It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from 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

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This Funding Opportunity Announcement (FOA) invites applications focusing on the mechanisms and/or behavioral outcomes of multisensory processing, the integration or processing of at least two distinct types of sensory input as defined by distinct receptor-type transduction, neural pathways and cognate perceptual quality. Specifically, multiple sensory inputs may include the major traditional modalities of hearing, vision, taste, smell, balance, and touch. Additional submodalities of body senses include but are not restricted to thermosensation, body position and proprioception, pain, itch, and general visceral sensation. This FOA encourages research grant applications investigating multisensory processing in perception or other behavioral and social outcomes and/or the mechanisms underlying multisensory processing in the context of the described specific areas of research interests from the participating ICOs. The FOA is intended to encourage basic, behavioral, and/or clinical research projects focused on two or more sensory modalities or research projects examining the interactions between other neural systems, such as cognitive, affective, or motor processes, and multiple sensory modalities. Multisensory research applications that do not align with the specific areas of research interests described below by the participating NIH Institutes and Centers (ICs) should be submitted in response to the relevant parent R01 FOA.

We perceive the world through a variety of senses, including vision, audition, olfaction, gustation, somatosensation (cutaneous and subcutaneous tactile sense, thermosensation, proprioception, nociception, and visceral sensation), and vestibular sensation. In general, the senses are studied separately. However, our experience of the world is mostly unitary; we do not perceive a barking dog as a visual stimulus, a sound, and perhaps a smell, but as a single multisensory object. Accordingly, mounting evidence indicates that the senses cannot be treated as independent channels. That is, perceptions in one modality can be enhanced, attenuated, or completely changed by sensory input from another modality. For example, touch can improve judgments of visual colors, even though touch itself cannot convey color, and vision can alter taste. Furthermore, multisensory processing can influence subsequent unimodal sensory processing (e.g., exposure to simultaneous auditory and visual stimuli can recalibrate the way that each of these stimuli is processed in the future, even in isolation), and can have synergistic effects on neural processing in cognitive, affective, motivational, or motor systems. In addition, there are enormous individual and lifespan differences in sensory processes across different senses, as well as other factors that could contribute to systematically differing perceptions of cross-modal stimuli. For example, research has uncovered a remarkable span of individual differences in gustation (e.g., supertasters), which may make the multisensory perception of flavor vastly different across individuals.

Sensory processes are relevant to a wide variety of health impacts, including neurological, mental and emotional health; consumption (e.g., food and alcohol intake, smoking); basic daily functions (e.g., walking, reaching/grasping); lifestyle activities (e.g., exercise, navigation, dancing, art activities, driving); communication and interpersonal transactions; medical diagnosis, and healthcare utilization. Understanding the scope and the limits of multisensory perception also informs the therapeutic space for sensory substitution in primary sense deficits (e.g. Braille reading for the blind) and temporary sensory alterations caused by disease or treatments for disease. Thus, the interplay among multiple sensory modalities also has important implications for neural, cognitive, behavioral and social science research and for subsequent health outcomes.

Despite growing interest in how individuals integrate these ubiquitous signals, the mechanisms by which different sensory systems are integrated, interact with each other, or influence the processing of the connected neural systems in the brain remain largely unknown. The roles of biochemical and physiological changes, genetics and epigenetics, psychological experiences, or physical environments in regulating multisensory processing are mostly unexplored. Furthermore, the impact of multisensory processing on behavior continues to be understudied.

In 2012, the NIH Basic Behavioral & Social Sciences Research Opportunity Network (OppNet, http://oppnet.nih.gov) sponsored an FOA on Basic Behavioral Research on Multisensory Processing (R21; RFA-EY-13-001), which supported 10 exploratory grants. The current FOA intends to expand on this previous initiative by encouraging studies of the neural circuitry and mechanisms of multisensory processing, in the context of relevant diseases and disorders of the nervous system, or in relevance to social behaviors, clinical diagnostics, or therapies.

Applications to this FOA will be assigned to an appropriate NIH IC according to research priorities of the participating ICs. Relevant assignment factors include primary sense(s) under study, and research impacts within IC funding priorities (see participating IC "Specific Areas of Research Interest" below).

