Neuroscience Research on Drug Abuse (R01)

Neuroscience Research on Drug Abuse (R01) is sponsored by National Institute on Drug Abuse (NIDA). The National Institute on Drug Abuse (NIDA) requests research grant applications in the areas of neuroscience and behavioral neuroscience research that are relevant to the understanding of the process(es) and mechanisms underlying drug abuse and addiction, including use, depende…

Expired PA-17-111: Neuroscience Research on Drug Abuse (R01) 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 ) of Participating Organizations National Institute on Drug Abuse ( NIDA ) Funding Opportunity Title Neuroscience Research on Drug Abuse (R01) R01 Research Project Grant November 03, 2017 - This PA has been reissued as PA-18-060 for due dates on or after January 25, 2018.

May 31, 2017 - Notice of Change to the Eligibility of Foreign Components in PA-17-111. See Notice NOT-DA-17-041 . May 10, 2017 - New NIH "FORMS-E" Grant Application Forms and Instructions Coming for Due Dates On or After January 25, 2018.

See NOT-OD-17-062 . Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity PA-17-112 , R21 Exploratory/Developmental Research Grant Additional Information on Eligibility . Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose Long-term misuse and chronic exposure to abused substances can produce widespread changes in brain structure and function.

Although much progress has been made, additional research is still needed to identify the neurobiological changes that result from substance use, and how these changes contribute to substance use disorders.

The overarching goals of the research areas described in this FOA are to understand the neurobiological mechanisms underlying substance use disorders, with special emphasis on identifying changes and neuroadaptations that occur during dependence, withdrawal, and relapse to chronic substance use.

An understanding of the basic mechanisms underlying substance use disorders can help to identify targets for prevention and treatment interventions. Research utilizing basic, translational, or clinical approaches is appropriate. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) Any due dates on or after Jan 25, 2018 must use reissued FOA.

dates apply , by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates. 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) dates apply, by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on these dates. 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.

New Date January 24, 2018 per reissuance of FOA (Original Expiration Date: January 8, 2020) It is critical that applicants follow the Research (R) Instructions (R&R) Application Guide , except where instructed to do otherwise (in this FOA or in a Notice from the 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 the Announcement I.

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

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

Agency Contacts Section VIII. Other Information Full Text of Announcement Section I. Funding Opportunity Description Substance misuse and addiction places a large burden on the nation’s health care systems and the economy, costing billions of dollars each year.

According to the 2015 National Survey on Drug Use and Health (NSDUH), an estimated 21. 7 million people aged 12 or older, or about 8. 1 percent of that segment of the population, needed treatment for substance use disorders (SUDs) in the past year.

Substance use often begins during adolescence, and its effects are more long-lasting and resistant to treatment than when initiation occurs during adulthood. Additionally, substance use often co-exists with other psychiatric disorders, can involve the use of multiple substances, and is more prevalent within certain populations such as those positive for HIV/AIDS infection and among individuals having chronic pain.

SUDs are serious national health issues; understanding their neurobiological and behavioral mechanisms would enable us to develop strategies for effective treatment and prevention. Drug addiction is a chronic, relapsing neurobehavioral disorder that is characterized by the compulsive self-administration of chemical substances despite their negative consequences.

NIDA-supported research has made significant progress in identifying the mechanisms of action, at a genetic, molecular, cellular, and systems level of analysis, for each major drug of abuse. In addition, there is a reasonable understanding of the changes that occur in the brain as a result of acute exposure to drugs.

However, there remains a need to know more about the changes that occur during the different stages of SUDs: initiation of use, transition from volitional to compulsive use, abstinence, relapse, and successful recovery.

Similarly, we need to understand how pharmacological, behavioral, or other therapeutic interventions affect the brain and which mechanisms the brain uses to protect itself from the deleterious effects induced by chemical substances. Finally, we currently have a limited understanding of individual differences resulting in differential susceptibility and resilience to SUDs.

The research encouraged by this FOA should lead to improved understanding of SUD, its determinants and consequences, and potential treatment. This FOA encourages basic neurobiological studies that use in vivo and in vitro model systems as well as studies in humans.

