Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
NIH Blueprint for Neuroscience Research (http://neuroscienceblueprint.nih.gov)
National Center for Complementary and Alternative Medicine (NCCAM) (http://nccam.nih.gov/)
National Center for Research Resources (NCRR) (http://www.ncrr.nih.gov/)
National Eye Institute (NEI) (http://www.nei.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/)
National Institute of Biomedical Imaging and Bioengineering (NIBIB) (http://www.nibib.nih.gov/)
National Institute of Child Health and Human Development (NICHD) (http://www.nichd.nih.gov/)
National Institute on Deafness and Other Communication Disorders (NIDCD) (http://www.nidcd.nih.gov/)
National Institute of Dental and Craniofacial Research (NIDCR) (http://www.nidcr.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 General Medical Sciences (NIGMS) (http://www.nigms.nih.gov/)
National Institute of Mental Health (NIMH) (http://www.nimh.nih.gov/)
National Institute of Neurological Disorders and Stroke (NINDS) (http://www.ninds.nih.gov/)
National Institute of Nursing Research (NINR) (http://www.ninr.nih.gov/)
Office of Behavioral and Social Sciences Research (OBSSR) (http://obssr.od.nih.gov/)

Title:  The Human Connectome Project (U54)

Announcement Type
New

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

Request For Applications (RFA) Number:  RFA-MH-10-020

Catalog of Federal Domestic Assistance Number(s)
93.213, 93.389, 93.867, 93.866, 93.273, 93.286, 93.865, 93.173, 93.121, 93.279, 93.113, 93.859, 93.242, 93.853

Key Dates
Release Date: July 15, 2009
Letters of Intent Receipt Date: October 24, 2009
Application Receipt Date:  November 24, 2009
Peer Review Date: February 2010
Council Review Date: May 2010
Earliest Anticipated Start Date: July 2010
Additional Information To Be Available Date (Url Activation Date): N/A
Expiration Date: November 25, 2009

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(s) 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. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Receipt, Review and Anticipated Start Dates
        1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
     D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

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
    A. Cooperative Agreement Terms and Conditions of Award
        1. Principal Investigator Rights and Responsibilities
        2. NIH Responsibilities
        3. Arbitration Process
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

Neural connectivity is a basic feature of brain organization and is also a major organizing principle of neuroscience knowledge.  For human brains, however, no connectivity data exist in any comprehensive, systematic, or modern sense.  In the past five years, several non-invasive imaging technologies have emerged that can acquire structural and functional connectivity data from human brains, in vivo.  Also in recent years, those studying human brain function in health and illness have increasingly realized the importance of connectivity data to unravel the mystery of the mind. 

The overall purpose of this five year Human Connectome Project (HCP) is to develop and share knowledge about the structural and functional connectivity of the human brain.  Under this initiative, “connectivity” is defined at the level showing structural and/or functional linkages from one major subdivision (cortical areas or subcortical nuclei) of the brain to others.  It is recognized that many current technologies are best suited to collect data from cerebral cortex, though, to the extent that it is possible, subcortical connectomic data are also of great interest to the Project.

The overall purpose of the Human Connectome Project will be achieved through the following specific efforts:  Existing, but cutting-edge, non-invasive imaging technologies will be optimized and combined to acquire structural and functional in vivo data about axonal projections and neural connections from brains of hundreds of healthy adults. In addition to multimodal imaging data, demographic data, as well as data regarding sensory, motor, cognitive, emotional, and social function, will be collected from each subject.  Also from each subject, DNA samples will be collected, from which whole genome single nucleotide polymorphism (SNP) genotype data will be derived, as will blood for generating cell lines. Models to better understand and use these data will be developed. Connectivity patterns will be linked to existing architectonic data. Data and models will be immediately made available to the research community via a user-friendly informatics framework to include tools to query, organize, visualize and analyze data and use the models.  Outreach efforts will be conducted to engage and educate the research community about the imaging tools, data, models and the informatics platform.

At the end of five years, these specific efforts are expected to deliver:

1)     A set of integrated, non-invasive imaging tools to obtain connectivity data from humans in vivo (which will be adoptable by the research community to collect human connectivity data from additional populations, such as those with particular brain disorders, or across developmental time points, etc.),

2)     A high quality and well characterized, quantitative set of human connectivity data linked to demographic, behavioral, and genetic data as well as to general, existing, architectonic data, and associated models, from up to hundreds of healthy adult female and male subjects (which will provide insight to normal biological variation and serve as control data for connectome research on other populations), and

3)     Rapid, user-friendly dissemination of connectivity data, models, and tools to the research community via outreach activities and an informatics platform (which will facilitate and spur additional human connectomics research).

