Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

Fogarty International Center (FIC)

National Eye Institute (NEI)

National Institute on Aging (NIA)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Deafness and Other Communication Disorders (NIDCD)

National Institute of Environmental Health Sciences (NIEHS)

National Institute of Mental Health (NIMH)

National Institute of Neurological Disorders and Stroke (NINDS)

Funding Opportunity Title
Global Brain and Nervous System Disorders Research Across the Lifespan (R21 Clinical Trial Optional)
Activity Code

R21 Exploratory/Developmental Research Grant

Announcement Type
Reissue of PAR-18-836
Related Notices

PAR-21-311 - Global Brain and Nervous System Disorders Research Across the Lifespan (R01 Clinical Trials Optional)

Funding Opportunity Announcement (FOA) Number
PAR-21-319
Companion Funding Opportunity
PAR-21-311 , R01 Research Project
Assistance Listing Number(s)
93.989, 93.853, 93.242, 93.867, 93.866, 93.173, 93.113, 93.865
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) encourages exploratory/developmental research grant applications, piloting innovative, collaborative research projects with low- and middle-income country (LMIC) institutions/ scientists on brain and other nervous system-related function and disorders throughout life, relevant to LMICs. Research on the full spectrum of neuro-health, neurological, neuromuscular, sensory, neuropsychiatric, cognitive, behavioral and neurodevelopmental function and disorders may span the full range of science from basic to clinical to translation and implementation research. Scientists in LMIC institutions may partner with scientists in other LMIC institutions and/or U.S. institutions . Income categories are defined by the World Bank at http://data.worldbank.org/about/country-classifications/country-and-lending-groups).

These grants are expected to foster the development of more comprehensive research programs that contribute to the long-term goals of building sustainable neuro-health research capacity in LMICs to address brain, nervous system and neuromuscular related development, function and impairment throughout life and to lead to diagnostics, prevention, treatment and implementation strategies. The proposed work may also contribute to developing a base for research networking and evidence-based policy beyond the specific research project.

Key Dates

Posted Date
September 13, 2021
Open Date (Earliest Submission Date)
November 09, 2021
Letter of Intent Due Date(s)

30 days before receipt date

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
December 09, 2021 December 09, 2021 December 09, 2021 March 2022 May 2022 July 2022
November 15, 2022 November 15, 2022 December 09, 2022 March 2023 May 2023 July 2023
November 15, 2023 November 15, 2023 December 11, 2023 March 2024 May 2024 July 2024

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Expiration Date
December 12, 2023
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

This Funding Opportunity Announcement (FOA) encourages exploratory applications for the development of innovative, collaborative neuro-health research projects on brain and other nervous system-related function, disease and disorders throughout life, relevant to low- and middle-income countries (LMICs). This includes but is not limited to neurological, neuromuscular, mental, cognitive, sensory, developmental, behavioral and substance use disease and disorders, and spans the full range of science from basic to prevention, clinical, translational and implementation research. Scientists in LMIC institutions may partner with those in other LMIC institutions and/or in the United States (U.S.). Income categories are defined by the World Bank at http://data.worldbank.org/about/country-classifications/country-and-lending-groups).

These developmental/exploratory research grants are expected to prepare the foundation for more comprehensive research programs that enrich the knowledge base and contribute to the long-term goals of sustainable strengthening of neuro-health research capacity in LMICs to 1) address the full spectrum of brain and other nervous system function and impairment throughout life and 2) lead to diagnostics, prevention, treatment, rehabilitation and implementation strategies. The proposed work may also contribute to developing a base for research networking and for evidence-based policy beyond the specific research project.

Background

During the past decades, improvements in health care have led to a decrease in mortality (including and especially among children) and an increase in life expectancy in LMICs. These positive trends have set the stage for a complex and paradoxical epidemiology of health and disease as more children survive past age 5, into adulthood and more survive into advanced age with their neuro-health affected by the sequelae of combined early illness, malnutrition and adverse environment and experiences. In addition to their immediate effects, these exposures may also advance the onset and severity of chronic neurological diseases and disorders, including cognitive and neurodegenerative disorders, in later life. Social and -economic factors, such as chronic adversity associated with poverty, war and conflict, stigma and gender inequalities, contribute to the initial risk factors and causes (such as injury, psychological trauma, genetic vulnerability and infection) of many nervous system disorders. These disorders, in turn can create a negative feedback loop handicapping the physical and cognitive ability of individuals and their societies to address the root causes of diseases, disorders and their risk factors. The biological and social effects may extend for generations.

According to systematic analysis of the Global Burden of Disease, neurological disorders are the leading cause of disability and the second leading cause of death worldwide. In the past decades, the absolute numbers of deaths and people with disabilities owing to neurological diseases have risen substantially, particularly in LMICs. Globally, the burden of neurological disorders, as measured by the absolute number of Disability Adjusted Life Years (DALYs, a measure of overall disease burden, expressed as the number of years lost due to ill-health and disability or early death), continues to increase. As populations grow and age, and the prevalence of major disabling neurological disorders steeply increases over the lifespan, governments face increasing demand for treatment, rehabilitation, and support services. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.

