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Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH) (http://www.nih.gov)
Canadian Institutes of Health Research (CIHR) (
http://www.cihr.ca)
Autism Speaks (
http://www.autismspeaks.org)

Components of Participating Organizations
Fogarty International Center (FIC) (http://www.fic.nih.gov)
National Institute on Aging (NIA) (
http://www.nia.nih.gov)
National Institute on Alcohol Abuse and Alcoholism (NIAAA) (
http://www.niaaa.nih.gov)
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (
http://www.nichd.nih.gov)
National Institute on Drug Abuse (NIDA) (http://www.nida.nih.gov)
National Institute of Environmental Health Sciences (NIEHS) (
http://www.niehs.nih.gov)
National Institute of Neurological Disorders and Stroke (NINDS) (
http://www.ninds.nih.gov)
Office of Dietary Supplements, Office of the Director (ODS) (
http://dietary-supplements.info.nih.gov)
Institute of Neuroscience, Mental Health and Addiction (INMHA/CIHR) (
http://www.cihr-irsc.gc.ca/e/8602.html)

Title: Brain Disorders in the Developing World: Research Across the Lifespan (R21)

Announcement Type

This Funding Opportunity Announcement (FOA) is a reissue of PAR-06-420.

Update: The following update relating to this announcement has been issued:

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four (4) weeks prior to the grant submission date. See Section IV.

Program Announcement (PA) Number: PAR-08-113

Catalog of Federal Domestic Assistance Number(s)
93.989, 93.866, 93.273, 93.209, 93.865, 93.279, 93.113, 93.114, 93.115, 93.853

Key Dates
Release/Posted Date: March 18, 2008
Opening Date:April 16, 2008 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): Applications not related to HIV/AIDS: April 16, 2008; April 15, 2009; April 14, 2010. HIV/AIDS-related applications: July 22, 2008; July 21, 2009; July 23, 2010
NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Submission/Receipt Date(s): Applications not related to HIV/AIDS: May 16, 2008; May 15, 2009; May 14, 2010
AIDS Application Submission/Receipt Date(s): HIV/AIDS-related applications: August 22, 2008; August 21, 2009; August 23, 2010
Peer Review Date(s): October/November 2008; October/November 2009; October/November 2010
Council Review Date(s): January 2009; January 2010; January 2011
Earliest Anticipated Start Date(s): April 1, 2009; April 1, 2010; April 1, 2011
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: August 24, 2010

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants

A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review, and Anticipated Start Dates
1. Letter of Intent
B. Submitting an Application Electronically to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)

2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

The collaborative research programs are expected to 1) conduct research on nervous system development, function and impairment at any stage of life and on topics particularly relevant to LMICs and 2) build research capacity among the LMIC partners and institutions involved in the specific research project. Both immediate objectives will contribute to the long-term goals of building sustainable research capacity in LMICs to initiate and conduct such research, ultimately leading to development of treatment and prevention strategies that are applicable worldwide.

The R21 grant will provide support to assess needs, to initiate preliminary studies and training, and to organize, plan, prepare, and assemble the information and data for an application for a more comprehensive R01 application involving collaboration between the HIC and LMIC investigators.

The main goals of the application should be to: 1) assess research needs (define the problem and determine the magnitude of and factors involved in the problem to be addressed in the countries in question) and training needs for conduct of a follow-up R01 submission; 2) develop collaborations and needed resources; 3) show feasibility and generate preliminary data for the collaborative research to be proposed in a follow-up R01 submission; and 4) integrate capacity building/collaborator training into the proposed research program.

Applicants should propose specific milestones and a timeline to meet these goals. During the R21 award period, the applicant should:

Pilot research projects should demonstrate feasibility of certain aspects of the research approaches and develop further research directions. Training, informal meetings, workshops and small conferences may be conducted as necessary to develop the research and collaboration and for assessment of needs. New analyses of extant data sets and development or use of new methodologies or approaches may also be proposed. These activities may also serve to identify which specific research questions show the greatest promise for advancement in specific countries and settings. Travel among sites for these purposes may be proposed.

Each exploratory/planning grant should also present a description of the anticipated longer-term goals of the collaboration as it develops into an application for an R01 grant. As one outcome of the work under the R21, grantees will be expected to provide a detailed assessment of the specific research issues and capacity building/training needs in the LMIC that the proposed follow-up R01 will address. The relevance of the focus of the proposed research to the health of the host endemic country should be justified. The assessment may include, but is not limited to, needed skills and expertise in laboratory, clinical, epidemiological and social science research.