Applicants are especially encouraged to include appropriate behavioral models and paradigms of behavioral components or stages of addiction in their research proposals, especially in response to chronic exposure to drugs, different drug administration regimens, withdrawal, or recovery. The subject of study can be at the level of a single protein or gene, neurobiological system, or the entire organism.

Research may be conducted across multiple levels of analysis, and applications that incorporate changes over time and/or across multiple scales (e.g., gene to behavior, abuse to dependence, adolescence to adulthood) are sought. Multi- and inter-disciplinary studies are especially encouraged. Topics that would be appropriate to this FOA are described below, but they are not intended to be exhaustive or exclusionary.

This FOA encourages the conduct of neurodevelopmental studies throughout the lifespan, such as: Neonatal abstinence syndrome Research that characterizes neural development and its interaction with abused substances during sensitive developmental periods, such as the Research on the effects of abused drugs, and those that are potential treatments for drug abuse, on neurogenesis, cell differentiation, proliferation, migration and survival in young and adult animals, including assessment of consequences and reversibility of these alterations Research during aging, particularly on interactions of drugs of abuse with therapeutic pharmaceuticals Molecular and Cellular Approaches NIDA encourages the use of genetic, such as human genetics, molecular genetics, epigenetics, and pharmacogenetics, cellular and molecular approaches to identify and understand the neurobiological mechanisms underlying addiction.

Research may include, but is not limited to: Use of genome or epigenome editing technologies to investigate neuroplasticity-relevant gene expression changes Functional comparisons of populations of subjects with different gene dosing, whether naturally-occurring (such as comparison of different strain along a dimension) or manipulated experimentally Mapping of gene variants in either animals or humans using linkage or association studies Genetic and epigenetic screening and analysis of addiction variations and genetic mechanisms using novel cellular systems, such as induced pluripotent stem cell (iPSC) derived from samples from SUD patients or substance-using participants Nucleosynaptic signaling studies to understand the mechanisms by which nuclear processes can influence synaptic structure and how synapses can signal back to the nucleus Identification and validation studies for novel targets or ligands on neurons and glia The use of patient- and disease-specific inducible pluripotent stem cells as a model system for the study of unique cellular and molecular events that occur in individuals with SUDs for the purpose of developing therapeutic agents or screening drug toxicity Functional studies of novel receptor-receptor interactions (homo- and hetero- dimerization of receptor subunits, or receptor mosaics) and their response to drugs.

Functional studies of the effects of novel receptor-protein interactions, including those with scaffold, RGS, kinase, arrestin, GPCRs, TRP ion channels, and PDZ proteins Investigations into cytoskeletal regulatory processes and how they can influence processes relevant to substance use disorders Development, characterization, and validation of organoid models to answer questions relevant to substance use disorders Circuit and Systems Neuroscience Approaches Applications using neural circuit and systems-level approaches are encouraged.

Of particular interest are studies that address how drug exposure and/or withdrawal leads to persistent changes that underlie relapse to compulsive use.

These approaches might include in vivo or in vitro studies of normal and drug-exposed tissues from humans and animals to determine the substances on neurophysiology, changes in distributions of receptors, or delineation of circuits through the use of neuroimaging or neuromodulation techniques such as two-photon imaging, photoacoustics, adaptive optics, in vivo spectroscopy, genetically encoded activators/inhibitors, PET or MR imaging, and Transcranial Magnetic Stimulation.

