Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute on Drug Abuse (NIDA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Institute of Biomedical Imaging and Bioengineering (NIBIB)

National Institute of Environmental Health Sciences (NIEHS)

National Institute of Mental Health (NIMH)

National Institute of Neurological Disorders and Stroke (NINDS)

National Institute on Minority Health and Health Disparities (NIMHD)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Behavioral and Social Sciences Research (OBSSR)

Office of Research on Women's Health (ORWH)

Funding Opportunity Title
HEAL Initiative: HEALthy Brain and Child Development Study (U01 - Clinical Trial Not Allowed)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number
RFA-DA-21-021
Companion Funding Opportunity

RFA-DA-21-020 - HEAL Initiative: HEALthy Brain and Child Development Study (Collaborative U01- Clinical Trial Not Allowed)

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.242; 93.273; 93.279, 93.286, 93.113, 93.307, 93.853, 93.313

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to seek applications for unlinked Research Project Sites for the HEALthy Brain and Child Development (HBCD) Study using the cooperative agreement award mechanism. This FOA runs in parallel with companion FOAs that seek applications for linked Research Project Sites (RFA-DA-21-020), a single Consortium Administrative Core (RFA-DA-21-022) and a single Data Coordinating Center (RFA-DA-21-023). It is expected that investigators, upon funding, will work jointly with NIH scientific staff to assist, guide, coordinate, or participate in project activities. This FOA seeks applications to create a consortium of research sites in service of the nationwide, multi-site, multi-modal, longitudinal cohort HBCD Study to prospectively examine brain and behavioral development from birth through childhood, including an emphasis on understanding the impact of in utero substance exposure on outcomes. Research sites will enroll pregnant women and collect data from them and their children using methodologies that include neuroimaging, neurophysiology, behavioral and cognitive assessments and collection of biospecimens.

Key Dates

Posted Date
January 11, 2021
Open Date (Earliest Submission Date)
March 01, 2021
Letter of Intent Due Date(s)

March 1, 2021

Application Due Date(s)

March 31, 2021

No late applications will be accepted for this Funding Opportunity Announcement

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

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

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

July 2021

Advisory Council Review

August 2021

Earliest Start Date

September 2021

Expiration Date
April 01, 2021
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

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

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

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

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

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


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

HEAL Initiative

This study will be part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed the development and implementation of scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative will bolster research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information and periodic updates about the HEAL Initiative are available at: https://heal.nih.gov/.

REMINDER: This FOA should be used for stand alone applications. Linked sets of collaborative U01 applications should be submitted under the companion U01 FOA RFA-DA-21-020, when two or more collaborating sites are essential to complete the proposed research.

Purpose:

The purpose of this FOA (and companion FOA RFA-DA-21-020) is to seek applications to create a consortium of research sites in service of a nationwide, multi-site, multi-modal, longitudinal cohort study to prospectively examine brain and behavioral development from birth through childhood, including an emphasis on understanding the impact of in utero substance exposure on outcomes.

Background:

The brain undergoes rapid development prenatally, through early childhood and into adolescence, supporting cognitive and emotional maturation. This rapid growth also represents a highly vulnerable period where a variety of environmental exposures can have a large and enduring impact. In utero and neonatal exposures are as likely to have significant impact on long-term health outcomes as they are likely to affect early neurodevelopment. For example, substance use during pregnancy, throughout breastfeeding, and while parenting has the potential to profoundly affect development in a variety of ways. Other environmental factors, such as exposure to environmental toxins, structural racism, SARS-CoV-2 exposure and pandemic-related stress, nutritional status, child-rearing practices, neighborhood factors, and access to healthcare, also influence physical growth and brain development. However, the relative paucity of research on normative brain development from birth through adolescence from a large, diverse cohort has limited our ability to fully understand how disruptions and experiences during early periods of growth impact individual developmental trajectories. To understand how these factors, alone and in combination, interact with genetics and other biological influences (e.g., viral exposures) to affect a child’s mental and physical health trajectory, a large prospective study is needed. To be successful, this study must include diverse populations to determine normal variability in development and factors that may disrupt it or build resilience. Additionally, the study must be of sufficient duration and scope to detect potential impact that may manifest as the child approaches school age.