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 the R21 mechanism is to foster initial development of collaborative work focused on brain disorders across the lifespan and relevant to LMICs; accordingly, investigators need not demonstrate any history of prior collaboration in the R21. However, those factors in the investigators background and/or institutional circumstances that would facilitate success in such collaboration should be clearly delineated.

Plans for coordination of research and associated collaborator training between the partner country institutions should be described and should include regular meetings (virtual and/or physical).

Research Capacity Building Activities

In addition to pilot research studies, which may lead to a future R01 application, the proposed program should contain explicit strategies or plans to assess the research and research capacity needs and to strengthen this capacity through research training, career development, mentoring and/or other models. Research training for the LMIC collaborators and their staff, in the context of the proposed R21 and subsequent R01 research, may take place at any of the collaborating sites and may vary, depending on the strengths of the particular investigators and institutions that apply and the need to build capacity to support research and future interventions in the LMIC. The major portion of the proposed research must be conducted at the LMIC site or sites and the majority of the funds must be used for research and research-related costs at the LMIC site (including collaborator training at the LMIC site). Any research at the HIC site must also involve training for participating LMIC country collaborators.

All projects should:

Activities undertaken under the R21planning grant may also include, but are not limited to:

Background

During the past several decades, improvements in health care have led to a decrease in child mortality and an increase in life expectancy in LMICs. These positive trends have set the stage for a complex epidemiology of health and disease as more children survive into adulthood handicapped by early disease, malnutrition and adverse experiences and/or later develop chronic diseases including cognitive and neurodegenerative disorders prevalent in old age. Adverse socio-economic factors, such as poverty, conflict and gender inequalities inherent in varying degrees to many countries contribute to the initial causes (such as injury, psychological trauma, chronic adversity, genetic vulnerability and infection) of many nervous system disorders. These disorders, especially those brain disorders affecting cognitive and mental function, in turn hinder the ability of individuals and their societies to address the root causes, and consequences of those adverse conditions.

World Health Organization data suggest that non-communicable diseases and disorders (NCDs) are rapidly becoming the dominant causes of poor health in all LMIC regions except sub-Saharan Africa (where they are second only to HIV/AIDS, as defined by contribution to years lived with disability or DALYs). Of the NCDs, nervous system diseases and disorders in aggregate contribute the most to the overall burden of disease and disability (more than a quarter, followed by cardiovascular disease and cancer) and contribute about a third of the burden due only to NCDs in LMICs (Global Burden of-Disease and Risk Factors Report, DCP2, 2006, http://www.dcp2.org/pubs/GBD/7/FullText ).

In fact, nervous system disorders account for four out of the six leading causes of years lived with disability (DALYs). They are: mental disorders, especially unipolar depression and bipolar affective disorder, substance-use and alcohol-use disorders, schizophrenia, and dementias. Neurological disorders specifically reported in the DCP2 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 poorly treated in LMICs as compared to HICs.

Depression, the most common psychiatric disorder and the worlds fourth largest cause of DALYs also contributes substantially to mortality due to suicide, which in 2001 was a leading cause of death in many regions, ranking fifth in Eastern Europe and Central Asia, according Global Burden of Disease and Risk Factors.

Neurodevelopmental disorders and related cognitive disorders (such as mental retardation, behavioral disorders, learning disabilities and cerebral palsy) that result from abnormal prenatal development or influences during the prenatal and perinatal period, or from injury or insult to the brain and central nervous system during infancy or childhood are also clearly burdensome in LMIC countries, however their incidence is less well characterized. Many of the causes of developmental disabilities including genetic and nutritional factors, infectious diseases, environmental toxins, and traumatic events are, however, particularly common in resource-poor countries, suggesting that the prevalence there is expected to be high.

