Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

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.  Prior to the Human Connectome Project (HCP), little neural connectivity data from humans was available.

Continuing to fill this knowledge gap is paramount because connectivity is a major organizing principle of the nervous system and is fundamental to understanding brain function and dysfunction.  Attempts to understand neural connectivity in model organisms are helping to develop 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 coordinates, or 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 has heretofore not been demonstrated, because human connectivity data were absent.  Linking such architectural features to the distribution of specific connections is providing 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.

The overall purpose of the HCP has been to develop and share knowledge about the structural and functional connectivity of the human brain. This purpose has been achieved through awards to two different multi-institutional research teams centered at Washington University (http://www.humanconnectome.org/) and Massachusetts General Hospital (http://www.humanconnectomeproject.org/). These teams have developed and optimized non-invasive imaging technologies to acquire structural and functional in vivo data about axonal projections and neural connections from brains of hundreds of healthy adults.  Demographic data and data regarding sensory, motor, cognitive, emotional, and social function have also been collected for each subject. Subjects have also donated DNA samples for genotyping and that data will be available before the awards end in September 2015. The data and experimental protocols have been made available to the research community, and both are now being widely used. Both research groups are now undertaking pilot studies to explore the issues with extending the HCP to children and to older adults to represent the lifespan. Those data will also be made available at http://www.humanconnectome.org/.

While the HCP project has provided an excellent start at providing connectivity data for a community sample of normal subjects, the purpose of this announcement is to expand the HCP data to disease/disorder cohorts of interest to the Institutes and Centers that are participating in this FOA. Applicants should review recent Notices related to Study Design (NOT-MH-14-004 and NOT-NS-11-023).

The bulk of the data collection in the HCP has been by the group at Washington University. By September 2015, they will have collected data on 1200 healthy young adults (ages 22-35), with release of the final subjects shortly thereafter. Most of these adults are monozygotic or dizygotic twins or their family members. The data collected includes non-invasive imaging, behavioral assessments, and genotyping assays. It is expected that data collected under this FOA will be compatible with the existing HCP dataset.

The Institutes and Centers that are participating in this FOA have different priority/disease areas of interest.

For NIMH, research cohorts should come from either a broad category such as those with psychiatric based psychosis, mood and anxiety disorders, or depression. Subject groups can also be based on RDoC categories or based on a specific genetic profile. Applicants must avoid cohorts from a narrowly defined DSM diagnostic group.

The NEI is interested in research in populations where the visual pathways may be compromised due to congenital or acquired disease, or injury (e.g. blindness, strabismus, amblyopia, and low vision). Cohorts of patients with visual disorders should be compared with normal age-matched controls. Studies of plasticity in the visual pathways associated with the loss or restoration of vision are of particular interest.

For NIA, research cohorts should be comprised of individuals with neurodegenerative diseases associated with aging such as Alzheimer s disease (preclinical, early- and late-onset), other dementias of aging, and/or age-related cognitive disorders such as Mild Cognitive Impairment (early, mild and late MCI).  Also of interest are cohorts with age-related hearing loss, sleep disorders, or delirium.  Normal, healthy cohorts will be critical as age-appropriate controls for connectome studies.  Disease/disorder and control cohorts should be well defined and characterized by clinical, biomarker, genetic, and/or behavioral data.

For NIAAA, the research cohorts to be studied must be explicitly defined by the applicant in terms of alcohol use patterns currently and in the past, presence of comorbid conditions, and other factors such as a specific genetic profile.  The information to be acquired must clearly relate to the mission of NIAAA to understand the effects of alcohol use and abuse on brain and behavior.  

For NIDA, research cohorts should be comprised of users or abusers of licit or illicit psychotropic drugs, either currently or in the past. Cohorts can also be composed of subjects who have known risk factors for future substance use or relapse. These subjects should be carefully characterized for quantification of historical and current patterns of use of alcohol and multiple substances (including toxicological evidence when possible), and, when appropriate, by DSM diagnoses of substance abuse or dependence as evidence for clinically-significant use. Because circuit-level abnormalities in abusing populations may co-occur with mental disorders, proposals featuring additional population (s) of other mental illness diagnosis or RDoC categories without substance use as comparison or control groups will be considered.

