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: Data Coordinating Center for the Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial (U24 Clinical Trial Required)
Activity Code

U24 Resource-Related Research Projects – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number
RFA-HD-21-032
Companion Funding Opportunity

RFA-HD-21-031 - Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial - Clinical Sites (UG1 Clinical Trial Required),  UG1 Clinical Research Cooperative Agreements - Single Project

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

93.865

Funding Opportunity Purpose

This FOA invites applications for a Data Coordinating Center (DCC) to design and implement a multi-center, comparative effectiveness, randomized controlled trial (RCT) to assess the optimal pharmacological treatment for Neonatal Opioid Withdrawal Syndrome (NOWS).

A separate FOA (RFA-HD-21-031) will invite applications for Clinical Sites.

Information obtained from this study is expected to inform clinical practice guidelines and the care of infants with NOWS.

The funding for this initiative is provided from the Helping to End Addiction Long-term (HEAL) initiative (https://heal.nih.gov/).

Key Dates

Posted Date
January 11, 2021
Open Date (Earliest Submission Date)
February 28, 2021
Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

March 30, 2021

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

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

AIDS Application Due Date(s)

Not Applicable

 

 

Scientific Merit Review

July 2021

Advisory Council Review

October 2021

Earliest Start Date

December 2021

Expiration Date
March 31, 2021
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

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

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

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

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

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


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose and Objectives

This FOA invites applications for a Data Coordinating Center (DCC) to conduct a multi-center, comparative effectiveness, randomized controlled trial (RCT) to assess the optimal pharmacological treatment for Neonatal Opioid Withdrawal Syndrome (NOWS) to inform clinical practice guidelines. The DCC selected must agree to be part of a consortium that will collaboratively develop and implement a uniform protocol.

A separate FOA (RFA-HD-21-031) will invite applications for Clinical Centers to recruit participants and conduct the study.

It is anticipated that there may be a pilot or vanguard phase before the study is fully launched. If additional sites are needed to recruit adequate numbers of participants, subcontracts may be added to individual study sites or the DCC.

The funding for this project is provided from the Helping to End Addiction Long-term (HEAL) initiative (https://heal.nih.gov/).

Background

At the 2018 National Prescription Drug Abuse and Heroin Summit, National Institutes of Health Director Francis S. Collins, M.D., Ph.D., announced the launch of the HEAL (Helping to End Addiction Long-term) Initiative, an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis. Part of this initiative is to evaluate treatments and long-term consequences of Neonatal Opioid Withdrawal Syndrome (NOWS).

Women and children bear a substantial part of the burden of the current opioid crisis in the United States. Hospitalizations for opioid use disorder in pregnant women more than quadrupled during 1999–2014. This is a significant public health concern, given that opioid exposure is associated with adverse maternal and neonatal outcomes, including preterm labor, stillbirth, NOWS, and maternal mortality. Cases of NOWS have increased 5-fold since 2004 – a baby is born suffering from opioid withdrawal approximately every 15 minutes, and recent data from the U.S. Pediatric Health Information System suggest an incidence of NOWS as high as 20 cases per 1000 live births (with a treatment cost of more than $560 million per year). In addition, not only can opioid use during pregnancy lead to NOWS, but both the mothers and babies may be at higher risk of opioid use and its consequences later in the life course, setting up intergenerational cycles of opioid overuse.

The Advancing Clinical Trials in Neonatal Opioid Withdrawal syndrome (ACT NOW) project's Current Experience study found a wide variation in NOWS care practices, including pharmacologic agents, with no consensus as to which medication regimen is better. Currently, the most common first-line medications for NOWS are morphine and methadone; phenobarbital and clonidine are the most commonly used adjunct agents.

A meta-analysis published in 2019 suggested that buprenorphine may be the optimal pharmacologic treatment for infants with NOWS. However, the primary findings of this meta-analysis need to be interpreted with caution and properly conducted direct comparative-effectiveness studies are needed to inform clinical practice.