Communicable diseases along with maternal, perinatal and nutritional conditions still contribute disproportionately to DALYs in LMIC countries as compared to HIC countries (more than half of the burden for low income countries as compared to about 20 percent for middle income and less than six percent for high income countries according to 2005 WHO estimates). All of these conditions may lead to varied nervous system problems. Infectious and parasitic diseases, such as HIV and malaria, are a particular burden for LMIC countries, and especially sub-Saharan Africa, where they affect large numbers of individuals who are not adequately treated. However, very limited data are 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 proportion of the global burden of disease attributable to mental, neurological and substance use disorders together is expected to rise worldwide in future because of the projected increase in the number of individuals entering the age of risk for the onset of many such disorders. However, the rise will be steeper in LMIC countries, because of the continuing and long lasting effects of early life trauma, infectious disease and malnutrition which contribute or lead to neurological and neurodevelopmental disorders and mental retardation. These problems pose a greater burden on vulnerable groups such as people living in poverty, those coping with disease and those exposed to emergencies. Disaster, war and conflict situations, especially prevalent in many LMIC countries, may lead to post-traumatic stress disorder (PTSD) which affects a substantial proportion of the overall population exposed to such conditions and which leads to persistent dysfunction. In addition, stigmatization and gender inequality amplify many of the key risk factors for nervous system disorders. At the same time, available care is frequently inadequate. In some countries, the overall physician-patient ratio can be low as 1:20,000, with even fewer psychiatrists and neurologists.

Despite their enormous burden of disease, nervous system disorders have been largely absent from the international health research agenda. In addition to research on the etiology, prevention and treatment of individual conditions and disorders, 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 LMIC countries and are likely to have more severe and complicated effects than any one in isolation and may even extend beyond the individual affected (for example maternal depression as a risk factor for infant stunting). 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 for effectively reducing the burden and to lay the ground work for, develop and test interventions, and promote research capacity building.

Some disabling brain disorders are readily treatable at low cost, and yet many in LMIC countries suffer untreated with detrimental individual, family and societal consequences. As an example, epilepsy is a common brain disorder that affects disproportionately people in LMIC countries, roughly 85 percent of the total number affected worldwide. Although inexpensive and effective treatments are available, epilepsy is frequently untreated and even unrecognized in LMIC countries often because of stigmatization and lack of knowledge. In such disorders, research into interventions taking social and cultural factors into account and involving education, media, policy and behavior are especially needed and appropriate.

Prevention of disability due to neurological impairment 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 to known neurotoxins by reduction in use or release to the environment and by appropriate safeguards in occupational settings.

Applicants are encouraged to refer for more background to the recent publications summarizing the state of knowledge on the burden of nervous system disorders around the world including 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, http://www.dcp2.org/file/64/WHO_DCPP%20mental%20health%20book_final.pdf) and Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World 2001, Institute Of Medicine, http://books.nap.edu/openbook.php?record_id=10111&page=R1).

Research Topics

Relevant research topics for this FOA are related to nervous system function and/or impairment from birth to advanced age and must be relevant to the collaborating LMICs.Research on co-morbidities and `conditions that affect nervous system function at different life stages as well as across the lifespan are especially encouraged. Relevant research for these applications may range from basic science to epidemiological, clinical, health services and translational (e.g. translation of basic research to therapy and of clinical research to applications in the field) research. Applicants may propose a research and capacity building program on some aspect of nervous system function and/or impairment at any stage of life. In all cases near-term or potential future implications for or relevance to prevention, diagnostics, treatment or other interventions should be indicated or included in the research plan.

Examples of nervous system 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 etc.), 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 etc), posttraumatic stress disorder, dementias, encephalopathy, peripheral neuropathies, motor neuron diseases etc.

Examples of specific conditions that influence nervous system function across the lifespan include, but are not limited to genetic predispositions, 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, nutritional deficiencies etc.), physical and psychological trauma (exposure to violence, rape, physical abuse, traumatic nervous system injury due to violence and accidents), infection of the nervous system by viral and parasitic diseases (such as HIV/AIDS, malaria, neurocysticercosis) and stroke.

Other factors affect healthy brain development, including access to appropriate health care and socioeconomic factors. Examples of some cross-cutting areas for research are:

Types of Research relevant to this announcement includes basic research and epidemiology, as well as 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 development of multidisciplinary research and the capacity in the LMIC to conduct such research, whenever relevant to the research question. Expertise may involve, but is not limited to, fields such as genetics, epidemiology, neurology, cognitive neuroscience, developmental neurobiology, neurotoxicology, neuroendocrinology, pharmacology, psychiatry, neuro-immunology, neuro-virology, 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.

Specific Research Interests of the FOA Sponsors

Applicants can obtain information and research interests for each of this FOAs sponsoring partners at their Web sites and by contacting the partner program contact listed in this announcement (Section VII., Agency Contacts). Some of the participating partners have provided additional statements of interest. National Institutes of Health (NIH)

The National Institute on Aging (NIA) is interested in applications relevant to Alzheimer's disease and other degenerative diseases of the nervous system, and age-related changes in cognition and memory. Of interest also are studies on reducing disability and/or preventing or slowing additional decline among persons with neurological disabilities as they continue to age.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is interested in applications that address alcohol-related birth defects (such as Fetal Alcohol Syndrome).

