Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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

Conformance to all requirements (both in the Application Guide and the NOFO) 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 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

The NIH Helping to End Addiction Long-term (HEAL) Initiative and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) invite applications from institutions currently participating as Clinical Center grantees in the Outcomes of Babies with Opioid Exposure (OBOE) consortium to complete the ongoing study.

Among infants covered by Medicaid in 46 states, from 2004 to 2014 the incidence of neonatal opioid withdrawal syndrome (NOWS) increased from 2.8 to 14.0 cases per 1000 hospital births. The Healthcare Cost and Utilization Project (HCUP) 2020 data estimated that six newborns were diagnosed with NOWS for every 1,000 newborns – approximately one baby is diagnosed with NOWS every 24 minutes in the United States. Infants with NOWS may experience: tremors, irritability, sleep problems, hyperactive reflexes, seizures, stuffy nose/sneezing, poor feeding and sucking, vomiting, loose stools, dehydration, and increased sweating (https://www.cdc.gov/pregnancy/opioids/basics.html). NOWS also puts these children at increased risk of adverse neurodevelopmental outcomes.

This OBOE consortium is part of the NIH’s HEAL initiative to speed the development and implementation of scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to: (1) improve treatment and prevention of opioid misuse and opioid use disorder 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. Within the HEAL Initiative, OBOE is part of the Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) program.

The purpose of the OBOE program is to assess the effects of antenatal opioid exposure on the trajectory of brain development over the first 2 years of life to better understand the long-term impacts of antenatal opioid exposure and NOWs, as well as associated environmental, maternal, and neonatal factors, on neuroanatomical, medical, neurodevelopmental, behavioral, and home, social, and family outcomes. The program will compare neuroanatomical (as measured by serial neuroimaging studies), medical, neurodevelopmental, behavioral, and home, social, and family outcomes between children who have been exposed to opioids in utero and those who have not been exposed. Such research is needed to inform development of intervention trials, appropriate care practices, and treatments to improve outcomes for these vulnerable infants.

The objective is for awardees to work together as a Consortium to complete implementation of the ACT NOW Longitudinal Study: Outcomes of Babies With Opioid Exposure Study (https://www.clinicaltrials.gov/study/NCT04149509) with multi-modal assessments conducted of infants exposed to opioids in utero compared to unexposed infants from birth to two years of age to better understand the consequences of in utero opioid exposure. The study will determine associations with developmental and neurobehavioral outcomes and explore how specific factors (differing antenatal and postnatal exposures, severity of neonatal opioid withdrawal, maternal stress/depression/parenting) modify these effects. Participants will be assessed at 2-years of age with serial measures including neuroimaging, medical, neurodevelopmental, behavioral, and home, social, and family life assessments.

CONSORTIUM STRUCTURE, ROLES, AND RESPONSIBILITIES

The OBOE Consortium currently consists of 4 Clinical Centers (CCs) and a Data Coordinating Center (DCC).  For this limited recompetition, the Clinical Centers/Performance Sites will submit separate grant applications under RFA- HD-24-016. Under this RFA-HD-24-015 , the DCC will include all the functions previously carried out by the Research Support and Administrative Cores, and will designate a lead Neuroimaging researcher.

It is each institution’s responsibility to:

• Meet, and continue to meet, the requirements outlined in RFA-HD-19-025 , and the Notices of Grant Award. This includes having adequate and qualified staff, facilities, and equipment available, and supervision to oversee its staff and that of any satellite sites to conduct OBOE protocols in a safe and effective manner.
• Abide by Federal, state, and local laws and regulations, including those of the Common Rule and the U.S. Food and Drug Administration (FDA), as applicable.
• Participate and communicate in a cooperative and interactive manner with the other consortium PIs, the Steering Committee, and NICHD staff.
• Follow all consortium policies and procedures. By accepting the Notice of Grant Award, each successful Awardee agrees to abide by the OBOE Policies and Procedures developed by the Steering Committee and adhere to OBOE study protocol(s).

The OBOE Steering Committee (SC) consists of:

• Clinical Center principal investigators (PIs) (one vote per center; multi-PI applications are allowed, but each awarded Center will only get one vote on the SC)
• Lead n euroimaging investigator (voting member)
• Data Coordinating Center PI (voting member)
• NICHD Project Scientist (voting member)
• Steering Committee chairperson, appointed by the Director of NICHD (tie-breaking vote only).

The SC has the primary responsibility for implementing the ACT NOW Longitudinal Study, including: completing enrollment, following participants over the course of 2 years, and conducting longitudinal assessments in multiple domains,  analyzing and publishing study results, and sharing study data.

The SC meets 4 times per year and has monthly teleconferences. At least two meetings per year  are expected to be face-to-face (weather and public health permitting), usually in the Washington, DC metro area. In general, SC meetings last for 1 day each, and are scheduled 12 months in advance. All SC members or their designees are expected to attend these meetings. The Steering Committee may create subcommittees to manage specific functions, such as a Publications Subcommittee.