Increases in substance use and ensuing harms over the past decade have heightened the urgency for understanding the complex ways in which exposure during pregnancy affects child outcomes. For example, the current opioid crisis affects the nation broadly across socio-demographic groups, with alarming increases in the use of opioids during pregnancy resulting in a sharp rise in babies born with neonatal withdrawal symptoms (8/1,000 hospital births) in the last 5-10 years. The HEAL Enhanced Outcomes for Infants and Children Exposed to Opioids initiative seeks to support research to address the medical and social needs of infants and children affected by opioid exposure and opioid use disorder. In addition, a growing body of evidence indicates that early exposure to potentially harmful substances, including pre- or perinatally, is linked to greater risk for low birth weight and preterm birth, which portend other health problems. These exposures have also been associated with altered brain structure and function early in life and with behavioral problems in childhood and adolescence, including attention deficit hyperactivity disorder (ADHD), conduct disorder, early drug use, and anxiety. Medications to treat opioid use disorder in pregnant women may mitigate opioid-related harms and improve pregnancy and child outcomes with potential gains projecting into adulthood, but the impact of those medications on neurodevelopment also remains unknown. Moreover, drug exposures during pregnancy are not limited to opioids. Marijuana, tobacco/nicotine, and alcohol are also used alone and in combination with opioids during pregnancy and reports of rising cocaine and methamphetamine use in pregnant women from some geographical areas over the last two decades, with corresponding increases in low birth weight, preterm delivery and maternal morbidity, are also worrisome. Most recently, the COVID-19 pandemic has added another layer of stress to many individuals and families and the virus itself may directly or indirectly affect neurodevelopmental outcomes. Thus, establishing causal links between early exposure to substances or other potential harms and future health and behavioral consequences is complex and will require a large prospective study of children beginning prenatally and followed into childhood. The HEALthy Brain and Child Development (HBCD) Study, is being established to provide a detailed characterization of brain development (using neuroimaging and physiological tools), genetics, social, behavioral, and other biological/environmental contexts to understand neurodevelopmental trajectories. Data collected on this cohort will be made widely available to the scientific community.

To provide an index of normative child development and to address critical questions surrounding the long-term impact of high-risk environments, including substance exposure, HBCD seeks to enroll a large, diverse cohort of pregnant women, who, along with their children, will be followed longitudinally. The cohort will consist of mother and baby dyads recruited beginning in the 2nd trimester of pregnancy and through birth. While a majority of the cohort is expected to be recruited from the general population of pregnant women, a subset will include pregnant women whose babies were exposed pre- or perinatally to prescription and illicit opioids, marijuana, stimulants, alcohol and tobacco/nicotine; as well as women from comparable high risk environments, who did not use substances during pregnancy. Advances in neuroimaging, bioinformatics, and genetic technologies (among others) will enable the collection of multi-modal data that will be made available on an ongoing basis (approximately annually) to the wider research community for timely analysis and as a long-term resource for studying neurodevelopment and other health outcomes. A deep, nuanced understanding of factors that affect a child’s health, brain and behavioral development is expected to emerge from this study, which is an essential first step toward designing policies and interventions that promote well-being and resilience in all children.

For additional information on the planning phase for the HEALthy Brain and Child Development Study, please see the summary reports from expert panel meetings, PI meetings, and neuroimaging and biospecimen workgroups at HBCD Study.

Objectives and Organization of the HEALthy Brain and Child Development (HBCD) Study Consortium

The NIH Helping to End Addiction Long-termSM (HEAL) Initiative and the National Institute on Drug Abuse (NIDA), the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Mental Health (NIMH), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the Eunice Kennedy Shriver Institute of Child Health and Human Development (NICHD), the Office of Behavioral and Social Sciences Research (OBSSR), the Office of Research on Women’s Health (ORWH), the National Institute of Environmental Health Sciences (NIEHS), and the National Institute on Minority Health and Health Disparities plan to establish the HBCD Study that will consist of three, highly integrated components: (1) a single HBCD Data Coordinating Center (HDCC), (2) a single HBCD Consortium Administrative Core (HCAC), and (3) a set of HBCD research project sites. Linked (see RFA DA-21-020) and unlinked applications for research project sites will be accepted. The HDCC and HCAC cannot be linked. At the time of award, a single consortium will be formed that will together determine the research protocol to be used in the study. Investigators are permitted to apply for only one component (HDCC, HCAC or research site) as the PD/PI, but may serve as co-investigator on more than one component.

The study objectives highlighted in each application should address the following overarching research questions that are central to the HBCD study:

  • What are typical neurodevelopmental trajectories and what is the normal range of variability in brain development from birth through childhood? How do biological and other environmental exposures affect these developmental trajectories??
  • How do genetic influences interact with environmental factors to influence neurodevelopment and cognitive, emotional, and social behavior?
  • How does early life exposure to opioids, other substances, and/or other adverse environmental circumstances affect developmental trajectories?
  • Are there key developmental windows during which the impact of adverse environmental exposures (e.g., stress, COVID-19) influence later neurodevelopmental outcomes?
  • Are there key developmental windows during which ameliorating influences (e.g, substance use disorder treatment; social/economic support) are protective against the potential neurodevelopmental insults of early adverse exposures?
  • What is the impact of early parent/caretaker interactions with their children on later health and other outcomes?