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is particularly interested in encouraging studies in response to this announcement which propose to address problems in child health and development, such as mental retardation, cognitive and behavioral disorders, neurodevelopmental disabilities and learning disabilities. Relevant research includes etiology, pathophysiology, screening, prevention, treatment, and epidemiology. Also of interest are studies on cognitive, social, and affective development, including studies in high-risk settings (e.g., in violent or abusive environments, or families experiencing stressors such as poverty, unemployment or parental depression). Biomedical, behavioral, and biobehavioral research in these areas is encouraged along with investigations of socio- and ethno-cultural, familial, individual, and biological influences. Also of interest are studies investigating the roles played by nutritional and hormonal factors in nervous system development and function.

The National Institute on Drug Abuse (NIDA) is interested in applications which focus on behavioral, cognitive and neurobiological factors as antecedents to, or impacting on, consequences of drug abuse. Of particular interest are studies aimed at reducing drug abuse and addiction and its associated adverse social, behavioral, and health consequences (e.g., violence and infectious diseases transmission and including research related to the interaction between HIV/AIDS and abuse). The NIDA especially encourages research capitalizing on unique opportunities to study adverse environmental and socio-cultural effects on drug abuse patterns and behaviors in populations of LMICs (e.g., caregiver neglect or abandonment, large orphan populations or street children at risk for both drug abuse and HIV or HCV). In countries where abuse of high doses of individual drugs is more common than in the U.S. and Europe, the NIDA is interested in supporting studies on prenatal effects, cognitive consequences, epidemiological patterns, and associations with HIV/ AIDS and other transmitted diseases. The NIDA will give priority to meritorious research that builds upon existing NIDA-funded collaborations between HIC and LMIC colleagues.

The National Institute of Environmental Health Sciences (NIEHS) is interested in supporting research in LMIC countries to identify the causes of, and opportunities to prevent or ameliorate, the consequences of, neurotoxic insult to the nervous system throughout life (pesticides, heavy metals etc.).

The National Institute of Neurological Disorders and Stroke (NINDS) is interested in supporting mechanistic, epidemiological, prevention, translational and clinical research across the spectrum of neurological disorders, neuromuscular diseases and stroke.

Canada

The Institute of Neurosciences, Mental Health and Addiction (INMHA), of the Canadian Institutes of Health Research (CIHR), is interested in co-sponsoring collaborative proposals between Canadian and low- to middle-income country investigators. Eligible applications include those dealing with the spectrum of research related to neurological disorders, mental illnesses and addictions. CIHR will provide direct funding to meritorious Canadian applicants.

Other Participating Organizations

Autism Speaks (http://www.autismspeaks.org ) will consider support for scientifically meritorious autism-related research proposals and will provide direct funding to meritorious applicants.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information


1. Mechanism of Support

This FOA will use the NIH Exploratory/Developmental Research Grant (R21) award mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses Just-in-Time information concepts see SF424 (R&R) Application Guide). It also uses the modular as well as the non-modular budget formats (see the Modular Applications and Awards section of the NIH Grants Policy Statement. Specifically, if you are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 3.4, Modular Budget Component, of the Application Guide).

U.S. applicants requesting more than $250,000 in annual direct costs and all Foreign applicants must complete and submit budget requests using the Research & Related Budget component.

Exploratory/developmental grant support is for new projects only; renewal (formerly competing continuation) applications will not be accepted. Applicants may submit a resubmission, but such application must include an Introduction addressing issues raised in the previous critique (Summary Statement).

If a consortium is involved, please see NOT-OD-05-004 for information on the relationship of F&A costs on subawards to the direct costs requested.

2. Funds Available

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the Institutes and Centers (ICs) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications relevant to the interests of each sponsor.

The participating organization(s), the Fogarty International Center (FIC), the National Institute on Aging (NIA), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute on Drug Abuse (NIDA), the National Institute of Environmental Health Sciences (NIEHS), the National Institute of Neurological Disorders and Stroke (NINDS), and the Office of Dietary Supplements of the Office of the Director (ODS/OD), all of the National Institutes of Health (NIH), along with the Institute of Neuroscience, Mental Health and Addiction (INMHA) of the Canadian Institutes of Health Research (CIHR), and Autism Speaks, intend to commit approximately $2 million in fiscal years 2009, 2010 and 2011 to fund five to fifteen applications. .

