Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Funding Opportunity Title

HEAL Initiative: Antenatal Opioid Exposure Longitudinal Study Consortium (PL1 Clinical Trial Not Allowed)

Activity Code

PL1 Research Program Projects and Centers

An application under this funding announcement should be prepared by a consortium of a Data Coordinating Center (lead institution and contact PI for the application) and 2 or more Clinical Sites who will conduct a 2-year prospective longitudinal cohort study of newborns exposed to opioids in utero compared to a group of unexposed newborns.

The Clinical Sites will be disaggregated from the PL1 at the time of award, and each Clinical Site will have its own Program Director/Principal Investigator and its own RL1 award.  The Data Coordinating Center will continue as a PL1 Data Coordinating Center (DCC) with 2 cores: an Administrative Core and a Research Support Core.  The 2 cores should be at the same institution.

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-HD-19-025  

Companion Funding Opportunity

 None

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

93.865  

Funding Opportunity Purpose

The purpose of this funding opportunity announcement is to invite applications from consortia composed of a Data Coordinating Center and 2 or more Clinical Sites to conduct a multi-center prospective cohort study of infants exposed to opioids in utero compared to unexposed infants.  During a 2-year follow-up period, infants will be assessed with serial measures including neuroimaging, medical, neurodevelopmental, behavioral, and home, social, and family life assessments.  

Key Dates
Posted Date

December 10, 2018

Open Date (Earliest Submission Date)

February 28, 2019

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

March 29, 2019, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

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

AIDS Application Due Date(s)

March 29, 2019, by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on these dates.

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.

Scientific Merit Review

July 2019  

Advisory Council Review

August 2019  

Earliest Start Date

September 2019 

Expiration Date

March 30, 2019  

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Multi-Project (M) 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.


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

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

  3. Table of Contents

    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

    Part 2. Full Text of Announcement
    Section I. Funding Opportunity Description

    BACKGROUND

    Among infants covered by Medicaid in 46 states, from 2004 to 2014, the incidence of neonatal opioid withdrawal syndrome (NOWs) increased 5-fold from 2.8 cases per 1000 hospital births to 14.0 cases per 1000 hospital births.1 In 2014, 82% of births affected by NOWs were covered by Medicaid, at a cost of $462 million. The proportion of neonatal hospital costs due to NOWs increased from 1.6 to 6.7% between 2004 and 2014.  NOWs puts children at increased risk of adverse neurodevelopmental outcomes often complicated by family dysfunction. Infants who are exposed prenatally to opioids are a unique population with specific medical and social needs. Finding the best ways to interrupt these cycles for mothers, babies, and families during several critical periods--pregnancy, the newborn period, infancy, childhood, and adolescence--is crucial, yet solution-oriented research in these areas is lacking.  To begin to fill these knowledge gaps, the HEAL -supported Antenatal Opioid Exposure Longitudinal Study Consortium program (hereon referred to as the Longitudinal Study Consortium, the Consortium, or the Longitudinal Study, as appropriate) will consist of an observational cohort study 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. It is expected that the results of this observational study will point to targets for intervention trials to improve outcomes for these vulnerable infants.

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

    Overall Longitudinal Study Consortium Organization

    The Longitudinal Study Consortium will be funded as a consortium of a Data Coordinating Center (DCC) and 2 or more Clinical Sites, which together, in a single application, will put forward a common longitudinal study application under the PL1 funding mechanism.  The PL1 supports shared resources for categorical research by a number of investigators who focus on a common research problem.  Under the PL1 Research Program Project mechanism, the DCC will house 2 Cores:  an Administrative Core and a Research Support Core.  The collaborating Clinical Sites are organized to increase sample size, accelerate recruitment, and/or increase sample diversity and geographic representation.  Ideally, at least 150 in-utero opioid exposed infants are to be included with at least 50 unexposed infants to serve as controls.  The DCC may be housed at the same institution as one of the Clinical Sites or may be at a separate institution.  The Consortium will collaboratively develop the common protocol prior to application submission.  Awardees will work together as a Consortium to implement a multi-site observational, prospective cohort study with multi-modal assessments of children from birth to two years of age to better understand the consequences of in utero opioid exposure.  The goal of the program is to 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 appropriate care practices and treatments that would benefit exposed infants. 

    PL1 Activity Code

    The PL1 activity code is to support shared resources and facilities for categorical research by a number of investigators who focus on a common research problem.  In a single PL1 application for the Longitudinal Study program, a consortium of a DCC and at least 2 Clinical Sites with clinical resources sufficient to conduct a study of this size and complexity form a consortium and work together in the pre-application period to develop a single, shared protocol for the conduct of a multi-site longitudinal cohort study comparing outcomes as delineated below among children from birth to 2 years of age who were either exposed or not exposed to opioids in utero.  At the time of award, the PL1 components will be disaggregated, with each Clinical Site being funded through individual but linked research project grants (RL1). The RL1 mechanism supports a discrete, specified, circumscribed project; the grants are linked, and the project is to be performed by the named investigators acting as a consortium.  The DCC and its 2 component Cores will be funded as a PL1.  The PD/PI for the Research Support Core should be the PD/PI for the PL1 application responding to this announcement. If the PL1 is submitted as a multi-PD/PI application, the Research Support Core PD/PI should be the contact PD/PI.

    Key activities of the Longitudinal Study Consortium will be to:

    • Communicate effectively with other Consortium members and NIH staff to achieve the objectives of the Longitudinal Study.  The Data Coordinating Center and the Clinical Sites are expected to work together as a collaborative Consortium in preparing their application and after award.
    • Form and participate on a Steering Committee, composed of the PD/PIs from each of the Clinical Sites and the DCC, as well as a non-voting independent chair, charged with the conduct of the protocol and the preparation of publications. The Steering Committee chairperson should not be affiliated with any of the Consortium institutions.  Each full Steering Committee member will have one vote, and a simple majority rules. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.  The Steering Committee will meet within 3 months of award in the Metro DC area to finalize the common protocol, discuss potential common data elements with other HEAL studies, revise the statistical analysis plan and power analysis as needed, and establish the capitation budget.
    • Hold conference calls for the Consortium Steering Committee and essential team members at least monthly and travel domestically for face-to-face meetings held in the Bethesda, MD area at least semi-annually during the funding period.
    • Implement a single, shared protocol enrolling opioid-exposed and non-exposed newborns, following them over the course of 2 years, and collecting longitudinal assessments in multiple domains.
    • Plan how they will collaborate with personnel from other HEAL program studies to implement, for example, common data elements that will facilitate combining data from multiple executed protocols in the future.
    • Deposit all patient assessment data and all primary data at the DCC Research Support Core during the project period and make data available to the research community on or before completion of the award.

    The Data Coordinating Center (DCC) should plan to address the following items through the activities of the Administrative Core and the Research Support Core:

    • How the DCC will collaborate with the Clinical Sites and assist with protocol finalization, preparing study documentation (e.g., manuals and case report forms), training clinical staff in study procedures, coordinating and monitoring study implementation at the Clinical Sites, data collection, and data analysis resulting in publication this longitudinal cohort study.
    • A power analysis that will justify the proposed sample size and study outcomes of interest.  A statistical analysis plan is also required.
    • Evidence of data management and program support capabilities by describing standard operating procedures for data collection, management, analysis and quality control.
    • If the DCC is at the same institution as one of the Clinical Sites, describe the conditions and measures that ensure justifiable separation between the two and analytic independence.
    • Capability to provide recruitment-based capitation funds to the Clinical Sites as well as logistical support for meetings, teleconferences, and the Steering Committee.
    • Developing and maintaining a study website with both public and private features.
    • Plans to prepare final study data for deposition in a publicly accessible data repository, such as the NICHD Data and Specimen Hub (DASH).