To accomplish these objectives, the NIH HEAL Initiative and several NIH Institutes, Centers, and Offices and Programs plan to support the following:

HBCD Research Project Sites: This Funding Opportunity Announcement along with the compannion FOA (RFA-DA-021-020) seeks applications for research projects from investigators whose scientific and technical expertise will allow them to address the objectives and research questions described above. Each research project site will be responsible for participant recruitment and retention, behavioral assessments, biospecimen collection, and neuroimaging. A research project site can be a single institution if all functions (e.g., neuroimaging, biospecimen collection, non-imaging assessments) can be accomplished at that site; or a central hub institution with other institutions as spokes for the hub, such that all the required data collection can be accomplished by the contributing institutions. In either organizational setup, the Program Director(s)/Principal Investigator(s) will have overall responsibility for the progress of the proposed studies.

HBCD Consortium Administrative Core (HCAC): A separate Funding Opportunity Announcement (RFA-DA-21-022) seeks applications for a single HBCD consortium administrative core led by the Program Director(s)/Principal Investigator(s) who is responsible for leadership and management of the HBCD consortium; including, budget, performance metrics, policies, communication, outreach and dissemination plans across the consortium.

HBCD Data Coordinating Center (HDCC): A separate Funding Opportunity Announcement (see RFA-DA-21-023) seeks applications for a single data coordinating center that will coordinate, standardize, and integrate all core data collection, processing, storage, and analytic activities of the consortium; facilitate data sharing and serve as a resource to the scientific community to enable broad use of the HBCD data. The HDCC will also provide real-time monitoring of consortium progress and performance.

It is expected that the proposed study will be designed to rigorously address the overarching objectives and research questions outlined above. To support the consortium reaching its stated goals/outcomes, a results-based accountability (RBA) approach will be used for all components. Additional information about the use of RBA for HBCD can be found in Section VI. Applicants are reminded that the use of a single Institutional Review Board (sIRB) is required for any multi-site study that will use the same protocol to conduct non-exempt human subjects research at more than one domestic site (please see the Single IRB Policy for Multi-Site Research).

For additional background information regarding the HBCD study, applicants can review the website (HBCD Study).

Special Considerations

HIV/AIDS Counseling and Testing Policy for the National Institute on Drug Abuse: In light of recent significant advances in rapid testing for HIV and in effective treatments for HIV, NIDA has revised its 2001 policy on HIV counseling and testing. NIDA-funded researchers are strongly encouraged to provide and/or refer research subjects to HIV risk reduction education and education about the benefits of HIV treatment, counseling and testing, referral to treatment, and other appropriate interventions to prevent acquisition and transmission of HIV. This policy applies to all NIDA funded research conducted domestically or internationally. For more information seethe NIDA Policy on HIV Education, Counseling, Testing, and Treatment for Research Subjects.

National Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human Subjects: The National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects. Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects. The guidelines are available on NIDA's website at the NACDA Guidelines for Administration of Drugs to Human Subjects.

Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants: The National Advisory Council on Drug Abuse (NACDA) encourages NIDA and its grantees to consider the points it has set forth with regard to existing or prospective sponsored research agreements with tobacco companies or their related entities and the impact of acceptance of tobacco industry funding on NIDA's credibility and reputation within the scientific community. Please see Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants for details.

Data Harmonization for Substance Abuse and Addiction via the PhenX Toolkit: NIDA strongly encourages investigators involved in human-subjects studies to employ a common set of tools and resources that will promote the collection of comparable data across studies and to do so by incorporating the measures from the Core and Specialty collections, which are available in the Substance Abuse and Addiction Collection of the PhenX Toolkit. Please see NOT-DA-12-008 for further details.

Data Sharing and Archiving: In addition to working with the HBCD Consortium Administrative Core (HCAC) and the Data Coordinating Center (HDCC), research sites are encouraged to consider additional data sharing, de-identification and archiving policies as set forth by the HEAL Public Access and Data Sharing policy, the NIAAA Data Archive policy, the NIMH Data Archive, and other relevant institutional policies.

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
New

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

Clinical Trial?
Not Allowed: Only accepting applications that do not propose clinical trials

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIH intends to fund approximately 20-25 research sites from this FOA and its companion (RFA-DA-21-020), corresponding to a total of $26,000,000 for fiscal year 2021. Future year amounts are contingent upon annual appropriations.