The NINDS is interested in a broad range of disorders affecting the brain and nervous system (http://www.ninds.nih.gov/about_ninds/ninds_overview.htm), and has a strong interest in the development of imaging connectomes as biomarkers.  For the NINDS, applications will be expected to 1) use HCP image acquisition protocols; 2) focus on connectomes that have been shown to be reliable and reproducible; and 3) select well-defined patient populations with clearly delineated phenotypes (e.g., defined by genetics, characteristic structural deficits, or unique pathophysiology).  Applicants may focus on neurological populations that are at-risk, prodromal, or affected.  Interested investigators are encouraged to contact program staff listed below to ensure that their application is consistent with the NINDS mission and appropropriate for this FOA.

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.

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

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

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

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

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

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

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

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

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

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

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

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

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

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

Other Attachments: Applicants should upload a single attachment including the following information relevant to data collection. Applicants should use the headers below in their description.

1) MRI Data Collection: It is understood that images acquired at institutions without a Prisma or the existing HCP scanners will likely not have exactly the same quality as images acquired using newer MRI scanners. Applicants must describe how they will harmonize their proposed imaging with the data that are currently available from the HCP. Applicants should detail the relevant experimental conditions such as the number of channels in the head coils they plan to use, the pulse sequences they plan to implement, and the number of directions they plan to use in their multi-band data collection. Preliminary data on implementing the HCP imaging protocol on either control or subject groups can be presented.

2) MRI Data processing/analysis pipelines: Applicants must describe any differences from the current HCP processing pipeline that they plan to use. If modified pipelines are proposed, applicants must describe how they will make those pipelines available to the research community.

3) Behavioral data: Applicants must justify any changes they propose to make from the HCP behavioral assays. Adding specific behavioral tests for a particular population is expected. Exclusion of behavioral tests that are available in the HCP data set will need strong justification. Applicants dealing with different age ranges than are currently available in the HCP should explain how their proposed behavioral tests are consistent with the data that is currently available in the HCP and why the chosen behavioral test is likely to be useful to other researchers who are studying that age group. When possible, NIH encourages the use of instruments that have already been made broadly available (http://www.nlm.nih.gov/cde/).

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

All instructions in the SF424 (R&R) Application Guide must be followed. NIH may ask awardees to come to the Washington area every 12-18 months to describe their research activities. Such travel expenses should be part of the requested budget. Applicants should budget funds to transfer the data to the Connectome Coordination Facility which will have the responsibility to preserve the data and to make it available to the research community.

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

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

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

Research Strategy: The Research Strategy section must include sections on

1) Definition of the population(s) that will be included

2) Data acquisition protocol

3) Data analysis and data release

4) Administration, operation, and project management.

1) Definition of the population that will be included

All applicants must define the population they plan to study and the control group they plan to use.

All applicants must explain the methods/metrics they will use to judge the variation in connectomes between the proposed proband and controls. Applicants should provide a power calculation or similar justification for their proposed sample size. Applicants are strongly encouraged to propose studies that are sufficiently powered to conduct gender-based analyses.

2) Data Acquisition Protocol

Both of the HCP scanners at Massachusetts General Hospital and at Washington University have high performing gradient inserts. The new Siemens Prisma scanner has similar inserts, but older 3T MRIs do not. Applicants should briefly describe how they will implement the HCP imaging protocol for their studies. Fuller details of all proposed data collection protocols should be presented in the Other Project Information Section.

Applicants must describe and justify any plans for genotyping or sequencing.

Applicants should describe the quality assurance procedures they plan to use as they acquire the data.

3) Data Analysis and Data Release

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.  It is expected that awardees will make their imaging data and behavioral assessments available from a new Connectome Coordination Facility that will be established at Washington University. That centralized database will work with the awardee to provide a single location for the community to find connectome data and will help the awardee ensure that the new imaging data can be easily compared with the existing data. Long term maintenance of the data following deposition is the responsibility of the Connectome Coordination Facility.

Applicants should think carefully about whether the existing HCP subjects can be used as controls for the proposed study. If that is not possible, applicants should explain how their control sample will be chosen both to serve the present study and to maximize the use of that control group by others using the combined dataset.

Applicants should describe any data analysis workflows beyond the ones made available by the HCP that they plan to use.

