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

Collaborative Pediatric Critical Care Research Network (PL1) (Clinical Trial Required)

Activity Code

PL1 Research Program Project or Center - Linked Center Core Grant

Announcement Type

New

Related Notices
  • June 23, 2020 - Notice to Extend the Application Due Date and Expiration Date for RFA-HD-21-016. See Notice NOT-HD-20-023.
Funding Opportunity Announcement (FOA) Number

RFA-HD-21-016

Companion Funding Opportunity

None

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

93.865

Funding Opportunity Purpose

The purpose of this funding announcement is to invite applications to form a research network to conduct multisite clinical studies in pediatric critical care medicine.  The Network will be comprised of a Data Coordinating Center (DCC) and at least seven Clinical Sites.  The Network is designed to investigate the efficacy of treatment and management strategies to care for critically ill and injured children, as well as to better understand the pathophysiological bases of critical illness and injury in childhood.

Key Dates

 

Posted Date

May 29, 2020

Open Date (Earliest Submission Date)

June 30, 2020

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

New Date August 31, 2020

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.

No late applications will be accepted for this Funding Opportunity Announcement.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

November 2020

Advisory Council Review

January 2021

Earliest Start Date

April 2021

Expiration Date

New Date September 1, 2020 per issuance of NOT-HD-20-023. (Original Expiration Date: July 31, 2020 )

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

    Purpose

    The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications from institutions proposing to serve as Clinical Sites and/or the Data Coordinating Center (DCC) in NICHD's multisite Collaborative Pediatric Critical Care Research Network (CPCCRN).  Originally established in 2004, this successful research network is designed to investigate the efficacy of treatment and management strategies to care for critically ill and injured children, as well as to better understand the pathophysiological bases of critical illness and injury in childhood.  Given the relatively small and widely heterogeneous pediatric critically ill and injured patient population, it is believed that the vigorous use of appropriate scientific methodologies, deployed across a network of sites, will achieve the numbers of patients required to provide robust clinical answers more rapidly than any individual Clinical Site acting alone.  This FOA will maintain the infrastructure needed to foster and support multisite research to enhance our understanding of critical illness in children, advance the care of critically ill and injured children, and to improve outcomes for this most vulnerable population

    Background

    The CPCCRN was established in 2004 to conduct multisite research among critically ill and injured children.  Given the relatively small and vastly heterogeneous pool of critically ill pediatric patients, multisite research is necessary to advance the field.  Despite significant advances in pediatric critical care research, there remains a need for evidence-based data to inform care of critically ill and injured children.  Given the urgent and complex milieu of pediatric critical care, treatment is often based on limited knowledge of new modalities not subjected to rigorous study.  As a result, pediatric critical care therapies may be incorporated into practice based on limited experience with efficacy and/or safety virtually unevaluated scientifically.  Further, the longer-term consequences of critical illness and/or injury in childhood are not well studied, either for individual children and their families or for the larger communities into which they are re-integrated.  Mortality has become a relatively rare outcome in U.S. pediatric critical care units, and the relationship of critical care treatments and strategies to morbidity, development, and the re-integration barriers for children, their families, and the larger communities of school and peer groups remain understudied and poorly understood.

    A well-supported Network with a high-functioning DCC and established Clinical Sites infrastructure and expertise is the most efficient and effective method to conduct such research.  The portfolio of studies completed by previous CPCCRN Networks included a wide array of critical care issues including, but not limited to sepsis, acute respiratory distress, and multiple organ dysfunction syndrome.  The Network also implemented a biorepository protocol as well as prepared and posted several robust public use datasets in the NICHD Data and Specimen Hub (DASH).

    This collaborative research network will accelerate pediatric critical care research, leading to evaluation of promising new approaches to life support and critical decision-making in complex childhood illnesses and injuries.  Multisite research projects including, but not limited to clinical trials, have the potential to reduce the number of patients needed at any individual clinical site and allow subject accrual and meaningful translational and descriptive research to be more rapidly completed.  Further, common protocols have the potential to reduce the effect of variables that contribute to patient outcomes, allowing for valid comparisons between treatments.  The network approach will increase the number of comparative trials and meaningful translational and descriptive studies that are conducted by providing a framework for rapid initiation of important studies as their public health significance for children becomes apparent, through the efficient use of pooled scientific and clinical expertise and data management resources.