Chronic and acute disorders of the nervous system, e.g. stroke and neurodegenerative disorders and dementias such as Parkinson's and Alzheimer’s Disease, combined with diseases affecting the nervous system, such as cerebral malaria, in aggregate contribute the most to the global burden of non-communicable diseases and disorders (NCDs) related illness, disability and death. They also contribute about a third of the burden due only to NCDs in LMICs.

Additional leading causes of years lived with disability (YLDs) include mental and behavioral disorders, especially unipolar depression and bipolar affective disorder, substance-use, schizophrenia and cognitive deficits. Mental, alcohol and substance use disorders were ranked as the 3rd leading contributors to the burden of disease when the burden attributable to suicide (which is a leading cause of death in many regions) is also considered. Depression, the most common psychiatric disorder, accounts for the largest proportion of suicide-related DALYs.

Poor maternal, perinatal and nutritional conditions (including anemia) along with communicable diseases still contribute disproportionately to DALYs in LMICs as compared to high-income countries (HICs). These conditions may also lead to impairment of nervous system development, function and long-term neuro-health.

Infectious and parasitic diseases, such as HIV/AIDS, tuberculosis, malaria and other neglected tropical diseases as well as emerging diseases such as Zika and Covid-19, are a burden for LMICs, where they continue to be important causes of YLDs by themselves and due to their long-term effects on the nervous system, especially of children. However, very limited data is available on the epidemiology, natural history and pathogenesis of neurological problems caused by these diseases and associated opportunistic infections and co-morbidities in these settings.

The incidence of neurodevelopmental disorders and related cognitive disorders (such as mental retardation, behavioral disorders, learning disabilities and cerebral palsy) is less well characterized in LMICs. However, many of the root causes of developmental disabilities – including genetic and nutritional factors, infectious diseases, environmental toxins, and traumatic events (both pre- and post-natal) are particularly common in resource-poor countries, and their prevalence is high. Early neurodevelopmental disorders, along with disability due to postnatal injury or insult to the brain and central nervous system during infancy or childhood, are also a heavy burden in LMICs.

Disability from disease and injury and the need for rehabilitation and accommodation will be an increasingly heavy burden on all health systems. The Global Burden of Disease analyses and updates have put an important spotlight on nervous system-related chronic disability (and its particularly heavy toll on women) from, for example, mental health disorders, substance abuse, musculoskeletal disease, accidents, chronic pain and loss of vision and hearing.

Chronic pain, especially of the neck and back, is also now recognized for its large contribution to the burden of disability. Neurological disorders such as epilepsy, migraine, Parkinson's disease, and multiple sclerosis make smaller but significant contributions. Stroke and perinatal asphyxia, with neurological complications, are also a significant problem in LMICs particularly since some of the causative factors of stroke such as hypertension are both increasing and poorly treated in LMICs as compared to high-income countries.

Overall, the burden of neurological, mental, behavioral and substance use disorders together is expected to rise worldwide, as a proportion of the global burden of disease and disability, because of the projected increase in the number of individuals entering the ages of risk for the onset of many such disorders. Humans are living longer and birth rates are down. As recently as 1950, about 5% of the people in the world were over 65 and about 15% under 5. Those age demographics are on track to reverse by 2050. Direct attention to research on diseases and disorders of later life is therefore needed. But the rise of these disorders is expected to be steeper in LMICs, because of the continuing and long-lasting contributing effects of early life trauma, infectious disease and malnutrition and inadequate health care, further highlighting the need for research on the influence and impact of early health/illness/treatment, experience and environment on development of those diseases and disorders, across the lifespan.

These problems pose a greater burden on vulnerable groups such as people living in poverty, those coping with disease, and those exposed to emergencies. For example, disaster, war and conflict situations are especially prevalent in LMICs and may lead to post-traumatic stress disorder (PTSD), which affects a substantial proportion of the overall population exposed to such conditions and may lead to persistent dysfunction on top of already existing disorders. In addition, stigmatization and gender inequality amplify many of the key risk factors for nervous system disorders and contribute to poor access to and quality of treatment.

Inadequate health care systems and lack of adequate prevention and treatment in LMICs are major contributors to the burden of disease and disability. In some countries, the overall physician-patient ratio can be low as 1:20,000, with even fewer psychiatrists and neurologists. Some disabling brain disorders are readily treatable at low cost, and yet many in LMICs suffer untreated with detrimental individual, family, and societal consequences. For example, epilepsy is a common brain disorder that disproportionately affects people in LMICs (roughly 85 percent of the total number affected worldwide). Although inexpensive and effective treatments are available, epilepsy is frequently untreated and even unrecognized in LMICs, often because of stigmatization and lack of knowledge. For such disorders, implementation science that integrates social and cultural factors into education, media, policy and behavior change research is especially needed and appropriate.