The Human Connectome Project will require a diverse array of expertise.  Solicited here is the best set of expertise available to achieve the goals and produce the deliverables of the Project.  Since the best laboratories to implement the various components of the Project may not all be located at the same site, inclusion of collaborators from different sites is welcomed in order to assure outstanding expertise for all components (assuming plans are in place to assure efficient conduct of the supported activities).

Background

There has long been an interest in understanding the connectional organization of the human brain, though interest in connectivity has recently increased, as the tools to obtain such data have emerged and as other lines of inquiry have made clear the importance of such data.  Still, neural connectivity data from humans are lacking.

Filling this knowledge gap in knowledge is paramount because connectivity is a major organizing principle of the nervous system and is fundamental to understanding brain function and dysfunction.  Understanding neural connectivity in model organisms has made possible an integrated understanding of the interplay of genes, molecules, cells, neural systems, and behavior.  Such understanding, in turn, provides the basis for detailed models from which hypotheses about brain function in health and illness can be generated.  Without connectivity data, this kind of understanding is not possible for human brain function and dysfunction.  Knowledge of human brain connectivity will transform human neuroscience by providing not only a qualitatively novel class of data, but also by providing the basic framework necessary to synthesize diverse data and, ultimately, elucidate how our brains work in health, illness, youth, and old age.

It is important to link connectivity data to architectonic features rather than merely to the locations of sulci and gyri.  The surface geometry of the human brain is extremely variable and idiosyncratic, and the relationship of surface features to functional subdivisions and their differential connectivity is imprecise.  Classical neuroanatomy shows strong correlations between connectivity patterns and features such as cytoarchitecture and the differential distribution of molecular tags (including enzymes, neurotransmitters, transmitter receptors, expressed genes, etc.).  For this reason, connectional studies in model organisms routinely relate connectional data to such architectonic data.  While architectonic features have been mapped extensively in the human brain, the relationship of projections and connections to these features have heretofore not been demonstrated, because human connectivity data were absent.  Linking such architectural features to the distribution of specific connections will provide a critical “anchor” that will permit connectional data to be related to a variety of other types of data, broadening and enhancing their utility.

Connectivity, in the context of brain architecture, has long figured in understanding, diagnosing, and treating certain neurological disorders.  Increasingly, disrupted or aberrant connectivity is being implicated or suspected in the etiology of disorders not previously considered from this perspective.  For example, it is very likely that quantifiable changes in connectivity accompany the variations in cortical thickness (as demonstrated with structural magnetic resonance imaging) that are seen in diseased brains (e.g., Alzheimer) relative to healthy brains, and that are seen in brains through the course of early development, through adolescence and senescence.  Similarly, it is likely that qualitative or quantitative changes in connectivity contribute to morphometric differences observed in brains of those with particular disorders, such as schizophrenia. Despite the manifest importance of connectivity, this entire class of data is non-existent for humans in any modern sense. 

The time for this initiative is propitious due both to the increasing recognition of the need for connectivity data to provide a more complete picture of human brain function, and to recent technological and methodological developments that allow collection of such data.  Over the last five years, several new neuroimaging approaches have emerged as promising ways to obtain data on structural and functional neural connectivity in humans.  This initiative will build on technologies that promise to provide connectivity data and upon the value added by their being integrated, directly (e.g., combining instrumentation) or indirectly (e.g., combining data resulting from different modalities).  Integrating these cutting-edge tools (or the data generated by them) will allow results from one modality to constrain, inform, and refine interpretations of data from other modalities, thus adding significant value to all.

After the imaging tools for collecting connectivity data are optimized and integrated, data will be acquired from hundreds of healthy female and male adults (with each subject being imaged by all modalities).  Data regarding sensory, motor, cognitive, emotional, and social function will also be collected for each subject, as will DNA samples (to be genotyped) and blood (to generate cell lines).  Models will be developed to help with the interpretation and use of the data (e.g., probabilistic views of data, models to allow integration of data across different sets and subsets of individuals and modalities, models of relationship among imaging and genotype data, etc.).  The exact number of subjects from whom data are collected will be determined by a number of factors, many of which will not be known until the research plan is developed and, to some extent, until data collection has commenced.

The Human Connectome Project will provide a qualitatively novel class of data for understanding the human brain in health and illness.  By advancing capabilities for non-invasively obtaining connectivity data from humans and by producing robust datasets, models, and analytic tools, the Human Connectome Project represents a potentially transformative initiative.  Dissemination of the fruits of this initiative (i.e., technological and methodological advances, connectivity data, models, and tools) and outreach to educate and engage the research community in human connectomics will help to assure that this transformative potential is realized.

Objectives and Scope

All applications submitted in response to this FOA must adhere to the overall goal of the Human Connectome Project, serve the stated specific purpose of the Project, and have a clear plan for delivering each of the:  1) optimized, integrated imaging tools, 2) high quality and well characterized datasets, models, and associated user-friendly informatics tools, and 3) dissemination and outreach.