    The Clinical Sites should plan to address the following items:

    • Applicants should describe how the Clinical Sites will collaborate with the DCC Cores and participate on the Steering Committee.
    • Each Clinical Site in the Longitudinal Study should describe its newborn source population and the prevalence of prenatal opioid exposure in newborns at the site.
    • A combined number of at least 200 infants including 150 opioid-exposed and 50 unexposed infants are needed in total from the participating clinical sites.
    • Applicants should consider partnering with existing groups or leveraging existing resources to achieve the goals of Longitudinal Study.  This could include Clinical and Translational Science Award (CTSA, https://ncats.nih.gov/ctsa) funded by NIH, or the National Center for Advancing Translational Sciences’ Trial Innovation Network (https://trialinnovationnetwork.org/), or other funded perinatal-neonatal research centers as resources for conducting the proposed research.
    • Key personnel at the Clinical Sites should participate in the development of the Longitudinal Study including the selection of content for the periodic assessments and their timing based on the scientific literature and/or from their own preliminary data.

    An NIH Program Official will:

    • Carry out continuous review of all activities to ensure that the objectives are being met and that all regulatory, fiscal, and administrative matters are handled according to NIH guidelines.
    • Perform other duties required for normal program stewardship of grants.
    • Monitor subject recruitment, retention, and dropout, and request and review procedures for adjustment if enrollment targets are not being met.
    • Monitor the acquisition of neuroimaging, clinical, and neuropsychological data and request and review procedures for remediation if a research site consistently lags in data acquisition benchmarks.
    • Attend site visits and Steering Committee meetings as needed to ensure that progress is being made and to verify the reliability and consistency of data collected across research sites.
    • Assure the scientific merit of the study, including the option to withhold support of a participating institution if technical performance requirements such as protocol compliance, enrollment targets, or retention of subjects are not met.
    • Initiate a decision to modify or terminate an award based on awardee performance.

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

    Section II. Award Information
    Funding Instrument

    Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

    Application Types Allowed

    New

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

    Clinical Trial?

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

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

     The following NIH components] intend to commit $11 million in multi-year funding in FY 2019 to fund 1 award to a consortium composed of a Data Coordinating Center (DCC) with 2 cores and 2 or more Clinical Sites. This is part of the NIH HEAL (Helping to End Addiction Long-term) initiative.

    At the time of award, the Clinical Sites will be disaggregated from the PL1, such that each individual Clinical Site in the consortium receives its own award (RL1), with each Clinical Site having its own PD/PI named on the award. The DCC comprising 2 cores will remain under the PL1.

    Award Budget

    Application budgets need to reflect the actual needs of the proposed project.

    For the Data Coordinating Center (Administrative Core + Research Support Core), the base budget is limited to $2 million ($500,000/year) in direct costs for the entire project period of up to 4 years. 

    Clinical Site applicants may request up to $500,000 ($125,000/year) in direct costs for the entire project period of up to 4 years. 

    The application should request protocol (capitation) costs, i.e., a flat fee for each participant who is successfully enrolled and who completes the longitudinal study.  The funds available for capitation will rely, in part, on the number of Clinical Sites included in the Consortium and the base budgets requested.  In general, capitation costs are not subject to facilities and administrative costs.

    Award Project Period

    The scope of the proposed project should determine the project period.  The maximum project period is 4 years. 

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

    Section III. Eligibility Information
    1. Eligible Applicants
    Eligible Organizations

    Higher Education Institutions

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

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

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

    Nonprofits Other Than Institutions of Higher Education

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

    For-Profit Organizations

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

    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
    Foreign Institutions

    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.

    Required Registrations

    Applicant Organizations

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

    • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
    • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
    • 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.

    Eligible Individuals (Program Director/Principal Investigator)

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

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

    The PD/PI for the PL1 application should be the PD/PI for the Research Support Core.  If the PL1 is submitted as a multi-PD/PI application, the Research Support Core PD/PI should be the Contact PD/PI.  This PD/PI must possess a doctoral degree in a relevant field such as statistics, biostatistics, or epidemiology.  The PD/PI must have multisite longitudinal study experience and expertise. 

    2. Cost Sharing

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

    3. Additional Information on Eligibility
    Number of Applications

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

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

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

    A single institution (normally identified by having a unique DUNS number or NIH IPF number) should contribute both Data Coordinating Center components but cannot also contribute more than 1 Clinical Site component to a single Consortium application.

    Section IV. Application and Submission Information
    1. Requesting an Application Package

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

    2. Content and Form of Application Submission

    It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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:

    Rosemary D. Higgins, MD
    Telephone: 301-435-7909
    Email: higginsr@mail.nih.gov  

    Page Limitations

    Available Component Types

    Research Strategy/Program Plan Page Limits

    Overall

    12

    Administrative Core

    12

    Research Support Core

    12

    Clinical Site (each)

    12

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

    Instructions for the Submission of Multi-Component Applications

    The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

    The application should consist of the following components:

    • Overall: required
    • Administrative Core: required; 1 minimum, 1 maximum
    • Research Support Core: required; 1 minimum, 1 maximum
    • Clinical Site: required; minimum of 2, maximum of 6
    Overall Component

    When preparing your application, use Component Type ‘Overall’.

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

    SF424 (R&R) Cover (Overall)

    Complete entire form.

    PHS 398 Cover Page Supplement  (Overall)

    Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

    Research & Related Other Project Information (Overall)

    Follow standard instructions. Other Attachments:  The filename provided for each attachment will be the name used for the bookmark in the application image.

    Consortium Organizational Structure. Applicants must include a diagram of the organizational structure of the Consortium. This diagram should demonstrate how the interactions among the Consortium components will achieve the stated goals of the Consortium. The diagram should be attached as a PDF titled "Consortium_Organizational_Structure".

    The PL1 application must include at least 2 Clinical Sites in addition to the 2 cores within the Data Coordinating Center.

    Project/Performance Site Location(s) (Overall)

    Enter primary site only.

    A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

    Research & Related Senior/Key Person Profile (Overall)

    Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

    The PD/PI for the Longitudinal Study Consortium should be the PD/PI for the Research Support Core.  If the PL1 is submitted as a multi-PD/PI application, the Research Support Core PD/PI should be the Contact PD/PI.  This PD/PI must possess a doctoral degree in a relevant field such as statistics, biostatistics, or epidemiology.  The PD/PI must have multisite longitudinal study experience and expertise.  Active participation of the PD/PI is expected during all phases of the Longitudinal Study.

    A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

    Budget (Overall)

    The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.  

    A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

    PHS 398 Research Plan (Overall)

    .

    Specific Aims: The overall programmatic goal of the Consortium is to implement the enrollment and multimodal longitudinal assessment 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. 

    Research Strategy:

    The Overall component of the application should primarily include the organization of the applicant Consortium and the proposed study design and protocol for the Longitudinal Study.

    Organization:  How the Consortium members interact, demonstrated or potential interdisciplinary collaborations, and how the Consortium as a whole is well suited to achieve the goals of the Longitudinal Study program are all important considerations.  Key roles and study governance structure should be described.  Plans for establishment of the Steering Committee and any anticipated subcommittees should be included.

    Longitudinal Study Design: The Consortium should propose a single Longitudinal Study protocol that meets the following minimum requirements:

    • A longitudinal cohort design to prospectively examine the neuroanatomical (via MRI neuroimaging), medical, neurodevelopmental, medical, behavioral, and home/social/family outcomes associated with prenatal opioid exposure from birth through 2 years of age.  Assessments, for example, of socioeconomic status, home environment and census, parental status, primary caregivers, participation in the foster care system, lifestyle factors and/or others
    • A data-collection schedule for recruitment of the proposed sample size of study participants both exposed and non-exposed to opioids in utero;
    • Capture of the timing, extent, and type of prenatal maternal opioid use and any use postpartum;
    • Longitudinal/prospective assessments with 3 or more time points over a 2-year period, with the potential for additional assessment beyond the initial 2-year period;
    • Detailed plans for ensuring high rates of recruitment and retention. Use of computer applications (APPs) is encouraged.