Prevention of disability due to neurological impairment from adverse or toxic environmental exposures is possible in many situations with appropriate research leading to knowledge and interventions. For example, research to identify neurotoxins and their mechanisms can be combined with interventions to minimize human exposure by a reduction in use or release to the environment and by appropriate safeguards in occupational settings.

More information is needed on co-morbidities among nervous system disorders, and between these disorders and other chronic NCDs. Many of these conditions exist together in LMICs and are likely to have more severe and complicated effects than any in isolation and often extend beyond the individual affected (for example both maternal depression and malnutrition are risk factors for infant stunting which itself is a risk factor for later chronic disease with epigenetic effects that may extend to the next generation). Research on the social and economic impact of neurological, psychiatric, and developmental disorders is needed to inform interventions, implementation and policy. Research is also needed to further define the burden and identify knowledge gaps, needs, opportunities and methods to effectively reduce the burden and to lay the groundwork for developing and testing interventions.

Applicants are encouraged to refer for more background to publications summarizing the state of knowledge on the burden of nervous system disorders around the world including but not limited to the following: Disease Control Priorities Related to Mental, Neurological, Developmental and Substance Abuse Disorders (contains five chapters from the Disease Control Priorities in Developing Countries, second edition, World Health Organization 2006,(https://apps.who.int/iris/bitstream/handle/10665/43565/924156332X_eng.pdf;sequence=1). Also for updates see Global Burden of Disease and Risk Factors Report, DCP2, 2006 (http://www.dcp-3.org/dcp2) and Mortality and global health estimates-who.int (www.who.int/data/gho/data/themes/mortality-and-global-health-estimates), the Global Burden of Disease 2010 (http://www.who.int/pmnch/media/news/2012/who_burdenofdisease/en/) and Global, regional, and national burden of neurological disorders,1990-2016: a systematic analysis for the Global Burden of Disease Study 2016 (https://doi.org/10.1016/S1474-4422(18)30499-X) and special resources at https://www.fic.nih.gov/ResearchTopics/Pages/neurological-mental-disorders-diseases.aspx including the FIC/NIH convened series of papers: "Brain disorders across the lifespan: Research to achieve nervous system health worldwide", Nature supplement, Nov 19, 2015 (http://www.nature.com/nature/supplements/collections/npgpublications/brain-disorders/index.html).

Research Topics

Research topics for this FOA are related to brain and other nervous system or neuromuscular function and/or impairment across the lifespan and across generations, and must be relevant to the collaborating LMICs. Applicants are especially encouraged to propose research on co-morbidities and conditions that affect nervous system function across the lifespan. Relevant research for these applications may range from basic science to epidemiological, clinical, health services, translational (e.g. translation of basic research to therapy and of clinical research to applications in the field) and implementation research. Applicants may propose a research and capacity building program on some aspect of neuro-health, brain, other nervous system or neuromuscular function and/or impairment at any stage of life.

Examples of brain, other nervous system and neuromuscular disorders contributing to the burden of disease in LMICs and relevant to this FOA include, but are not limited to, neurodevelopmental disorders (including autism, cerebral palsy, fetal alcohol syndrome, learning disabilities, hydrocephaly, microcephaly), neuromuscular disorders (including muscular dystrophies and inherited or acquired peripheral neuropathies), neurodegenerative diseases (such as Alzheimer's and Parkinson's Diseases), addictive disorders, seizure disorders (such as epilepsy), neuropsychiatric disorders (such as unipolar depression, bipolar disorder, schizophrenia), post-traumatic stress disorder, dementias, encephalopathy, peripheral neuropathies, sensory and motor neuron diseases.

Examples of influences on nervous system function across the lifespan include, but are not limited to: genetic predispositions and epigenetic changes in response to pre-, peri- and post-natal trauma and environmental factors (such as maternal depression, in-utero drug and alcohol exposure, neurotoxic insults, perinatal hypoxia, child abuse and neglect, inadequate environmental stimulation, and nutritional deficiencies), physical and psychological trauma (exposure to violence, sexual and physical abuse, traumatic nervous system injury due to violence and accidents), infection of the nervous system by bacterial, viral and parasitic diseases (such as Zika, HIV/AIDS, malaria, neurocysticercosis, neonatal sepsis) and stroke. Other factors affecting healthy brain development include access to appropriate health care, environmental and socioeconomic factors.