All applicants must address the following elements:

  1. Administration, operation, and project management
  2. Optimization of existing, cutting-edge, non-invasive imaging tools
  3. Combination of imaging tools and/or their data
  4. Acquisition of data from healthy adults and model development
  5. Linkage of acquired connectivity data with existing architectonic data
  6. Informatics platform
  7. Outreach to engage and educate research community

1. Administration, operation, and project management

The Human Connectome Project will include a number of diverse components and activities.  Since this initiative seeks to engage outstanding expertise for each of the components, and since it is likely that such expertise will not all be concentrated at a single site, it is likely that the Project will include collaborators distributed across disparate locations.  All components will need to be carefully overseen and coordinated in order to achieve the specified goals within five years.  This complex effort will require robust administrative structures and processes, objective and independent advice by appropriate experts, and strong professional project management by the grantee.  In addition, the support of the Project through a cooperative agreement mechanism will allow significant involvement of NIH staff in its conduct.

Although a detailed timetable with clear milestones is expected as part of the application, it is anticipated that the optimization and integration of imaging technologies will take about two years, and that the scanning of subjects and other data collection will commence in the third year.  Outreach activities and informatics development are expected to begin in the first or second year and continue throughout the Project.  The data and informatics framework will be maintained and supported for no less than five years after the termination of the award.

2. Optimization of existing, cutting-edge, non-invasive imaging tools

This initiative seeks to use existing, but cutting-edge, tools to collect structural and functional connectivity data.  By definition, such advanced tools will require further optimization for the purpose of conducting large-scale imaging required to achieve the goals of the Human Connectome Project.  It is important to emphasize that this initiative is not focused on technology development, per se; but, it will support such technology optimization for the specific purpose of collecting human connectivity data.  This optimization may take any of many possible forms, including, but not limited to: modifying or fabricating equipment, developing algorithms and implementing them in software, identifying and validating novel behavioral tasks to activate putative circuits, etc.  It is expected that this technology optimization component will be finished in about two years.

Three specific non-invasive approaches (described below) seem especially promising and their use for this initiative is solicited, though not required.  Each of these modalities provides different and complimentary perspectives on connectivity:  anatomical locations and trajectories of fiber bundles running among cortical and subcortical subdivisions, identification of functionally-linked networks of brain subdivisions, and identification of circuits and networks of brain subdivisions, and the temporal sequence of their engagement, in particular functional activation tasks.

Although the use of these three specific modalities is solicited, the current state-of-the-art of each does not appear ready for large-scale scanning required by the Human Connectome Project and optimization of them to produce a high quality and well characterized dataset of human connectivity data will likely be necessary.  Since this optimization must occur in the first two years, if this is an unrealistic timetable for one or more of these modalities to become robust enough for use in the Human Connectome Project, or if there are more promising modalities to serve the purpose of this initiative, applicants may propose additional modalities and/or offer alternative modalities with clear statements of how their use would be superior to the modalities specified here. 

a) High Angular Resolution Diffusion Imaging (HARDI) with Magnetic Resonance – These approaches (e.g., Q-Ball or Diffusion Spectrum Imaging) collect and analyze data that provide structural information about the location and trajectories of axonal bundles.  And, unlike some other diffusion methods such as diffusion tensor imaging, HARDI approaches collect and analyze such data in ways that do not present intravoxel ambiguities due to crossing (or otherwise directionally discordant) fibers.  HARDI approaches can be used to collect cortical and subcortical data in comprehensive, systematic ways.

b) Resting State Functional Magnetic Resonance Imaging (R-fMRI)R-fMRI approaches demonstrate which brain regions (typically cortical) have correlated, non-correlated, or anti-correlated oscillations of Blood Oxygen Level Dependent signals when compared to another brain region.  While these oscillations are seen during task activation, they are also seen (more clearly) when the subject is not performing any particular task (“resting”).  Data from R-fMRI studies are thought by some to show interconnected nodes of neural networks.  R-fMRI data would not, however, show whether any two nodes of the network are directly connected with each other or connected via intervening node(s).

c) Electrophysiological or Magnetoencephalographical Recording Combined with fMRI (E/M-fMRI)E/M-fMRI combines task-generated functional activation data from electrophysiological or magnetoencephalograpical and fMRI modalities; some laboratories are working on simultaneous use of these combined modalities, while others have combined these modalities serially.  Combining the electrophysiologic or magnetoencephalographic data and fMRI data theoretically allows the advantages of each approach to be seized and the disadvantages of each to be mitigated.  Unlike HARDI or R-fMRI approaches, E/M-fMRI approaches require the use of task activation of particular neural circuits.  As the purpose of this initiative is to reveal the structural and functional brain connectivity, applicants proposing task-activated modalities, such as these, will be asked to identify tasks that are collectively (across all tasks, not in any one task) known to engage as many cortical areas as possible. If appropriate for the proposed approach, applicants might consider using one or more of the tasks associated with the NIH Toolbox (a comprehensive set of brief, standard set of behavioral assessments; see http://www.nihtoolbox.org).