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

F&A costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004, November 2, 2004.

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

EXCEPTIONS: Financial institutions and international intergovernmental organizations are not eligible to apply for FIC research or training programs. However, staff of such institutions, if invited by eligible applicants, may serve as unpaid collaborators or consultants on such projects.

At least two institutions, one in a HIC and one in a LMIC will be involved as partners in the grant application. See http://www.worldbank.org/data/countryclass.htm for World Bank country classification tables to identify those countries considered low- or middle-income.

Hong Kong-based institutions are not eligible as the primary LMIC partner institution. A second institution in mainland China must be involved as the primary collaborating HIC institution if an institution in Hong Kong is included as a partner institution. Taiwan is not listed in the World Bank income classification list but is considered high-income.

1.B. Eligible Individuals

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

More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD/PI model.Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH electronic Research Administration (eRA) Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

This FOA provides an avenue for investigators in HICs and those in LMICs, with shared interests in brain and other nervous system disorders, to explore, initiate and implement research collaboration between themselves and their institutions. Therefore, at least two investigators, one from an institution in a HIC and one from an institution in a LMIC (see definitions above, in the Eligible Institutions section) must collaborate on the application. The contact PD/PI may be from the LMIC institution or from the HIC institution, but the collaborators must prepare the proposal jointly. While there is no cap on the maximum number of investigators or institutions involved, the applicant must discuss how the contributions of each member will be integrated in the proposed activities.

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. When considering the multiple PD/PI option, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically.Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Exploratory/developmental grant support is for new projects only; competing renewal (formerly competing continuation) applications will not be accepted.

Applicants may submit a resubmission, but such application must include an Introduction addressing issues raised in the previous critique (Summary Statement).

Applicants may submit more than one application, provided each application is scientifically distinct.

An individual investigator may be involved as PD/PI or primary collaborator on more than one application for the submission/receipt dates of this FOA, provided the applications are scientifically distinct.

Section IV. Application and Submission Information


To download a SF424 (R&R) Application Package and SF424 (R&R) SBIR/STTR Application Guide for completing the SF424 (R&R) forms for this FOA, use the Apply for Grant Electronically button in this FOA or link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

PDs/PIs should work with their institutions/organizations to make sure they are registered in the NIH eRA Commons.

Several additional separate actions are required before an applicant SBC can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Registered.

2) Organizational/Institutional Registration in the eRA Commons

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

Both the PDs/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo -- Telephone 301-710-0267, Email: [email protected].

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide (MS Word or PDF).

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PIs assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY will include all applicable components, required and optional. A completed application in response to this FOA will include the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget or Research & Related Budget, as appropriate (See Section IV.6., Special Instructions, regarding appropriate required budget component.)

Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

Foreign Organizations (Non-domestic [non-U.S.] Entities)

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from Foreign organizations must:

Proposed research that provides special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States (U.S.) or that augment existing U.S. resources, is encouraged.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in Item 13 of the SF424 (R&R) Cover component.All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of PD/PI.Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission.The Commons ID of each PD/PI must be included in the Credential field of the Research & Related Senior/Key Person component.Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan, must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts.The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award (NoA).

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component.All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form.See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form.

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only.Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 3.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Submission, Review, and Anticipated Start Dates
Opening Date:April 16, 2008 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): April 16, 2008; April 15, 2009; April 14, 2010. HIV/AIDS-related applications: July 22, 2008; July 21, 2009; July 23, 2010
NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Submission/Receipt Date(s): May 16, 2008; May 15, 2009; May 14, 2010
AIDS Application Submission/Receipt Date(s): August 22, 2008; August 21, 2009; August 23, 2010
Peer Review Date(s): October/November 2008; October/November 2009; October/November 2010
Council Review Date(s): January 2009; January 2010; January 2011
Earliest Anticipated Start Date(s): April 1, 2009; April 1, 2010; April 1, 2011

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent (preferably emailed) to:

Kathleen Michels, Ph.D.
Program Director
Division of International Training and Research
Fogarty International Center
Building 31, Room B2C39
31 Center Drive, MSC 2220

Bethesda, MD 20892-2220
Telephone: (301) 496-1653
Fax: (301) 402-0779
Email: [email protected]

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow steps 1-4. Note: Applications must only be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED.

In order to expedite the review, applicants are requested to notify the FIC by email to [email protected] when the application has been submitted.Please include the FOA number and title, PD/PI name, and title of the application.