This FOA supports innovative studies using animal or human subjects to examine two or more senses (visual, auditory, olfactory, gustatory, somatosensory including pain or other submodalities of body senses, and vestibular) for the elucidation of mechanisms and behavioral outcomes of multisensory processing. Therefore, applications submitted to this FOA should focus on mechanisms, or the behavioral impact, or both. The initiative encourages the use of diverse methodologies, including basic biochemical, molecular, cellular, genetic approaches, neuroimaging and neurophysiological analyses, experimental psychophysics, "real world" settings, immersive virtual technology, and animal models.

For this FOA, applicants should address multisensory integration across at least two of the broadly different senses (smell, sight, taste, touch, hearing, balance) or the submodalities of body senses including but not restricted to thermosensation, body position and proprioception, pain, itch, and general visceral sensation. Audio-visual, visual-vestibular and chemo-tactile integration already have been noted as examples. However, the perception of form by integrating color contrast with shape-from-shading would be considered visual, and integration of linear with angular acceleration would be considered vestibular, and not appropriate here. This FOA also supports research on the interaction of pain (as part of the somatosensation) with other sensory systems. This FOA may support clinical trials in which the primary outcomes are mechanistic. A mechanistic study is designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention. Applications should not include any specific aims that propose to measure efficacy or effectiveness of any intervention.

Applicants are strongly encouraged to contact the Scientific/Research Contacts from various NIH ICs listed in Section VII prior to submission to discuss IC program relevance.

Below lists the areas of research interest from the participating NIH ICs of this FOA:

The National Institute on Aging (NIA) supports multisensory research in the context of aging and age-related neurodegenerative diseases, in particular Alzheimer's disease (AD). Topics of interest include, but are not restricted to: 1) mechanistic studies to understand changes in multisensory processing in aging or disease; 2) the interplay between multisensory processing and motor, cognitive, or affective function in aging or disease; 3) the impact of multisensory processing on daily functioning (e.g. walking, reaching, grasping, eating, swallowing, and other basic movements) , lifestyle activities (e.g. exercises, navigation, driving, dancing, art activities), and social interactions in older adults with or without neurodegenerative diseases; 4) assessments of multisensory function as potential early detections of AD or other age-related neurodegenerative diseases; and 5) strategies or therapies to improve multisensory processing and related behaviors in aging or disease. NIA will support both human and animal model (including invertebrate model) studies.

The National Center for Complementary and Integrative Health (NCCIH) is interested in studies that elucidate multisensory mechanisms by which complementary or integrative approaches (e.g. natural products, dietary supplements, probiotics, acupuncture, meditation, yoga, Taichi, hypnosis, message, spinal manipulation) alter pain processing, sleep, stress, anxiety, mild to moderate depression, eating disorders or promote general or emotional well-being. NCCIH is especially interested in the mechanisms and impact of interoception and its interactions with other sensory modalities. For the purposes of this FOA, NCCIH will support basic and mechanistic research in both human and animal models but will not support efficacy/effectiveness clinical trials, where the primary outcomes are clinical outcomes.

The National Cancer Institute (NCI) supports multisensory research in the context of cancer and cancer control. Topics of interest include, but are not restricted to: 1) Studies of multisensory interactions with taste that might govern healthy vs unhealthy eating, drinking, or smoking; 2) disruption of multisensory perception by cancer and cancer treatments; 3) the potential for using multisensory interactions to enhance health communications; 4) multisensory control of attention, as might be relevant in complex oncology or cancer care settings; 5) circadian and sleep-dependent influences on multisensory interactions. NCI will support both human and animal model studies.

The National Eye Institute (NEI) supports research that addresses blinding eye diseases, visual disorders, mechanisms of visual function, preservation of sight, and the special health problems and requirements of the blind. Under this PA, NEI will accept applications investigating multisensory interaction (vision combined with additional sensory input) when the research would inform fundamental mechanisms of visual function or disease/disorder mechanisms related to loss of vision. Topics of interest include, but are not restricted to, the impact of other senses on visual perception, the impact of multisensory input on sensory substitution in the visually impaired, and multisensory strategies in low vision rehabilitation.