Key activities of the OBOE Consortium will be to:

• Implement the ongoing ACT NOW Longitudinal Study, enrolling opioid-exposed and non-exposed newborns and collecting longitudinal assessments in multiple domains
• Submit accurate study data in a timely manner into the study data management system
• Collaborate with other HEAL program studies. 
• Analyze and publish the results of the study and submit results to ClinicalTrials.gov.
• Deposit anonymized study data in a NIH-approved data repository to the extent feasible and in a timely manner, per the NIH Data Management and Sharing Policy, as amended.

Scientific and Safety Monitoring Board (SSMB). A Scientific and Safety Monitoring Board (SSMB) has been established in accordance with the NICHD DSMB Policy for Clinical Trials to monitor the ACT NOW Longitudinal Study. The SSMB is responsible for safeguarding the interests of study participants and protecting study participants from unacceptable risk. The DSMB provides recommendations to the NICHD Director and consortium investigators on research design, data quality, and analysis issues, as well as conducting interim monitoring of trials for safety, efficacy, feasibility, and ethical conduct. Full members of the SSMB cannot be from any of the CCs, their satellite sites, or the DCC; the DCC PI is an ex officio member, providing statistical reports for SSMB review and logistical support for its meetings.

CLINICAL CENTER RESPONSIBILITIES

The clinical centers participating in the Consortium represent academic institutions with experience in multicenter clinical research. They must agree to abide by Consortium study objectives, policies, and procedures and have comparable staff, facilities, and equipment.

CC Resources

The CC base budget for this application should cover:

• Principal Investigator (PI)
• Research Coordinator
• Data Entry

CC Principal Investigator Roles and Responsibilities

Each clinical site must designate a Principal Investigator (PI) responsible for all aspects of the center's participation in the Consortium. The Principal Investigator participates, with the NIH, the Steering Committee chair, the lead Neuroimaging investigator, and Data Coordinating Center PI, as a member of the Consortium Steering Committee.

The Principal Investigator has primary responsibility for:

• Identifying priority areas for research
• Developing and implementing the protocol and meeting recruitment goals
• Collecting and transmitting the data to the DCC in an accurate and timely manner
• Participating in analysis of the data and publishing results of the Consortium studies.

As such, the PI’s oversight responsibilities include:

• Ensuring that the research is conducted in accordance with all applicable federal regulations and guidelines, such as from the NIH and OHRP.
• Preparing the site's annual progress report.
• Obtaining and maintaining required Institutional Review Board (IRB) approvals and ensuring that the necessary financial arrangements and federal assurances are in place before participation in, and during implementation of, the study. This includes submitting single IRB (sIRB) reliance documentation to the DCC and notifying NIH and the DCC in a timely manner of any suspensions, changes, and other activities affecting study integrity and recruitment.
• Notifying the Data Coordinating Center and NIH of any serious adverse events, protocol deviations, and protocol violations in a timely manner.
• Ensuring collection and transmission of accurate data to the DCC in a timely manner.
• Participating in Consortium quality assurance efforts, including cooperating during site visits, responding promptly to data center inquiries, etc.
• Hiring and supervising qualified study personnel.
• Securing the cooperation of his/her institution and colleagues in Consortium research efforts.
• Communicating Consortium activities and issues to their research staff in a timely fashion, particularly those issues likely to affect the day-to-day operations of ongoing or upcoming study procedures.Notification to NICHD and the DCC of any staff changes in a timely manner.
• Participation in HEAL Annual Investigator Meetings. The NIH HEAL Initiative requires a high level of coordination and sharing between investigators. It is expected that HEAL awardees will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, including an annual HEAL Investigators Meeting, as well as in other activities.

CC Research Coordinator Roles and Responsibilities

One research coordinator will be appointed at each CC to oversee the conduct of Consortium studies. Under the direction of the PI, the Research Coordinator is responsible for ensuring the successful conduct and coordination of the protocol. Research coordinators participate in Consortium protocol development and implementation as members of protocol subcommittees.

Under the supervision of the PI, the research coordinator is responsible for:

• Assisting in the day-to-day operations of implementing the study protocol, including adhering to the protocol, collecting data, supervising data transmission, monitoring data quality, training staff, and procuring adequate equipment and supplies to support the study.
• Maintaining routine data quality assurance methods for staff under his/her supervision.
• Supervising data entry activities, including instructing and certifying data entry personnel in software and hardware usage, quality assurance of data entry, etc.
• Maintaining a central file of protocols, manuals, data forms, regulatory documents, Consortium correspondence, and performance reports in accordance with Good Clinical Practice (GCP).
• Collaborating with the PIs and DCC in developing protocols, manuals of operation, and data collection forms.
• Attending trainings and Steering Committee meetings as necessary.

CC Data Entry Roles and Responsibilities

Data entry personnel are responsible for: collecting completed data forms, entering data accurately into the electronic data capture system(s), and transmitting the entries to the DCC in a timely manner.