Unfortunately, findings from previous studies that compared different treatment medications for NOWS have been limited:

  • Several studies were not blinded.
  • No large studies have directly compared buprenorphine with methadone.
  • All studies are limited by the choice of weaning protocol used for each medication. For example, studies comparing buprenorphine and morphine have been limited by use of particularly slow weaning approaches for morphine.
  • Studies may be influenced by the preparation (e.g., containing alcohol) or route of administration (e.g., oral vs sublingual) of the medications.
  • Few studies have either compared, or even controlled adequately for the use of adjunct medications.
  • Few studies have controlled for varying use of non-pharmacologic therapies.
  • Comparison studies have not adequately accounted for the possibility of differences in populations of infants being treated. For example, it is possible that buprenorphine may be preferable for infants of women using buprenorphine for medication-assisted treatment for opioid use disorder, whereas morphine or methadone may be superior for infants of mothers actively using opioids.

To address these scientific gaps, a workshop supported by the HEAL initiative and addressing issues related to the treatment of infants with NOWS was held on August 24-25, 2020. Contents of the workshop are archived on the following website: https://heal.nih.gov/events/2020-buprenorphine-infants.

As such, this FOA invites applications for a Data Coordinating Center (DCC) to conduct a multi-center, large-scale RCT that directly compares morphine, methadone, and buprenorphine, and takes into account non-pharmacologic factors and adjunct therapies. The expected follow-up is at least 24 months. A separate FOA (RFA-HD-21-031) will provide support for Clinical Centers to support these efforts. The goal is to generate results that can inform clinical practice guidelines.

Study Structure

NICHD anticipates making awards to multiple Clinical Centers and one DCC.

Governance and Oversight: Principal Investigators from these awards, plus NICHD Program staff, will form a Steering Committee, which will be in charge of: designing a common protocol; implementing the study; analyzing and interpreting the data; reporting results; and depositing de-identified data in a public repository. The Director of NICHD will appoint an independent Steering Committee Chair.

NICHD will also appoint an independent Data and Safety Monitoring Committee (DSMC) for this trial.

The DCC is not expected to submit a trial design at the time of the application.

Data Coordination Center: The DCC will provide needed statistical expertise and analysis for the trial and logistical support to the Steering Committee and DSMC. The DCC and the NIH will closely monitor participant accrual and retention. The DCC will be responsible for administering capitation and implementation costs to the Clinical Centers based on recruitment and retention. It will also be responsible for submitting and obtaining necessary approvals via a single Institutional Review Board (IRB). If required by the U.S. Food and Drug Administration, it will work with the Steering Committee and NIH staff to obtain Investigational New Drug (IND) waivers and/or approvals, meeting the IND reporting requirements.

Clinical Centers: Each Clinical Center will support a team of a Principal Investigator, an Alternate Principal Investigator, and a Research Nurse Coordinator.

Clinical Centers may propose collaborations with other institutions as needed to enhance research expertise, recruitment capacity for the target population, and diversity of population.

Successful Clinical Centers must demonstrate (and grantees must continue to meet) the following requirements:

  • Research Staffing. The respective roles of staff and a management plan for how staff interact with subspecialists and senior/key persons, and plans for availability for staff to cover patient recruitment at night and on weekends.
  • Patient population available for the trial. At least 3 infants treated pharmacologically for NOWS per month (on average).
  • Follow-up program. A designated facility for follow up with experience in tracking and retaining patients must already be in place. Examiners must also be trained in the use of the Bayley Scales of Infant and Toddler Development 4th Edition. A Follow-up Investigator (can be the PD/PI) must be designated in the application. A minimum of 80 percent follow-up rate at 2 years of age is required; a 2-year follow-up rate of 90% is highly desirable.
  • Successful participation in multi-center clinical trials. Evidence of research productivity by the clinical center in previous or ongoing clinical studies and trials, especially those of a cooperative or multicenter design.

