the National Institute of Mental Health (NIMH) is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. 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 This Notice of Funding Opportunity (NOFO) encourages mechanistic and translational research on the onset and worsening of mood and psychosis during the menopausal transition.

For the purpose of this NOFO, the menopausal transition (or perimenopause) is defined as the time of onset of menstrual cycle changes and menopause-related symptoms to early post-menopause.

Because mood disruption (including but not limited to depressed mood, mood lability, emotion dysregulation, and mania), as well as psychosis, occur along a continuum of severity, this NOFO encourages projects that take a dimensional approach to studying this continuum.

However, this does not preclude projects that characterize participants using existing diagnostic criteria (e.g., including but not limited to diagnoses of depressive disorders, anxiety disorders, bipolar and related disorders, or schizophrenia spectrum and other psychotic disorders).

This NOFO will support research projects addressing the aging-related etiology and underlying neurobiology of mood disruption and psychosis during the menopausal transition and projects that aim to identify targets for future development of novel treatment interventions.

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 manipulation of that process, or to understand the mechanism of action of an intervention) (see NOT-OD-15-015 ; NOT-MH-23-375 ).

See the NIMH Clinical Trials website for further details about submission of mechanistic clinical trials to NIMH. This NOFO encourages applications that incorporate teams with varied scientific backgrounds.

Teams may include but are not limited to members from the fields of neuroscience, engineering, endocrinology, epidemiology, reproductive medicine, gerontology, gynecology, pharmacology, psychiatry, and psychology with the expertise necessary to conduct rigorous research. Teams led by or including those with lived experience with perimenopausal depression or psychosis are highly encouraged.

The menopausal transition is a window of vulnerability for the development and worsening of mood and psychotic disorders. However, there is no consensus on clinical recommendations on how to identify, assess, and treat clinical mood and psychotic symptoms during the menopause transition.

Women are at increased risk for both new-onset and recurrent depression during the menopausal transition compared with both pre-menopause and several years post-menopause. The rate of major depressive disorder and clinically meaningful elevations in depressive symptoms increases two to three-fold during the menopausal transition.

Risk factors may include having experienced a depressive episode earlier in life and experiencing substantial vasomotor symptoms during the menopausal transition. The menopausal transition also represents a vulnerable time period where there is a substantial increase in the cases of first-onset psychosis including schizophrenia, which is not observed in men of similar ages.

Research shows that women with a previous diagnosis of schizophrenia and related disorders are also at heightened risk for reemergence or exacerbation of symptoms, resulting in serious functional deterioration during the menopausal transition.

Women with mood and psychotic symptoms are at increased risk of all-cause mortality over a five-year period, including increased risk of cardiovascular disease compared with age, reproductive status, and metabolic-risk matched women without mood or psychotic symptoms. Women with mood and psychotic disorders during menopausal transition also have poorer quality of life, decreased psychosocial function, and increased economic burden.

Though research suggests that ovarian hormones and their derived neurosteroids play a role in the manifestation of mood and psychotic symptoms during menopause transition, the mechanisms are largely unknown.

There is a need for research focused on deciphering the underlying biobehavioral mechanisms in order to advance the development of prevention efforts and treatments specifically for women during the menopausal transition, for which there is an unmet need.

This NOFO is intended to support research designed to identify the neurobiological, behavioral, and social mechanisms underlying the onset and exacerbation of mood and psychotic disorders during the menopausal transition, with consideration for identification of novel targets for future development of prevention and intervention efforts.

Studies that leverage concepts, methods, and findings emerging from research on normative aging, as well as those that extend research on mood disruption and psychosis in mid-to-late life to focus specifically on the menopausal transition, are encouraged. Research must target populations transitioning through menopause. If scientifically justified, relevant comparison populations may be used.

Research is encouraged that assesses symptoms relevant to mood and psychotic disorders dimensionally, integrates across multiple levels of analysis (including but not limited to brain-level measurements), and employs cutting-edge methodology from fields such as cognitive and affective neuroscience, neuroimaging, neurophysiology, neuroendocrinology, lifespan psychology, and geroscience.

Research is also encouraged that adopts an intersectionality framework (i.e., a framework that addresses the multiple dimensions of individuals’ identity and social systems as they intersect with one another).

A Research Domain Criteria (RDoC) approach encourages taking a dimensional perspective with respect to assessing psychopathology, and 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.

However, it is not inconsistent with the RDoC approach to additionally characterize transdiagnostic samples of participants, recruited to represent the clinical phenomena of interest across the full range of variability, into existing diagnostic criteria – this allows investigators to draw links from novel approaches of characterization and classification to existing diagnostic categories and extant research.

Under this NOFO, if study hypotheses and/or enrollment criteria are not based on existing diagnostic criteria (i.e., an RDoC or other dimensional construct is proposed to serve as the primary variable representing psychopathology), the study design and sampling plan must include an adequate number of individuals assessed as falling within the more severely impaired ranges of that dimension.