4) Administration, Operation, and Project Management

Extensions to the Human Connectome Project will include a number of diverse units and activities.  Since this initiative seeks to engage outstanding expertise for each of the units and since it is possible that such expertise will not all be concentrated at a single site, it is possible that collaborators will be located across disparate locations.  All units will need to be carefully overseen and coordinated in order to achieve the specified goals within four 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.  It is likely that a dedicated project manager will be needed for this project. In addition, the use of a cooperative agreement mechanism will allow significant involvement of NIH staff in the conduct of this award.

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 one year and that IRB approval and recruitment will be well underway during the first year. Technological development in image acquisition and processing, while a useful by-product of project activities, should not be the primary focus of projects funded under this FOA. Therefore, pilot scanning is to be limited to improving optimization and integration, e.g., quality control and cross-site compatibility. Scanning of subjects and other data collection will thus commence by the second year. It is likely that the budget requested for the first year will be significantly lower than for the years when data will be collected.

Applicants must propose a detailed recruitment plan including milestones for all stages of the project. Applicants are strongly encouraged to use existing recruitment tools available from CTSA awards (http://www.ncats.nih.gov/research/cts/ctsa/about/about.html) or other sources. If appropriate, applicants may propose to use subjects that are taking part in existing studies.

Applicants may propose an External Advisory Panel for this award, but such a panel is not required. Applicants should outline the duties of this panel. If such a panel is planned, applicants should not name the members of the panel in the application or contact potential members in advance. Applicants should simply describe the composition of the panel in terms of the expertise that will be sought. For Revision applications, if an External Advisory Panel exists, the members of the panel should be named.

For the present funding opportunity, it is expected that applicants will either exactly replicate the Washington University HCP experimental protocol, will approximate the HCP collection protocol to the limits of their instrument sensitivity, or will propose small modifications for their experimental cohort that will still allow the new data to be aggregated with the existing HCP dataset. Any deviations from the behavioral testing paradigms or the imaging experiments (e.g. image acquisition protocols) must be strongly justified. The applicant must explain the methods that will be used to harmonize the newly measured data with the extant HCP data. Applicants must describe their data collection strategy in the Other Attachments section of the SF424 Other Project Information.

Clearly, many of the applications submitted to the announcement will deal with age ranges that are not currently covered in the HCP dataset. In those situations, applicants must describe how they will harmonize their proposed imaging and clinical data with the data that are currently available from the HCP.

It is expected that data generated from both probands and controls will be added to the existing HCP data set. Even in the situation where the proposed proband group has the same age distribution as the existing HCP subjects, it is possible that some data will need to be collected from a control population. These controls will increase the information that is available concerning the variation that is present in a large sample and will allow the research community to understand the size of the differences that occur due to data collection in multiple laboratories.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

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

• It is expected that data will be released to the research community as soon as it has undergone basic quality assurance procedures. The release schedule is expected to be similar to what has been done in the Human Connectome Program. Applicants should plan to implement the existing HCP data analysis workflows, but they can propose additional data analysis workflows. If additional data analysis workflows are proposed, applicants should explain how those workflows will be made available to the research community.
• Applicants must use appropriate consent forms to allow the data to be deposited in and distributed from the Connectome Coordination Facility. Those consent forms must make the data broadly available to qualified researchers.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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

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

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

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

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

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

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

NIH encourages the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

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? If the aims of the application are achieved, will scientific knowledge of the group that is being studied be advanced?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Does the project manager have appropriate qualifications and experience to operationally coordinate a project of this size and complexity?  Is there evidence that the PD/PI and key personnel can work together effectively to achieve the goals of the project? Does the overall research team have sufficient expertise in all of the critical aspects of this undertaking, e.g., knowledge about the group being studied, neuroimaging, informatics, and recruitment?

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? Will any changes to the HCP data collection protocol, either imaging or behavioral measures, degrade the ability of the new data to be aggregated with the existing HCP dataset?

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 human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed? Will it be possible to aggregate and harmonize the new data with the existing HCP data? Will the data be deposited in a timely fashion to allow rapid access by the research community to the data? 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 proposed goals and objectives to be achieved? 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?

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? Does the institution have an appropriate MRI scanner to conduct the proposed HCP experiments? What are the nature and level of resource commitments from the home institution and from other participating institutions?

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

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. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

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

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. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Resubmissions

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

Renewals

Not Applicable

Revisions

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

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

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.