Again, the three modalities described above (HARDI, R-fMRI, and E/M-fMRI) are of particular interest because they each provide different information about connectivity and so complement each other.  Additional or substitute modalities may be offered by applicants, and the value of such modifications to fulfilling the purpose of this funding opportunity must be clearly stated. In any case, it is important that whatever modalities are proposed, they should provide complementary types of information about structural and functional brain connectivity.  Finally, it is important that this technology optimization be finished in the first two years of the award. 

3. Combination of imaging tools and/or their data

Although each of these (i.e., HARDI, R-fMRI, and E/M-fMRI) tools holds great promise for developing a comprehensive and systematic set of human connectivity data, allowing data from these approaches to be combined offers significant additional scientific opportunity and technical value by allowing one approach to constrain, corroborate, inform, and refine the other.  For example, R-fMRI might be used to suggest that particular brain regions (e.g., A, B, C, and D) are interconnected with each other in some, unspecified, way.  HARDI might show the structural basis of these connections (e.g., major fiber bundles running between A and B and between A and C, with D connected directly only with B).  Data from E/M-fMRI might provide information about the temporal sequence of activation of these regions in a particular task (e.g., in a visual reaching task, A is activated first, B and C second, and D third), and mathematical models could provide heuristic information about functional connectivity as it relates to this particular task.  Combining these approaches (or whatever modalities are used ultimately) and/or combining the data generated by them will add value to the Human Connectome Project, and will further understanding of the limits and uses of each of the modalities.

4. Acquisition of data from healthy adults and model development

With the time and budget provided for the Human Connectome Project, structural and functional connectivity data will be acquired from hundreds of healthy female and male adults, with each subject being imaged with all modalities.  Also collected from each subject will be basic demographic data, DNA samples (to be genotyped for approximately one million SNPs), and blood (to allow for generation of cell lines for further genomic analyses). 

In addition to demographic data, data from each subject will also be collected from basic assessments of sensation, motor, cognition, emotion, and social behavior. These basic behavioral assessments, however, are not intended to exclude subjects who had previously met the Project’s inclusion criteria as healthy adults. Strongly encouraged is the use of such assessments from the NIH Toolbox (http://www.nihtoolbox.org).  The Toolbox comprises a set of brief, comprehensive, standard assessment tools designed to be psychometrically sound and to assess change over time.  Over the course of the next year or two, these will be validated and normalized across thousands of subjects.  The NIH Blueprint for Neuroscience Research will make Toolbox assessments freely available to the research community for data collection on cognitive, emotional, motor and/or sensory function in humans, ages 3 – 85 years.  It is expected that these assessments will likely come to serve as a form of ‘common currency’ across diverse study designs and populations.  Thus, their use in the Human Connectome Project will have significant added value.

Blood samples will be submitted to the NIMH Human Genetics Initiative to develop cell lines that will be available to researchers.  The awardee should contact Dr. Thomas Lehner, NIMH, for further information (tlehner@mail.nih.gov).

This initiative aims to collect data representative of the healthy adult brain.  Therefore, the age range of subjects should be narrow and scientifically justified as providing such a sample.  Inclusion and exclusion criteria will be detailed by applicants, but subjects should not have a history of significant psychiatric, neurologic, substance abuse, or cardiovascular disorders/conditions.  Female and male subjects should each represent about half the subject pool.  The proportional racial and ethnic make-up of the subject pool should approximately represent that of the United States.  It is important to note that it is not expected that any of the data collected in the Human Connectome Project (neither imaging, genetic, nor behavioral data) would allow testing of hypotheses regarding gender, racial, or ethnic differences.  These data will, however, be useful for estimates of effect sizes, power analyses, and they could be used to inform the design of future studies.

Many factors will influence the exact number of such subjects to be scanned.  One factor affecting the number subjects scanned might be changes in technology that occur between now and when the award is made.  Such changes might significantly affect the throughput rate of imaging.  Another factor is variability observed across subjects.  For example, if the vast majority of variation in the data is accounted for in the first 100 subjects, it would be neither scientifically interesting nor fiscally prudent to scan 300 - 500 more subjects from the same population.  Whether subjects from a different population should be recruited (and, if so which population), or whether some other direction should be taken by the Project would be determined at that time by the program officer, in concert with the NIH Blueprint project team and the grantee.