DATA COORDINATING CENTER (DCC) RESPONSIBILITIES

The DCC is expected to participate collaboratively on the Steering Committee to achieve OBOE’s objectives. As such, the DCC’s specific objective is to develop, implement, and analyze results for study protocols, especially providing biostatistical expertise, computer programming, and project management to design protocols, develop statistical analysis plans, develop data management systems, manage study funds, monitor data integrity and study safety, and work with study investigators to analyze and publish study results, and comply with the NIH Data Management and Sharing Policy. The DCC is responsible for:

• Collaborating with study investigators in developing OBOE protocols and budgets.
• Supporting OBOE protocol design, training, implementation, and study monitoring. The DCC works with study investigators to design protocols, including developing statistical analysis plans, power analyses, and study budgets. As part of this, the DCC and the study team will review available NIH Common Data Elements (CDEs) and include them in studies, as appropriate, to ensure data harmonization with uniform collection of demographic, clinical, imaging, and biological data to the extent feasible. If relevant CDEs have not been developed, the DCC and study investigators may collaborate with NIH staff to develop them. In addition, the DCC may coordinate external services, including procuring study drugs, equipment, and other supplies, implementing masking and randomization methods, and executing subcontracts, such as for additional recruiting sites, vendor services for diagnostic tests, specimen analyses, etc., and consultancy agreements with outside experts.
• Coordinating closely with and/or managing the OBOE sIRB to obtain and maintain IRB approvals and continuing renewals for all studies and ensure all Recruiting Sites have appropriate reliance agreements in place.
• Providing data management, including developing protocol manuals and forms, programming data management systems, and preparing reports for the DSMB, the SC, OBOE subcommittees, CCs, and NICHD/NIH.
• Conducting statistical analyses of study data for interim monitoring, final results, and secondary data analyses, and collaborating with study investigators to publish results of OBOE studies in a timely and accurate manner.
• Managing study (“capitation”) funds, disbursing payments to CCs based on enrolled patients and other study milestone triggers specified in the study protocols and budgets. Working with NICHD Program Staff to develop a detailed financial reporting system, reporting at least quarterly and/or as needed on capitation budget expenditures and projections through the anticipated protocol end dates.
• Providing the Neuroimaging  expertise for the consortium, either directly or via subcontracts or other mechanisms, to help ensure standardization of neuroimaging data acquisition, monitor image acquisition, promote sharing among sites, review and assess images, and provide subject matter expertise for study result analyses for the OBOE studies.
• Managing consortium-wide reporting and data and specimen sharing requirements, including, but not limited to: submitting annual data to the NIH Human Subject System; creating and updating ClinicalTrials.gov records for OBOE studies, including reporting study results within required timelines; fulfilling NIH and HEAL Initiative Data Sharing requirements by preparing and submitting study data and documentation to NIH-approved data repositories; and submitting, or managing the submission of, remaining biospecimens to a NIH-approved specimen repository.
• Providing the logistical support necessary to run an efficient and productive consortium, including video/teleconference support, meeting facilitation, and taking meeting minutes. The DCC also creates and maintains a website that includes both public-facing pages about the consortium and its studies, and private/investigator-only pages to facilitate communication – to distribute study documents, track study enrollment and follow-up completion, etc.

As with the CCs, the DCC will be required to set up appropriate master agreements (memoranda of understanding, subcontracts, data use agreements, etc.) with each CC to enable transfer of earned capitation funds and study data for all OBOE protocols between the DCC and each CC.

The DCC will have the following categories of personnel:

• Principal Investigator
• Statisticians
• Research Coordinator
• Lead Neuroimaging investigator
• Programming staff
• Logistics and support staff

Additional details about the DCC can be found in RFA-HD-24-015 (U24)  - HEAL Initiative: Limited Competition: Data Coordinating Center for Completion of the Outcomes of Babies with Opioid Exposure (OBOE) Study (U24 Clinical Trial Optional).

EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT (NICHD)

NICHD provides funding to each CC and the DCC through Clinical Research Cooperative Agreements. NICHD uses this assistance mechanism when it anticipates its scientific and/or programmatic staff will need to have substantial involvement with the awardee(s) during performance of clinical research. The NICHD Program Staff will assist PIs in identifying research topics of high priority and designing and implementing protocols in the targeted research area.

The NICHD’s Office of Clinical Research (OCR) staff, Program Official, and Grants Management will be responsible for overall grant stewardship. The Program Official, or his/her/their designee, will serve as the NICHD representative on the consortium’s Scientific and Safety Monitoring Board (SSMB) in the manner delineated in the NICHD Data and Safety Monitoring Policy. A NICHD Project Scientist will be involved substantially with the awardees, serving as NICHD’s voting representative on the Steering Committee, and working with investigators to design and implement protocols and analyze results. A Clinical Trials Specialist or Program Analyst will work with the Program Official and Project Scientist to help coordinate consortium management. The NICHD’s OCR will work with the NICHD Program Staff to develop efficiencies, support grant stewardship, and provide policy guidance. OCR staff may attend SC and subcommittee/working group meetings as observers.

Independent of the governance above, the NICHD Director retains responsibility for all NICHD funded research. The NICHD Director receives the SSMB’s recommendations on whether studies should be continued or terminated and can make an independent decision on how to proceed. The NICHD Director can override the decisions of the Steering Committee when it is in the strategic interest of the NIH/NICHD, human subject protection, and/or dependent on funding availability.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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) 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• 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.
  • 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.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; 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 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 their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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.