The successful Data Coordinating Center will:

  • Collaborate with the Clinical Centers in the development, implementation, and monitoring of the study protocol(s), the collection and analysis of data, and publication of results of the trial. The DCC conducts data cleaning and quality control efforts, reviewing study participant data and working with the recruiting sites to resolve any outstanding missing or inconsistent data items.
  • Provide data management, including development of appropriate data collection forms and systems, implementing masking and randomization methods, and distributing study documents (protocol, manual, data collection forms, technical memos, etc.). The DCC serves as the central repository for clinical and laboratory data, including biological specimens, if applicable. It provides a computerized data management system that allows Clinical Center staff to enter and transmit data to the DCC. The DCC provides training of study personnel on data entry and processing procedures, as needed.
  • Monitors and reports on data quality, protocol adherence, and recruitment status. It reviews eligibility and monitors enrollment of study patients. DCC staff assists in the coordination of, and participates in, site and data review visits, as required for quality assurance.
  •  Prepare reports for the Steering Committee, its subcommittees, and the clinical centers, and prepares study data files for submission into public data repositories in compliance with the NIH data sharing requirements. It also created and maintains ClinicalTrials.gov records, including reporting of results, for the Steering Committee.
  • Report to the DSMC, as needed, any unexpected, serious, and protocol-related adverse events or apparent trends in data possibly relevant to patient safety. At periodic intervals, as specified in the protocol, the DCC PI provides the DSMC with confidential interim analyses of study data related to protocol performance, patient safety, and emerging results related to efficacy and futility.
  • Coordinate external services, including procuring study drugs, equipment, and other supplies, and executing subcontracts/vendor services, such as for study drug distribution, subcontract with additional recruiting sites, and consultancy agreements with outside experts.
  • Provide a central/single IRB for protocol implementation, working with all recruiting sites to put in place necessary reliance agreements and other approvals to do so. The single IRB can be at the DCC’s institution, at one of the Clinical Centers, or a commercial IRB.
  • May sponsor (or share sponsor obligations for) FDA Investigational New Drug (IND) and applications on behalf of the Steering Committee, if required, including coordinating and/or submitting all necessary reports to the FDA.
  • Disburses capitation payments to clinical centers on the basis of enrolled patients and other study-specific milestone triggers.
  • Provides the logistical support necessary to run an efficient and productive network, including assisting with in-person or virtual meeting logistics, developing a website and/or other shared online space to facilitate communications with Clinical Center staff.

Institutional applicants must clearly express their intent:

  • To participate in a cooperative manner with the Clinical Sites and NIH staff in all aspects of research including but not limited to, protocol development, implementation, data analysis, publication of results, and data sharing. This includes support such as, grants management, personnel provision and management, space allocation, procurement, and equipment, as well as general support of the research.
  • To participate in the Steering Committee. Steering Committee meetings are expected to occur two times per year. Meetings may be virtual or in-person (for budgeting purposes, assume at least 1 in-person meeting per year held in the Washington, DC metro area). The PD/PI or his/her designee and the research coordinators are required to attend the meetings in their entirety. Follow-Up investigators will also meet twice yearly.
  • To cooperate with the policy for capitation of research costs.  The DCC will be responsible for setting up agreements with the Clinical Centers to enable distribution of protocol funding, including per-patient capitation costs.
  • To participate in a cooperative manner with other clinical centers, the DCC, and NIH staff in the development of the clinical trial protocol.
  • To comply with the NIH and HEAL policies regarding data sharing.

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

Section II. Award Information

Funding Instrument

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

Application Types Allowed
New

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

Clinical Trial?
Required: Only accepting applications that propose clinical trial(s)

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NICHD intends to commit approximately $2,000,000 of HEAL funds in FY21 to fund one award that includes base costs (described in R&R Budget in Section IV) plus capitation costs. Future year amounts will depend upon annual appropriations.

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

HEAL has committed a total of $7,000,000 in FY21 to support this FOA as well as its accompanying FOA (RFA-HD-21-031).

Award Budget

Application budgets must reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is five years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
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.
  • 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(s)/PI(s) must possess a doctoral degree in a relevant field such as statistics, biostatistics, or epidemiology, and is required to commit 6.0 person-months (50%) effort to the DCC activities in the first year of the project period. The PD(s)/PI(s) must have clinical trials, administrative, and statistical expertise. Active participation of the PD(s)/PI(s) is expected during all phases of a clinical research study.

One individual must be designated as an Alternate PD(s)/PI(s), who is able to serve in the absence of the PD(s)/PI(s). The alternate PD(s)/PI(s) must possess a doctoral degree in a relevant field such as statistics, biostatistics, or other relevant area.