The Eunice Kennedy Shriver National Institute on Child Health and Human Development (NICHD) is particularly interested in applications pertaining to rehabilitation and child development. Specifically, the National Center for Medical Rehabilitation Research is interested in research including but not limited to the following: to elucidate changes in the processing of sensory information including visual, auditory, mechanical (touch, pain, temperature) processes after traumatic brain injury, both in the acute stages of injury and at more chronic time points; persistent abnormalities in sensory processing that may affect cognitive processes known to be at risk after traumatic brain injury such as working memory, reading, attention, anger, sleep; changes in sensory perception after stroke that accompany common chronic conditions such as aphasia, spatial neglect, or loss of motor function; factors that lead to "sensory stroke" or lacunar infarction, and unique approaches to rehabilitation; multisensory processing (vision, proprioception, tactile, etc.) related to the integration of prosthetic devices for functional use by people with amputations; the role of multisensory processing in autonomic dysreflexia and bowel and bladder voiding impairments following spinal cord injury; the role of multisensory processing in pain secondary to a disabling condition such as stroke, spinal cord injury, amputation, or traumatic brain injury. The Child Development and Behavioral Branch at NICHD is interested in the research applications pertaining to the developmental aspects of multisensory processing. NICHD will support both human and animal model studies.

The National Institute on Drug Abuse (NIDA) encourages research on multisensory integration in the context of drug abuse and addiction in humans and animal models. Research of interest includes, but is not limited to behavioral, imaging, and mechanistic neurobiological studies of integration and encoding of multisensory cues, including interoceptive cues, that trigger drug craving, drug-seeking and relapse; integration of multisensory information involved in reward valuation and decision-making; top-down influences on the salience of multisensory drug-related cues; the effects of drugs of abuse on multi-sensory processing; and multisensory processing of emotional and social cues in individuals with substance use disorders or in animal models. NIDA is also interested in research on the interaction of sensory information signaling rewarding vs. aversive outcomes.

The National Institute on Deafness and Other Communication Disorders (NIDCD) mission supports research in the areas of hearing, balance, smell, taste, voice, speech and language. Multisensory integration is well known to modulate some of these functions even though specific mechanisms are not yet understood well. NIDCD encourages applications where the main goal is to clarify how neuronal mechanisms underlie multisensory modulation of function within the NIDCD mission areas, in humans or animal models, with particular interest when the modulation is in the context of disorder or disease. As examples, in humans the sense of smell begins in the nose and is carried by olfactory pathways to the cortex, while taste begins in the oral cavity and is carried by gustatory pathways to the cortex; these two separate sensations, coming from entirely different cranial nerve systems, are integrated to form the common multisensory perception of flavor. This combined percept itself can be modified further by visual and tactile stimuli such as color and smoothness, and a disorder in any of these pathways can affect appetite, nutrition and well-being. Similarly, our sense of balance depends on inputs from the vestibular organs of the inner ear along with substantial multisensory input from somatosensory and visual systems, and multisensory reweighting is critical for balance when disorders occur in any of the contributing senses. In hearing, auditory misperception often can be improved by vision for functions like sound source localization. NIDCD support for voice, speech and language is focused on disordered processes, but here too audio-visual interactions can be important for speech perception disorders, and language and reading impairments.

The National Institute of Dental and Craniofacial Research (NIDCR) encourages applications that would inform fundamental mechanisms of how sensory systems impact physiological function of the dental, oral, and craniofacial complex, and, for oral health behaviors, how different sensory modalities interact with and influence one another in determining perception. Discovery of mechanisms underlying hypersensitivity of multiple sensory systems, sometimes seen in chronic pain conditions, is of interest. In particular, studies on neuropathies of craniofacial tissues including temporomandibular joint disorders (TMD) and overlapping painful disorders are a high priority. NIDCR also supports research that would further the understanding of how sensory systems impact mastication and adaptations to altered dentition and oral prostheses. NIDCR seeks to further the exploration of how cognitive expectations, memories, and affective states contribute to or modify perceptual and behavioral outcomes which includes but is not limited to inputs that influence the decision to seek dental care, stimuli that impact dental fear or dental anxiety, and psychosocial adjustment to craniofacial disorders. Applications that propose a clinical trial or study to test an intervention are not appropriate for this FOA and should instead use the R34 mechanism under the NIDCR Clinical Trials Program (NIDCR Behavioral or Social Intervention Clinical Trial Planning Grant (R34) - See more at: https://grants.nih.gov/grants/guide/pa-files/PAR-14-342.html).