Such studies might include, Examination of the temporal course of the addictive process on dendritic spine development and retraction in na ve, drug-treated, and drug-withdrawn tissues within specific brain regions and circuits, especially in compulsively using animals and those in recovery, linked to their physiological and behavioral outcomes Modulation of neural systems by the neurochemical environment, including steroid hormones and peptides, trophic factors and cytokines/chemokines Use of systems-level approaches to understand the effects of drugs on the biology of glia and neurons The interaction of abused substances with the neuronal-glial interface, the study of glial-derived inflammatory and protective factors (neuroimmunology), and the linkage of the anatomy and physiology with outcomes Comparison of the neural circuits and behaviors that are central to non-drug reward processes with those directly linked to drug-induced reward Drug-induced modifications of glia that impact the function of the neural circuit, including synaptic excitability, alterations of neurotransmission, or the formation of synapses and/or synaptic elements such Investigation of brain regions or processes that underlie avoidance learning including those involved in behaviors and cognitive strategies maintained by negative reinforcement Investigation of individual differences in neural circuitry underpinning SUD-related behavior and outcomes, including studies to understand the neurobiology underlying important risk factors for drug use and addiction (e.g., stress, impulsivity) Resting state functional connectivity studies examining specific SUD-related neural circuits or large-scale network function in the context of SUDs, including those that predict SUD-related behavior and clinical outcomes Modulation of SUD-related circuits using non-invasive brain stimulation to investigate neural mechanisms underlying cognition, behavior, and clinical outcomes relevant to substance use disorders Studies investigating gene environment interaction effects on SUD-related behavior and neural circuitry Studies that further investigate hemispheric asymmetries in cognitive function, neurocircuitry, neurotransmitter concentration, and neuronal activation relevant to drug use and addiction Studies of the relationship between glymphatics, circadian rhythm, and/or sleep on aspects of SUDs such as craving, relapse, susceptibility or resilience Studies employing novel genetic tools to map circuits critical to the understanding of SUDs.

These may include tools such as spatial-temporal, or conditional knockouts, receptor- or subtype-selective antagonists that can demonstrate conclusively the site, developmental stage, and the receptor type(s) involved in the action of drugs of abuse NIDA is committed to supporting behavioral neuroscience research on SUDs, conducted with human participants or using animal models that best mimic the complexity of the human condition.

Research may include, but are The study of behavioral or cognitive processes (e.g., learning, memory, emotion), and their neurobiological mechanisms, as variables contributing to substance use initiation, escalation, maintenance, abstinence, Characterization of transition points and stages in the development of SUDs, including the use of biomarkers or other neurobiological signatures that predict transition to more compulsive patterns of intake Behavioral and neurobiological phenotyping to characterize patterns of vulnerability and resilience; to identify propensity for transition to more compulsive patterns of behavior and responsivity to interventions (i.e., malleability in SUD trajectories) Vulnerability phenotyping that considers complex patterns or constellations of individual differences across multiple dimensions (e.g., cognitive processes, drug sensitivity, response to environmental stimuli including social stimuli, reward reactivity, punishment sensitivity) and levels of analysis (e.g., individual differences at genetic or neurobiological levels) Influences on decision-making, risk-taking, attention or higher order executive functions involved in SUDs, including interactions with emotional processing involved in top-down or bottom-up control Use and development of refined measures of behavioral choice in complex environments in preclinical models that mimic the human phenomenology of SUDs (e.g., value assessments, probability, flexibility, economic trade-off), including models of compulsive behaviors and behavioral Testing of environmental, behavioral or pharmacological manipulations that leverage potential treatment or prevention targets in all phases of drug taking behavior seen in the progression to development of SUDs, and identification of mechanisms of action Investigation of individual differences in the role of negative affective processes and their associated neurobiological substrates to the progression through phases of abuse to the development of SUD of Tools and Reagents for the Study of Substance Use The study of the genetic, molecular, cellular, behavioral, and circuit-based mechanisms involved in SUDs, and the development of associated therapeutic strategies, will benefit from method, tool, and reagent development research and approaches as well.

There is a need for: Improved neuroimaging techniques as well as novel, innovative molecular probes/ligands for receptors, transporters, enzymes, and other neurobiological targets that permit non-invasive deep imaging of neuronal activity at the level of the single cell Development and application of genetically encoded voltage sensors to map neural activity with circuits involved in SUDs and Development and use of high throughput screening methods and application of associated technologies to discover new endogenous ligands and critical biomarkers of known drug effects Development of innovative technologies in the service of behavioral and neurobiological assessments and the assessment of novel therapeutic regimens aimed at producing favorable neuroadaptations Classification of cell types by genetic and/or protein complement and activity before and after chronic exposure to/withdrawal from abused substances or therapeutics aimed at mitigating drug use Single cell analysis-based approaches to study heterogeneities of the neurons that form identified circuits that underlie learning and motivation Development of novel cellular and behavioral screens that predict treatment the response to potential medications for SUDs Modeling and Secondary Data Analysis Development of computational models of neural function in the presence and absence of drug to integrate structural and behavioral Development of computational models of network-level neural function and connectivity in the context of substance use disorders0 Methods for analyzing and interpreting large data sets (preclinical and clinical data) related to substance abuse and its treatment using big data analytical tools Secondary data analysis of molecular, preclinical, and clinical HIV/AIDS and SUDs: There is a need to characterize the interactions and synergies of addictive drugs with the functional and structural alterations and neuroadaptations within the central nervous system produced by HIV-1 infection that cause the development and expression of neuroAIDS.