At a minimum, the DCC PD(s)/PI(s) and staff must be prepared to cooperate effectively in all trial functions with the NIH and the Clinical Centers. The PD(s)/PI(s) must have prior experience operating a data coordinating center in multicenter studies in the previous five years. Together, the DCC PD/PI and staff should have the following minimum qualifications in terms of experience and expertise in:

  • Planning, developing, and executing pediatric studies, and the special consent and IRB procedures needed for the conduct of research in children, is strongly preferred.
  • A broad range of clinical trial study design and statistical expertise, including pragmatic clinical trial methodology.
  • Designing data collection systems, including distributed data entry, capabilities and experience with research performance and data quality control systems, and experience interacting with the FDA and designing and implementing FDA-approved data management systems.
  • Project management and knowledge of workflow and research team practices in implementation of clinical trials.
  • Distributing scientific protocol funds to the Clinical Sites, and accounting for such funds with regular reporting to the NIH Program Officer and Project Scientist.

Working with a variety of stakeholders including research participants and families, practitioners, researchers, hospital/clinic and research informatics and technical personnel, and research organizations on workflows and practices of health care systems.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

Andrew A. Bremer, MD, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Telephone: 301-402-7886

Email: andrew.bremer@nih.gov

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Facilities and Other Resources:

Applicants should describe facilities and other resources that may be relevant to this research. This can include state-of-the-art data management systems for use with this trial.

SF424(R&R) Senior/Key Person Profile

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

Biographical Sketch: The biographical sketch of the PD(s)/PI(s) should reflect the strengths, leadership, and administrative skills, and scientific expertise. The applicant must demonstrate staff experience and expertise in biostatistics, data management, data analysis, data quality assurance and project management in multicenter research.

PD(s)/PI(s) must demonstrate prior experience in the design, conduct, data collection, analysis and management of major collaborative multicenter clinical trials research projects, preferably in NOWS-related clinical research, and provide evidence of successful performance as a DCC for multicenter studies within the past five years. Further, the applicants need to show evidence of monitoring of trials, including the ability to generate monthly reports of enrollment and follow up for the Clinical Sites, safety reports for the DSMC, and provision of support of data files. Contributions in key areas of research development and design, data collection and analysis, monitoring of trial progress, and track record of publications that resulted from participating in the studies should be described and related to the proposed DCC structure and function.

Previous experience in pediatric clinical research studies and Food and Drug Administration Investigational New Drug/Device protocols is preferred. 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.

In addition, special administrative strengths or experience, as well as participation in administrative aspects of clinical research (Single IRB, DSMC, Advisory Board for clinical research, clinical research committees, and so forth) for the PD(s)/PI(s) and additional staff members should be highlighted. The level and support of clinical trials can be described.

If the PD(s)/PI(s) has substantial experience with or staff expertise in, research involving vulnerable populations, special sensitivity to the issues of informed consent in the critically ill, research under emergency circumstances, or experience in multicenter research in children, it should be summarized here.

R&R Budget

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

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

  • Principal Investigator (PD/PI): 6.0 person-months (50%) effort.
  • Alternate PD/PI: 1.2-3.6 person-months (10 to 30 percent) effort.
  • Data center coordinator: 6.0 person-months (50%) effort.
  • Data center assistant: 6.0 person-months (50%) effort.
  • Statisticians/Research Assistants.
  • Programmers/analysts.
  • Costs associated with data entry, management, collection, and analysis.
  • Supplies and small equipment (itemized and justified): Not to exceed $10,000.
  • Travel (two trips for four staff members to conduct site and data review visit of network clinical centers): as appropriate.
  • Data entry, management, quality control.
  • Software and/or online systems.
  • Report generation, including FDA reporting (if required).
  • Data analysis, manuscript preparation.
  • Arrangement of logistical services for protocol-specific costs, including subcontracts and supplies.
  • Support for the activities of the Consortium's Steering Committee and the DSMC through provision of materials/documentation support, meeting planning and logistics and conference call coordination.
  • DCC resource management, subcontracting (the DCC will prepare reports and provide coordination, support and funding for travel and logistical arrangements related to DSMC meetings and actions).
  • Administrative management of subcontracts with the clinical sites for disbursement of capitation costs.
  • Other costs (itemized and individually justified).