The National Institute of Neurological Disorders and Stroke (NINDS) is interested in applications that focus on mechanisms of multisensory interactions at the cellular, circuit or systems level when such research would inform fundamental knowledge of neurological function or mechanisms related to understanding, treating or reversing the burden of neurological disease. There are mechanistic interactions among sensory systems neurology, co-morbidities across sensory systems, and implications for sensory substitution for disorders and disabilities. Under this FOA, research topics of interest to NINDS include, but are not limited to: mechanisms of sensory transduction or integration of multiple sensory modalities in the normal nervous system, alterations in multisensory mechanisms in the context of neurological diseases or conditions, or mechanisms of multisensory adaptive or maladaptive plasticity or recovery of function following disease or trauma to the brain, spinal cord or peripheral nervous system. Primary impacts of the research should inform fundamental mechanisms or disease/disorder mechanisms within the NINDS funding mission (http://www.ninds.nih.gov/about_ninds/ninds_overview.htm). Applicants should develop specific aims to test mechanistic hypotheses which go beyond descriptive studies of multisensory phenomena. Applications can investigate mechanisms from sensory transduction, to modality tract tracing, to nervous system recording/imaging/manipulating, to quantitative behavioral assay (i.e., psychophysics) and must contain an in vivo component. Applications that address technology development are not appropriate and should be submitted to the appropriate bioengineering research grant opportunity (http://www.ninds.nih.gov/research/bioengineering/). Applications that seek to develop or test therapeutics or devices for clinical use are not appropriate and should be submitted to the appropriate translational research funding opportunity http://www.ninds.nih.gov/funding/areas/translational_research/index.htm). For NINDS, applications that propose human research studies should be designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention for the purpose of understanding basic biological mechanisms or pathogenesis of a disease, identifying potential therapeutic targets, or examining an intervention's mechanism of action. Traditional phase I, phase II, phase III, or pivotal clinical trials will not be considered for award.

The Office of Behavioral and Social Sciences Research (OBSSR) will support research of scientific interest to the participating Institutes and Centers named in this announcement that investigate behavioral outcomes/behavioral impact of multisensory processing.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• 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

Other

• 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
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (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.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number 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 submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

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.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

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

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions.

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

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH's electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

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

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

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 review system.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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 project proposed).

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?

In addition, for applications proposing clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

In addition, for applications proposing clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition, for applications proposing clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

In addition, for applications proposing clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

In addition, for applications proposing clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline

Specific to applications proposing clinical trials

For all CT FOAs, add the following questions, before the Human Subjects Protections criterion.

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

For Renewals, the committee will consider the progress made in the last funding period.

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee's business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA. ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain "applicable clinical trials" on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person's race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator's scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant's integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 "Federal awarding agency review of risk posed by applicants." This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)

Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)

Telephone: 301-945-7573

Coryse St. Hillaire-Clarke, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-827-6944
Email: coryse.sthillaire-clarke@nih.gov

Wen G. Chen, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-451-3989
Email: chenw@mail.nih.gov

Todd Horowitz, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6963
Email: horowitzts@mail.nih.gov

Cheri Wiggs, Ph.D.
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: wiggsc@mail.nih.gov

Theresa Cruz, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-9233
Email: cruzth@mail.nih.gov

Rita Valentino, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-1887
Email: rita.valentino@nih.gov

Amy Poremba, Ph.D.
National Institute on Deafness and Other Communication Disorders (NIDCD)
Telephone: 301-496-1804
Email: porembaa@nidcd.nih.gov

Yolanda F. Vallejo, Ph.D.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-827-4655
Fax: 301-480-8319
Email: Yolanda.Vallejo@nih.gov

James Gnadt, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Email: gnadtjw@ninds.nih.gov

Dana Greene-Schloesser, Ph.D.
Office of Behavioral and Social Sciences Research (OBSSR)
Telephone: 301-451-3975
Email: Dana.schloesser@nih.gov

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Jennifer Edwards
National Institute on Aging (NIA)
Telephone: 301-827-6689
Email: edwardsj@mail.nih.gov

Shelley M. Carow
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3788
Email: carows@mail.nih.gov

Carol Perry
National Cancer Institute (NCI)
Telephone: 240-276-6282
Email: perryc@mail.nih.gov

Karen Robinson Smith
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: kyr@nei.nih.gov

Bryan Clark, MBA
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: clarkb1@mail.nih.gov

Christine Kidd
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1372
Email: christine.kidd@nih.gov

Christopher Myers
National Institute on Deafness and Other Communication Disorders (NIDCD)
Telephone: 301-402-0909
Email: myersc@nidcd.nih.gov

Diana Rutberg, MBA National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: rutbergd@mail.nih.gov

Tijuanna DeCoster
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: decostert@mail.nih.gov

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.