Only the current Principal Investigators of the OBOE CCs are eligible to apply under this limited competition NOFO.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may not submit more than one application.  .

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. 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 NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

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 NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity 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:

Nahida Chakhtoura, MD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6872
Email: nahida.chakhtoura@nih.gov 
 

Page Limitations

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 NOFO.

SF424(R&R) Cover

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

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. The additional instructions apply:

Other Attachments

1. Protocol

Please provide a copy of the IRB-approved protocol as a pdf attachment using the filename “Attachment 1. OBOE Protocol”.

2. Available Population

Please provide a summary of the CC’s patient population as a pdf attachment using the filename “Attachment 2. Available Population”.

In the attachment, applicants must include:

• Inclusion Enrollment Report. A completed copy of the center’s inclusion enrollment report data showing a breakdown of the cumulative enrollment by race and ethnicity.
• Describe whether the CC and/or its satellite sites anticipate an increase or decrease in the of eligible study subjects for the upcoming calendar year (2024).

3. Clinical Research Experience

Please provide a summary of the CC’s clinical research experience as a pdf attachment using the filename “Attachment 3. Research Experience”.

Center Trials and Studies. Provide a table summarizing research productivity of completed studies at the CC and its satellite sites related to neonatal opioid withdrawal syndrome or neonatal abstinence syndrome. The following information must be included .  A table format is recommended:

• Column A: Study Title
• Column B: Brief Description
• Column C: Funding Source(s)
• Column D: Site Planned Average Monthly Enrollment
• Column E: Site Actual Average Monthly Enrollment

The attachment may include interventional trials, observational studies, biospecimen collection, and/or translational studies that highlight your institution’s clinical research experience in relation to the purpose and objectives of OBOE. Included studies do not need to have been completed (they can be ongoing) or have publications available. Applicants may include studies from fellows, but do not need to include every study. Select what is pertinent for highlighting institution/PI expertise that is relevant to the objective of the application.

Publications. Provide a bibliography of publications authored or coauthored by study team members related to neonatal opioid withdrawal syndrome or neonatal abstinence syndrome. The publication list should include any publications related to the studies listed in the “Center Trials and Studies” table and may also include other publications that show the applicant’s experience in clinical research, particularly related to the purpose and objectives of OBOE.

SF424(R&R) Senior/Key Person Profile

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

Principal Investigator(s)

Applicants must include a biosketch for a PI and Research Coordinator. Multi-PI applications are allowed. The biosketches should include a track record demonstrating successful implementation of neonatal clinical trials.

The PD/PI of each Clinical Center must be a practicing board certified, eligible, or otherwise qualified pediatrician and/or neonatologist and should describe his/her/their clinical, research, administrative, and academic commitments in the Biosketch. He/she should be able to devote the required time to the development, implementation, and management of the Consortium Clinical Center. For Centers that propose multiple sites, the PI must have the management experience to monitor and oversee study activities at non-contiguous sites, including those at other institutions. Clinical Centers with multiple recruiting sites should identify the investigator responsible at each site.

Research Coordinator(s)

A clinical research Nurse Coordinator for each Clinical Center (and sub-sites, if applicable) must be designated, with the biographical sketch included as part of the application. Applicants may include one or more clinical research coordinators, who have medical expertise and/or extensive clinical research experience conducting clinical trials in neonatal medicine. 

R&R Budget

All instructions in the SF424 (R&R) Application Guide must be followed. The additional instructions apply:

BASE BUDGET

Total funding for clinical centers will include a combination of the base awards and reimbursements for approved protocol-related expenses from the DCC. Each applicant should submit base budget estimates to cover support to complete OBOE study enrollment and all follow-up assessments. Level of effort for the personnel listed below may decrease each budget year as enrollment and then follow-up are completed.

• PD/PI
• Research Coordinator
• Data Entry
• Other costs (itemized and individually justified): Not to exceed $3000 per year
• Travel: Steering Committee meetings will be held in the Washington, DC metro area approximately two times per year. The PI or designee and Research Coordinator are required to attend the meetings in their entirety.

The level of effort for the various positions can be combined/split as needed as long as the required duties are covered at the proposed site(s). How duties are delineated or shared should be described in the Staffing and Management section of the Research Plan.

The clinical centers' F&A rates on the initial competitive awards will not be adjusted in future years due to changes in their negotiated rate agreements.

CAPITATION FUNDS

The DCC will be responsible for issuing payments to the CCs for protocol expenses. These funds can be used to support study implementation at the site(s), such as additional staff level of effort or other study expenses. To receive these study payments, each awarded institution must set up an agreement with the DCC.

Participating sites will be required to accept protocol budgets for those studies underway in the consortium. CC researchers are encouraged to assist in the development of protocol budgets. The protocol budgets will consist of specific protocol-related expenses, capitated per subject enrolled in each study. Capitation funds may include Center F&A rates for allowable line items.

The DCC may establish a recruitment limit. If a CC believes that it is able to exceed the limit, then it may request permission to do so from the DCC.

PEER NAVIGATORS

The continued inclusion of peer navigators through the end of the follow-up assessments is strongly encouraged, either through the Base Budget and/or via Capitation funds.