    The plan for Neuroimaging should describe the following:

    • It is expected that MRI imaging will be obtained in the newborn period and at least twice more by the age of 2 years. The proposed number and timing of assessments must be justified;
    • Applicants should make every effort to design the imaging protocol so that data from the Longitudinal Study can be easily combined with imaging data from other large-scale infant neuroanatomical studies to maximize scientific impact.

    The plan for Medical Condition assessment should describe:

    • The plan for a thorough newborn medical examination performed during the newborn hospitalization;
    • The proposed nature and extent of assessments and evaluations for medical conditions occurring from birth through 2 years of age;
    • Plans for medical record abstraction or standardization and utilization of information from electronic medical records;
    • Capture of medical diagnoses and treatments over time.

    The plan for Neurodevelopmental Assessments should include:

    • Clinical Sites must describe plans to conduct the Bayley III Scales of Infant and Toddler Development, including all five domains:  cognitive, language, motor, social-emotional, and adaptive behavior.
    • Clinical Sites must be capable of performing standard hearing and vision assessments and have expertise in performing complete neurological examinations.
    • Applicants must describe and justify plans for any additional neurodevelopmental assessments and the timeline for administration.
    • The willingness to discuss potential use of common data elements in this domain between this and other HEAL-related studies should be described.

    The plan for Behavioral Measures should describe the following:

    • A neuropsychological battery that is developmentally sensitive and that allows for the assessment of major neurobehavioral domains;
    • The proposed assessments and their timing of administration should be described and justified.
    • The willingness to discuss the potential use of common data elements in this domain between this and other HEAL-related studies should be described.

    The plan for assessment of home/social/family outcomes should describe:

    • Assessments, for example, of socioeconomic status, home environment and census, parental status, primary caregivers, participation in the foster care system, and/or others. 
    • The proposed assessments and their timing of administration should be described and justified.
    • The willingness to discuss the potential use of common data elements in this domain between this and other HEAL-related studies should be described.

    The Longitudinal Study description provided should contain sufficient detail that it closely approximates a study protocol.  To that end, the applicants should include, at a minimum, the following sections without duplicating information contained in the PHS Human Subjects and Clinical Trial form:

    • Brief Protocol Summary including a schedule of activities and graphical study timeline
    • Brief Background
    • Objectives
    • Key outcomes of interest and hypotheses
    • Study population and eligibility criteria
    • Strategies for screening, recruitment and retention
    • Study assessments and procedures, their timing, and justification
    • Safety and adverse event assessment and reporting
    • Sample size determination and power analysis
    • Statistical analysis plan
    • Data quality assurance and quality control
    • Ethical and study oversight considerations, including informed consent process, confidentiality and privacy, conflict of interest policy

    Letters of Support: Include letters of support if appropriate

    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:

    • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
    • A primary goal of the Longitudinal Study Consortium is to facilitate discoveries by the broad scientific community. Restrictive sharing practices could substantially diminish the data value and public benefit. Accordingly, awardees are expected to manage data, resources, protocols, and software in a way that achieves this goal. The development of policies, methods, and standards for data sharing is critically important. The NIH expects that the awardees will develop policies, methods, and standards in concert with the NIH. These policies, methods, and standards must remain consistent with the NIH-wide policies on data and resource sharing.  Applicants are encouraged to prospectively share study materials with other investigators to facilitate future studies of combined data.
    • Specific Plan for Data Sharing: the NIH expects that information such as collected data (e.g., clinical measures, brain images, patient reported outcomes, sensory testing) technical protocols, and any other data or metadata collected under this FOA will be deposited in a public access repository, such as the NICHD Data and Specimen Hub (DASH).  Applicants should identify potential repositories and describe plans for deposition. Applicants should describe plans for ensuring timely data sharing, such as how the data will be formatted initially to facilitate data sharing.  For data types that lack suitable public repositories, applicants should indicate their willingness to identify an appropriate alternative solution consistent with achieving the goals of the program.
    • Genomic Data Sharing Plan: if applicants propose to generate genomic data, they must indicate their willingness to abide by the NIH Genomic Data Sharing Policy and should indicate their agreement to it in the data sharing plan.

    Appendix:

    Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Overall)

    When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

    Study Record: PHS Human Subjects and Clinical Trials Information

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

    Because this study involves a common protocol across components (i.e., across the DCC cores and the individual sites), applicants should include the PHS Human Subjects and Clinical Trials Information form in the Overall component per the instructions above. There are also instructions in the SF424 about how to reference the PHS Human Subjects and Clinical Trials Information form in other components.

    The finalized protocol will require approval by NICHD.

    Section 2 - Study Population Characteristics

    2.7 Study Timeline

    The Longitudinal Study program is a 4-year effort.  The study timeline should list milestones that indicate progress at critical junctures of the longitudinal study.  The timeline and milestones should be concrete enough to evaluate what has been achieved during the course of the project.  Prior to award, NICHD staff will negotiate with the PD/PI(s) a final series of concrete milestones and associated dates for their achievement. In the event of lower than expected enrollment or poor retention of patients, the SSMC will make recommendations to the Steering Committee to either increase enrollment or terminate the study. NICHD Program staff must approve these plans prior to implementation.

    Section 3 - Protection and Monitoring Plans

    3.3 Data and Safety Monitoring Plan

    Scientific and Safety Monitoring Committee (SSMC) 

    In the Data and Safety Monitoring Plan, applicants must include the establishment of a Scientific and Safety Monitoring Committee, (SSMC), composed of subject matter experts who have no real or potential conflicts of interest with the Longitudinal Study program, and who report to the Steering Committee. The SSMC is charged with reviewing the finalized protocol, periodically evaluating study progress and results, reviewing any cumulative participant safety events, and recommending interim changes to the study, if necessary. The SSMC must include individuals with expertise in, at a minimum, longitudinal clinical research, biostatistics, epidemiology, pediatrics, neonatology, and developmental psychology. Additional members with other specific expertise may be proposed.  NICHD must approve the SSMC membership and plan.

    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 (Overall)

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

    Administrative Core

    When preparing your application, use Component Type ‘Administrative Core.’

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

    SF424 (R&R) Cover (Administrative Core)

    Complete only the following fields:

    • ·    Applicant Information
    • ·    Type of Applicant (optional)
    • ·    Descriptive Title of Applicant’s Project
    • ·    Proposed Project Start/Ending Dates
    PHS 398 Cover Page Supplement (Administrative Core)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Administrative Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Administrative Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Administrative Core)
    • ·    In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Core PD/PI and provide a valid eRA Commons ID in the Credential field.
    • ·    In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • ·    Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • ·    If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

    The PD/PI of the Administrative Core may also serve as the PD/PI of the Research Support Core.

    Budget (Administrative Core)

    Budget forms appropriate for the specific component will be included in the application package.

    Although the average Administrative Core PD/PI for a multi-site clinical study consortium will commit more time to consortium activities than the minimum, it is expected that the DCC Admin Core PD/PI will commit at least 1.8 person months effort to administration. 

    Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

    PHS 398 Research Plan (Administrative Core)

    Specific Aims:   Concisely describe how the Administrative Core in the Consortium will coordinate and manage the activities of the Consortium and coordinate the interaction among the components.   

    Research Strategy: The Administrative Core is expected to have a scientifically and administratively qualified Core PD/PI with responsibility for providing administrative and operational support to the Steering Committee and the Consortium.  The Core PD/PI should provide leadership, ensure interaction and collaboration among scientists and staff of the Consortium, and foster efficiency and synergies through effective organizational capabilities.

    The application should describe plans to accomplish the following required functions of the Administrative Core. 