Examples of some cross-cutting areas for research are:

  • Ethnographic studies and other areas of social science, particularly to address health systems, availability of resources, preventive or screening practices, and appropriate interventions within a given society or group;
  • Gender and socio-cultural and economic factors in the etiology, prevention and treatment of the disorders to be addressed;
  • Sex differences at all levels of brain and nervous system function and disorders;
  • The influence of socio-cultural or other environmental variables on the natural history of common neurological diseases/disorders and how this knowledge can be used for treatment and intervention;
  • Factors associated with aging affecting cognitive, emotional/mental and physical health and survival in older persons along with interventions and treatments;
  • Co-occurring risk factors or conditions, especially common in the LMIC or region (e.g. neuro-toxic or traumatic insult plus infectious disease and/or malnutrition);
  • Mechanisms (e.g. neurotoxic, epigenetic) underlying genetic, physiological, environmental, social and economic factors and interactions that affect brain function or development and result in behavioral outcomes (e.g., expression of cognitive impairment, coping, adaptation, response to intervention);
  • Genetic and environmental contributions to various psychiatric outcomes across diverse global populations
  • Epidemiology: 1) Descriptive epidemiology to describe and define the problem in the countries in question by assessing the needs and determining the magnitude of factors involved in the problem to be addressed (e.g., research on trends in incidence, prevalence or mortality; distribution of disease; determination of population at risk; determination of case definition/disease classification). 2) Analytical epidemiology to identify potential etiological factors in the populations of interest, including factors responsible for predispositions to the neurological consequences of various infection and/or neurotoxins (e.g., identification of risk factors for neurological consequences of disease onset or progression; classification and measurement of exposure; magnitude and distribution of known risk factors).

Types of research relevant to this announcement include basic research and epidemiology, as well as translational research, research on diagnostics, early interventions, clinical treatment, prevention, and health services that are culturally appropriate, feasible, and acceptable for implementation within the LMIC. This FOA encourages the development of multidisciplinary and interdisciplinary research and the capacity in the LMIC to conduct such research, relevant to the research question. Expertise may involve, but is not limited to, fields such as genetics/epigenetics, epidemiology, neurology, cognitive neuroscience, developmental neurobiology, neuro-toxicology, neuro-endocrinology, pharmacology, psychiatry, neuro-immunology, neuro-virology, neurosurgery, neuro-rehabilitation and biotechnology (e.g., for development of diagnostic tools and treatments), as well as the behavioral and social sciences including health economics, health services and implementation science.

Research Capacity Building

The proposed collaborative developmental research is expected to help build the capacity for full research programs by improving the research environment and strengthening LMIC individual and institutional research capabilities in the proposed research areas. The proposed work and follow up research are expected to contribute to the long-term goals of building sustainable neuro-health research capacity for brain and nervous system diseases and disorders in LMICs. The proposed project may also contribute to the development of research networks and evidence-based policy.

All applicants are encouraged to become familiar with other relevant research and research training being conducted at the LMIC institution, and more widely within the country and region as feasible. The goal is to take advantage of synergies for networking and collaboration for research and for activities to strengthen research capabilities. As an option, where a strong research base exists in the relevant LMICs, applicants may submit an application with plans to form an interdisciplinary research network to share activities that will strengthen research capabilities and to conduct collaborative neuro-health research, involving for example: multiple departments within an institution, multiple institutions within a country, or even multiple institutions in different countries. Consultation with NIH Scientific/Research staff is recommended when developing this option.

For purposes of the research capacity building and networking encouraged in this FOA, and for background, applicants are also encouraged to use as a resource the compilation of the past awards under the Brain Disorders in the Developing World: Research Across the Lifespan program (http://www.fic.nih.gov/Programs/Pages/brain-disorders.aspx) along with the resources there and including the symposium highlighting a decade of research under the program (http://www.fic.nih.gov/News/GlobalHealthMatters/january-february-2014/Pages/brain-disorders-program-10th-anniversary.aspx ).

Specific Research Interests of the FOA Sponsors

Participating NIH Institutes and Centers (ICs) provided specific statements of interest for this FOA below. Applicants can obtain more information on research interests for each of the NIH participants in this FOA at their web sites and through their Scientific/Research contact listed in this announcement.

The Fogarty International Center (FIC) is interested in all eligible applications relevant to the focus of this FOA and its mission. The FIC Strategic plan (http://www.fic.nih.gov/About/Pages/Strategic-Plan.aspx) states the following relevant goals: 1) Build research capacity through individuals, institutions, and networks to meet future and evolving global health challenges; 2) Stimulate innovation in the development and implementation of technologies and other locally relevant solutions to address global health problems; 3) Support research and research training in implementation science; 4) Advance research on prevention and control of the dual burden of communicable and non-communicable diseases and disabilities; and 5) Build and strengthen partnerships to advance global health research and research capacity.

The National Institute on Aging (NIA) is interested in applications relevant to Alzheimer's disease (AD) and Alzheimer’s disease related dementias (ADRD), other degenerative diseases of the nervous system in aging, and/or age-related changes in cognitive, sensory, emotional and/or motor function, and in brain structural and functional connectivity at the cell, circuit, and network level. Of interest also are studies on reducing disability and/or preventing or slowing additional decline among persons with cognitive, sensory, or motor disabilities as they continue to age. The studies may be laboratory-, clinic-, or population-based. Cross-cultural studies with data harmonization are welcome if focused on the topics above.