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:

Specific Aims:

The overall objective of the OBOE consortium is to complete enrollment and multimodal longitudinal assessments from birth to age 2 years of a diverse cohort of newborns either exposed or unexposed to opioids in utero. Applicants should describe the specific aims and hypotheses for the Longitudinal Study, and activities and goals of the Consortium for the performance period of this project.

The application should indicate that the clinical center will continue its current participation in OBOE study, including conducting participant follow-up. The application should NOT propose a new clinical trial or study.

Research Strategy:

INVESTIGATORS

Staffing. Applications should describe their proposed staff and that staff’s participation in the OBOE study to date in detail, including patient enrollment and particular contributions to the OBOE study, subcommittee activities including chairmanship(s), and publications and other academic productivity related to the purpose and objective of OBOE.

Management Plan. Applicants should describe their staff and staffing levels to cover all recruiting sites and a detailed plan for how to manage recruitment, study implementation, data collection, data entry, and data editing at those sites. Management plans should cover personnel supervision, training, in-service training, required certifications, data handling, quality assurance, cost effective management, and communication for the main clinical center and any non-contiguous recruiting sites.

INNOVATION

Special Strengths. Applicants are encouraged to describe special or unique strengths that may be relevant to OBOE research. This can include state-of-the art scientific capabilities such as imaging and assessment techniques as examples which may be shared or may be available to develop and expand the scientific productivity of the consortium.

Integration of research programs. If the applicant institution is also an NICHD Neonatal Research Network clinical center, the applicant must describe how the two research programs will be integrated.

APPROACH

Study Recruitment, and Follow-up. Applications should describe:

• Recruitment capabilities to enroll a large cohort of newborns eligible for the OBOE study – both those exposed and those non-exposed to opioids in utero. Eligibility and enrollment in previous clinical research studies should also be described. Applicants should also describe their  strategies  to  increase participant recruitment  and  enroll  a diverse  population .
• Neuroimaging strategies for successfully obtaining MRIs from the infants per the OBOE protocol (0-1 month, 6 months, and 24 months of age). Provide information about procedure(s), MRI technical details and capabilities, and use/non-use of sedation. Applicants should demonstrate that each recruiting site has a radiology service highly experienced in infant neuroimaging. Each facility must demonstrate minimum requirements for cranial magnetic resonance imaging:
  • T1-weighted structural acquisition
  • T2-weighted structural acquisition
  • Diffusion tensor acquisition (minimum of 60 directions)
  • Field strength of the MR scanners is required to be at least 3T;
  • Ability to conduct one (baseline) imaging session at entry into the study during the newborn hospitalization, and at least two repeat sessions prior to two years of age;
  • Demonstration of experience and success conducting brain-imaging research among study participants: newborns, infants, and toddlers;
  • A plan to accommodate changes in instrumentation in response to technological advances that will occur during the project.
• Follow-up Strategies. Ability to follow up infants in clinical trials and observational studies is critical. Describe the center’s strategies for ensuring compliance with neonatal follow-up up to 2-years of age: procedures for maintaining contact with families, scheduling appointments, actions taken for missed appointments, home visit appointments including staff participating in home visits, and creative measures instituted at the center to insure excellence in follow-up rates and compliance with clinical research study protocols. The follow-up portion of the clinical capabilities must include expertise in performing Bayley Developmental assessments, neurological examinations, and hearing and vision assessments. The current system of follow-up assessment including data collection, population demographics, compliance rates, schedule of follow-up visits, funding sources, policies and procedures for conducting research in the follow-up setting and appropriate specialist involvement in the follow-up program should be delineated in the application.

ENVIRONMENT

Clinical Capabilities. The clinical center should be located in an institution with a neonatal intensive care unit for care of high-risk neonates that admits and treats inborn and outborn infants with pharmacologic and non-pharmacologic interventions for opioid withdrawal. A Clinical Center may consist of a single institution and/or facility or may be comprised of multiple institutions and/or facilities working as a unit. They must have at least 40 admissions per year with NOWS. For each of its proposed recruiting sites, the applicant should describe its neonatal clinical and research capabilities, support staff, and neonatal follow-up capabilities and facilities. In addition, please describe any connections with community substance abuse programs and how these may enhance study recruitment and follow-up efforts.

Concurrent Research Activities. If the institution’s recruiting sites have ongoing or pending studies/trials that will limit availability of patients for the OBOE study, these must be described in the application. If there is to be a projected increase or decrease in subjects eligible for study, this should also be described in the application.

Letters of Support: 

Because this program requires a team effort across an Institution’s neonatal department to be successful, departmental and institutional commitments to participate in OBOE research should be clearly documented. Please provide letters of support from appropriate individuals detailing:

For the Clinical Center institution:

• Institutional support in grants management, personnel provision and management, space allocation, procurement, and equipment, as well as general support of the research. Evidence of past support can also be cited.
• Clearly expressed intent to:
• Participate in a cooperative manner with other consortium CCs, the data coordinating center, and NICHD staff in all aspects of research as outlined in this RFA;
• Cooperate with the policy for capitation of research costs as outlined in this RFA and the OBOE policy manual
• Comply with the NIH and HEAL Initiative Data Sharing requirements and the OBOE protocol, manual of operations, and policy manual regarding Data Management and Sharing Plan  (DMS Plan) ; and
• Keep confidential and do not disclose any confidential or proprietary information when working with the consortium other than to employees, agents, subcontractors, consultants, vendors, or affiliates who have a need to know that information.