    Administrative and organizational capabilities should include:

    • Establishing an organizational framework for the management, direction, and overall coordination of the multi-site study that effectively promotes communication among Consortium components.
    • Providing an internet-based communications system for Consortium members, including Clinical Site PD/PIs, Research Coordinators, Administrative and Research Support Core and other Consortium staff.
    • Providing logistical support for efficient day-to-day functioning of the Consortium.
    • Providing logistical arrangements for: support of Steering Committee meetings (at least semi-annually), Scientific and Safety Monitoring Committee (SSMC) meetings (1 per year in person; several by teleconference), as well as other selected meetings required for operations; assisting with formation and meetings of subcommittees (e.g., neuroimaging, recruitment and retention, as needed); organizing regular Steering Committee teleconferences (at least monthly).  This includes coordinating schedules, preparing and distributing agendas and meeting materials, providing conference call lines and/or web-based conferencing, and maintaining records as appropriate.
    • Documenting and disseminating minutes for meetings and conference calls.
    • Supporting electronic mail and communication lists for the Consortium, Steering Committee, SSMC, and any other groups within or affiliated with the Consortium.
    • Coordinating external services, e.g., executing subcontracts for consultancy agreements with outside experts.
    • Developing and maintaining a web site to publicize activities and to serve as a portal for investigators and key personnel to submit, access, and retrieve important study documents. The website should have public and private access links available.
    • Efficiently and accurately managing Clinical Site capitation.

    Letters of Support: 

    • The departmental and institutional commitments to participate in this research study should be clearly documented with letters of support from appropriate individuals. Evidence of past support can also be cited. Support in areas of grants management, personnel provision and management, space allocation, procurement, equipment, as well as general support of the research should be described as well as evidence of past research support.
    • Applications from institutions that have a Clinical and Translational Science Award (CTSA) funded by NIH, plans to access a National Center for Advancing Translational Sciences’ Trial Innovation Network (https://trialinnovationnetwork.org/), or other funded perinatal-neonatal research centers as resources for conducting the proposed research should provide a letter of agreement that identifies the level and type of support from the CTSA program director, NCATS TIC director, or PD/PI of the perinatal-neonatal research resource center.

    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:  The Data and Resource Sharing Plan for the Consortium as a whole should be described in the Overall component and should NOT be repeated here.

    Appendix:

    Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Administrative Core)

    When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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 a 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, with the following additional instructions:

    Note that the PHS Human Subjects and Clinical Trials Information form should be included in the Overall component and should NOT be repeated here.  Follow the SF424 instructions for how to indicate in this component where the human subjects study information is located.

    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.

    Research Support Core

    When preparing your application, use Component Type ‘Research Support Core’

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

    SF424 (R&R) Cover (Research Support Core)

    Complete only the following fields:

    • ·    Applicant Information
    • ·    Type of Applicant (optional)
    • ·    Descriptive Title of Applicant’s Project
    • ·    Proposed Project Start/Ending Dates
    PHS 398 Cover Page Supplement (Research Support Core)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Research Support Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Research Support Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Research Support Core)
    • ·    In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Core PD/PI’ and provide a valid eRA Commons ID in the Credential field.
    • ·    In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • ·    Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • ·    If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used. 

    The Research Support Core PD/PI should be the PD/PI for the PL1 application. 

    The following personnel are integral to ensuring successful operation of the Research Support Core:   

    • PD/PI with doctoral training in a relevant field, such as statistics, biostatistics, or epidemiology, and multisite longitudinal study experience and expertise.  The PD/PI of the DCC Research Support Core may also serve as the PD/PI of the DCC Administrative Core. 
    • Because of the importance of the Research Support Core functions, one of the Senior/Key Persons must be designated in the application to direct the Core in the absence of the PD/PI.  This individual must possess a doctoral degree in a relevant field, such as statistics, biostatistics, or epidemiology.
    • Statisticians
    • Coordinators or Research Project Assistants
    • Programming and analytic staff (including supervisory staff and software expertise staff)
    • Data processing staff
    • Logistics and support staff
    Budget (Research Support Core)

    Budget forms appropriate for the specific component will be included in the application package.

    It is expected that the Core PD/PI will make a substantial commitment of time and effort to the Core and Consortium, at least 2.4 person months effort to administrative and research support-related activities directly provided by the Core.

    Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

    PHS 398 Research Plan (Research Support Core)

    Specific Aims:  

    Concisely describe how the Research Support Core will provide services to the Consortium to successfully meet the goals of the Longitudinal Study program.  

    Research Strategy:    

    Without duplicating information in the biosketches, describe the qualifications and experience of the Research Support Core PD/PI and staff in providing scientific leadership, overall management, and oversight and assessment of the research activities of the consortium, including the Clinical Sites.  Provide evidence of appropriate and capable leadership and expertise in biostatistics, study design, data management, data analysis, and project management. These activities should include, but are not limited to, protocol implementation and monitoring, Clinical Site staff training, and quality assurance procedures.

    Evidence of Successful Past Performance:

    • Applicants must describe the activities of their team as a whole, via demonstration of performance as a data coordinating center for a large multi-site longitudinal clinical research project under any support in the past 10 years.
    • Applicants must document research productivity in previous or ongoing clinical trials or longitudinal observational studies, especially those with focus on neonatal health and infant follow up.
    • Contributions in key areas of research development and design, protocol implementation, recruitment monitoring, data collection and analysis, monitoring of trial progress, statistical analysis and interpretation, track record of publications, and timely provision and sharing of de-identified data sets should be provided.
    • Applicants should explain how the team has fostered synergy and maintained it through the course of past projects.

    Research Project Support Capabilities:      

    • Training and technical expertise of the entire team and how the team will work together should be described.
    • The applicant should describe plans to ensure that the Clinical Sites fully comply with NIH policy requirements, including single Institutional Review Board submissions and queries, Human Subjects Protections, issues of informed consent, reporting of adverse events, and human welfare provisions. 
    • Establishing a plan for utilizing a single IRB for the Longitudinal Study without duplicating information provided in the PHS Human Subjects and Clinical Trials form (section 3.2).  Collecting and retaining all single Institutional Review Board (IRB) and related reports and communications.
    • Knowledge of federal patient-privacy and data confidentiality requirements and appropriate experience in ensuring that relevant mechanisms and procedures are in place must be provided in the application. 
    • Applicants should describe plans for production and maintenance of study documentation, such as the final study protocol and any revisions, case report forms, Manual of Procedures, consent form templates, training manuals, and other documents for study implementation.  Applicants should also describe plans for sharing documents prospectively with other investigators in order to facilitate possible combining of data for future analyses.
    • Applicants should describe capabilities for establishing protocol training procedures, organizing and conducting multisite study initiation education, and plans to train study staff for protocol implementation, and ensure certification of staff performing neuroimaging, neuropsychological, clinical, and other phenotypic assessments.  In particular, the application should describe how the Research Support Core will work with Clinical Sites to ensure standardization of neuroimaging data acquisition, monitor image acquisition, and promote sharing among sites. Because the neuroimaging field undergoes rapid technical advances, the Research Support Core will need to plan for integrating technological advances into the longitudinal study and determine how changes in hardware and analytic approaches will be coordinated across multiple research sites.
    • Training sessions during protocol implementation, e.g., yearly certifications for participant assessments (e.g., developmental tests, standardized physician examinations, follow up), and data entry are also expected to be arranged through the Research Support Core.
    • Describe plans for data collection systems, electronic technology, data entry systems, and data quality assurance.  Use informatics and electronic data technologies to design and produce data collection systems and modify and redesign such systems as appropriate for the Longitudinal Study protocol. Data collection systems should comply with international standards for interoperability such as those developed by the Clinical Data Interchange Standards Consortium (www.cdisc.org (http://www.cdisc.org)). When feasible, Common Data Elements as defined by the NIH should be used. For examples and resources, see the NIH Common Data Element Portal at http://www.nlm.nih.gov/cde/ (http://www.nlm.nih.gov/cde/). Data collected is expected to be
    • collected in such a manner to make it readily interoperable and readily integrated with other systems including relevant data repositories for data sharing as appropriate and consistent with achieving the goals of the program.
    • The applicant must describe methods used in developing and maintaining data control and transmission systems.  Applicants should provide evidence of data management and program support capabilities by describing their standard operating procedures to include data collection, management, analysis, data security, data sharing, privacy protections, and quality control.
    • Monitor performance metrics, milestones, timelines, and quality-control measures and provide for a detailed system for regular tracking and reporting of study progress, participant recruitment, retention, and dropout, and develop procedures for adjustment if enrollment targets are not being met; this system must also include strategies to identify and mitigate problems as they arise;
    • Provide for mechanisms to monitor study data acquisition and transfer as described in the study protocol, and describe procedures for remediation if a research site consistently lags in data acquisition and/or transfer benchmarks;
    • Develop a quality assurance and quality control program to ensure high quality and timely data collection and delivery and maintenance of data integrity. The applicant should describe plans for  attending to data errors, needed edits, and protocol deviations.
    • Describe plans for organizing and conducting both on-site and off-site monitoring for quality control of research methods, collected research data, including timeliness and completeness, to ensure integrity in research conduct and adherence to the Longitudinal Study protocol across sites.
    • Describe plans to generate periodic reports on subject enrollment, including NIH Inclusion Tracking for studies, real-time reports on enrollment, reports on clinical center performance, adverse events, serious adverse events, protocol deviations, resource allocation, appropriate reports for use by the Science and Safety Monitoring Committee, and other reports such as newsletters and monthly updates as needed.
    • Provide leadership and expertise in biostatistical methods, collaborate in data analysis and interpretation of longitudinal data.
    • The applicant must describe examples of collaborative team efforts in assisting clinical investigators in the preparation of manuscripts on multicenter research for publication, including rapid turnaround of abstracts for national and international meetings.
    • Develop policies for presentation (e.g., at scientific conferences) and publication of findings in peer-reviewed journals from the Consortium’s research activities;
    • Describe explicit plans, procedures, milestones, and timelines for adherence to the existing terms and conditions concerning federal, Agency and NICHD policies concerning research data sharing. The applicant must describe protocols and processes for de-identifying research data and preparing and submitting datasets including neuroimaging data for archival in publicly available websites (e.g., the NICHD Data and Specimen Hub, DASH).  Plans for timely creation of public use datasets and providing relevant data dictionaries according to NIH requirements are also required. The timeline should be as aggressive as possible to permit prompt access without compromising data quality, confidentiality, and security. 