3.C. Application Processing
Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time(of the applicant institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s) and time, the application may be delayed in the review process or not reviewed. All applications must meet the following criteria to be considered on-time:

Please visit http://era.nih.gov/electronicReceipt/app_help.htm for detailed information on what to do if Grants.gov or eRA system issues threaten your ability to submit on time.

Submission to Grants.gov is not the last step - applicants must follow their application through to the eRA Commons to check for errors and warnings and view their assembled application!

3.C.2 Two Day Window to Correct eRA Identified Errors/Warnings

IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond. As of January 25, all corrections must be complete by the due date for an application to be considered on-time. See NOT-OD-10-123.

Once an application package has been successfully submitted through Grants.gov NIH provides applicants a two day error correction window to correct any eRA identified errors or warnings before a final assembled application is created in the eRA Commons. The standard error correction window is two (2) business days, beginning the day after the submission deadline and excluding weekends and standard federal holidays. All errors must be corrected to successfully complete the submission process. Warnings will not prevent the application from completing the submission process.

Note that the following caveats apply:

3.C.3 Viewing an Application in the eRA Commons

Once any eRA identified errors have been addressed and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday Friday, excluding Federal holidays) to view the assembled application before it automatically moves forward to NIH for further processing.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR/SO receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status in the Commons.

The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. However, the NIH will accept a resubmission application, but such application must include an Introduction addressing the critique from the previous review.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. 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. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See the NIH Grants Policy Statement.

It is expected that the majority of funds awarded will be used for supplies, equipment, services, travel and personnel at the LMIC site, and that any funds spent at the HIC site will involve the LMIC collaborators and will be directly related to the collaborative research or training under the R21 award.

6. Other Submission Requirements and Information

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD/PI to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Registration FAQs Important Tips -- Electronic Submission of Grant Applications.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Warning: Please be sure that you observe the direct cost, project period, and page number limitations specified above for this FOA. Application processing may be delayed or the application may be rejected if it does not comply with these requirements.

PHS398 Research Plan Component Sections

While each section of the Research Plan needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporating "Just-in-Time" information concepts.

Application Research Strategy Length: The R21 application Research Strategy component of the PHS398 (Item 3) may not exceed 6 pages, including tables, graphs, figures, diagrams, and charts. See http://grants.nih.gov/grants/funding/funding_program.htm

Introduction (required for a resubmission application) is limited to one page.

Preliminary data are not required but may be included if available.

Renewal (formerly competing continuation or Type 2) applications are not permitted.

Appendix Materials

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).

Do not use the Appendix to circumvent the page limitations. An application that does not comply with the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value and further the advancement of the research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in the Resource Sharing section of the application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.)

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact (see Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.)

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources or state appropriate reasons why such sharing is restricted or not possible (see Sharing Model Organisms Policy, and NOT-OD-04-042.)

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (e.g., blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (go to NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.)

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590). See Section VI.3., Reporting.

Foreign Applications (Non-domestic (non-U.S.) Entity)

Indicate how the proposed project has specific relevance to the mission and objectives of the IC and has the potential for significantly advancing the health sciences in the United States and around the world.

Supplemental Budget Information:

Networking meetings (two days long) involving grantees of these awards will be held at a site in the U.S. each year, to share information and discuss new insights, and will include grants-writing and other workshops according to the needs of the awardees and program. Funds should be budgeted for travel for these meetings by the PDs/PIs, LMIC collaborators, and/or other relevant individuals with significant day-to-day involvement in the activities performed under this award.

Supplemental Instructions:

Research Strategy: Applications should include within the Research Strategy a plan for assessment of needs for resources and capacity building to enable the proposed research to be carried out (including training in research, research ethics, and human and animal subjects guidelines, as appropriate)

Section V. Application Review Information


1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications submitted for this funding opportunity will be assigned to the ICs on the basis of established Public Health Service (PHS) referral guidelines.


Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the Center for Scientific Review in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

This NIH R21 exploratory/developmental grant is a mechanism for supporting the planning, development and initiation of innovative collaborative research and scientific or new model systems, tools, or technologies that have the potential to significantly advance our knowledge or the status of health-related research.

Because the Research Strategy component is limited to 6 pages, an exploratory/developmental grant application need not have extensive background material or preliminary information as one might normally expect in an R01 application. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will place less emphasis on methodological details and certain indicators traditionally used in evaluating the scientific merit of R01 applications, including supportive preliminary data. 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.

Research on an important topic in a LMIC with underdeveloped research infrastructure but with unique resources, environment, or knowledge not readily available in the U.S. or other HIC nations may be slower to achieve their scientific goals, but may receive special consideration for their potential to build research capacity along with scientific impact in the long-term.