Importantly, the data collected in this initiative will be multidimensional, complex, and quantitative.  This will require the development of models to integrate and understand the data.  Such models would provide the ability to compare and combine data from: individuals, sets of individuals, single modalities, sets of modalities, genotypes, behavioral assessments, etc.  Other capabilities, such as probabilistic models and analytic tools, will be developed that will be applicable to datasets beyond those collected here.

Consideration should be given to human factors that may constrain data collection or otherwise inform protocol design.  These might include informed consent and issues of protection and confidentiality, handling of incidental findings, subject fatigue or testing anxiety, missing data handling, etc.  The applicant should provide clear evidence that such issues have been or can be adequately addressed during the conduct of the award.

5. Linkage of acquired connectivity data with existing architectonic data

It is important that the patterns of connections obtained here be related to at least some architectonic features of the human brain, rather than merely to the locations of sulci and gyri.  Architectonic features have been mapped extensively and intensively in the human brain.  Modern studies of quantitative cytoarchitecture and the distribution of autoradiographic molecular tags for neurotransmitter receptors across the human cerebral cortex have been conducted with post mortem tissue, and the distribution of molecular tags for neurotransmitter receptors has been studied in healthy human brains using positron emission tomography.  Such existing data, perhaps augmented by acquisition of some additional critical architectonic data, would be linked to the structural and functional connectivity data acquired in the Human Connectome Project.

It should be noted that the objective of this component is not to define borders or to map each scanned subject’s brain to these existing architectonic data.  Nor is it expected that the architectonic data be comprehensive. Rather, this component is meant to merely make conveniently available to users an architectonic context to which they might consider the connectivity data.  This linkage is expected to be technically straightforward and low-cost. 

6. Informatics platform

The value of data and models generated by the advanced technical capability in this initiative will be maximized by disseminating those data, models, and associated tools widely and quickly to the research community at-large.  The data from hundreds of subjects will be provided as, or on the basis of:  each individual brain, populations of brains, each individual modality, combined modalities, and as probabilistic models.  Also made available via an easy- to-use platform will be analytic, visualization, and search tools.  It is expected that data will be released to the research community as soon as it has undergone basic quality assurance procedures, and that the database and associated tools and models will be maintained and supported by the grantee for not less than five years beyond the termination date of this award. 

In order to allow Human Connectome Project data to be confederated with other significant neuroscience data resources, such as the Biomedical Informatics Research Network-based NIH Pediatric MRI Data Repository (www.NIH-PediatricMRI.org) and the NIH National Database for Autism Research (www.ndar.gov), the informatics platform developed should be able to accommodate such linkage.

7. Outreach to engage and educate the research community

The Human Connectome Project will result in imaging tools optimized for collecting human connectivity data, a high quality and well characterized connectomic dataset and models from healthy adults, as well as robust informatics tools to explore and understand this novel class of human neuroscience data.  Since these tools and data will be novel, it is important to educate the research community about human connectomics and about the tools used to collect and explore the data. Engagement of the community should also inform requirements for the informatics platform, the nature of the models developed, etc.  As this initiative is likely to launch a new aspect of human neuroscience research, preparing the community to make use of the data and tools in subsequent research is very important.

Outreach is expected to be made to the neuroscience, neuroimaging, and neuroinformatics research communities, and should include both physical (e.g., presentations at relevant professional meetings) and virtual interactions.

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

Section II. Award Information


1. Mechanism of Support

This funding opportunity will use the NIH Specialized Center Cooperative Agreement (U54) 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. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). 

This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI.2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award."

2. Funds Available

The NIH Blueprint for Neuroscience Research has designated $6 million for total costs for FY 2010 to fund one grant in response to this funding opportunity.  The total project period and costs for an application submitted in response to this FOA may not exceed five years or $6 million total costs per year.  Future year amounts will depend on annual appropriations, but are expected to be at the same level.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004. However, please note the cost limits in this RFA are for total costs, which will therefore include the facilities and administrative costs by consortium participants.

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.

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

Non-Domestic (i.e., Foreign) organizations are NOT eligible for application submission but may participate (under subcontractual arrangements) in an application proposed by an eligible Domestic applicant institution.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her institution 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.

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

Number of Applications. Applicants may submit more than one application, provided they are scientifically distinct.

Resubmissions.  Resubmission applications are not permitted in response to this FOA.

Renewals. Renewal applications are not permitted in response to this FOA.

Section IV. Application and Submission Information


1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

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

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PD/PIs are proposed, use the Face Page-Continued page to provide items 3a – 3h for all PD/PIs. NIH requires one PD/PI be designated as the “contact PD/PI” for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the “Contact PD/PI, et. al.” The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

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.

Additional information is available in the PHS 398 grant application instructions.