    Letters of Support: 

    • Letters of support should be provided that clearly express intent to participate in a cooperative manner with other Consortium components, the Steering Committee, and the SSMC in all aspects of the research as outlined in this FOA.
    • The departmental and institutional commitments to participate in this research study should be clearly documented with letters of support from appropriate individuals. Evidence of past support can also be cited. Support in areas of grants management, personnel provision and management, space allocation, procurement, equipment, as well as general support of the research should be described as well as evidence of past research support.
    • Applications from institutions that have a Clinical and Translational Science Award (CTSA) funded by NIH, plans to access a National Center for Advancing Translational Sciences’ Trial Innovation Network (https://trialinnovationnetwork.org/), or other funded perinatal-neonatal research centers as resources for conducting the proposed research should provide a letter of agreement that identifies the level and type of support from the CTSA program director, NCATS Trial Innovation network (TIN) director, or PD/PI of the perinatal-neonatal research resource.

    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:  The Data and Resource Sharing Plan for the Consortium as a whole should be described in the Overall component and should not be repeated here.

    Appendix:

    Only limited items are allowed in the Appendix.  Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Research Support Core )

    When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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 a 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, with the following additional instructions:  

    Note that the PHS Human Subjects and Clinical Trials Information form should be included in the Overall component and should NOT be repeated here.  Follow the SF424 instructions for how to indicate in this component where the human subjects study information is located.

    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.

    Clinical Site

    When preparing your application, use Component Type ‘Clinical Site.’  Each Clinical Site should submit its SF424 (R&R) section individually as a separate component of the Consortium.

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

    SF424 (R&R) Cover (Clinical Site)

    Complete only the following fields:

    • ·    Applicant Information
    • ·    Type of Applicant (optional)
    • ·    Descriptive Title of Applicant’s Project
    • ·    Proposed Project Start/Ending Dates
    PHS 398 Cover Page Supplement (Clinical Site)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Clinical Site)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Clinical Site)

    List all performance sites that apply to the specific component.

    Document neuroimaging and infant follow up capabilities as required below.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Clinical Site)

    ASSIST will default to “Project Lead”. If you would like to use a different category, then replace “Project Lead” below with a different Category (e.g., Core Lead).

    • ·    In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
    • ·    In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • ·    Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • ·    If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   

    The PD/PI of each Clinical Site in the Consortium must be a practicing board certified, eligible or otherwise qualified pediatrician and/or neonatologist and should describe his/her 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 Site.

    One clinical research Nurse Coordinator for each Clinical Site (and subsites, if applicable) must be designated, with the biographical sketch included as part of the application.

    Clinical Sites with multiple subsites should identify the investigator responsible at each collaborating site(s).

    Budget (Clinical Site)

    Budget forms appropriate for the specific component will be included in the application package.

    Each Clinical Site should submit base budget estimates for all years. The budget at the time of application will be limited to a BASE BUDGET with maximum allowances as follows:

    • PD/PI: 1.2 person-months (10 percent) effort per year
    • Nurse Coordinator (1 per site/subsite): 6 person-months (50 percent) effort per year
    • Data Entry Clerk: 3 person-months (25 percent) effort per year
    • Supplies and small equipment (itemized and justified): Not to exceed $5000 per year
    • Travel: A total of at least 8 trips to the DC Metro area per Consortium Clinical Site team, as appropriate. Steering Committee meetings are held in the Washington, DC Metro area at least 2 times per year. The Clinical Site PD/PI or designee and Nurse Coordinator are required to attend the meetings in their entirety.
    • Other costs (itemized and individually justified): Not to exceed $3000 per year

    Total funding for Clinical Sites depends on the base awards and reimbursements for approved protocol -related expenses (capitation payments) from the DCC Administrative Core.

    Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

    PHS 398 Research Plan (Clinical Site)

    Specific Aims:  Briefly describe how the Clinical Site as a whole will contribute to the successful conduct and completion of the Longitudinal Study. 

    Research Strategy: A Clinical Site may consist of a single institution and/or facility or may be comprised of multiple institutions and/or facilities working as a unit.  Management plans including supervision, training, in-service, certification, data handling, quality assurance, cost effective management, and communication are required for Clinical Sites with > 1 institution and/or facility.

    Population Available for Enrollment

    Without duplicating information provided in the PHS Human Subjects and Clinical Trials form, applicants must demonstrate the ability to enroll a large cohort of newborns both exposed and non-exposed to opioids in utero.  Eligibility and enrollment in previous clinical research studies should also be described. Large eligible populations with low study enrollment numbers in the past are considered less favorably than smaller populations with higher enrollment rates.

    Every recruitment facility included in a Clinical Site must be at a center that admits and treats inborn and outborn infants with pharmacologic and non-pharmacologic interventions for opioid withdrawal.  The application must contain information describing the available population for the study as well as a willingness to enroll eligible patients. 

    • Applicant Clinical Sites should be located in an institution with a neonatal intensive care unit for care of high-risk neonates.
    • Applicant recruitment clinical centers must have at least 40 admissions per year with neonatal opioid withdrawal.
    • In order to provide peer reviewers with the specific neonatal population available for study at the Clinical Site(s), include information regarding admissions over the last one-year period (2017) in tabular format:
    • ·    Number of births
    • ·    Number of neonatal admissions with any maternal opioid exposure
    • ·    Number of neonatal admissions with only maternal opioid exposure (i.e., no other substance(s))
    • ·    Number of infants that are treated for opioid withdrawal
    • ·    Number of infants treated with non-pharmacologic care (indicate type of care)
    • ·    Number of infants treated with pharmacologic care (indicate specific medications and number of infants for each medication as well as number of infants treated with multiple medications)
    • ·    Average length of stay for infants with opioid withdrawal (include median, 25th and 75th quartiles)
    • ·    For Clinical Sites including more than one institution/facility, please include each site's information in a separate section or column of the table. Large perinatal sites are ideal and may be given preference over institutions with multi-site arrangements.
    • Clinical Sites comprised of multiple institutions and/or facilities with a long-standing, well-documented collaboration and interaction together should clearly state so in the application.
    • Institutions with pediatric and neonatology staff at different locations must provide evidence of collaboration on recent clinical research studies.
    • If there are ongoing or pending studies that will limit the availability of patients for the Longitudinal 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 be described in the application.