Capitation costs for the clinical trial are not to be included in the BASE BUDGET.

Capitation costs include per-patient and other study costs.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy:

In addition to the sections in the SF424 (R&R) Application Guide, without duplicating information in the biosketches, applications must address the following items:

Evidence of Successful Past Performance

DCC applicants must describe prior experience in the design, conduct, data analysis, and management of major collaborative clinical research projects preferably in perinatal medicine, and provide evidence of successful performance as a DCC for multi-site studies within the past three to five years. Further, applicants need to show evidence of monitoring of trials, including the ability to generate monthly reports of enrollment and follow up for the clinical centers and subcommittees, data and safety reports for DSMC, and provision of support of data files.

Academic Productivity

DCC applicants must provide evidence of research productivity in previous or ongoing clinical trials, especially those of a cooperative or multicenter design in the field of neonatology. Contributions in key areas of research development and design, data collection and analysis, monitoring of trial progress, and track record of publications that resulted from participation in the studies should be listed.

Staffing Plan and Capabilities

The application should describe plans for staffing DCC functions and provide evidence of multicenter collaboration on recent clinical trials, especially those in neonatology, including publications resulting from these studies. The proposed DCC should have some degree of flexibility in staffing to be able to respond to the changing needs and seasonal variation in work effort of the trial. For instance, meeting deadlines, trial startup and completion, and other variables necessitate increases and decreases in staff effort from the DCC over time. Logistical staff for day-to-day functioning of the consortium, and support staff to manage clinical site capitation, must be described and justified. It is expected that staff effort will decrease over time as the study is completed.

Capacity and Ability to Manage Data and Communications

Applications must describe the ability to assist in protocol development with respect to design of procedure manuals, data collection forms, data management systems, electronic technology, and data entry systems. Prior experience in data quality assurance is required. Applicants should provide evidence of data management and program support capabilities by describing their standard operating procedures to include data collection, management, analysis, and quality control. A system to ensure availability of patient randomization for studies outside of normal business hours (i.e., nights, weekends, and holidays) is required. Applicants must include plans for support of electronic mail and communication. The DCC must develop and maintain a website for both public access and private, secure investigator access. Previous experience in neonatology studies and FDA IND and IDE (Food and Drug Administration Investigational New Drug/Device) protocols are preferred. 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.

Evidence of Reporting Capabilities

Applications must provide evidence of experience with generation of monthly reports on subject enrollment for multiple concurrent studies, reports for use by the DSMC, and reports for Steering Committee meetings. Documentation and dissemination of meeting minutes and minutes of conference call meetings are required to be performed in a timely manner. The applicant should delineate previous history of such activities in the application. Further, experience in preparing data presentation and manuscripts for publication is to be described in the

Research Plan. The DCC PD/PI will give a report to the Steering Committee quarterly at the Steering Committee meetings.

Logistical and Other Support Services

Applications must describe experience and capabilities with respect to logistical and support services relevant to the consortium. The DCC is responsible for supporting the infrastructure for meetings and teleconferences. The DCC provides arrangements and documentation in the form of minutes for Steering Committee meetings (at least two face-to-face meetings per year [if possible] in the DC metropolitan area and others conducted virtually, as necessary) and conference calls, DSMC meetings (one per year and as needed) and committee conference calls, and other meetings as needed by the consortium. On occasion, the DCC handles travel arrangements for selected consultants as needed. The consortium communicates on an ongoing basis via email and teleconference; these activities are supported by the DCC. Expertise in coordinating sample storage and study drug/equipment assignment is required. The DCC oversees the capitation system for the studies and trials and maintains subcontracts/Memoranda of Understanding with the clinical sites for disbursement.

Onsite and Off-site Monitoring Ability

Applications must provide evidence of experience in organizing and conducting both onsite and remote monitoring for clinical research studies. Generation of data errors and needed edits is required. The DCC needs to ensure that the clinical centers fully comply with NIH regulatory requirements, including Human Subjects Protections, informed consent, reporting of adverse events and protocol deviations, human and animal safety and welfare provisions, and FDA requirements as indicated by specific studies.

