It is critical that applicants follow 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 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

Background

It is well established that the first few years of life are a period of exponential brain growth and development, however, there is much to be learned about typical brain development beginning prenatally through early childhood, its variability, and how it contributes to cognitive, behavioral social, and emotional function. Knowledge of normative brain trajectories is critical to understanding how brain development may be affected by exposure to opioids and other substances (e.g., alcohol, tobacco, cannabis), stressors, trauma and other significant environmental influences. This knowledge is critical to help predict and prevent some of the known impacts of pre-/postnatal exposure to certain drugs or adverse environments, including risk for substance use, mental disorders, and other behavioral and developmental problems.

The current opioid epidemic has led to dramatic increases in the number of children pre- or postnatally exposed to opioids. In 2014, one infant was born with neonatal abstinence syndrome (NAS) every 15 minutes. But this is not the only risk to infants other substances (some prescribed) are also used during pregnancy and continued during breastfeeding; and other adverse experiences, such as parental stress, food or housing insecurity, and exposure to toxic metals (e.g., lead) also occur. At the same time, protective factors such as prenatal vitamins, good nutrition, adequate sleep, physical activity, and supportive partners, family, or communities may counter some of the impact of the risks noted above.

Currently, no large prospective cohort study has been conducted to comprehensively assess typical brain development or the long-term consequences of early adverse experiences or exposure to opioids, other drugs (including prescribed medication), or other substances (e.g., tobacco, alcohol, cannabis), on the developing child’s brain and behavior. Furthermore, a causal link to substance exposure itself is often difficult to establish due to confounding factors such as socioeconomic, environmental, cultural, and genetic influences. Given the plasticity of the infant brain, it is even more important to understand the protective and resiliency factors that may ameliorate the effects of these exposures and may inform the development of early interventions.

Input for this project from the extramural community was provided in two expert panel meetings at the NIH. For summaries of the discussion please visit https://d14rmgtrwzf5a.cloudfront.net/sites/default/files/bbcd_expert_panel_summary_10-15-18-final.pdf and https://www.drugabuse.gov/news-events/meetings-events/2018/10/expert-panel-meeting-to-discuss-study-design-longitudinal-study-impact-prenatal-opioid-other.

Scope

This Funding Opportunity Announcement (FOA) solicits applications for planning and initial development (Phase I) for a large scale multi-site research study (Phase II) to prospectively examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally through childhood (e.g., age 9-10), and the long-term impacts of pre/postnatal drug (expected oversampling for opioid prenatal exposures) and adverse environmental exposures on brain and behavioral health and risk for substance use and mental disorders. The current Phase I FOA solicits applications to explore the requirements for, and to develop and test the feasibility of, research designs that address the key research objectives of the planned large scale multi-site Phase II project, which will be similar in scale and scope to the current Adolescent Brain Cognitive Development (ABCD) study (https://abcdstudy.org/). Planning activities may include the establishment of the research team; identification and plans to address legal and ethical issues critical to the implementation of the study; the development of research designs and other essential elements of the study or project, such as the protocol and recruitment (including oversampling of opioid exposed infants) and retention strategies; and to collect feasibility data. Phase II will not be limited to investigators that applied for/or were awarded Phase I planning grants.

This FOA should be used when two or more collaborating sites are essential to complete the proposed research. It is required that the Research Strategy be identical across linked collaborative R34 applications, with the exception of a short section describing the specific function of each application under "elements unique to that site." For a linked set of collaborative R34 applications, each application must have its own Program Director/Principal Investigator (PD/PI) and the program must provide a mechanism for cross-site coordination. Applications that stand alone and are not collaborative should be submitted under the companion R34 FOA (RFA-DA-19-036).

This funding opportunity will be offered as part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed 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 about the HEAL Initiative is available at: https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative. As such, it is expected that the cohort will be enriched for prenatal opioid exposure, including licit and illicit opioids as well as medications to treat an opioid use disorder.

Specific Areas of Research Interest for ORWH: The Office of Research on Women’s Health (ORWH) is part of the Office of the Director of NIH and works in partnership with the 27 NIH Institutes and Centers to ensure that women's health research is part of the scientific framework at the NIH and throughout the scientific community. Given the higher prevalence of pain disorders in females and their greater sensitivity to pain, there is a crucial need to include women in pain and opioid-related research. Integrating the purposeful accounting for sex as a biological variable (SABV) in biomedical research on pain and opioid use throughout the life span will fill gaps in our knowledge and inform more effective, personalized approaches to improve heath for women and men. For additional guidance, the 2019-2023 Trans-NIH Strategic Plan for the Health of Women covering is available on the ORWH website (https://www.nih.gov/women/strategicplan) for additional guidance.