3. Submission Dates and Times
 
Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates

Letters of Intent Receipt Date: October 26, 2009
Application Receipt Date: November 24, 2009
Peer Review Date: February 2010
Council Review Date: May 2010
Earliest Anticipated Start Date: July 2010

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 to:

Michael F. Huerta, Ph.D.
National Institute of Mental Health
6001 Executive Boulevard, Room 7202, MSC 9645
Bethesda, MD 20892-9645
Telephone: (301) 443-1815
FAX: (301) 443-1731
Email: mhuert1@mail.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the forms found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Shuang-Bao Hu, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6156, MSC 9606
Bethesda, MD  20892-9606
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 443-5160
FAX:  (301) 594-0702
Email:  shuangbaohu@mail.nih.gov

3.C. Application Processing

Applications must be received on or before the application receipt date) described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed.  Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute.  Incomplete and/or non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

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. The Grants Policy Statement can be found at 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: 1) are necessary to conduct the project, and 2) 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 NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)

6. Other Submission Requirements

Awardees must agree to the “Cooperative Agreement Terms and Conditions of Award” in Section VI.2.A “Award Administration Information.”

Applicants must demonstrate in the application their ability to meet:

Instructions for the Preparation of HCP Applications

RESEARCH PLAN: The standard PHS398 Research Plan (Items 2-5 as per Revision 11/07 of the PHS 398 Table of Contents, previously known as “Sections A-D”) is altered as follows:

Specific Sections to be included in Research Plan are described below. (Table of Content should be modified accordingly).  Contextual information (e.g., background, significance, preliminary data) should be described in each section as it pertains to the substance of that section, as appropriate.

Section N1:  Administration, operation, and program management (10 pages)

This section should provide an overview of how the entire proposed Project will be implemented from an administrative and operational perspective.  Included should be a general overview of the Project’s components, the manner in which they will relate to each other administratively and operationally, and a timetable that will assure by the end of five years delivery of each of: 1) A set of integrated, non-invasive imaging tools to obtain connectivity data from humans in vivo, 2) A high quality and well characterized, quantitative set of human connectivity data linked to existing architectonic data, genotype and behavioral assessment data, demographic data, and associated models, from up to hundreds of healthy adult female and male subjects, and 3) Rapid, user-friendly dissemination of connectivity data, models, and tools to the research community via outreach activities and an informatics platform.  This section should focus on the implementation of the Project rather than on scientific or technical considerations. 

This section should also describe the administrative, organizational, and operational structures and processes that will be used by the Project, including the manner in which strong, professional project management will be used to assure that the diverse components and activities proceed efficiently and appropriately. The means for making decisions, communicating across the components and activities, and addressing discordant opinions among the components and activities should be clearly stated.  Finally, institutional support specifically contributing to the conduct of the Human Connectome Project should be described in this section. 

The role of an external advisory panel, an independent, objective group of expert advisors, as well as the types of expertise to be represented and the manner in which this group will provide guidance to the Project, should be described in this section.  To avoid conflicts during review of the application, however, specific members of this group should not be named, nor should they be contacted by applicants in this regard.

The applicant should explain how different elements of the organization, including key personnel, will interact, and who will be responsible for which components of the Project.  Multi-institutional/site teams are welcome under this solicitation.  If any of the elements are physically or administratively separated from each other, the applicant should address how necessary interactions will be assured and managed.  Within the confines of the above specifications, the NIH Blueprint for Neuroscience Research is not specifying a particular organizational structure, allowing instead applicants to develop the structure that would allow them to best achieve the goals and produce the outputs specified in this FOA.

In addition to the plans described in this section, letters of support from participating institutions should be appended to the application indicating what resources will be committed to the proposed project beyond what is now provided to participating investigators.

Section N2:  Optimization of existing, cutting-edge, non-invasive imaging tools (25 pages)

This section should describe the specific, existing, cutting-edge, non-invasive modalities chosen to achieve the goals and generate the products specified in this FOA.  While the three modalities described in this FOA (i.e., HARDI, R-fMRI, and E/M-fMRI) seem well-poised to accomplish the goals of the Human Connectome Project, additional or alternate technologies may be proposed for use by applicants.  The advantages and disadvantages of all proposed modalities (including HARDI, R-fMRI, and/or E/M-fMRI, if proposed) should be discussed, including in comparison to other widely-used modalities which might be appropriate, but which are not being proposed.

The manner in which proposed modalities will be further developed and implemented to optimize their use for collecting data about the structural and functional connectivity of the human brain should be described.  Ideally, the Human Connectome Project will produce comprehensive connectivity data for all of the major brain subdivisions, but limits of the approaches are real and it is recognized that this ideal will not be achieved.  This section should describe how the proposed modalities will be modified to provide the capability to demonstrate (or provide the basis for strong inferences about) the structural and functional connectivity of major subdivisions of the nervous system. The anticipated limits for each of the proposed technologies as well as possible pitfalls in the further development of the technologies, and alternative strategies to overcome them, should also be described.