The National Eye Institute (NEI) is interested in applications relevant to its mission as stated on the NEI website: http://www.nei.nih.gov/about/mission.asp.

The National Institute on Deafness and Other Communication Disorders (NIDCD) conducts and supports research in 7 scientific program areas: hearing, balance/vestibular, voice, speech, language, taste and smell. The mission of the NIDCD is to reduce the burden of communicative disorders and improve public health. NIDCD is especially interested in applications that strengthen research capacity building & clinical intervention by otolaryngologists, audiologists, speech-language pathologists and related medical and health professionals. Areas focused on newborn screening of hearing ability and early identification and treatment of voice, speech, and language delay or disorders are highly desirable.

Normal hearing ability is central to development of effective verbal expression. Communication disorders occur throughout the lifespan and can occur in isolation (e.g. hearing loss, stuttering) or may occur within the context of a hearing impairment or a neuro-developmental disorders (e.g. autism). Communication disorders may be heritable, due to in utero exposure, or result from injury, neurologic condition (e.g. stroke), head and neck cancer, or coexist with congenital physical conditions (e.g. cleft lip/palate). Developing research capacity of a health-related workforce fluent in the languages spoken in the LMIC is a plus. Applications from institutions within a geographic region which shares the same spoken language e.g. Latin America, Middle East and North Africa would offer nodes on which to build future regional networks for communication disorders or for the development of national and regional Centers of Excellence in Communication Sciences & Disorders.

NIDCD is interested in funding the development and implementation of epidemiological studies on the incidence, prevalence, and determinants of hearing impairment and other communication disorders across the lifespan, including risks associated with behavioral, demographic, environmental, genetic, or other health factors.

The National Institute of Environmental Health Sciences (NIEHS) is interested in supporting research in LMICs to identify the causes of, and opportunities to prevent or ameliorate the consequences of neurotoxic insult to the nervous system throughout the lifespan. Research in LMICs is encouraged in how exposures to toxic environmental insults alter biologic processes, are linked to disease initiation or progression, or affect the risk of either disease development or distribution in populations. Examples of environmental exposures of interest include industrial chemicals or manufacturing byproducts, metals, pesticides, herbicides, air pollutants and other inhaled toxicants, particulates or fibers, fungal, food or bacterially derived toxins (but not infectious agents, per se) and indoor air pollutants from cooking stoves and other sources.

The National Institute of Mental Health (NIMH) encourages studies across the research spectrum, from basic through translational science to intervention development and efficacy, effectiveness, and implementation research. Mental disorders may be defined according to existing diagnostic criteria or along dimensions of neurobehavioral functioning according to the NIMH Research Domain Criteria (RDoC) framework. If existing diagnostic criteria are to be used, investigators should include plans for addressing heterogeneity within the diagnostic category or categories.

All applications that propose clinical trials to develop or test preventive, therapeutic, or services interventions, including studies that test dissemination and implementation strategies, are encouraged to follow the NIMH’s experimental therapeutics approach to intervention development and testing (see NIMH Clinical Trials FOAs). It is recommended that investigators contact NIMH Scientific/Research staff well in advance of submitting applications to discuss the match to NIMH priorities.

Relevant research topics include, but are not limited to, research that:

  • Charts the course of neuropsychiatric disorders over the lifespan in order to: (a) understand ideal times and methods for intervention to preempt or treat mental disorders and hasten recovery; (b) examine the interactions of neurobiological systems and environmental/social factors that affect brain development, resulting in maladaptive behavioral outcomes (e.g., cognitive impairment, inability to respond to intervention); or (c) identify molecular or circuit pathways of neural function that are promising new intervention targets.
  • Seeks to understand sex, genetic, or other biological differences implicated in the presentation, course, severity, or disease burden of mental disorders or in treatment response.
  • Assesses new psychosocial and biomedical interventions, with a focus on mediators, moderators, and predictors (e.g., biological, genetic, behavioral, experiential, environmental) of intervention response and side effects in diverse patient populations.
  • Examines approaches to care for people with chronic, severe mental illnesses in institutional and community settings.
  • Examines implementation models and measures of care quality and outcomes that produce optimal results for: (a) early identification of mental disorders, (b) scaling up of training and supervision for mental health care providers, (c) integrating screening and core packages of care for mental illnesses into existing delivery platforms (e.g., primary health care, schools, HIV services, workplaces), or (d) delivering transdiagnostic interventions for mental disorders in health sector and non-health sector settings.
  • Assesses data collection and feedback models for monitoring the reach, accessibility, quality, costs, and/or effectiveness of preventive, treatment, or rehabilitative health services for mental disorders (e.g., how models enable data-driven decision-making for optimal delivery of care).
  • Targets HIV/AIDS related topics such as epidemiology, natural history and pathogenesis and genetics of HIV-associated CNS dysfunction and neuropsychiatric disorders before and after treatment initiation in adult and pediatric populations; examination of the neurobehavioral consequences, with respect to in-utero exposure to a dysregulated immune environment and/or antiretroviral medication and consequences of being born to an HIV-positive mother. NIMH encourages development of common standardized assessment instruments with appropriate norms that can provide reliable and valid measurement of neurobehavioral consequences of HIV and its treatments throughout the age-span in low- and medium-resource environments; and develops interventions to improve neurobehavioral functioning compromised by HIV/AIDS and its associated conditions that can be implemented in LMICs. NIMH encourages studies to understand the social and structural determinants of health related to human mobility which affect mental health and/or HIV outcomes.
  • NIMH also supports research toward a cure including developing novel approaches and strategies to identify and eliminate CNS viral reservoirs that could lead toward a cure or lifelong remission of HIV infection, including studies of viral persistence, latency, reactivation, and eradication.
  • NIMH would also like to encourage the NIMH mission centered research networks option as described in this FOA.