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o 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)

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) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not 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) 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.
• o 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 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.

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 requires linked applications. Multiple PDs/PIs are allowed on a single application. PD/PI(s) for a given application in a set of linked applications should not be designated as multiple PDs/PIs on every application of that linked set. Applicants may also not be PD/PI on more than one type of application (e.g., on a linked set and a single application).

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).

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.

It is critical that applicants follow 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.

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 CSR 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/NIH/DHHS
6001 Executive Boulevard, Suite 4243, MSC 9550
Bethesda, MD 20892-9550

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.

Descriptive Title of Applicant's Project: To allow NIH to identify a group of applications as a related set of collaborative applications, the titles for each application in the set must have the following format: a 1/N indicator + Title (e.g., 1/3 , where the 1/3 means this is site 1 of 3 sites in the set. The other sites will be labeled 2/3, etc.). A set of applications is defined as all applications for a single consortium submitted in response to this FOA.

Cover Letter Attachment: The Cover Letter is one pdf file only. The following collaborative information is required in the Cover Letter: a listing of all the applications that are a part of the set of collaborative applications being submitted, including for each: 1) the PD/PI(s) name(s), 2) the Title (including the tag, e.g., 1/3 ), and 3) the Applicant Institution.

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.

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.

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

Applications from each site must contain an identical Research Plan across linked collaborative R34 applications that clearly describes those aspects of the project that are common to all sites of the linked applications, with the exception of a section under the header "Elements Unique to This Site," which should describe all variations in the Research Plan between sites, no matter how minor (estimated to be no more than 1 page of the Research Plan Section).

Applications for this FOA need to detail planning goals and activities to address the key research objectives that include, but are not limited to:

(1) Characterization of developmental trajectories (e.g., brain, cognitive, behavioral, social, emotional, academic) beginning prenatally through childhood (e.g., age 9-10).

(2) Evaluation of the impact of pre/postnatal exposure to opioids, opioid treatment medications, or other substances (e.g., cannabis, alcohol, tobacco, other prescription or illicit substances, alone or in combination), on developmental trajectories.

(3) Delineation of the roles of sex, genetic, epigenetic, social and other environmental factors on risk/resilience related to structural and functional brain development, social/behavioral maturation, and substance use and mental disorders.

Supported activities may include:

• Establishment of a broad interdisciplinary team of investigators with collective research expertise in: pregnancy and maternal health; neonatal and early childhood cognitive, behavioral, social, and emotional development; longitudinal cohort studies; epidemiology and statistics; recruitment and retention of vulnerable populations; developmental neuroimaging; substance use; and pertinent social/legal/ethical and environmental issues
• Development of a sampling strategy (including sample size) and recruitment procedures for assessing typical development as well as oversampling pregnant women who are using opioids or opioid treatment medications
• Development of partnerships with medical providers, child protective services, faith-based organizations, substance use disorder treatment facilities, and other partners necessary for recruitment of participants
• Establishment of a study protocol, including neuroimaging and a developmentally-appropriate assessment battery
• Collection of feasibility data. This should include pilot testing of recruitment strategies and assessment methods, including imaging. Testing the feasibility of the design does not mean conducting a small-scale version of the study. For example, the full-fledged study may involve subjects all recruited at the same age, while feasibility testing may involve recruiting subjects of different ages to determine whether assessment/imaging methods can be accomplished.
• Travel to meetings to inform planning activities and form collaborations

Addressing the key questions about brain, cognitive, behavioral, social, and emotional development beginning prenatally and continuing through childhood is a challenging problem that will require creative designs and innovative solutions in three broad areas: (1) legal and ethical considerations; (2) recruitment and retention; and (3) imaging and assessment methodology. Partnerships with other applicants having complementary expertise are encouraged. Specifically, applicants should address at least one of the following areas:

Legal and ethical considerations for successful implementation of a longitudinal multi-site study of pregnant women and their children. It is vital to the success of this study that pregnant women do not experience additional risks for legal or child protective service consequences as a result of their study participation. Research questions to assess approaches to mitigate risk can also be proposed. Examples of issues to address include, but are not limited to:

• Consideration of how state laws could impact the recruitment and retention of substance-using pregnant women/mothers and their children
• Solutions that mitigate such risks (e.g., legal, social, psychological) for substance-using pregnant women and their children
• Service needs for populations without sufficient access to medical care or addiction treatment (e.g., mechanisms to provide access or linkages to services/benefits)
• Whether tangible benefits can be provided to families, what these may be, how they would be managed throughout the course of the study (e.g., if mother loses custody of child participant), and their impact on study design
• IRB requirements for following children removed from their biological parent's home (e.g., in child protective services or foster/kinship care).
• Consideration of the role of the biological parent throughout the course of the study if the child is temporarily or permanently removed for their custody.