Award Budget
Application budgets are not limited but need to reflect the actual needs of the proposed project.
Award Project Period

The maximum project period is five years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
  • Non-domestic (non-U.S.) Entities (Foreign Institutions)
  • Eligible Agencies of the Federal Government - including the NIH intramural program
Foreign Institutions

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

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

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

Required Registrations

Applicant organizations

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

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

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

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

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. 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.

Investigators are permitted to apply for only one component of the overall HBCD Consortium (HDCC, HCAC or research site) as the PI/PD, but may serve as co-investigator on more than one component.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  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).

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to: NIDALetterofIntent@mail.nih.gov.

Applicants are encouraged to send the letter of intent by email to the email address above but as an alternative the letter may also be sent to:

Office of Extramural Policy and Review
National Institute on Drug Abuse
3WFN 9th Floor, MSC 6021
301 North Stonestreet Ave
Bethesda, MD 20892

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

Cover Letter Attachment:The Cover Letter is one pdf file only.

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Other Attachments: Provide the listed additional materials below. All the listed materials should be provided as a single PDF file, labeled as “Organizational Data”.

  1. Research Site Roles: A table listing all sites in the application with a list describing the role each site will play within the proposed research, if more than one. Please include both roles that are overlapping between sites as well as roles that are distinct to each site.
  2. Locations where study participants will be recruited: A table listing all sites in the application with a list of the locations where study participants for the normative, high-risk substance using, and high-risk non-substance using participants will be recruited, if more than one.
  3. Collaborations with community organizations that may provide benefits to study participants: A table listing organizations that study participants will be referred to for services provisionas needed (see ethics and legal considerations below). Services to be provided may also be listed.
SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy

Within the Research Plan, the proposed research designs and sampling strategies should describe the following:

  • A longitudinal single-cohort design to prospectively examine neurodevelopment and behavior beginning at birth and continuing through early childhood;
  • The study should include 1) a normative sample that represents the diversity of pregnant women in the U.S. population; 2) a cohort of pregnant women who used opioids and other substances during pregnancy; and 3) a comparison group of pregnant women from similar backgrounds/environments as the cohort of pregnant women who used substances;
  • A sufficient sample size to achieve the dual study goals of assessing normative brain development and analyzing the effect of substance exposures and environmental adversity on brain development. Preliminary estimates suggest a total HBCD Study consortium sample size of approximately 7,500 participants at the end of the 5-year funding cycle would be needed though a smaller sample size can be proposed if justified by feasibility and statistical-power analyses;
  • A sampling design with appropriate weights to produce geographical variation of macro-level factors associated with opioid use and other substance use (e.g., state-level policies concerning OUD treatment availability; permissiveness of marijuana, alcohol, and tobacco use; rural, urban and suburban populations);
  • Approaches to address the issue of non-random selection of participation into these samples;
  • Recruitment strategies to enroll pregnant women (from normative and high risk/substance-using populations) beginning during the 2nd trimester and continuing through birth. It is expected that different strategies may be required to successfully enroll these populations;
  • A data-collection schedule to recruit all study participants over an approximately three-year baseline period;
  • Longitudinal assessments including neuroimaging, neurophysiology, biospecimen collection, and maternal, child neurodevelopmental, and contextual assessments;
  • Consideration of the multi-faceted and complex nature of conducting longitudinal research, including how to achieve high rates of recruitment and retention over the short- and long-term with high risk and substance-using populations, pregnant women and mothers, infants and children;
  • Detailed plans for ensuring high rates of retention of vulnerable populations;
  • The HEAL Initiative has an overall data strategy goal to collect structured data from a wide variety of preclinical and clinical research programs such that data can be shared, standardized, and analyzed. The aim is to make the data findable, accessible, interoperable, and reusable (FAIR) for the benefit of researchers and the public. In all cases this sharing is subject to established governance, abiding by HEAL Data Sharing policy, and respectful of individual and community consent. The data management challenges around HEAL research and its data sets include protecting participant privacy, storing large data volumes, and creating shared data management processes and platforms.

Ethical and legal considerations should be described and include the following:

Research on pregnant women and their children, especially women who use substances or are otherwise vulnerable, must carefully consider the legal, ethical and regulatory complexities that could put research participants in jeopardy. Applications should address the imperative to maximize benefit to participants and minimize risk, including, e.g., referral to local services for pregnant and parenting women with and without substance use disorders.