The National Institute of Neurological Disorders and Stroke (NINDS) has interest in supporting mechanistic, epidemiological, prevention, translational and clinical research across the spectrum of neurological, neuromuscular, neuroinfectious and neurovascular diseases and disorders in all ages. In addition to prevalent neurological disorders and stroke, NINDS is also interested in supporting research and capacity building in areas of rare and neglected neurological diseases that are relevant to the collaborating LMICs (NINDS Disorder Index http://www.ninds.nih.gov/disorders/disorder_index.htm). NINDS encourages the development of networks in topical disease-related areas (e.g., stroke, epilepsy or other high burden neurological disorders in LMICs) or projects that are linked to existing programs or resources in LMICs (e.g., H3Africa or other NIH-funded programs) to share capacity building activities and conduct collaborative research.

For the current FOA, the NINDS has interest in applications that lay the groundwork for future clinical trials, such as those that propose conducting surveys of available patient populations, developing clinical trial protocols and training materials, and establishing trial infrastructure for recruiting and treating subjects and collecting, receiving, storing and distributing study drugs, and processing data and laboratory specimens.

For applications proposing a clinical trial, please review the following definitions for this funding announcement:

  • Clinical trials are research studies in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. NINDS will only support the following types of clinical trials under the Global Brain Disorders R21 program:
  • Clinical trials that seek to answer specific questions regarding safety, tolerability, clinical efficacy, effectiveness, clinical management, and/or implementation of pharmacologic, behavioral, biologic, surgical, or device (invasive or non-invasive) interventions, preventive, therapeutic, and services interventions, will not be supported under this R21. Applicants interested in answering these types of questions are encouraged to refer to the companion FOA,  PAR-21-311 Global Brain and Nervous System Disorders Research Across the Lifespan (R01) (Clinical Trial Optional) and to the NINDS listing of currently active clinical trial FOAs (https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Clinical-Research)

NINDS encourages the reuse of Common Data Elements/Data Standards whenever appropriate. The following is not an exhaustive list of data standards and standardized instruments. Applicants are encouraged to reuse standards developed by other recognized groups that are not funded by NIH:

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

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New
Resubmission

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Optional: Accepting applications that either propose or do not propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets are limited to $125,000 per year in direct costs, but must reflect the actual needs of the proposed project.

Award Project Period

The project period may be up to 2 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local 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)

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)

To determine country income categories, please view the following: http://data.worldbank.org/country. The subcategories of LMICs are upper-middle-income (UMIC), lower-middle-income and low-income countries.

LMIC institutions, are eligible to partner either with U.S. institutions, and/or with other LMIC institutions with or without a U.S. partner. Applications may be submitted from any of the institutional partners as appropriate.

Exceptions:

Foreign high income-country institutions are not eligible institutional partners under this FOA (but individual investigators may be involved as described below in "Eligible Individuals").

LMIC components of US institutions are generally not eligible as the LMIC institution.

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. 

Required Registrations

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) – 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.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Women and 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 provides an avenue for investigators in LMICs and the U.S., with shared interests in brain and other nervous system disorders, to establish collaborative research and research capacity strengthening activities. Therefore, one or more investigators from an LMIC institution, and one or more from another LMIC institution and/or a U.S. institution (see definitions above, in the “Eligible Institutions” section) must collaborate on the application. PLEASE NOTE: Use of the multiple PD/PI format is encouraged but not required. Where there are multiple PD/PIs, the contact PD/PI may be from the LMIC institution or from the U.S.

NOTE: Non-U.S.-based HIC investigators are NOT eligible as PD/PIs but may be included as consultants, especially if they present special opportunities for furthering research programs, present special expertise, opportunities and/or unusual talent for furthering research programs, or provide resources relevant to the proposed project that either are not readily available in the eligible LMIC or the U.S. institution or which augment existing resources.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

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

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

Kathleen Michels, Ph.D.
Telephone: 301-435-6031
Fax: 301-402-0779
Email: brainfic@nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of 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 application to this FOA.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

If there is not a PD/PI from all the collaborating institutions, then there must be a Senior/Key Person from each institution.