    Neuroimaging Capabilities

    MRI facilities – all facilities included in a Clinical Site should describe procedures for research MRI for infants and toddlers through the age of two at their institutions.  Provide information about procedure(s), MRI technical details and capabilities, and use/non-use of sedation.

    • Applicants should demonstrate that every facility in each Clinical Site included in the Consortium has a radiology service highly experienced in infant neuroimaging.
    • Each facility in every Clinical Site 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.

    Infant follow-up and outcome assessments

    • Without duplicating information in the PHS Human Subjects and Clinical Trials form, the application should include a description of neonatal follow-up capabilities for the Clinical Site.  At least one designated facility for follow up with experience in tracking and retaining patients must already be in place at the Clinical Site(s).  A minimum of 80 percent follow-up rate at 2 years of age is required.  Demonstration of a history of successful (90% or more) participant retention and birth to 2-year follow-up and outcome assessment is highly desirable.
    • Applicants must report the number of clinic visits in 2017 as well as each Clinical Site’s criteria for follow-up (e.g. substance or opioid-exposed, low birth weight, extremely low birth weight, neurological issue, extracorporeal membrane oxygenation, etc.) and post conceptual age at which the children are seen in clinic visits in the application.
    • Applicants should describe in detail the mechanisms in place to insure compliance and assistance with neonatal follow-up including procedures for identifying infants for follow-up while in the nursery, maintaining contact with families, scheduling appointments, actions taken for missed appointments, number of  home visit appointments (including staff participating in home visits), assisting with participant and caregiver transportation, and other creative measures instituted at the site to ensure excellence in follow-up rates and compliance with clinical research study protocols.
    • Applicants must demonstrate that the follow-up portion of the clinical capabilities includes expertise in performing Bayley III Developmental assessments, complete neurological examinations, thorough medical evaluations, hearing and vision assessments, behavioral assessments, and measures of home, social and familial outcomes.
    • The current system of follow-up assessment for infants with neonatal opioid withdrawal 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.    

    Clinical Site Staffing

    • The application should describe the respective roles of staff and a management plan for how staff interact with other individuals listed under Senior/Key Persons.
    • Plans for availability for staff to recruit participants should be included in the application. If an institution includes multiple, non-contiguous sites, then applicants should include appropriate staffing levels to cover all subsites and include a detailed plan for how to manage recruitment, study implementation, data collection, data entry, and data editing among the subsites.

    Institutional Collaboration

    • Evidence of research productivity by the individual Clinical Sites in the Consortium in previous or ongoing clinical studies, especially those of a multicenter design, should be provided. Contributions in key areas of patient recruitment, retention and study completion, data collection and analysis, and track record of publications should be included in the application
    • Demonstration of experience and success conducting longitudinal research (without duplicating the biosketches) should be included in the application, including a track history depicting high rates of recruitment and retention over the short- and long-term;
    • There must be a clearly expressed intent to participate with other selected Clinical Sites and the Data Coordinating Center in all aspects of research as outlined in this FOA. A history of collaboration on previous multi-site clinical research studies is highly preferred. Past performance in any previous multisite studies should be described.

    Academic Productivity

    • Provide evidence of research productivity by the Clinical Site in previous or ongoing clinical studies and trials, especially those of a multicenter longitudinal cohort design. Contributions in key areas of research development and design, patient recruitment, retention and study completion, data collection and analysis, and track record of publications should be included in the application.

    Letters of Support: 

    • The departmental and institutional commitments to participate in this research study should be clearly documented with letters of support from appropriate individuals. Evidence of past support can also be cited. Support in areas of grants management, personnel provision and management, space allocation, procurement, equipment, as well as general support of the research should be described as well as evidence of past research support.
    • There must be a clearly expressed intent to participate in a cooperative manner with other components of the Longitudinal Study Consortium in all aspects of research as outlined in this FOA.
    • Applications from institutions that have a Clinical and Translational Science Award (CTSA) funded by NIH, plans to access a National Center for Advancing Translational Sciences’ Trial Innovation Network (https://trialinnovationnetwork.org/), or other funded perinatal-neonatal research centers as resources for conducting the proposed research should provide a letter of agreement that identifies the level and type of support from the CTSA program director, NCATS TIC director, or PD/PI.
    • A letter of assurance of cooperation with the policy for capitation of research costs as outlined below should be provided from the departmental and institutional offices of sponsored research programs.  Clinical Site institutions should demonstrate understanding and acceptance of the following:
    • ·    The Data Coordinating Center (DCC) Administrative Core will be responsible for issuing payments for the protocol expenses including a per-patient capitation. These funds can be used to fund staff positions listed above as well as other research staff and expenses.  To receive reimbursements, a funded Clinical Site must set up an agreement with the DCC Administrative Core. 
    • ·    Capitation funds can be utilized to fund key personnel. 
    • ·    The Clinical Site PD/PI or designee will be required to help the DCC Administrative Core manage protocol costs.  The PD/PI or designee should propose estimates of recruitment efforts for the protocol to the DCC Administrative Core and update these at least annually. 
    • ·    The DCC Administrative Core may establish a recruitment limit.  If a Clinical Site investigator believes that their site(s) is able to exceed the limit, then permission to do so must be obtained from the DCC Administrative Core. 
    • ·    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.   

    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:  The Data and Resource Sharing Plan for the Consortium as a whole should be described in the Overall component and should not be repeated here.

    Appendix:

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

    PHS Human Subjects and Clinical Trials Information (Clinical Site )

    When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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 a 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, with the following additional instructions:

    Note that the PHS Human Subjects and Clinical Trials Information form should be included in the Overall component and should NOT be repeated here.  Follow the SF424 instructions for how to indicate in this component where the human subjects study information is located.

    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.

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

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

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

    5. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    6. Funding Restrictions

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

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

    7. Other Submission Requirements and Information

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

    For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

    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) and component Project Leads 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.

    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 (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

    See more tips for avoiding common errors.

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

    Post Submission Materials

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

    Section V. Application Review Information
    1. Criteria

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

    Overall Impact - Overall

    Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Longitudinal Study Consortium 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 Longitudinal Study proposed).

    Scored Review Criteria - Overall

    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 Consortium that by its nature is not innovative may be essential to advance a field.

    Significance

    Does the Consortium 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 Consortium 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? 

    How well does each individual component fit in and contribute to the overall Consortium?  

    Is the Consortium as proposed likely to successfully complete a rigorous observational cohort study comparing outcomes at 2 years of age between neonates who were exposed to opioids in utero and those who were not exposed?

    Investigator(s)

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Consortium? 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?

    Do the Consortium PDs/PIs have the ability to contribute to the Consortium as documented by scientific achievements, productivity, stature in their field, and planned activities?  Do the key personnel have the knowledge and experience in areas relevant to the conduct of collaborative clinical research, especially multisite longitudinal cohort studies, including experience in research design, particularly in neonatal medicine?  Is there adequate commitment of time and effort for the research and administrative functions of the Consortium?  As a group, are the investigators well-suited to the project?  Is there evidence of multidisciplinary backgrounds and interests?  Does the application demonstrate the commitment, availability, and flexibility of staff time for the satisfactory conduct of the Longitudinal Study?

    Innovation

    Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

    Does the Consortium use innovative ways to communicate, to allocate resources, to promote collaborations, to recruit and retain research participants, or other research activities?  

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Consortium and the proposed longitudinal study? Have 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 Consortium 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?