Research sites will be strongly encouraged to coordinate with the HCAC to address legal and ethical considerations pertinent to the study on both a local and consortium-wide level. Applicants should consider developing memoranda of understanding with state and local law enforcement, institutional policy makers, etc. to navigate the assessment and confidentiality related to substance use and use disorders. Applicants should describe the following:

  • Knowledge and expertise of state/local reporting and other requirements related to substance use during pregnancy;
  • Plans to address and minimize stigma related to drug use during pregnancy;
  • Proposed approaches to minimize legal risks to mothers/infants from participation in the research study;
  • Inclusion of benefits to participants that will not interfere with the study goals; particularly for parents who use substances; or are exposed to other adversity, such as poverty, discrimination, COVID-19; other social, behavioral and economic adversity. Examples include:
    • Providing childcare, transportation, and other services to foster engagement and retention;
    • Providing referrals to treatment services and interventions;
    • Hiring a case manager to navigate services and resources;
  • Partnerships with relevant agencies and community stakeholders to ensure protection of research participants and engagement on key study procedures and expectations;
  • Measures to protect the confidentiality of participants;
  • Plans to involve ethicists in the study design and implementation;
  • Consideration of return of results on exposures, healthcare or other issues and concerns to study participants in aggregate or individual format.

Assessments of environmental, social and other contextual variables should also be described:

Assessments should cover parents and other caretakers, their infant(s), and other family members, and include detailed measures of the home and neighborhood environment. The measures should be developmentally appropriate, address brain-behavior linkages, use state-of-the-art tools and modes of data collection and coding, be socially and culturally sensitive, and include strengths-based assessments. Biospecimen collection from mother and child is expected to be part of these assessments.

Assessments should include the following:

  • State-of-the-art data-collection procedures (e.g., computer-administered/assisted interviews; multi-modal neuroimaging, biospecimen collection, passive data via wearable devices), including practices that are culturally appropriate, and data quality-control processes;
  • Standardized measures that, where possible, are compatible with data-harmonization efforts (e.g., PhenX Toolkit, NIH Toolbox);
  • Comprehensive assessment of substance use history to permit accurate estimates of pre-/perinatal exposure of substance use (e.g., opioids, marijuana, tobacco/nicotine, alcohol, psychostimulants, hallucinogens, etc.) using multi-modal approaches such as interviews and other self-report methods, biospecimen collection from mother and infant and/or drug metabolite and toxicology screening, and/or survey of medical records;
  • Assessment of COVID-19 exposure through diagnostic testing and/or antibody status of mother and infant.

Applications should also address, but are not limited to, the constructs listed below:

Social, Biomedical, and Environmental Domains

  • Maternal and family history of psychiatric and substance use disorders;
  • Adverse Childhood Experiences (ACEs);
  • Neurological disorders and neurodevelopmental diagnoses;
  • Prenatal substance use history obtained through multiple assessments including interview, self-report, biosample analysis (e.g., plasma/serum, whole blood, urine, saliva, nail clippings, diapers, meconium, hair, umbilical cord), etc.;
  • Environmental exposures (including nutrition);
  • Additional biomarker assays, including genetics and epigenetics; inflammation, and microbiomes;
  • Prenatal stress/pregnancy distress;
  • Prenatal infection (e.g., SARS-CoV-2);
  • Pregnancy complications and birth outcomes;
  • Socioeconomic status and related factors such as education, location and geographical resources, access to healthcare, food security, exposure to discrimination, cultural context, etc.;
  • Parent or caregiver-child interactions and social connectedness, including child rearing practices and/or assessment of maltreatment;
  • The influence and interaction of sex (a biological variable), race and ethnicity in questions about risk, prevention, and health outcomes.

Neurodevelopmental Domains

  • Social-emotional development (e.g., temperament, reactivity, regulation);
  • Cognitive development (e.g., learning, memory, executive function);
  • Impulsivity, self-control and attention;
  • Language development;
  • Motor and physical development;
  • Neurological diagnoses;
  • Health and growth, including brief assessments of sleep, physical activity, and nutrition;
  • Developmental psychopathology (internalizing, externalizing behaviors, neuropsychological conditions).

Biospecimens

  • Detailed plans and procedures to collect, process, analyze (where appropriate), and ship biospecimens (e.g., urine, blood, saliva, hair) indicative of substance exposure and other environmental contaminants (lead, heavy metals, etc.); plans must include a prioritized list and details about chain of custody of samples from collection to analysis (i.e., barcode system). Biospecimens will be sent to the NIDA Developmental Repository for analysis and subsequent distribution to qualified researchers.

Neuroimaging and neuropysiology plans should describe the following:

Implementation of an imaging protocol that is developmentally sensitive; can be reliably administered at multiple sites and is feasible for infants and children over the course of the study. Compatibility with other datasets in similar age children should also be considered.