If taking an RDoC approach, projects must employ assessment methods that converge on the construct from at least two levels of analysis. RDoC units of analysis (potential levels of measurement) include genes, molecules, cells, circuits, physiology, behavior, and self-report.

If the proposed research involves magnetic resonance (MR) neuroimaging, applicants are encouraged, but not limited, to use very high field (>7 Tesla) multimodal MR applications to study dynamic brain processes in precise regions and circuits that could identify subtle pathophysiological mechanisms driving the emergence and worsening of mood disruption, emotion dysregulation, and psychosis symptoms during the menopause transition that are unlikely identifiable in vivo at lower MR field strengths.

A dynamic component is one that samples brain changes over time either in conjunction with a challenge (e.g., task-based, inducing or during different physiological/psychological states) or over multiple periods of time, such as with a longitudinal design and is encouraged.

Specific Areas of Interest Areas of interest include, but are not limited to: Improved understanding of the neurobiological, physiological, and behavioral mechanisms underlying mood disruption and psychosis during the menopausal transition. Identification of factors that increase a woman’s risk of mood disruption and psychosis during the menopause transition.

Such factors include, but are not limited to biological, genetic, psychosocial, and environmental factors (e.g., mental health history, age, stress, race, ethnicity, zip code, socioeconomic status, disability, marital status, nulliparity. Use of an intersectionality framework – i.e., a framework that addresses the multiple dimensions of individuals’ identity and social systems as they intersect with one another is encouraged).

Investigations into proximal or distal psychological, biological and neurobiological mechanisms underlying mood and psychosis symptoms during the menopause transition. Research clarifying the mechanistic role of reproductive steroids in generating, moderating or mitigating mood and psychosis symptoms during the menopause transition.

Identification and regulation of brain circuits and/or neurobiological systems that may be targets for treatment development or mechanisms of mood and psychosis pathophysiology during the menopause transition. Investigations into the mechanisms that precipitate or predispose women who experience mood and psychotic symptoms during the menopause transition to an increased risk of all-cause mortality.

Studies identifying neurobiological, psychological, or biological targets which, when engaged, can prevent progression from typical functioning to disrupted mood or psychosis. Computational approaches to identify predictive and/or explanatory causal patterns of factors associated with mood and psychosis during menopausal transition. Novel methods of neural or behavioral recording and stimulation are encouraged.

This could include novel electrodes, recording devices, passive sensing or digital phenotyping/dense behavioral trackers. However, this NOFO does not support the stand-alone development of novel technology. New methods should be incorporated into an underlying scientific question.

The companion R21 grant mechanism of this NOFO PAR-25-282 encourages shorter, higher-risk applications supported by little (or no) preliminary data. Applications Not Responsive to this NOFO Applications proposing the following studies will be considered non-responsive and will not be reviewed: Studies that do not target populations transitioning through menopause.

Studies whose purpose is to evaluate safety; clinical efficacy, effectiveness, management; and/or implementation of new interventions. Studies that are descriptive and do not address mechanism. Studies that assess 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).

Studies that fail to validate that participants are undergoing some phase of the menopausal transition (e.g., studies the assume relevance to the menopausal transition based on participants’ age). Stand-alone development of novel technology studies. 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.

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 Renewal of RFA-MH-21-105 and PAR-22-035, PAR-23-097 , and PAR-25-282 Resubmission of RFA-MH-21-105 , PAR-22-035 , PAR-23-097 , and PAR-25-282 Revision of RFA-MH-21-105 and PAR-22-035 , PAR-23-097 , and PAR-25-282 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.

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 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.

The Biographical Sketches of investigators for whom it is appropriate should include the following information: As appropriate to the proposed study, in the Personal Statement and/or under Contributions to Science, describe or present information documenting the investigator's expertise in studying menopausal transition at the proposed levels of analysis.

As appropriate to the proposed study, in the Personal Statement and/or under Contributions to Science, describe or present information documenting the investigator's prior experience in conducting research on mood and/or psychosis. 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: The Research Strategy should include the following information: Factor 2.

Rigor and Feasibility As part of the conceptual framework, indicate clear mechanistic hypotheses and have adequate capacity to test and potentially refute the hypotheses. Describe methods to assess phase of menopausal transition. If taking an RDoC approach, describe assessment methods that converge on the construct from at least two levels of analysis (e.g., genes, molecules, cells, circuits, physiology, behavior, and self-report).

If using a dimensional construct, the study design and sampling plan should assure that an adequate number of individuals falling within the more severely impaired ranges of that dimension will be included in the study. Describe plans for assessing comorbid medical conditions and controlling or accounting for their potential confounding influence.

If applicable, describe justification for the use of comparison populations (e.g., men of the same age, younger or older women, or women of the same age who have already completed surgical menopause (i.e., oophorectomy) and/or who are undergoing hormone replacement therapy). 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 by NIMH under this 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) t he 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 Management and 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. The Portal provides guidance about and access to NIH-supported CDE initiatives