R&R or Modular Budget

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

It is expected that the majority of funds awarded (greater than 51% of the total direct costs) will be used for supplies, research capacity building costs, equipment, services, travel, and personnel at the LMIC site(s).

A Networking meeting (3 days) involving grantees of these awards will be held in the U.S. each year (most likely at NIH in Bethesda).

Funds should be budgeted for travel to the three-day networking meeting each year by the PDs/PIs and LMIC collaborators who are key personnel. As budget allows attendance by research fellows and/or other relevant individuals with significant day-to-day involvement in the activities performed under this award is also encouraged.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims

Describe how the proposed research is relevant to the interests of one of the participating NIH Institutes or Centers.

Describe how the proposed work will:

  • Build or expand on research collaborations between LMIC and/or U.S. country institutions, individuals and teams;
  • Use basic, epidemiological, clinical, prevention, intervention or health services research paradigms, tools and techniques, to address nervous system development, function and/or  impairment at any stage of life on topics particularly relevant to LMICs;
  • Assess and strengthen the research capabilities of LMIC partners and institutions to enable further research to take place during and beyond the R21 period;
  • Contribute to developing a base for further networking and research to support evidence-based policy in the LMICs beyond the R21-specific research project

Research Strategy

Applicants must:

  • Describe an exploratory/pilot research project
  • Describe an associated plan for assessing, developing and strengthening LMIC research capabilities.
  • Define the health issue/research problem and determine the magnitude of and factors involved in the problem to be addressed in the countries in question;
  • Describe the research capabilities needed to carry out the proposed research and how research capacity needs will be assessed; Assess current resources and processes to carry out any proposed research involving human or animal subjects, including those of the performance site institutional review board (IRB), or community advisory board.
  • Describe plans to address previously identified needs and gaps in knowledge or practice in the context of the R21.
  • Describe how collaborative relationships and understandings with the partners in the countries involved will be developed and solidified to meet the research goals;
  • Describe how the feasibility of the approach proposed will be assessed
  • Describe how the data generated may be used in generating hypotheses for proposed follow-up research.
  • Describe how the data will be collected (e.g., case report forms, data dictionaries, plans for data curation, sustainability, etc.) and the use of Common Data Elements/Data Standards, as appropriate.
  • Explain how research capacity strengthening will be integrated into the proposed research program;
  • Identify, as appropriate to the stage of the research, opportunities for relevant research networks within and/or between institutions, countries and regions;
  • Propose specific milestones and a timeline to meet the stated research and capacity building goals. For applications proposing clinical trials, these may reference but should not duplicate information provided on the PHS Human Subjects-Clinical Trial Information form.
  • Describe planned steps to solidify partnerships, expertise, information and data obtained from the R21 as needed to organize, prepare for and assemble an application for a more comprehensive research grant (e.g. FOA, PAR-21-311 Global Brain and Nervous System Disorders Research Across the Lifespan (R01) or other similar NIH or non-NIH funding opportunity) depending on the results of the pilot research.

Describe meetings, workshops and small conferences as necessary to further develop research plans and collaborations or for assessment of needs and to discuss specific research questions that show the greatest promise for follow up. Where multiple sites or countries are involved, travel among sites for these purposes may be proposed.

Justify the relevance of the proposed research to the health of the target LMIC countr(ies).  

In addition, the planned involvement, if any, of the LMIC institution and faculty in formulating treatment and prevention policies locally, nationally, regionally or internationally should be noted.

Collaboration

The purpose of this grant is to foster initial development of collaborative work focused on neuro-health, brain and other nervous system disorders across the lifespan, which is relevant to LMICs. Accordingly, investigators are not required to demonstrate in the application any history of prior collaboration. However, those factors in the investigators' background and/or institutional circumstances that would facilitate success in such collaboration should be clearly delineated.

While there is no cap on the maximum number of investigators or institutions involved, the contributions and roles of each individual and institution and how they will be working with the whole team should be clearly delineated.

Plans for coordination of research and activities to strengthen research capabilities between the partner country institutions should be described and should include regular meetings (virtual and/or physical).

Networking

For applications proposing to develop research networks where a strong research base exists in the relevant LMICs: 

1) Describe relevant related research and research training, if any, that is already being conducted at the LMIC institution, and/or more widely within the country and region.

2) Discuss the potential to take advantage of synergies for networking and collaboration for research and for activities to strengthen research capabilities.

3) Describe plans to share activities that will strengthen research capabilities and to conduct collaborative research, involving for example: multiple departments within an institution, multiple institutions within a country, or even multiple institutions in different countries.

Letters of Support: Provide Letters of Support from each collaborator and collaborating institution.