  • Required measurements for neuroimaging and neurophysiology:
    • Use of MR scanners with a field strength of at least 3T (Siemens, Philips or GE);
    • T1-weighted structural acquisition;
    • T2-weighted structural acquisition;
    • Diffusion tensor acquisition;
    • Resting-state fMRI acquisition;
    • Task fMRI when age appropriate;
    • MRS for measures of molecules involve in neuronal metabolism, neurotransmission and oxidative stress;
    • Relaxometry;
    • EEG measurements, including hardware/equipment, data collection software, age-appropriate acquisition protocols and tasks in lab and/or home settings.

Additional considerations that applicants should also provide include:

    • A plan for evaluation (imaging and other assessments) at intervals sufficient to provide a detailed measure of early neurodevelopment that will not overburden study participants. Longer intervals between scans can be considered as the child matures;
    • Demonstration of experience and success conducting brain-imaging research among infants and children in the age range proposed in the application;
    • Strategies for creating and maintaining optimal scanning environments to maximize scan completion rates and retention (e.g., scanner setups for infants and families);
    • Suggestions for optimizing scan parameters across age and processing pipelines;
    • A plan to accommodate changes in instrumentation in response to technological advances that will occur during the project, as well as the need for change as the child develops (e.g., from sleeping scans to awake scans) and adjustments necessary to account for growth;
    • Strategies for motion detection/correction and data harmonization across sites;
    • For applications proposing to use scanners from different vendors across research sites, there must be at least two research sites with scanners from the same vendor in order to disentangle potential site vs. scanner effects; in these situations, the applications should describe how to harmonize data across sites and scanner manufacturers and models.

For additional background information regarding study-design issues related to this initiative, applicants can review the Summary of the HBCD Working Groups (Neuroimaging and Biospecimens) and the reports of two Expert Panel meetings (Research Methodologies and Study Design).

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

 

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan.
    • All applications submitted for the January 25, 2015 due date or after are expected to comply with the NIH Genomic Data Sharing Policy as detailed in NOT-OD-14-111, as applicable.
    • Applicants are expected to use the NIDA Neurodevelopmental Studies repository (to be named) for biospecimen storage and subsequent processing for genetic and epigenetic studies.
    • The development of policies, methods, and standards for data sharing are critically important for the HBCD Study. As such, it is expected that data from the HBCD Study will be released to the research community as soon as it has undergone basic quality assurance procedures. The HBCD awardee is expected to follow policies, methods, and standards for the project that will remain consistent with NIH-wide policies on data and resource sharing and will be developed by the HBCD Data Coordinating Center (HDCC).
    • The NIH is committed to the principle of rapid data, model, and software release to the scientific community. Applicants will comply with all data sharing requirements established through the HDCC.
    • In order to advance the goal of widespread data sharing, investigators funded under this FOA are expected to share those data via the concurrently funded HDCC.
    • The members of the consortium will be expected to disclose their ties to profit-making organizations to aid the project in avoiding conflict of interest situations or the appearance thereof. Applicants are also reminded that the grantee institution is required to disclose each invention to NIH within two months after the inventor discloses it in writing to grantee institution personnel responsible for patent matters.
    • Investigators will also be expected to comply with policy guidelines provided here: HEAL Public Access and Data Sharing
    • Applicants are expected to use appropriate consent forms to allow the data to be deposited in and distributed from the HBCD Data Coordinating Center, consistent with achieving the goals of this project.
Appendix:

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

Foreign Institutions

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

Overall Impact

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

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA: Does the research application adequately address both 1) typical neurodevelopmental trajectories and normal variability in development, and 2) the impact of early life exposure to opioids, other substances, and/or adverse environmental circumstances on developmental trajectories?

Investigator(s)

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

Specific to this FOA: Do the investigators have a track record of performing the specialized work required for the project? Do the investigators demonstrate adequate experience and success conducting brain-imaging research among infants and children in the age range proposed in the application (e.g., sampling, recruitment and retention of high risk participants, comprehensive phenotypic assessments, neuroimaging in infants and young children, biospecimen collection)?

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?

 Specific to this FOA: Does the application include sufficient state-of-the-art tools and modes of data collection and coding to conduct developmentally appropriate assessments of the infant, family, home and neighborhood environments and assess brain-behavior linkages? Do the applicants adequately consider optimization of neuroimaging parameters across ages and plan to accommodate changes in instrumentation in response to technological advances that occur during the project?

Approach

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

 Specific to this FOA: Have the applicants satisfactorily addressed the imperative to maximize benefit to participants and minimize risk, including, e.g., referral to local services for pregnant and parenting women with and without substance use disorders?

Do the applicants provide sufficiently detailed recruitment and retention strategies to enroll (and retain) pregnant women (from normative and high risk/substance-using populations) beginning during the 2nd trimester and continuing through birth?