This section should focus on modality choice as it relates to the goals of this FOA, and how each will be further developed and optimized.  Specific plans for how these will be combined should be addressed in Section N3, and plans for how they will be used to collect data (e.g., workflows for subject scanning, etc.) should be addressed in Section N4.

Section N3:  Combination of imaging tools and/or their data (15 pages)

This section should describe how the imaging tools proposed for use and described in Section N2 (and/or data generated by them) will be combined and how this will benefit the Project.  The manner in which the imaging technologies, or the data they generate, will be combined should be described.  Also, the manner in which this combination will be used to constrain, corroborate, inform and refine interpretation of results, and, in general, add value to the Project, should be discussed.

Section N4:  Acquisition of data from healthy adults and model development (20 pages)

This section should describe the manner in which material (e.g., DNA and blood) and data will be collected from subjects, including connectivity data, demographic data, data regarding sensory, motor, cognitive, emotional, and social function, as well as DNA data. (Blood samples will be submitted to the NIMH Human Genetics Initiative, and awardees should contact Dr. Thomas Lehner, NIMH, for further information; tlehner@mail.nih.gov.)

The type of data to be collected and the manner of its collection should be described, including details about how genotyping will be conducted, which behavioral assessments will be used, etc.  Workflows for recruiting and collecting data from subjects should be given, including inclusion and exclusion criteria, the sequence of data collection from each subject, etc.

Although the time and budget available to this Project are sufficient to support data collection from hundreds of subjects, it is possible that most of the variation of connectivity data will be accounted for in fewer subjects.  Plans for how this possibility will be assessed should be provided in this section.

Also described in this section should be the data models to be used to allow for combining, parsing, and exploring datasets in a variety of ways.

Section N5:  Linkage of acquired connectivity data with existing architectonic data (5 pages)

This section should describe how existing architectonic data for the human brain will be linked to connectivity data collected in this Project.  The nature of the architectonic data and related information should be described in this section.

If there is a compelling need to augment the existing architectonic data with additional data to be collected during the course of this project, the need for such data collection should be described here, but aspects regarding the modality of collection should be described in Section N2, how this modality will be integrated with other modalities (if it needs to be so) should be described in Section N3, and the manner in which data will be collected should be described in Section N4.

Section N6:  Informatics platform (10 pages)

This section should describe the informatics platform that will be used to host and disseminate data, models, and associated tools to the research community.  In addition to the platform itself, the manner in which the platform and its implementation will serve key needs of the research community should be described (e.g., interface, tools, data access policies, etc.)  The ability of the platform to connect deeply (e.g., through confederation) with other data resources should be discussed.  Plans for curation and annotation of data, models, and tools should be given. This section should also describe the plan for in-kind matching by the grantee institution to support and maintain the informatics platform to disseminate informatics tools, data, and models for no less than five years beyond the termination of this award.

Section N7:  Outreach to engage and educate research community (5 pages)

As the Human Connectome Project will be developing significant new tools and new data for human neuroscience, outreach to the research community will facilitate their use and adoption.  Outreach will include both engagement of the community, for example, to solicit ideas for requirements of data models, analytic tools, and other aspects of the informatics platform, as well as education about how to use informatics tools, the relevance of connectivity data to other types of human neuroscience data, etc.  This section should describe how this outreach will be conducted.

Site Visits and Meetings with NIH Staff. Because of the complexity and interactions of the HCP, the NIMH program officer and other NIH Blueprint program staff members will conduct site visits at mutually agreeable times.  This will assist program in evaluations of progress on the grant.  In addition to site visits, the principal investigator and key HCP staff must agree to participate in meetings in the Bethesda, Maryland area to present progress to relevant NIH staff; these meetings are expected to be held at the end of the first, third, and fifth year of the Project.  Funds should be requested in this application for this travel. 

External Advisory Panel (EAP).  The HCP center should also form an External Advisory Panel (EAP) of appropriate experts to provide feedback and suggestions to the Project.  It is expected that the Panel will interact as needed, and will visit a/the Project site several times over the course of the Project.  The selection of the EAP is to be made by the PIs in consultation with the NIMH program officer.  In Section N1 of this application, the desirable profiles of prospective EAP members should be described. However, to facilitate application review, the applicants must refrain from identifying the names of specific individuals in their application and must not contact such candidates.

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CDs only. Include five identical CDs in the same package with the application. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe 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 of, and advance 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 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 NIH Guide 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 (such as 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, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

In addition to the above stated NIH-wide requirements, applicants responding to this FOA must agree to the following requirements:

Plan for Sharing Research Data, Models, and Software:

The NIH Blueprint is committed to the principle of rapid data, model, and software release to the scientific community.  HCP awardee is expected to release to the research community data, models, and software in a timely fashion through an informatics platform and other standard mechanisms.  The development of policies, methods, and standards for model sharing are critically important for the HCP.  The NIH Blueprint expects that the HCP awardee will develop such policies, methods, and standards for the HCP in concert with the NIH Blueprint.  These policies, methods, and standards will remain consistent with NIH-wide policies on data and resource sharing.