PHS 398 Cumulative Inclusion Enrollment Report

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

The following modifications also apply:

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

Appendix:

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

  • No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the 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.

Delayed Onset Study

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

PHS Assignment Request Form

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

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

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.

In order to expedite review, applicants are requested to notify the FIC Referral Office by email at brainfic@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:
 

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

In addition, for applications involving clinical trials:

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

Overall Impact

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).

Scored Review Criteria

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 the prior research that serves as the key support for the proposed project rigorous? 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 involving 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?
 

Is the research on a problem of relevance for the LMIC(s) involved in the application?

 

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 involving 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 involving 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?

Does the project make use of unique or special expertise, resources, circumstances or environment of the LMIC site to frame or address the research question? Does the project incorporate innovative strategies for strengthening research capabilities at the LMIC site/in the LMIC relevant to the research proposed?

 

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed 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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

For projects with multiple sites and/or multidisciplinary components, is there an adequate plan to coordinate and integrate the research among the sites/components? Are the administrative plans for the management of the research project appropriate, including plans for resolving conflicts.
 

In addition, for applications involving 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?

For projects with multiple sites and/or multidisciplinary components, is there an adequate plan to coordinate and integrate the research among the sites/components? Are the administrative plans for the management of the research project appropriate, including plans for resolving conflicts?

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 involving 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?
 

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?
 

Additional Review Criteria

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.

Research Capacity Strengthening

Does the proposed research strategy include plans to enhance the LMIC research capabilities at the individual and institutional level and/or build research networks in the context of the proposed research?

 

Specific to applications involving clinical trials

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  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  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 individuals of all ages (including children and older adults) 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.

 

 

Not Applicable

 

Not Applicable

Additional Review Considerations

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by{LOCUS OF 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 will receive a written critique.

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.

Applications 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 Fogarty International Center Advisory 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.
  • Program priorities for regional or country distribution of awards.

3. Anticipated Announcement and Award Dates

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.

Section VI. Award Administration Information

1. Award Notices

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 recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. 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 and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient 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).

2. Administrative and National Policy Requirements

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, Recipients, and Activities, including of note, but not limited to:

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

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.

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.

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 and 2 CFR Part 200.206 “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

3. Reporting

When multiple years are involved, recipients 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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients 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 the threshold.  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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and 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)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Kathleen Michels, Ph.D.
Fogarty International Center (FIC)
Telephone: 301-435-6031
Email:  michelsk@nih.gov

NIMH Non AIDS: Andrea Horvath Marques, M.D., MPH, Ph.D.
National Institute of Mental Health (NIMH)
Phone: 301-646-7320
Email: andrea.horvathmarques@nih.gov

Sujata Bardhan, Ph.D.
Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD)
Telephone: 301-496-5061
Email: sujata.bardhan@nih.gov   

Lana O Shekim, Ph.D.
National Institute On Deafness And Other Communication Disorders (NIDCD)
Phone: 301- 496-5061
E-mail: shekiml@nidcd.nih.gov

NIMH AIDS: Jeymohan Joseph, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 240-627-3869
Email: jjeymoha@mail.nih.gov 

Lisa Neuhold
National Eye Institute (NEI)
Phone: 301-443-5401
E-mail: lneuhold@mail.nih.gov

Dallas Anderson, Ph. D. 
National Institute on Aging (NIA)
Phone: 301-402-6693
Email: dallas.anderson@nih.gov
 

Kimberly A Gray. PhD
National Institute Of Environmental Health Sciences (NIEHS)
Phone: 984-287-3262
E-mail: gray6@niehs.nih.gov

Richard T. Benson, MD, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Phone: 301-496-9135
E-mail: richard.benson@nih.gov

Stacey D. Chambers, MS
National Institute of Neurological Disorders and Stroke (NINDS)
Phone: 301-496-0690
E-mail: stacey.chambers@nih.gov

Peer Review Contact(s)

Center for Scientific Review (CSR)
Email: FOAReviewContact@csr.nih.gov  

Financial/Grants Management Contact(s)

Mollie Shea
Fogarty International Center (FIC)
Telephone: 301-496-1653
Email:mshea@mail.nih.gov

Maggie Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: youngmar@mail.nih.gov

Christopher Myers
National Institute On Deafness And Other Communication Disorders (NIDCD)
Phone: (301) 435-0713
E-mail: myersc@nidcd.nih.gov

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: siscor@mail.nih.gov
 

Karen Robinsonsmith
National Eye Institute (NEI)
Phone: (301) 451-2020
E-mail: kyr@nei.nih.gov

Heidi Young
National Institute on Aging (NIA)
Phone: 301-451-8789
Email: heidi.young@nih.gov
 

Barbara Gittleman
National Institute Of Environmental Health Sciences (NIEHS)
Phone: 984-287-3261
E-mail: gittlemanbj@mail.nih.gov

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.nih.gov  

Section VIII. Other Information

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.

Authority and Regulations

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 and 2 CFR Part 200.


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