Are the plans to recruit from ethnically, geographically, and socioeconomically-diverse participant populations and communities adequate/sufficient to ensure a diverse sample? Does the study design generate a cohesive data set that will allow future researchers to compare infants born to women who used opioids and other substances during pregnancy to infants born to women from similar high risk backgrounds/environments that did not use substances during pregnancy, despite potential differences in the underlying processes (recruitment strategies, etc.) that may be used to generate these samples?

Does the study protocol comprehensively assess pre- and post-natal factors that may confound analyses of the impact of substance exposures and other environmental adversities on developmental trajectories?

Do the type and frequency of proposed assessments provide adequate statistical power and number of timepoints to evaluate critical developmental milestones?

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

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?

Specific to this FOA: Is there demonstration of availability of the required populations for participant recruitment (ethnically, geographically, and socio-economically-diverse, opioid and other substance use and similar high risk backgrounds, etc.)?

Additional Review Criteria

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

Ethical and Legal Consideration

Have the high-risk ethical and legal aspects of the study design, on a local and national level, been adequately identified and appropriate measures proposed to address them?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

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

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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

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)  Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

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

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.

2. Review and Selection Process

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 will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

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 submitted in response to this FOA. 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.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

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

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

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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

Cooperative Agreement Terms and Conditions of Award

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 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this project 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:

The PD(s)/PI(s) will be responsible for the scientific and technical direction of the project and agrees to abide by the policies and rules set up by the consortium. This includes accepting the actions and recommendations approved by the Steering Committee. In addition, each PD/PI will agree to accept close coordination, cooperation and participation with the NIH HEAL Initiative and participating NIH ICs in those aspects of management of the project as described below. Each U01 research site project, the U24 data coordinating center, and the U24 consortium administrative core will receive a separate award, and the PI will have control over the project's operating budget. Awardees will be required to attend consortium committee meetings and participate in the cooperative nature of the consortium. Awardees will implement the approved data sharing plan which will be incorporated as an additional term of award, and will be expected to share (make available) these data both within the consortium and with the scientific community. Awardees should comply with their institutional intellectual property policies and practices as approved in the award.

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

The NIH Project Scientist(s) will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The NIH Project Scientist(s) may not be involved in the normal programmatic stewardship of the project including the evaluation of supplemental applications. If such participation is essential, this individual will seek IC waiver. An NIH Program Official will handle the normal stewardship of the award, as described below.

The NIH Project Scientist(s) will have substantial scientific involvement during conduct of this activity, through technical assistance, advice and coordination above and beyond normal program stewardship for grants, as described below. The dominant role and prime responsibility for the activity resides with the awardees for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardees, the NIH Program Official, and the NIH Project Scientist(s).

The NIH Project Scientist(s) will have voting membership (one combined vote) on the Steering Committee and, as determined by that committee, its subcommittees. The NIH Project Scientist(s) will coordinate and facilitate the Consortium project, will attend and participate as a voting member in all meetings of the Steering Committee, and will provide liaison between the Steering Committee, the Consortium, the NIH HEAL Initiative and other involved NIH ICs.

The NIH Project Scientist(s) will assist the Steering Committee in developing and drafting operating policies and policies for dealing with recurring situations that require coordinated action.

The NIH Program Official will review the scientific progress of individual components, and review them for compliance with the operating policies developed by the Steering Committee, and may recommend withholding of support, suspension, or termination of an award for lack of scientific progress or failure to adhere to policies established by the Steering Committee. A results-based accountability approach will be used to support the consortium reaching its stated goals/outcomes. Additional metrics (i.e. % data quality, % missing data points, % participant withdrawals) will be added as a term and condition of the award throughout the duration of this 5-year project. If at any time an outcome is not being met, the program official will ask the PD/PI for a resolution plan and increased progress reporting to ensure compliance. If scientific progress is not met the NIH Program Official may ask the Consortium Coordinator to provide technical assistance and can recommend withholding of support, suspension, or termination of an award for lack of scientific progress or failure to adhere to these award conditions.

The NIH Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The NIH Program Official may elect to attend the Steering Committee meetings, but not as a member of the committee.