    • Does the application clearly demonstrate, in a diagram, the feasibility of the organizational structure?  Does the organizational structure have clear lines of authority that allow for efficient implementation of the Longitudinal Study?
    • Is the plan for use of a single Institutional Review Board (sIRB) adequate?
    • Is it likely that the Consortium, as described, has the ability to recruit, retain and follow up infants to two years of age in a longitudinal cohort study?
    • Are the overall strategy, operational plan, study design, schedule of assessments, sample size and power analysis well-reasoned and appropriate to accomplish the goals of the research Consortium?
    • Are the individual components well integrated into the Consortium?
    • Is appropriate administrative organization proposed for establishing and maintaining communication and cooperation between the Consortium investigators?
    • Is there a well-developed and justified system for administration and disbursal of capitation funds?
    • Is there an adequate plan for establishment of the Steering Committee, selection of an independent Chair, development of Steering Committee Standard Operating Procedures, and selection and implementation plan for the SSMC?
    • Does the Consortium research team have the institutional support and capabilities, including the patient population, to participate fully in a collaborative effort?
    • Are there appropriate administrative, clinical, and data organizational management facilities?
    • Are there arrangements for internal quality control of research conduct and publications? 
    • Are an appropriate plan for work-flow and a well-established timeline proposed?

    Does the application clearly demonstrate the willingness of each Consortium component to work and cooperate with the others to achieve the project's goals?

    Environment

    Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? 

    • Do past experience and productivity indicate likely future successful implementation of the Longitudinal Study?  Will the institutional environment in which the Consortium will operate contribute to the probability of success in facilitating the research it serves?
    • Are there appropriate and adequate facilities for administrative, management, statistical, and clinical activity as well as fiscal administration, personnel management, space allocation, procurement, planning, and budgeting that assure necessary functions of the Consortium can occur?
    • Is there adequate institutional support; for example, letters of support, space and resources to be allocated from the applicant institution(s), substantial commitment to the Consortium and appreciation of its goals and role in public health?
    • Does the environment provide adequate high-quality data analytic capacity, database facilities, coordination, and data resources?
    • Are the institutional support, equipment and other physical resources available to the investigators adequate for the Longitudinal Study proposed?
    • Will the Consortium benefit from unique features of the institutional environment, infrastructure, or personnel?
    • Is there institutional assurance to provide support to the study in such areas as fiscal administration, personnel management, procurement, planning, and budgeting?
    • Does the application demonstrate optional administrative strengths, such as affiliations with other research units?
    Additional Review Criteria - Overall

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

    Protections for Human Subjects

    For research that involves human subjects but does not involve one of the 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 Consortium involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed.  For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

    Vertebrate Animals

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

    Biohazards

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

    Resubmissions

    Not Applicable

    Renewals

    Not Applicable

    Revisions

    Not Applicable

    Additional Review Considerations - Overall

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

    Applications from Foreign Organizations

    Not Applicable

    Select Agent Research

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

    Resource Sharing Plans

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

    Authentication of Key Biological and/or Chemical Resources

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

    Budget and Period of Support

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

    Scored Review Criteria – Administrative Core

    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 Core that by its nature is not innovative may be essential to advance a field.

    Significance

    Does the Core 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 Core 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?

    • Does the proposed Core address the needs of the research that it will coordinate, administer, and serve?
    • Is the scope of activities proposed for the Core appropriate to meet those needs?
    • Will successful completion of the aims bring unique advantages or capabilities to the research conducted by the consortium?

    Investigator

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Core and to the Consortium? 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/P , do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the Core and Consortium?

    • Do the PD(s)/PI(s) and other personnel have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in coordinating and managing multisite longitudinal research, especially in neonates, either as an independent Core, or as part of an individual Data Coordinating Center?
    • Does the applicant provide examples of overseeing and managing sub awards, if needed?

    Innovation

    Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

    • Does the application propose novel management or administrative strategies in coordinating the research Consortium the Core will serve?
    • Are the concepts, strategies, or processes novel to one type of research program or applicable in a broad sense?
    • Is a refinement, improvement, or new application of management strategies proposed?

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Consortium? Have 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 Core 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?

    • Does the approach provide high quality performance as an Administrative Core in the recent past, either as an independent Core, or as part of an individual Data Coordinating Center that will lead to success?
    • Does the application clearly demonstrate the willingness to work and cooperate with the Steering Committee and Clinical Sites?
    • Is the proposed plan for work-flow and timeline well-established and appropriate?
    • Does the application describe and provide examples of past experience with the ability to arrange face-to-face meetings and associated logistics, as well as conference calls and support the complexity of workflow within the Consortium?
    • Does the application provide examples of procedures for communication of relevant information among investigators during the conduct of the clinical study, and examples of procedures for dissemination of the study results to the public at large when such results become available that indicate likely future success in this project? 
    • Does the application demonstrate capable performance in developing and maintaining websites? 
    • Does the application provide convincing evidence of capabilities in overseeing capitation systems to clinical sites during an ongoing study? 

    Environment

    Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

    • Will the institutional environment in which the Core will operate contribute to the probability of success in facilitating the research it serves?
    • Are the institutional support, equipment and other physical resources available to the investigators adequate for the Core proposed?
    • Will the Core benefit from unique features of the institutional environment, infrastructure, or personnel?
    • Does the application demonstrate adequate administrative and organizational management facilities?
    • Is there institutional assurance to provide support to the study in such areas as fiscal administration, personnel management, space allocation, procurement, planning, and budgeting?
    • Does the application demonstrate optional administrative strengths, such as affiliations with other research units?

    Additional Review Criteria – Administrative Core

    Protections for Human Subjects

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

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

    Inclusion of Women, Minorities, and Individuals Across the Lifespan  

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

    Vertebrate Animals

    Not applicable

    Biohazards

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

    Resubmissions

    Not Applicable

    Renewals

    Not Applicable

    Revisions

    Not Applicable

    Additional Review Considerations - Administrative Core

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

    Applications from Foreign Organizations

    Not Applicable

    Select Agent Research

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

    Resource Sharing Plans

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


    Authentication of Key Biological and/or Chemical Resources

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

    Budget and Period of Support

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

    Scored Review Criteria – Research Support Core

    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 Consortium that by its nature is not innovative may be essential to advance a field.

    Significance

    Does the Core 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 Core 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?

    • Does the proposed Core address the needs of the research that it will coordinate, administer, and serve?
    • Is the scope of activities proposed for the Core appropriate to meet those needs?
    • Will successful completion of the aims bring unique advantages or capabilities to the research conducted by the consortium?

    Investigator

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Consortium? 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 demonstrate the scientific, administrative, statistical and academic qualifications of the PD/PI, the individual identified as backup to the PD/PI, and the research team at the Research Support Core, as well as the qualifications of the applicant institution to participate fully as the Research Support Core in the Consortium?
    • Do the key personnel possess appropriate and adequate knowledge and experience in areas relevant to the conduct of collaborative clinical research, especially multisite longitudinal cohort studies, including experience in research design, execution, data management and quality control, preferably in neonatal-perinatal medicine?
    • Does the application demonstrate the commitment, availability, and flexibility of staff time for the satisfactory conduct of the studies?
    • Does the application demonstrate the experience and qualifications of team members who would be responsible for data quality and management activities?

    Innovation

    Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

    • Does the application propose novel management strategies and statistical approaches in coordinating the research Consortium the Core will serve?
    • Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense?
    • Is a refinement, improvement, or new application of management strategies and statistical approaches proposed?

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Consortium? Have 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 Core 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?