For any satellite recruiting sites:

• If any satellite sites are included in this application, please provide similar Letters of Support from each such institution.

If the center or any satellite sites have Clinical and Translational Science Awards (CTSA):

• Provide a letter of agreement from the CTSA PI that identifies the level and type of support that will be provided for this grant, should it be awarded.

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.

Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

Plans for Sharing Human and Non-Human Biospecimens

For sharing biospecimens, the DCC is responsible for maintaining an inventory of biospecimens managed across the consortium and, upon NICHD approval, coordinating submission of any remaining biospecimens to an NIH-approved repository on behalf of the consortium.

For this NOFO, applicants must indicate in their institution’s (and any satellite site’s) Letter of Support their agreement to comply with the OBOE Data and Specimen Sharing Plans – including abiding by the negotiated Data Management and Sharing Plans for OBOE, the HEAL data sharing policy and DEC – and cooperate with consortium procedures needed to finalize and share study data per these Plans. All data collected as part of the NIH HEAL Initiative should be collected under a Certificate of Confidentiality and entitled to the protections thereof. Institutions who receive Data and/or Materials from this award for performance of activities under this award are required to use the Data and/or Materials only as outlined by the NIH HEAL Initiative, in a manner that is consistent with applicable state and federal laws and regulations, including any informed consent requirements and the terms of the institution’s NIH funding, including NOT-OD-17-109 and 42 U.S.C. 241(d). Failure to adhere to this criterion may result in enforcement actions.

Each Clinical Center and/or satellite recruiting site is responsible for ensuring that each study’s informed consent forms contain language allowing broad sharing and future use of study data and biospecimens in alignment with federal and local regulations and policies. Consent forms must notify participants that their data and, when relevant, imaging data and biospecimens (potentially for both maternal and child) may be shared with other consortium investigators, the study sponsor(s), applicable federal agencies, and, when relevant, industry partners. In addition, de-identified data, imaging data, and remaining biospecimens from each study may be shared with researchers outside of the consortium, including depositing them in NIH-approved public repositories. Clinical Centers and/or recruiting sites may also be required to obtain approval(s) from appropriate regulatory authorities (e.g., IRB) for sharing that data, particularly for studies conducted under a waiver of consent.

 All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.Plans for Sharing Human and Non-Human Data

The award recipients and their collaborators must comply with all NIH HEAL Initiative Data Sharing Policy (https://heal.nih.gov/data/public-access-data), in line with broader efforts across NIH, as outlined in the NIH Strategic Plan for Data Science. Research teams funded by the NIH HEAL Initiative®, must make their HEAL data Findable, Accessible, Interoperable, and Reusable (FAIR).

NIH Data Management and Sharing Policy expects the timely release and sharing of data to be no later than the time of an associated publication, or the end of the award/support period, whichever comes first. Per the Policy, all applications, regardless of the amount of direct costs requested for any one year, are required to include a Data Management and Sharing Plan (“the Plan”) outlining how scientific data and any accompanying metadata will be managed and shared, regardless of whether the data are used to support scholarly publication. The Plan should describe data types, file formats, submission timelines, standards used in collecting or processing the data and other elements described in Supplemental Information to the NIH Policy for Data Management and Sharing: Elements of an NIH Data Management and Sharing Plan (NOT-OD-21-014). The Plan will be subject to assessment and approval by NIH Program Staff prior to funding. Awardees are required to comply with the approved Plan and any approved updates to the Plan. The Plan should be included with the final protocol for IRB approval as well.

For sharing human and non-human data, unless stipulated otherwise the approved Plan, the DCC is responsible for preparing and submitting protocol datasets. These HEAL-specific requirements should be integrated into the data management and sharing plan and implemented during data generation for HEAL-funded projects:

• Select a HEAL compliant repository for long-term data storage (such as the NICHD Data and Specimen Sharing Hub).
• Register your HEAL study in the HEAL Data Platform.
• Submit metadata to the HEAL Data Platform.
• To the extent possible, HEAL awardees should use broad consent language.

All data collected as part of the NIH HEAL Initiative should be collected under a Certificate of Confidentiality and entitled to the protections thereof. Institutions who receive Data and/or Materials from this award for performance of activities under this award are required to use the Data and/or Materials only as outlined by the NIH HEAL Initiative, in a manner that is consistent with applicable state and federal laws and regulations, including any informed consent requirements and the terms of the institution’s NIH funding, including NOT-OD-17-109 and 42 U.S.C. 241(d). Failure to adhere to this criterion may result in enforcement actions.