    PL1 Activity Code

    Although the purpose and goals of the CPCCRN remain largely unchanged as it enters its fourth cycle of investigation, and the basic structure of multiple Clinical Sites and a unifying DCC working collaboratively under the guidance of a Steering Committee will be maintained, there will be fundamental differences in the CPCCRN structure in the upcoming funding cycle.  First, given the growth in pediatric critical care medicine and the development of a stronger and broader research base, the funding mechanism used to support the Network will no longer be a Cooperative Agreement, removing the substantial scientific input previously provided by the NIH Project Scientist.  Instead, a PL1 mechanism, which is a Research Program Project or Center - Linked Center Core Grant will be used.  In the past, separate FOAs were issued for the CPCCRN Clinical Sites and the DCC; however, with this new mechanism, a DCC and Clinical Sites will be incorporated into a single PL1 application for a group proposing to serve as the CPCCRN (see below for more details).  Second, in contrast to previous cycles when applications only required a concept proposal as evidence of the Clinical Sites' ability to conduct research, the current application must include an actual research project proposal(s) that will be conducted by the Network.  The proposed project(s), one of which must be a multisite clinical trial addressing an issue of high relevance to pediatric critical care (see below), will undergo rigorous peer review by the Scientific Review Group.  Third, the purpose of this project is to expand the scope of the CPCCRN by facilitating the participation of more Clinical Sites and investigators.

    The PL1 activity code is designed to support shared resources and facilities for research by a group of investigators who focus on a common research problem.  In a single PL1 application for the CPCCRN, at least seven Clinical Sites, along with a site serving as the Data Coordinating Center, will work together in the pre-application period to develop, at a minimum, a single, shared protocol for the conduct of a large-scale, multisite clinical trial of high priority to pediatric critical care.  Thus, the Clinical Sites will predetermine who will participate in the Network based on the submitted application(s).  This differs from previous cycles when Clinical Sites submitted individual site applications and the NIH formed the Network from the individual Clinical Site applications that were most well-received.  At the time of the Network award, the PL1 components will be disaggregated, with each Clinical Site being funded through individual, but linked research project (RL1) grants.  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 Network.  Investigators applying to serve as Clinical Sites in the Network should invite at least one ancillary site(s) to work under the auspices of each Clinical Site.  The inclusion of ancillary sites working under each Network Clinical Site, serves to increase the access to additional study populations and improve efficiency of subject enrollment.  The DCC will be funded as a PL1 grant.  The PD/PI for the DCC must be the PD/PI for the overall PL1 application responding to this announcement.  If the PL1 is submitted as a multiple PD/PI application, the DCC PD/PI serves as the contact PD/PI.

    Scope of Work

    The collaborative applicants will propose a clinical trial protocol(s) that is appropriate and feasible to be completed by the Network.  All Clinical Sites will be required to participate in a cooperative and interactive manner with one another and the DCC.  Applicants may include an additional study(ies) in their application if sufficient funds are available within the allotted budget. If additional clinical studies are proposed in addition to the required clinical trial, those studies may or may not be clinical trials.  Also, if the Network chooses to do so, it may develop additional studies, solicit external funding and conduct such research throughout the 5-year funding cycle, as long as the external funding provides full funding for the project(s), including infrastructure costs.  Ideas for these subsequent studies may come from investigators within the Network or from the pediatric critical care field at large.  All proposed studies must go through the standard peer review process and be selected for funding of all aspects of the study.

    The Network will form a Steering Committee (composed of the PDs/PIs from each of the Clinical Site awards and the DCC, as well as an independent Chairperson) to oversee the activities of CPCCRN, including the conduct of the protocol(s) and the preparation of publications.  The CPCCRN Steering Committee will meet on a regular basis to discuss topics of mutual scientific interest, the current clinical study(ies), and potential collaborations. The Steering Committee Chairperson should not be affiliated with any of the Network institutions.  The CPCCRN Steering Committee will hold a scientific meeting within 3 months of award to finalize the common protocol(s) and develop the Network Manual of Operations (policies and procedures).

    Awardees should agree to actively implement the Network protocol(s) and enroll patients in the Network study(ies).  Clinical Sites that do not enroll patients in Network protocols or do not collaborate in the scientific development activities of the Network may not receive continuing support at the discretion of the Program Official. 