Technology Transfer, Data Management and Protocol Training Capabilities

Applications are expected to describe capabilities in technology transfer, data management, and protocol training. The DCC must be able to assist the clinical centers in data management and communication activities. Training and technical expertise as well as experience and resources must be delineated.

Administrative and Management Capabilities

The PD/PI should delineate his/her skills as a manager or administrator for a DCC. The PD/PI must provide evidence of experience and ability to estimate the appropriateness and reasonableness of resources needed for individual projects and ability to manage those resources efficiently during the course of the research. Flexibility of personnel based on needed effort is required. Prior experience with meeting deadlines (e.g., FDA reporting requirements, national meetings, SteeringCommittee meetings, DSMC meetings, and so forth) should be delineated in the application. Experience with capitation for study subject recruitment by clinical centers is mandatory. This includes providing and monitoring funds to the clinical centers for patient recruitment at regular intervals. Experience with subcontracts is required as there is occasional need to supplement resources through arrangements with outside organizations based on protocol requirements.

Preparation of Data and Biospecimens for Sharing

The DCC must describe plans for ensuring that all datasets from the study are prepared for data sharing as per the Research Sharing Plan noted below. This plan should be consistent with the content of the consent forms collected during the study. This should include the preparation of any linking files necessary to associate clinical data with biospecimens stored.

Special Strengths of the PD/PI or Institution

Applicants are encouraged to describe special or unique strengths that may be relevant to this trial. These can include state-of-the art data management systems, which may be shared or may be available to develop and expand the scientific productivity of the consortium. In addition, special administrative strengths or experience as well as participation in administrative aspects of clinical research (IRB, DSMC, scientific board for clinical research, clinical research committees and so forth) for the PD/PI and additional staff members should be highlighted. Level of support for clinical trials can be described.

Letters of Support:

Include letters of support from partnering institutions, appropriate leaders of institutional component services, or outside collaborators with statement of roles/responsibilities. The application must include a statement from the applicant institution (senior institutional official) describing the commitment to the planned program, senior and junior investigators, research staff, and infrastructure needed.

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.

  • The DCC will be responsible for issuing payments for protocol expenses, including a per-patient capitation. To receive reimbursements, a funded clinical center must set up an agreement with the DCC.
  • The clinical center PD/PI or designee will be required to help the DCC manage protocol costs. The PD/PI or designee should propose estimates of recruitment efforts for each protocol to the DCC and update these at least annually.
  • The DCC may establish a recruitment limit. If a clinical center investigator believes that their site(s) is able to exceed the limit, then permission to do so must be obtained from the DCC
  • The DCC's F&A rates on the initial competitive awards will not be adjusted in future years due to changes in their negotiated rate agreements.

Describe support in areas of grants management, personnel management, space allocation, data coordination and confidentiality (including electronic data systems, such as hardware, software, maintenance and informatics technology), procurement, and equipment as well as general support of the research, as well as evidence of past research support.
Applications from institutions that have a Clinical and Translational Science Award (CTSA) funded by NIH or other funded perinatal research centers as resources for conducting the proposed research should provide a letter of agreement that identifies the types and level of support from the PD/PI or the CTSA program director.

There must be a clearly expressed intent to participate in a cooperative manner with the Clinical Centers, the NIH, and the DSMC in all aspects of research in a manner consistent with the terms of the award.

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

The following modifications also apply:

Appendix:

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

 Only the following fields are required:
1.1 Study Title
1.2 Is this Study Exempt from Federal Regulations?
1.3 Exemption Number (if applicable)
1.4 Clinical Trial Questionnaire
2.1 Conditions or Focus of Study
2.4 Inclusion of Women andMinorities
3.1 Protection of Human Subjects

.

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.

Of note, The Data Coordinating Center (DCC) is not expected to submit a complete trial design at the time of the application. Many of the PHS Human Subjects and Clinical Trials information (e.g., the data and safety monitoring plan and the narrative study description) will be dependent on the final protocol.