For protocols that generate large-scale human genetic data, recruiting sites will have to provide a Provisional or Institutional Certification specifying whether the individual-level data can be shared through an NIH-approved repository, such as dbGaP, in line with the NIH Genomic Data Sharing Policy

 As part of the response to the national opioid public health crisis, NIH intends to maximize the availability of publications and the sharing of underlying data for NIH HEAL Initiative supported research projects. Award recipients are expected to cooperate and comply with all NIH data sharing developed for this public health emergency during the project period.

For this NOFO, applicants must indicate in their institution’s (and any satellite site’s) Letter of Support their agreement to comply with the OBOE Data and Specimen Sharing Plans – including abiding by the negotiated Data Management and Sharing Plans for OBOE, the HEAL data sharing policy and DEC – and cooperate with consortium procedures needed to finalize and share study data per these Plans.

Each Clinical Center and/or satellite recruiting site is responsible for ensuring that each study’s informed consent forms contain language allowing broad sharing and future use of study data and biospecimens in alignment with federal and local regulations and policies. Consent forms must notify participants that their data and, when relevant, imaging data and biospecimens (potentially for both maternal and child) may be shared with other consortium investigators, the study sponsor(s), applicable federal agencies, and, when relevant, industry partners. In addition, de-identified data, imaging data, and remaining biospecimens from each study may be shared with researchers outside of the consortium, including depositing them in NIH-approved public repositories. Clinical Centers and/or recruiting sites may also be required to obtain approval(s) from appropriate regulatory authorities (e.g., IRB) for sharing that data, particularly for studies conducted under a waiver of consent.

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

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

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.

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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 form. 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 NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier 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.

For this particular announcement, note the following:

The review of this application will emphasize the overall research environment, capabilities, and experience of the Applicant and its personnel. In addition to the review criteria below, the merit of the application will include how well the Applicant can carry out the OBOE study, with particular emphasis on the population available for research, recruitment, retention, and follow up, as well as collaboration with other members of the consortium.

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.

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.

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NICHD, in accordance with NIH peer review policies and practices, 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 will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Child Health and Human Development (NACHHD) Council. 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 2.4.4 Disposition of Applications.

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 recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. 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 NOFO 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: Recipient 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 recipient 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, Recipients, and Activities, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a term and condition of receiving the grant, to administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity. 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 https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/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 NOFO.

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/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.

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 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.”

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 (HHS) grant administration regulations at   2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

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

• Staffing
  • Obtaining prior written approval of the NICHD Grants Management Specialist, in consultation with the Program Official for any change in any of the key personnel identified in the Notice of Grant Award.
  • For multi-PI awards, designating a PI to be the voting representative on the Steering Committee.
• Protocol Development and Implementation
  • Providing input and subject matter expertise for study development, data analysis and interpretation, preparation of publications, and collaboration with other investigators. When working with other investigators, recipients will keep confidential and not disclose any confidential or proprietary information other than to employees, agents, subcontractors, consultants, vendors, or affiliates who have a need to know that information.
  • Participating in OBOE study(ies) at all recipient recruiting sites.
  • Meeting recruitment and follow-up targets. The individual recipients may be required to project patient enrollment; continuation and level of funding will be based on actual recruitment. For specific studies, recipients, either individually or collectively as a consortium, who do not accomplish negotiated milestones may be required to submit a milestone report which will discuss why the milestones were not met in the agreed upon timeframe and propose a corrective action plan. The corrective action plan shall include: amended milestones, plans to achieve the amended milestones, and any additional items required by NICHD Program staff. The plan must be approved and signed by the Institutional Officials and the PD(s)/PI(s) listed on the awards prior to submission.
  • Maintaining quality control measures to ensure protocol adherence and collection and transmission of accurate data within required timeframes to the data coordinating center.
• Protocol Results Reporting and Data and Specimen Sharing
  • Publishing, and/or assisting in the publishing and publicly disseminating study results, in accordance with OBOE and NIH policies, including publishing results on ClinicalTrials.gov and submitting study publications to the PubMed Central within the required timeframes.
  • Complying with OBOE data and specimen sharing plans, including ensuring the appropriate language is included in study informed consent forms, consistent with the approved Data Management and Sharing Plan (DMS Plan).
  • Acknowledging NIH funding support in all relevant publications and presentations of work performed under this agreement.
  • Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

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

NICHD’s Office of Clinical Research staff, a Program Official, and a Grants Manager will be responsible for overall grant stewardship. A NICHD Project Scientist will provide scientific input to the consortium. A Clinical Trials Specialist or Program Analyst will work with the Program Official and Project Scientist to help coordinate consortium management.

NICHD Office of Clinical Research

NICHD’s Office of Clinical Research will work with NICHD Program Staff to develop efficiencies, support consortium stewardship, and provide policy guidance. Staff from the NICHD Office of Clinical Research (OCR) may attend SC and subcommittee/working group meetings as observers.