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact. Reviewers will provide an overall impact/priority 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 five core review criteria, and additional review criteria (as applicable for the project proposed).

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical 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.

Significance: Does the project address an important problem or a critical barrier to progress in the field? 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? Is the research on a problem of particular relevance for the LMIC involved?

Investigator(s): Although the collaborators may each be at various stages in their respective careers, are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, 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? If training of the LMIC PD/PIs is necessary to carry out this work is the training well integrated into the research plan?

Innovation: 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? 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 propose innovative or special ways to incorporate capacity building or training into the research program at the LMIC site?

Approach: Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, 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?

Environment: 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? Are the resources necessary to perform the research available or obtainable at the LMIC site? Has the primary LMIC Collaborators home institution made a convincing commitment (e.g., provided a research/academic appointment and salary support)? Does the R21 proposal include a plan to assess what specific resource and training needs exist at the LMIC site to enable the site to successfully conduct the proposed research? Does the proposal include plans to begin to meet those needs?

International Research Collaboration: In the course of the research, what is the potential for sustainable collaborations between the HIC and the LMIC scientists to be established? Does the research constitute a substantial scientific endeavor for the LMIC Collaborator, including creative and scientific input into the research proposal? The LMIC site and investigators should not be used merely to gather biological samples (clinical, plants, etc.) or behavioral data (interviews, surveys, etc.). In all cases, the LMIC Collaborators should be actively involved in analyzing and interpreting the data.

Research Capacity Building: What is the potential for the LMIC institutions to improve their capacity and ability to address important issues in brain disorders research, develop independently-supported research programs and obtain financial support nationally and internationally? How will this occur? Does the proposed program contain explicit strategies or plans to assess the research capacity needs and to strengthen this capacity through research training, career development, mentoring and other models? Will the proposed research and collaboration lead to enhancement of specific departments in LMIC institutions and contribute to overall institutional excellence? Does the proposed project describe a plan to assess research and capacity building needs and ways to address those needs?

The potential of the R21 planning grant to lay the foundation for future collaborative research grant applications and the potential significance of the proposed research and capacity building will be major considerations in the evaluation of the R21 exploratory/developmental grant mechanism. Because the R21 is designed to support planning, development and initiation of innovative collaborative research and ideas, preliminary data as evidence of feasibility of the project are not required to apply, although it is useful to include or cite pilot data where relevant and available. The applicant is, however, responsible for presenting the background literature that provides a sound basis for the approach and for developing a rigorous research plan.

Additional Review Criteria

As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

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

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children. When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals. The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia.

Resubmission Applications. When reviewing a Resubmission application (formerly called an amended application), 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.

Renewal Applications. When reviewing a Renewal application (formerly called a competing continuation application), the committee will consider the progress made in the last funding period.

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

Biohazards. 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.



Additional Review Considerations

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

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

Select Agents Research. 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).

Applications from Foreign Organizations. 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.

Resource Sharing Plans. 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 (http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

3. Anticipated Announcement and Award Dates

Not Applicable.

Section VI. Award Administration Information


1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his/her Summary Statement (written critique) via the NIH eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

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. See Section IV.5., Funding Restrictions.

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, Grantees, and Activities.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

In the Performance Site block on the PHS2590, grantees must list BOTH the HIC and LMIC sites at which the work is being carried out and the primary collaborator contact at the LMIC site.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts


We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

General inquiries regarding the scope and content of this Funding Opportunity Announcement should be directed to:

Kathleen Michels, Ph.D.

Program Director
Division of International Training and Research
Fogarty International Center

Building 31, Room B2C39r
31 Center Drive, MSC 2220
Bethesda, MD 20892-2220
Telephone: (301) 496-1653
Fax: (301) 402-0779
Email: [email protected]

Direct your questions about Scientific/Research issues to the contacts below:

Canada:
Canadian Institutes of Health Research:

Astrid Eberhart
Assistant Director, International Relations
Institute of Neurosciences, Mental Health and Addiction
Douglas Hospital Research Centre
6875 LaSalle Blvd.
Verdun, QC H4H 1R3
Canada
Telephone: (514) 761-6131 ext. 3936
Fax: (514) 888-4060
Email: [email protected]