This includes studies that examine the role of substance use in exacerbating the pathophysiology underlying HIV-associated neurocognitive disorder (HAND). Additionally, research to develop methods and approaches that protect and potentially repair neurons damaged or dysregulated by exposure to combined HIV-1 infection and drugs of abuse, anti-retroviral therapies (ARTs), and/or host inflammatory factors, is needed.

Applicants are strongly encouraged to include relevant animal behavioral models or study substance abusing populations in their Chronic Pain: Studies are needed that aim at understanding the underlying neurobiological mechanisms of chronic pain and its treatment by opioid analgesics.

Research might include the study of the changes that occur in response to chronic pain and exposure to its treatment; mechanisms that underlie the sex differences in the response to chronic pain; and the development of non-addicting analgesics for the control of chronic pain.

For example, the development of non-opioid analgesics or analgesic approaches that combine different classes of drugs with opiates to reduce opioid abuse liability Psychiatric Comorbidity and Polysubstance Abuse: The high incidence of comorbidity between SUDs and other psychiatric disorders, or the concurrent misuse of multiple substances by individuals, are well documented.

The neurobiological mechanisms underlying these associations remain poorly understood. Preclinical and clinical studies could further our understanding of the extent to which these disorders do or do not share a common neurobiological etiology.

Research is encouraged that incorporate comorbidity behavioral models or models of polysubstance use to discern the neurophysiological and neural circuitry similarities and differences between these co-occurring disorders.

National Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human Subjects: The National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects.

Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects. The guidelines are available on NIDA's Web site at http://www. drugabuse.

gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects .

Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants: The National Advisory Council on Drug Abuse (NACDA) encourages NIDA and its grantees to consider the points it has set forth with regard to existing or prospective sponsored research agreements with tobacco companies or their related entities and the impact of acceptance of tobacco industry funding on NIDA's credibility and reputation within the scientific community.

Please see http://www. drugabuse. gov/about-nida/advisory-boards-groups/national-advisory-council-drug-abuse-nacda/council-statements/points-to-consider-regarding- for details.

Data Harmonization for Substance Abuse and Addiction via the PhenX Toolkit: NIDA strongly encourages investigators involved in human-subjects studies to employ a common set of tools and resources that will promote the collection of comparable data across studies and to do so by incorporating the measures from the Core and Specialty collections, which are available in the Substance Abuse and Addiction Collection of the PhenX Toolkit ( www.

phenxtoolkit. org ). Please see NOT-DA-12-008 ( http://grants.

nih. gov/grants/guide/notice-files/NOT-DA-12-008. html ) VIII.

Other Information for award authorities and regulations. Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed Glossary and the SF424 (R&R) Application Guide provide details on 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 maximum project period is 5 years.

Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

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 Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions 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 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) are Non-domestic (non-U.S.) components of U.S. Organizations are not eligible Foreign components, as defined in the NIH Grants Policy Statement , are not 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.

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 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) (formerly CCR) 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.

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. must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.

gov registration. 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 must have an active DUNS number and SAM registration in order to complete the 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 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 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 A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission 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 Buttons to access the online ASSIST system or to download application forms 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 Research (R) Instructions (R&R) Application Guide , including Supplemental Grant Application Instructions 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 For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant All page limitations described in the SF424 Application Page Limits must be followed.

Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an All instructions in the SF424 (R&R) Application Guide SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) not use the Appendix to circumvent page limits.

Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. PHS Inclusion Enrollment Report When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 PHS Assignment Request Form All instructions in 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 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 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 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 This initiative is not subject to intergovernmental 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 .

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 Electronically .

If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must for Applicants Experiencing System Issues . 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 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 Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy .

Section V. Application Review Information Only the review criteria described below will be considered in the review process.

As part of the NIH mission , all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each.

An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field. Does the project address an important problem or a critical barrier to progress in the field?

Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators those in the early stages of