NICHD Program Official

An agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the notice of award. In addition to general grant stewardship, a NICHD Program Official will:

• Monitor progress of study milestones to ensure that the objectives are being met and that all regulatory, fiscal, and administrative matters are handled according to NIH guidelines. Continuation of funding will be dependent upon the recipient's ability to show adequate progress towards milestone accomplishment.
• Conduct site visits, as needed, to review/on-board new sites and monitor study implementation at existing sites. In conjunction with the Grants Manager, the Program Official may withhold support of a recipient if technical performance requirements such as protocol compliance, enrollment targets, or randomization and/or follow-up of subjects are not met.
• Serve as the NICHD representative, or designate a NICHD representative, on the OBOE Scientific and Safety Monitoring Board (SSMB) in the manner delineated in the NICHD Data and Safety Monitoring Policy.
• Monitor consortium base budgets and study funding and developing annual budget projections for out-years with assistance from the NICHD Program Analyst/Clinical Trials Specialist.

NICHD Project Scientist

A NICHD Project Scientist will have substantial programmatic involvement that is above and beyond the typical stewardship role in other awards. As described below, the Project Scientist will:

• Serve as the NICHD’s voting representative on the Steering Committee and all subcommittees.
• Provide scientific/programmatic support and input for study design, implementation, results analysis, publication, study closeout, and development of solutions to major problems, such as insufficient participant enrollment. He/she/they will work with investigators, both within and outside the consortium, to design protocols, manage study implementation, and analyze and publish results.
• Assist in the development and review of study budgets, including the identification of capitation costs and special institutional needs.
• Have access to study data and may periodically review the data and administrative progress reports. For these purposes, any individual-level data should be de-identified, and data from ongoing trials should be blinded until it is time to analyze study results. Program staff may use information obtained from the data for the preparation of internal reports on the activities of the study.
• Oversee the adequacy of adverse event management and reporting.
• Monitor study progress, of each participating facility and of the consortium as a whole, through recipient's annual reports, study reports, site visits, screening logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting enrollment and participant follow-up targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting.

Director of the NICHD

NICHD reserves the right to terminate or curtail a study (or an individual award) under a range of scenarios including but not limited to: (a) failure to implement the study protocol; (b) a substantial shortfall in subject recruitment, follow-up, data reporting and dissemination, quality control, or other major breach of the protocol; (c) substantive changes in the agreed-upon protocol with which NIH does not concur; (d) reaching a major study objective substantially ahead of schedule with persuasive statistical evidence; (e) human subject safety or ethical issues that may dictate a premature termination; or (f) a change in the state of science that changes equipoise or has other significant impact on the relevance of the question under study. Studies in which recruitment and/or participant follow-up milestones are not met, or for which regulatory approval has not been met within one year, and are unlikely to improve sufficiently to bring the study to completion within an acceptable budget or timeframe, may be closed for lack of progress. If NIH or the recipient concludes that the study is no longer feasible, the consortium shall submit a close-out plan to NIH within 2 months.

Independent of the governance above, the NICHD Director retains responsibility for all NICHD-funded research. The NICHD Director receives the SSMB’s recommendations on whether OBOE studies should be continued or terminated and can make an independent decision on how to proceed. The NICHD Director can override the decisions of the Steering Committee when it is in the strategic interest of the NIH/NICHD, and/or due to considerations of human subjects protection, and/or based on  funding availability.

Areas of Joint Responsibility include:

• All parties will agree to accept the coordinating role of the group and the participatory and cooperative nature of the group process. As part of this, all parties will form a joint Steering Committee to govern the Consortium, consisting of:
  • One PI from each recipient Clinical Center (one vote per center)
  • Lead Neuroimaging investigator (voting member)
  • One PI from the recipient Data Coordinating Center (voting member)
  • NICHD Project Scientist (voting member)
  • Steering Committee chairperson  (tie-breaking vote only).
• The Steering Committee has primary responsibility for implementing the OBOE objectives, including:
  • Identifying areas of potential research
  • Overseeing the organization and execution of the study(ies)
  • Analyzing and publishing study results
  • Depositing results in ClinicalTrials.gov
  • Complying with NIH requirements for data and specimen sharing and software development, subject to Government rights of access consistent with the approved Data Management and Sharing Plan (DMS Plan) and  current HHS, PHS, and NIH policies, including for data and specimen sharing.
• As part of its governance responsibilities, the Steering Committee will develop a Policies and Procedures Manual that delineates the structure and function of the consortium, its standard operating procedures, and general rules (e.g., publication authorship). The NICHD Program Staff will help ensure that these policies follow NIH and other Federal guidelines and appropriately address the strategic interests and stewardship responsibilities of the NIH. The Steering Committee will vote on the overall Policies and Procedures Manual and any amendments; the NICHD Program Official will have approval authority for this Manual.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: 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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients 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. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients 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 the threshold.  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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 – Award Term and Condition 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.

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: https://www.era.nih.gov/need-help (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: 301-480-7075

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

Nahida Chakhtoura, MD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-402-7886
Email: nahida.chakhtoura@nih.gov

Beda Jean-Francois, Ph.D. 
National Center for Complementary & Integrative Health (NCCIH)
Phone: 202-313-2144
Email: beda.jean-francois@nih.gov

Joanna Kubler-Kielb, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6916
Email: kielbj@mail.nih.gov 

Saiyda Khan 
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-451-6260
Email: Saiyda.Khan@nih.gov 

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: debbie.chen@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.

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 and 2 CFR Part 200.