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; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

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

As part of the scientific peer review, all applications:

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

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

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

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

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

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

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) 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.

The PD(s)/PI(s) will have the primary responsibility for:

• Determining and coordinating research approaches and procedures, conducting experiments, and analyzing and interpreting research data;
• Working closely with the NIH project scientist and NIH program officer to ensure progress towards achieving all goals within 4 years;
• Meeting annual milestones for progress, and otherwise making satisfactory progress, toward accomplishing the goals of the funded project;
• Overseeing the release of data, software and models according to the awardee’s data sharing and software release plan and specific procedures to be developed by the awardee and consistent with NIH Resource Sharing Policy;
• Releasing to the research community data, models, and informatics tools as soon as they have undergone basic quality control and quality assurance procedures in a timely manner;
• Depositing the data into the Connectome Coordination Facility;
• Providing information on progress of the Project to the NIH program officer in a standard format on an annual basis, and as needed;
• Planning for, facilitating, and participating in pre-arranged site visits by NIH staff members;
• Deciding whether this award will have a formal External Advisory Committee.
• Providing a summary of information from External Advisory Committee meetings, if one is proposed for this award, to the Program Officer;
• Participating and facilitating evaluations by NIH.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

The NIH Project Scientist will have the primary responsibility for:

• Participating in project status, planning, and implementation meetings;
• Providing a public health perspective;
• Providing a perspective on the priorities of the participating Institutes and Centers;
• Discussing approaches to enhance collaboration;
• Providing technical assistance, advice, and coordination to the project, but with the dominant role and prime authority and responsibility for the activity residing with the awardee.
• Serving as a member of the External Advisory Board, if one is proposed.

The NIH Program Officer, in consultation with the HCP Blueprint Project Team, will have programmatic stewardship, which encompasses the following:

• Serving a resource to facilitate interactions with other NIH programs and to take advantage of existing NIH resources and infrastructures;
• Monitoring the operations of the award and providing normal programmatic stewardship on assessment of overall project directions and allocations of funds;
• Evaluating the effectiveness of data, model, and software sharing;
• Reviewing the progress of the awardee in achieving the goals of the HCP;
• Conducting periodic site visits, and taking other actions as needed;
• Determining the appropriateness of the plans for sharing data, models, and informatics tools
• Serve as an observer at meetings of the External Advisory Board, if one is proposed.

Areas of Joint Responsibility include:

None; all responsibilities are divided between awardees and NIH staff as described above.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: 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 right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

Recruitment Reporting and Trial Registration

NIMH requires reporting of recruitment milestones for participants in clinical trials as noted at http://grants.nih.gov/grants/guide/notice-files/NOT-MH-05-013.html.  While trials in response to this FOA might not seek 150 subjects or more (the level at which this reporting has been required), all trials funded under this FOA must report recruitment milestones, including those with fewer than 150 subjects. This expectation will be stated in the notice of grant award. 

The NIMH expects the registration and results reporting for all NIMH-supported clinical trials, regardless of whether or not they are subject to FDAAA (see http://grants.nih.gov/ClinicalTrials_fdaaa/at-a-glance.htm). This expectation will be stated in the notice of grant award.

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Finding Help Online: http://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

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

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
Email: GrantsInfo@nih.gov

Gregory K. Farber, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-435-0778
Email: farberg@mail.nih.gov

Michael A. Steinmetz, Ph.D.
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: steinmem@mail.nih.gov

Bradley C. Wise, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9350
Email: wiseb@nia.nih.gov

John A. Matochik, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-451-7319
Email: jmatochi@mail.nih.gov
Steven Grant, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-8869
Email: sgrant@nida.nih.gov

Debra Babcock, Ph.D., M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Email: dbabcock@ninds.nih.gov

Joseph Rudolph, PhD.
Center for Scientific Review (CSR)
Telephone: 301-408-9098
Email: josephru@mail.nih.gov

Tamara Kees
National Institute of Mental Health (NIMH)
Telephone: 301-443-8811
Email: tkees@mial.nih.gov

William Darby
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: darbyw@mail.nih.gov

Richard Proper
National Institute on Aging (NIA)
Telephone: 301-402-7735
Email: properr@mail.nih.gov

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: jfox@mail.nih.gov

Pam Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-253-8729
Email: pfleming@mail.nih.gov

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

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.