    • Does the approach provide high quality performance in Research Support in the recent past, either as an independent Core, or as part of an individual Data Coordinating Center?
    • Are the descriptions of experience and contributions in key areas of research development and design, protocol implementation, recruitment monitoring, data collection and analysis, monitoring of trial progress, statistical analysis and interpretation, track record of publications, and timely provision of de-identified data sets convincing and do they portend future success?
    • Does the application demonstrate the Research Support Core is highly capable of ensuring that the Clinical Sites fully comply with NIH policy requirements, including Central Institutional Review Board submissions and queries, Human Subjects Protections, issues of informed consent, reporting of adverse events, and human welfare provisions? 
    • Does the application demonstrate willingness to work and cooperate with other centers and the data coordinating center in a manner summarized in this FOA? Is there commitment to use common data elements with other HEAL studies?
    • Are the plans for high-quality protocol training, plans to ensure certification of staff performing neuroimaging, neuropsychological, clinical, and other phenotypic assessments, and refresher training thorough and reasonable?  In particular, are the methods for how the Research Support Core will work with Clinical Sites to ensure standardization of neuroimaging data acquisition, monitor image acquisition, and promote sharing among sites clear and effective?  Is the plan for integrating technological advances into the longitudinal study and determining how changes in hardware and analytic approaches will be coordinated across multiple research sites acceptable? 
    • Are the skills, experience, and plans for production and maintenance of study documentation, such as the final study protocol and any revisions, case report forms, Manual of Procedures, consent form templates, training manuals, and other documents for study implementation adequate to serve the Consortium? 
    • Are the experience and plans for data collection systems, electronic technology, data entry systems, and data quality assurance robust?
    • Are the proposed methods for maintaining data control and security adequate?
    • Does the application provide a rigorous plan to conduct reporting to the investigators with respect to monthly reports, trial subject enrollment, and other performance reports?
    • Is the proposed quality assurance and quality control program sufficient to ensure high quality and timely data collection and delivery and maintenance of data integrity? Does the application describe a reasonable plan for attending to data errors, needed edits, and protocol deviations?
    • Does the application demonstrate appropriate capabilities and procedures with regard to conducting on-site and off-site monitoring and study oversight, and remediation when problems arise?
    • Is the plan for generating reports and maintaining study records, as required, clear and effective?
    • Does the application provide evidence that the Research Support Core will collaborate with investigators to produce abstracts and manuscripts for publication?
    • Does the application describe an acceptable methodology and plan to de-identify research data and prepare and submit datasets--including neuroimaging data--for timely submission of data archived in publicly available websites?

    Environment

    Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

    • Will the institutional environment in which the Core will operate contribute to the probability of success in facilitating the research it serves?
    • Are the institutional support, equipment and other physical resources available to the investigators adequate for the Core proposed?
    • Will the Core benefit from unique features of the institutional environment, infrastructure, or personnel?
    • Does the application demonstrate adequate administrative, statistical, and data organizational management facilities?

    Additional Review Criteria DCC Research Support Core

    Protections for Human Subjects

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

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

    Inclusion of Women, Minorities, and Individuals Across the Lifespan  

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

    Vertebrate Animals

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

    Biohazards

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

    Resubmissions

    Not Applicable

    Renewals

    Not Applicable

    Revisions

    Not Applicable

    Additional Review Considerations - DCC Research Support Core

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

    Applications from Foreign Organizations

    Not Applicable

    Select Agent Research

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

    Resource Sharing Plans

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

    Authentication of Key Biological and/or Chemical Resources

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

    Budget and Period of Support

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

    Scored Review Criteria – Clinical Site

    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 Consortium that by its nature is not innovative may be essential to advance a field.

    Significance

    Does the Clinical Site 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 Clinical Site 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?

    • Does the Clinical Site have experienced leadership, the necessary patient population, and organizational capacity to make an important contribution to the Longitudinal Study Consortium?

    Investigator

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Consortium? 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?

    • Do the PD/PI and other Key Personnel have the scientific, administrative, clinical and academic qualifications to conduct a successful clinical research study in opioid-exposed newborns? 
    • Does the Clinical Site PD/PI have a significant track record of productivity in clinical research in the recent past?
    • Are there staff at the Clinical Site and all subsites (if applicable) who have demonstrated expertise in the neuroimaging of newborns, infants, and toddlers? 
    • Is there commitment of staff time for the satisfactory conduct of the study? 
    • Do the investigators have experience as well as qualified team members who would be responsible for data quality and management activities? 

    Innovation

    Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

    • Does the application propose novel recruitment and retention strategies, infant neuroimaging, or other approaches to support the successful completion of the Longitudinal Study?

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Consortium? Have 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 Clinical Site 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?

    • Does the application reflect commitment on the part of the Clinical Site to collaborate with the other Consortium components and the Steering Committee?
    • Does the research team at the Clinical Site have the institutional support and capabilities including the patient population to participate fully in a collaborative effort?
    • Does the application demonstrate that the Clinical Site achieves an infant follow up and retention rate of at least 80 percent at 2 years of age?  Are there robust and creative methods for ensuring complete follow up of infants enrolled in the Longitudinal Study?
    • Does the application provide evidence that the Clinical Site is capable of enrolling a large cohort of neonates exposed and unexposed to opioids in utero and following them longitudinally for 2 years?
    • Will there be competition with other studies for enrolling eligible newborns and will the Longitudinal Study have precedence?
    • Is the diversity of the source population, in terms of race/ethnicity, sociodemographics, methods of NOWs treatment and other criteria as outlined acceptable?
    • Are staffing levels at the Clinical Site and any subsites appropriate to cover the Longitudinal Study schedule of enrollment and assessments?
    • Do the staff proposed for conducting the longitudinal assessments have the appropriate expertise and experience?
    • Is there institutional assurance to provide support to the study in such areas as fiscal administration, personnel management, space allocation, procurement, planning, and budgeting?
    • Does the recent track record in clinical research indicate that the proposed study will be completed successfully?

    Environment

    Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

    • Is there evidence of institutional commitment to cooperate with the policy for capitation of research costs as outlined?
    • Does the research team at the Clinical Site have the institutional support and capabilities including the patient population to participate fully in the Longitudinal Study Consortium?
    • Are there support resources such as a Clinical and Translational Science Award (CTSA, https://ncats.nih.gov/ctsa) funded by NIH, or the National Center for Advancing Translational Sciences’ Trial Innovation Network (https://trialinnovationnetwork.org/), or other funded perinatal-neonatal research centers available to leverage as resources for conducting the proposed research?
    Protections for Human Subjects

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

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

    Inclusion of Women, Minorities, and Individuals Across the Lifespan  

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

    Vertebrate Animals

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

    Biohazards

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

    Resubmissions

    Not Applicable

    Renewals

    Not Applicable

    Revisions

    Not Applicable

    Additional Review Considerations - Clinical Site

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

    Applications from Foreign Organizations

    Not Applicable

    Select Agent Research

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

    Resource Sharing Plans

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

    Authentication of Key Biological and/or Chemical Resources

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

    Budget and Period of Support

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

    2. Review and Selection Process

    Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by NICHD 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 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.  
    • Geographic distribution of Clinical Sites.
    • The adequacy of the data and resource sharing plan.
    3. Anticipated Announcement and Award Dates

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

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

    Section VI. Award Administration Information
    1. Award Notices

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

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

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

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

    2. Administrative and National Policy Requirements

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

    Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights 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

    3. Reporting

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

    Progress reports for multiyear funded awards are due annually on or before the anniversary of the budget/project period start date of award.  Information on the content of the progress report and instructions on how to submit the report are posted at https://grants.nih.gov/grants/policy/myf.htm.

    In addition, because of the nature of this study, milestones may be established and necessitate more than annual updates to NICHD staff on progress in meeting those milestones.

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

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

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

    Section VII. Agency Contacts

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

    Application Submission Contacts

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

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

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

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

    Scientific/Research Contact(s)

    Rosemary D. Higgins, M.D
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
    Telephone: 301-435-7909  
    Email: higginsr@mail.nih.gov

    Peer Review Contact(s)

    Sherry Dupere, Ph.D.
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
    Telephone: 301-496-1485
    Email: duperes@mail.nih.gov 

    Financial/Grants Management Contact(s)

    Bryan S. Clark, M.B.A.
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
    Telephone: 301-435-6975
    Email: clarkb1@mail.nih.gov

    Section VIII. Other Information

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

    Authority and Regulations

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

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