Recruitment and retention should address the following:

• Feasibility of various sampling strategies optimized for development (e.g. staggering assessments, accelerated cohort designs, planned missingness, etc.)
• Recruitment strategies for participants in at least their second trimester of pregnancy; or at delivery, especially substance-using women
• Procedures for oversampling opioid-using women, including women who use illicit opioids, prescription opioids, or opioid treatment medications
• Strategies to recruit a diverse population in terms of race/ethnicity, socioeconomic status, urbanicity, and strategies for matching substance-using women on key characteristics that may confound the association between substance use and health outcomes
• Identification of challenges to and plans for retaining high-risk populations (e.g., the involvement child protective services or the justice system)

Feasibility of imaging and other assessment methodologies should include the following:

• Assessments of family psychopathology, substance use by parents and others residing in the home environment, parental IQ and executive function, adversity exposures, protective and resiliency factors, pregnancy and fetal development, delivery
• Neuroimaging (e.g., structural MRI, resting state and task-based fMRI, myelination) and other measures of brain function (e.g., EEG, fNIRS) in children at different developmental stages and ages
• Assessments of social-emotional development (e.g., early temperament, behavioral inhibition, emotional regulation, including parent-child interactions), early language development, cognitive/behavioral assessment of executive function (e.g., working memory, cognitive flexibility, inhibitory control, delay of gratification, processing speed), psychiatric symptomatology, and global development
• Identification of biological and physiological measures that may predict adverse outcomes later in life
• Determination of optimal timing, frequency, and duration of neuroimaging and other assessments, including feasibility of staggering of assessments
• Identification and means for addressing issues related to image quality in this population (e.g., signal-to-noise; motion; harmonization)
• Collection of parent and child biospecimens, including but not limited to saliva, blood, placenta, cord blood, meconium, urine, feces
• Identification of technologies and methods that could enhance studies of infants and young children; and strategies to take advantage of these opportunities

Applicants must propose activities that will achieve outcomes at the end of the Phase I planning period that include, but are not limited to:

• Determination of sample size, optimal sampling and retention strategies, and duration of enrollment period
• Demonstration of ability to recruit participants during pregnancy and at birth reflecting demographics of the U.S., as well as opioid exposed mothers (licit, illicit, and OUD medications) and demographically matched controls
• Plans for retention over the Phase II project period
• Demonstration of feasibility of MRI imaging and other measures of brain function (EEG and fNIRS); as well as cognitive/behavioral assessments, at different developmental stages.
• Establishment of a core multi-site study protocol, including but not limited to:

o Pregnancy measures

o Postnatal neuroimaging

o Age-appropriate parent/child questionnaires/survey measures

o Early childhood cognitive and behavioral measures

o Collection of parental and child biospecimens

• Plan to support mothers to maximize retention
• Plans for data harmonization and sharing
• Applicants may also consider supplemental measures (e.g., fetal neuroimaging, wearables).

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, with the following modification:

• Generally, Resource Sharing Plans are expected, but they are not applicable for this FOA.

Appendix:

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

When involving NIH-defined human subjects research, clinical research, and/or 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.

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

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

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.

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 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.

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.

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.

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.

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?

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?

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?

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

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?

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.

Have the investigators formed appropriate collaborations/partnerships for study planning and feasibility testing?

Have the high-risk ethical and legal aspects of the study design been adequately identified and appropriate feasibility testing proposed to address them?

Is the proposed Phase I study designed to yield sufficient input to guide preparation of the Phase II study?

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.

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

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

Not Applicable

Not Applicable

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.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by Center of 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.

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.

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.

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. 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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Not Applicable

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.

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, 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

Gayathri J. Dowling, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-4877
Email: dowlingg@nida.nih.gov

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

Heidi Friedman, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-279-5623
Email: hfriedman@csr.nih.gov

Pam Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-253-5819
Email: pfleming@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 Part 75.