Areas of Joint Responsibility include:

HBCD Consortium Administrative Core Coordinator’s Rights and Responsibilities: The HCAC coordinator (the PD(s)/PI(s),) is charged with coordinating the scientific and administrative activities of the consortium. The HCAC coordinator has the responsibility for the scientific and technical direction of the research projects, and the administration and overall operation of the consortium. Therefore, the HCAC coordinator is responsible for ensuring that projects awarded are fully integrated within the scientific scope and mission of that consortium. This includes assuring that all investigators have access to the resources within the resource facilities of the consortium. A Steering Committee serves to assist the HCAC coordinator with the governance of the consortium. The HCAC coordinator chairs this committee. In addition, the HCAC coordinator must abide by the operating rules and guidelines developed by the Steering Committee. Furthermore, the HCAC consortium coordinator has agreed to accept participation of NIH staff members in those aspects of management of the project described under "NIH Staff Rights and Responsibilities." Lastly, the HCAC coordinator ensures the timely dissemination of information generated by the consortium component projects to both the consortium project members and the scientific public.

Expert Scientific Board: The consortium includes an Expert Scientific Board whose purpose is to meet with the HCAC coordinator and the Steering Committee to assess progress and provide feedback to the investigators on proposed goals for the next year of support. The panel members are designated by NIH Project Scientist(s) in consultation with the Steering Committee, and consist of research scientists not actively involved with the consortium. The Expert Scientific Board should be formed soon after award and meet with the consortium investigators after the release of the Notice of Award to review and revise the protocol before formal data collection activities begin. Thereafter, the Expert Scientific Board should meet at least once a year immediately prior to the submission of the consortium annual progress report.

Steering Committee: The consortium has a Steering Committee, which is the main governing board of the consortium. The members of the Steering Committee for the consortium are selected by the HCAC coordinator with input from the NIH Project Scientist(s). The Steering Committee is primarily composed of the HCAC coordinator, several principal investigators of the research project components and HDCC component, and the NIH Project Scientist(s). The Steering Committee may, when deemed necessary, invite additional, non-voting scientific advisors to the meetings at which research priorities and opportunities are discussed. The NIH also reserves the right to augment the scientific expertise of the Steering Committee when necessary, and to appoint additional NIH staff as nonvoting members of the Steering Committee and Subcommittees. Each primary member of the Steering Committee has one vote. The chairperson of the Steering Committee is the HCAC coordinator. The Steering Committee may establish subcommittees as it deems appropriate to facilitate the planning and operation of the consortium. The Steering Committee meets at least twice annually to discuss and refine the scientific mission and objectives of the consortium, and to evaluate the scientific progress being made both within the consortium research components and by outside laboratories. The Steering Committee discusses the various experimental approaches that were proposed in the individual components and any relevant new information, and subsequently sets the research priorities for the consortium. In the interest of facilitating research in the neurodevelopment field, the Steering Committee of the consortium evaluates the progress of any new technology being developed and decides when the technology is sufficiently validated for distribution to the research community. The NIH will provide the means to disseminate the technologies and the information related to them.

The Steering Committee will plan one or more meetings a year to which non-consortium participants will also be invited to enable the consortium to explore scientific or technologic advances and innovations that occur during the course of the project. For the second and subsequent years of operation of the consortium, the Steering Committee will plan a symposium or workshop to inform the research community of the progress made. The NIH Program Official and other NIH Project Scientist(s) will provide the Steering Committee with advice on appropriate topics and participants for the workshops and symposia.

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.

3. Reporting

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

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

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

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

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

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

Scientific/Research Contact(s)

Minki Chatterji
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-5435
Email: minki.chatterji@nih.gov

William Dunty
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-7351
Email: duntyw@mail.nih.gov

Julia Zehr
National Institute of Mental Health (NIMH)
Telephone: 301-443-1617
Email: zehrj@mail.nih.gov

Kimberly Gray
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3262
Email: Kimberly.Gray@nih.gov

James Griffin
Eunice Kennedy Shriver National Institute on Child Health and Human Development (NICHD)
Telephone: 301-435-2307
Email: James.Griffin@nih.gov

Adam Hartman
National Institute on Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9135
Email: Adam.Hartman@nih.gov

Benyam Hailu
National Institute on Minority Health and Health Disparities (NIMH-D)
Telephone: 301-594-8696
Email: benyam.hailu@nih.gov

Erica Spotts
Office of Behavioral and Social Sciences Research (OBSSR)
Telephone: 301-594-2105
Email: spottse@mail.nih.gov

Rebecca DelCarmen-Wiggins
Office of Research on Women's Health (ORWH)
Telephone: 301-451-8689
Email: rdelcarm@nih.gov

Peer Review Contact(s)

Dr. Heidi Friedman
Scientific Review Officer
Email: HFRIEDMAN@mail.nih.gov
Telephone: 301-379-5623

Financial/Grants Management Contact(s)

Lennin Greenwood
National Institute on Drug Abuse(NIDA)
Telephone: 301.827.6686
Email: greenwoodl@mail.nih.gov

Section VIII. Other Information

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

Authority and Regulations

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


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.