United States:
National Institutes of Health:
FIC:
Kathleen Michels, Ph.D.
Program Director
Division of International Training and Research
Fogarty International Center
Building 31, Room B2C39
31 Center Drive, MSC 2220
Bethesda, MD 20892-2220
Telephone: (301) 496-1653
Fax: (301) 402-0779
Email:
[email protected]

NIA:
Andrew A. Monjan, Ph.D., M.P.H.
Chief, Neurobiology of Aging Branch
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
Gateway Building, Suite 350
7201 Wisconsin Avenue, MSC 9205
Bethesda, MD 20892-9205 (use 20814 for express mail)
Telephone: (301) 496-9350
Fax: (301) 496-1494
Email:
[email protected]

NIAAA:
Margaret M. Murray, M.S.W.
Chief, Health Sciences Education Branch
Office of Research Translation and Communications
National Institute of Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3105, MSC 9304
Bethesda, MD 20892-9304
Telephone: (301) 443-2594
Fax: (301) 443-2594
Email:
[email protected]

NICHD:
Mary Lou Oster-Granite, Ph.D.
Health Science Adminstrator
Acting Chief
Mental Retardation and Development Disabilities Branch
Center for Developmental Biology and Perinatal Medicine
The Eunice Kennedy Shriver National Institute of Child Health and Human Development
Room 4B09G, MSC 7510
6100 Executive Boulevard
Bethesda, MD 20892-7510
Telephone: (301) 435-6866
Fax: (301) 496-3791
Email:
[email protected]

NIDA:
L. R. Stanford, Ph.D.
Developmental Neurobiology Program
Behavioral and Brain Development Branch
Division of Clinical Neuroscience, Development, and Behavioral Treatment
National Institute on Drug Abuse
6001 Executive Boulevard, Room 4232, MSC 9593
Bethesda, MD 20892-9593
Telephone: (301) 402-3869
Fax: (301) 443-6814
Email:
[email protected]

NIEHS:
Annette Kirshner, Ph.D.
NIEHS-DERT
Box 12233, MD EC-23
Research Triangle Park, NC 27709
Telephone: (919) 541-0488
Fax: (919) 541-5064
Email:
[email protected]

NINDS:
Yuan Liu, Ph.D.
Chief, Office of International Activities

National Institute of Neurological Disorders and Stroke
National Institutes of Health
NSC, 6001 Executive Blvd. Room 2187
Bethesda, MD 20892-9523
Phone: (301) 496-0012
Fax: (301) 480-1080
Email:
[email protected]

ODS/OD:
Mary Frances Picciano, Ph.D.
Senior Nutrition Research Scientist
Office of Dietary Supplements
Office of the Director
National Institutes of Health
6100 Executive Boulevard, Suite 3B01
Bethesda, MD 20892-7517
Telephone: (301) 435-3608
Fax: (301) 480-1845
Email:
[email protected]

Other Participating Organizations:

Autism Speaks
Andy Shih
Chief Science Officer
99 Wall Street
Princeton, NJ 08540
Telephone: (609) 430-9160
Fax: (609) 430-9163
Email:
[email protected]

2. Peer Review Contacts:

Sherry L. Dupere, Ph.D.
Chief, Biology of Development and Aging IRG
Center for Scientific Review
6701 Rockledge Drive, Room 5136, MSC 7840
Bethesda, MD 20892-7840 (for express/courier: 20817)
Telephone: (301) 435-1021
Fax: (301) 480-3567
Email:
[email protected]

3. Financial or Grants Management Contacts:

National Institutes of Health:
FIC:
Bruce Butrum
Grants Management Officer
Fogarty International Center
Building 31, Room B2C29
Bethesda, MD 20892-2220
Telephone: (301) 496-1670
Fax: (301) 594-1211
Email:
[email protected]

NIA:
Deborah Stauffer
Lead Grants Management Specialist
National Institute on Aging
Gateway Building, Suite 2N212
7201 Wisconsin Avenue
Bethesda, MD 20892-9205
Telephone: (301) 496-1472
Fax: (301) 402-3672
Email:
[email protected]

Section VIII. Other Information


Required Federal Citations

Vertebrate Animals:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing). Investigators should seek guidance from their institutions, on issues related to institutional policies and local institutional review board (IRB) rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the impact/priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh-Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are: (1) first produced in a project that is supported in whole or in part with Federal funds; and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Inclusion of Women, Minorities, and Children:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for Federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-116.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy, investigators funded by the NIH must submit or have submitted for them to the National Library of Medicines PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication. The NIH Public Access Policy is available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html). For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (HHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles.Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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 Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.


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NIH Funding Opportunities and Notices



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