PHS Assignment Request Form

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

Foreign Institutions

Not Applicable

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Pre-Application Materials

A workshop supported by the HEAL initiative and addressing issues related to the treatment of infants with NOWS was held on September 24-25, 2020. Contents of the workshop are archived on the following website: https://heal.nih.gov/events/2020-buprenorphine-infants.

 

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

The DCC will work with the clinical sites to conduct a multi-center, comparative effectiveness, randomized controlled trial (RCT) to assess the optimal pharmacological treatment for Neonatal Opioid Withdrawal Syndrome (NOWS). The protocol will be developed in coordination with the other clinical centers.

The clinical trial will be delayed onset.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

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

Scored Review Criteria

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

Significance

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

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

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

Are the scientific, administrative, statistical and academic qualifications of the PD(s)/PI(s) and the research team at the DCC sufficient for the applicant institution to participate fully as the DCC for the study ?

Do the key personnel possess appropriate and adequate knowledge and experience in areas relevant to the conduct of collaborative clinical research, especially multi-center randomized clinical trials, including experience in research design, execution, data management and quality control, preferably in pediatric clinical research?

Are the appropriate commitment, availability, and flexibility of staff and PD(s)/PI(s) time for the satisfactory conduct of the study demonstrated?

Are the experience and qualifications of team members who would be responsible for data quality and management activities appropriate?

Are the appropriate expertise and capability in biostatistics, the special needs of pediatric subjects, institutions and IRBs, study development and support, data analysis, project management, staff site training, and monitoring/quality assurance procedures described?

Is the evidence of management capability, including assessment of the PD(s)/PI(s)' ability to estimate appropriate and reasonable resources for research studies, to manage research resources efficiently during study execution, and to enhance collaboration among the Clinical Sites of the consortium adequate?

 Does the PD(s)/PI(s) possess prior experience in the design, conduct, data analysis, and data management of major collaborative research projects, experience in pediatric research, and successful performance as a data coordinating center in the previous five years?

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Specific for this FOA:

Are the scientific, administrative, statistical and academic qualifications of the PD(s)/PI(s) and the research team at the DCC sufficient for the , as well as the qualifications of the PD(s)/PI(s) and applicant institution to participate fully as the DCC for the study demonstrated?

Do the key personnel possess appropriate and adequate knowledge and experience in areas relevant to the conduct of collaborative clinical research, especially multi-center randomized clinical trials, including experience in research design, execution, data management and quality control, preferably in pediatric clinical research?

Are the appropriate commitment, availability, and flexibility of staff and PD(s)/PI(s) time for the satisfactory conduct of the study demonstrated?

Are the experience and qualifications of team members who would be responsible for data quality and management activities appropriate?

Are the appropriate expertise and capability in biostatistics, the special needs of pediatric subjects, institutions and IRBs, study development and support, data analysis, project management, staff site training, and monitoring/quality assurance procedures described?

Is the evidence of management capability, including assessment of the PD(s)/PI(s)' ability to estimate appropriate and reasonable resources for research studies, to manage research resources efficiently during study execution, and to enhance collaboration among the Clinical Sites of the consortium adequate?

Does the PD(s)/PI(s) possess prior experience in the design, conduct, data analysis, and data management of major collaborative research projects, experience in pediatric research, and successful performance as a data coordinating center in the previous five years?

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 design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

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

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

 

Specific for this FOA:

Does the applicant demonstrate an effective clinical trials skills development plan that is likely to positively impact the research team's ability to design and implement clinical trials in their institution?

Does the applicant demonstrate the ability to successfully implement multicenter clinical trials including the ability to recruit, retain and follow up children in clinical studies?

Is there evidence of a willingness to work and cooperate with other Clinical Sites, the DCC and the NIH in a manner summarized in this FOA?

Does the research team, with proposed partner institutions or collaborators, have the ability to design multicenter clinical trials?

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

 

Environment

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

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Specific for this FOA:

Does the institution demonstrate the commitment to support the proposed program? Are the research infrastructure and facilities that are available and accessible to this program described? Is there adequate institutional assurance to provide support to the program in areas of fiscal administration, personnel management, space allocation, procurement, planning, and budgeting?

Is there demonstrated adequacy of administrative, clinical, and data organizational management facilities as described in the requirements?