    The provision for a Data and Safety Monitoring Board (DSMB) and use of a single Institutional Review Board (sIRB) will be required to monitor CPCCRN interventional studies and clinical trials according to NICHD policy.  Funding for the functioning of the DSMB and IRB will be provided through the protocol funds (part of the award administered by the DCC). 

    In order to hasten accrual in Network studies, the DCC along with the Clinical Site PDs/PIs, should consider identifying qualified and interested investigators at non-CPCCRN sites who wish to enroll patients in these studies.  Additionally, Clinical Site applicants are encouraged to identify an ancillary site during the pre-application process and include that scientific collaboration in their section of the PL1 application.  Arrangements for data collection and reimbursement of trial-related data collection costs at non-CPCCRN sites will be the responsibility of the DCC. 

    The functions of the DCC will include developing protocol data management aspects, devising novel comparative study designs, providing sample size calculations and statistical advice, developing data forms and protocol tools, performing data analyses, administering scientific protocol funds for sites with NICHD approval/concurrence, coordinating and providing logistical support for the activities and meetings of the CPCCRN Steering Committee (at least 2 to 3 times per year), single IRB review coordination, Data and Safety Monitoring Board (as needed), Family Network Collaborative (as needed), and overall study coordination and quality assurance measures.   

    Priority Areas

    The overarching goal of the CPCCRN remains to provide the scientific basis of pediatric critical care practice.  Given the diverse and expansive lists of potential areas of research in the field, the following high priority areas of research have been identified based on a host of criteria including prevalence of the condition, impact and severity of the disease process, available funding, alignment with the NICHD Strategic Plan, and other existing resources.  The areas of study determined to be of highest priority for advancing the field of pediatric critical care include the following (not in ranked order):

    • ·    Multiple Organ Dysfunction Syndrome in Children
    • ·    Pediatric Sepsis
    • ·    Pediatric Acute (Critical) Brain Injury
    • ·    Pediatric Acute Respiratory Distress Syndrome
    • ·    Critical Illness in Children with Complex, Chronic Health Conditions
    • ·    ICU Processes, including (but not limited to) cardiopulmonary resuscitation, mechanical ventilation, extracorporeal therapies, etc.
    • ·    Palliative Care in Pediatric Critical Illness
    • ·    Life-Threatening Pediatric Trauma

    Applicants considered responsive to this FOA will have submitted a study(ies) that clearly addresses one of the above high-priority areas for pediatric critical care.  Prospective applicants are strongly encouraged to discuss their ideas with the Scientific/Research Staff listed under Section VII. Agency Contacts. 

    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. 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 up to $4,300,000 in FY 2021 to fund a Network composed of a Data Coordinating Center (DCC) and a minimum of seven Clinical Sites.

    At the time of the award, the Clinical Sites will be disaggregated from the PL1 application, such that each individual Clinical Site in the Network receives its own RL1 award, with each Clinical Site having its own PD(s)/PI(s) named on the award.  The DCC will be awarded under the PL1 award mechanism.

    Award Budget

    Within the PL1 mechanism, Clinical Site applicants may request up to $175,000/year in direct costs for the entire project period of 5 years.  Clinical Sites need not request the same amount of funding.  The total budget requests for all Clinical Site applicants must not exceed $1,250,000 in direct costs per year.

    The Data Coordinating Center may request a base budget up to $900,000/year in direct costs (budget must be commensurate with the proposed work) for the entire project period of 5 years.  The DCC, as the responsible party for administration of protocol funds (including capitation fees) to the Clinical Sites, should request protocol funds at a minimum of $700,000/year.  Protocol funds must be commensurate with the proposed work. In general, capitation costs are not subject to facilities and administration costs.  The exact funds that may be requested for protocol funds will rely, in part, on the number of Clinical Sites included in the Network application and the base budgets requested, as well as the number of proposed projects.   

    Award Project Period

    Applicants for the CPCCRN Network may request a project period of 5 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:

    o   Hispanic-serving Institutions

    o   Historically Black Colleges and Universities (HBCUs)

    o   Tribally Controlled Colleges and Universities (TCCUs)

    o   Alaska Native and Native Hawaiian Serving Institutions

    o   Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

    Nonprofits Other Than Institutions of Higher Education

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

    For-Profit Organizations

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

    Governments

    • ·        State Governments
    • ·        County Governments
    • ·        City or Township Governments
    • ·        Special District Governments
    • ·        Indian/Native American Tribal Governments (Federally Recognized)
    • ·        Indian/Native American Tribal Governments (Other than Federally Recognized)
    • ·        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.
    • o   NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. 
    • ·        eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
    • ·        Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

    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 will be the PD/PI of the Data Coordinating Center.  If the PL1 is submitted as a multi-PD/PI application, the DCC PD/PI should be the contact PD/PI.  