In their grant applications, all applicants should provide specific plans for data, model, and software release. 

The reasonableness of the applicant’s data and model sharing and software release plans will be assessed by the reviewers.  However, reviewers will not factor the proposed data and model sharing and software release plan into the determination of scientific merit or the impact/priority score.

After completion of the initial review, NIH Blueprint program staff will be responsible for any additional administrative review of the data and model sharing and software release plans.  The adequacy of these plans will be considered by program staff of the funding organization when making recommendations about funding applications.  The accepted data and model sharing and software release plans will become a condition of the award of the cooperative agreement.  The applicant’s progress in implementing the data and model sharing and software release plan will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

Section V. Application Review Information


1. Criteria

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

2. Review and Selection Process

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 NIMH and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

The following will be considered in making funding decisions:

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? If the aims of the application are achieved, will scientific knowledge of human brain connectivity be advanced? 

Investigator(s).  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? Does the proposed PI have the appropriate qualifications and experience to lead and scientifically coordinate a project of this size and complexity?  Does the project manager have appropriate qualifications and experience to operationally coordinate a project of this size and complexity?  Is there evidence that the PI and key personnel can work together effectively to achieve the goals of the HCP as described in this FOA? Does the overall research team have sufficient expertise in all of the critical aspects of this undertaking, e.g., neuroanatomy, neuroscience, neuroimaging, informatics, and training/outreach?

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?

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 aims of the application are achieved, how effective will be the dissemination of the knowledge about optimizing and combining imaging tools for collecting human connectivity data?  If the aims of the application are achieved, how effective and timely will be the dissemination of the:  data collected, data models, informatics tools, and knowledge about the informatics framework? If the aims of the application are achieved, how effective will the outreach efforts to the research community be?  Are project management plans (including timetable, relationship of project management to governance structure, etc.) clear and are they consistent with a smooth implementation of the proposed project?  Will the proposed operational implementation, including plans for leading, managing, governing, coordinating, and integrating the efforts of the various components, allow the goals and objectives of this FOA to be achieved by the end of five years?  Is there an adequate plan to make good use of external scientific advice in the implementation of the proposed project?

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? Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the HCP as described in this FOA (within the limits inherent in an emerging, complex approach to this area of neuroscience)?  Is the outreach plan to engage and educate the research community appropriate?  Will the outreach activities be effective in meeting the goals and objectives stated in the FOA?

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?    What are the nature and level of resource commitments from the home institution and from other participant institutions?

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.

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 Agent 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).

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 or her Summary Statement (written critique) via the 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 (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the 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 Also 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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

2.A.1. Awardee and Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for:

Awardees will put forward a plan to provide resources for hosting, supporting, and maintaining the informatics platform, sharing data, models, and informatics tools with the research community for no less than five years after the termination of this award.

2.A.2. NIH Responsibilities

NIH staff acting as the NIH Science Officer will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The NIMH Program Officer, in consultation with the HCP Blueprint project team, will have programmatic stewardship, which encompasses the following:

The NIMH Program Officer will be named in the award notice.

2.A.3. Collaborative Responsibilities

A governance structure for the collaborative responsibilities across the various components of the award will be determined by the PI/PIs of the award, and will be approved by the Program Officer.  The responsibilities of the governance structure will include those described below.

2.A.4. Dispute Resolution

A Dispute Resolution Panel composed of three members will be convened to resolve any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH. The three members of the panel will include: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's rights to appeal an adverse action that is otherwise appealable in accordance with 42 CFR Part 50, Subpart D and 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

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:

Michael F. Huerta, Ph.D.
National Institute of Mental Health
6001 Executive Boulevard, Room 7202, MSC 9645
Bethesda, MD 20892-9645
Telephone: (301) 443-1815
FAX: (301) 443-1731
Email: mhuert1@mail.nih.gov

2. Peer Review Contacts:

David Armstrong, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6138, MSC 9606
Bethesda, MD 20892-9606
Telephone: (301)443-3534
FAX:  (301)443-4720
Email:  armstrda@mail.nih.gov

3. Financial or Grants Management Contacts:

Victoria Carper
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6118, MSC 9605
Bethesda, MD 20892-9605
Telephone: (301) 443-3858
FAX: (301) 443-6885
Email: carpervictoria@nih.gov

Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
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 (45CFR46) 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 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 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/

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.

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 http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, 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.

Inclusion of Women And Minorities in Clinical Research:
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 new PHS Form 398; 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-02-005.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 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award.  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 (DHHS) 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 DHHS 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) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

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. 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 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 NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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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