Are there additional administrative strengths, such as affiliations or collaborations with other research units, institutions, or organizations that strengthen the environment of the applicant Clinical Site?

Is evidence of the ability to administer patient and protocol costs to Clinical Sites, and to budget and administer support for the Steering Committee and DSMC meetings provided?

Is the ability to estimate resources needed for the study and manage those resources efficiently during the course of research demonstrated?

Additional Review Criteria

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

Study Timeline

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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

Applications from Foreign Organizations

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

As noted above, does the research team demonstrate the ability to successfully comply with the HEAL Data Sharing Policy and Resource 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 will receive a written critique.

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

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

 

Under clinical trial directions- Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm. The DCC will be responsible for creating and maintaining ClinicalTrial.gov records, and reporting results, as required.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. The DCC will be required to provide, or engage the services of, a single-IRB for this trial. This may be through its own institution, via one of the Clinical Centers, or via a commercial IRB. IRB costs will be included in the Capitation Budget. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety

Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

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

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

  • Assistance with identification of priority areas for research
  • Developing and implementing the protocol including meeting recruitment goals based on information provided at the time
  • of application
  • Collection and transmission of the data to the DCC
  • Local data Management and quality control monitoring
  • Analysis of data and publication of results of the trial
  • Agreeing to accept the coordinating role of the group and the participatory and cooperative nature of the group process
  • The PD/PI will be a voting member of the Steering Committee; all parties will agree to accept the coordinating role of the group and the participatory and cooperative nature of the group process, and the decisions of the steering committee.
  • Clinical site awardees will retain custody of and have primary rights to the data and software developed under their awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

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

The NICHD Project Scientist or Project Coordinator will:

  • Provide technical assistance and participate as one voting member of the Steering Committee.
  • Assist with the identification of important areas of study.
  • Assist in the development of study protocols.
  • Assist in the development and review of capitation-based budgets, including the identification of study costs and special institutional needs.
  • Assist in the review and evaluation of each stage of the program before subsequent stages are started, in conjunction with the Steering Committee.

The NICHD 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.
  • Assure the scientific merit of the trials, including the option to withhold support of a participating center if technical performance requirements such as protocol compliance, enrollment targets, or randomization of subjects are not met.
  • Initiate a decision to modify or terminate a study based on the input of the DCC, DSMC, and/or Steering Committee

The  Steering Committee will:

  • Assist in publications and reporting results to the community of investigators and health care recipients.
  • Assist in the conduct of the trials, including ongoing review of progress.

Areas of Joint Responsibility include:

The management of the consortium includes committees with the following functions:

Steering Committee

  • The Steering Committee will be responsible for protocol implementation. The Steering Committee will have primary responsibility for the conduct of protocols and the preparation of publications. The Steering Committee will be composed of all PD(s)/PI(s), one representative from the data coordinating center, and one NICHD staff.
  • Participating NICHD staff will include the Project Scientist or Project Coordinator. The Project Scientist will be the only voting NICHD staff member of the Steering Committee. A member of the NICHD Grants Management Branch advises the Steering Committee on funding matters. An independent outside chairperson, who is not participating as a PD/PI, will be selected by the NICHD Director.
  • Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

Data and Safety Monitoring Board:

  • A Data and Safety Monitoring Committee (DSMC) conducts oversight and monitoring of the conduct of clinical trials to ensure the safety of participants and the validity and integrity of the data for the clinical trials. The DSMC is established by the NICHD and reports to the Director of NICHD. The DSMC is composed of individuals with expertise in clinical trial design and conduct, neonatology, basic science, and ethics.

In addition, the consortium will develop policies and procedures that govern its operations, including publications. These policies and procedures can be amended by the Steering Committee and the NICHD.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

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

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm.

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

Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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)

Andrew A. Bremer, MD, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Telephone: 301-402-7886

Email: andrew.bremer@nih.gov

Peer Review Contact(s)

Sherry Dupere, PhD

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

Telephone: 301-451-3415

Email: duperes@mail.nih.gov (mailto:duperes@mail.nih.gov)

Financial/Grants Management Contact(s)

Mario Martinez
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-402-4078
Email: martinem@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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