    Minimum Requirements for the DCC PD(s)/PI(s):

    • ·        The PD(s)/PI(s) and other key personnel must have prior experience operating a DCC in multisite studies in the previous five years.  Experience in planning, developing and executing pediatric studies, and the special consent and IRB procedures needed for the conduct of research in critically ill children and their families is strongly preferred.
    • ·        The PD(s)/PI(s) must have the ability to assist in designing protocols, data collection systems, including distributed data entry, and capabilities and experience with research performance and data quality control systems.
    • ·        The PD(s)/PI(s) should have the ability to manage and analyze data for several studies concurrently if more than one project is submitted in the application.
    • ·        The PD(s)/PI(s) must have the ability to hold and distribute scientific protocol funds to the Clinical Sites, and to maintain accounting for such funds with regular reporting to the NICHD Program Official and Grants Management Specialist.
    • ·        The PD(s)/PI(s) should have clinical experience in pediatrics, critical care medicine or preferably both.

    Minimal Requirements for the Clinical Sites PD(s)/PI(s):

    PD(s)/PI(s) for the Clinical Sites must be board-certified pediatric critical care specialists/intensivists (MD/DO).  Non-physicians holding a research doctorate (e.g. PhD) will be considered if they are able to provide descriptions of training, experience, research and publication history that affords them recognition as an academic and clinical pediatric critical care expert.

    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 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:

    Tammara Jenkins, MSN, RN, PCNS-BC, FCCM
    Telephone: 301-435-6837
    Email: tjenkins@mail.nih.gov

    Page Limitations

    Available Component Types

    Research Strategy/Program Plan Page Limits

    Overall

    12

    Data Coord Ctr

    12

    Clinical Sites

    6 (each Clinical Site)

    Addtl Res Project

    12 (each additional project)

    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
    • ·        Data Coordinating Center: required (minimum 1, maximum 1)
    • ·        Clinical Sites: required (minimum 7, maximum 12)
    • ·        Additional Research Projects: optional/not required (minimum 0, maximum 2)
    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.

    • ·    CPCCRN Network Organizational Structure. 

    Applicants must include a diagram and description of the organizational structure of the Network.  This diagram/description should demonstrate how the interactions among the Network components will achieve the stated goals of the Network.  The diagram should be attached as a PDF titled "CPCCRN Network Organizational Structure".  The PL1 application must include at least 7 Clinical Sites in addition to the Data Coordinating Center.   Each Clinical Sites is encouraged to identify ancillary sites to participate in the clinical trial to enhance subject accrual and data collection.

    • ·    Population Available for Clinical Research

    Each Clinical Site applicant for the Network must describe its pediatric critical care population.  Applicant Clinical Sites must have at least 1,500 admissions per site per year.  The total number of admissions at a Clinical Site may include admissions from ancillary sites. No more than 30 percent of such admissions may be transfers from other facilities.  In order to provide reviewers with the relevant characteristics of the specific pediatric critical care population available for study at each applicant Clinical Site (including ancillary sites), provide the following information regarding admissions over the designated two-year period of January 1, 2017 to January 1, 2019.  If there are ongoing or pending clinical studies/trials that will limit availability of patients for CPCCRN trials, these must be described for the review panel's consideration at the time of the review.

    The following information should be provided in tabular or other format:

    o  Number of PICU admissions

    o  Number of Emergency Department visits

    o  Number of PICU admissions in each of the following categories:

    o  Medical, non-oncologic/non-hematopoietic stem cell transplantation

    o  Medical, oncologic and/or hematopoietic stem cell transplantation

    o  Cardiac surgical

    o  Surgical, non-cardiac, non-trauma

    o  Surgical, trauma

    Additional tables or summaries should be included that clearly describe:

    o  Number of pediatric critical care unit admissions based on age groups:

    § Birth to one year

    § One to three years

    § Three to six years

    § Six to twelve years

    § Twelve to eighteen years

    o  Number of transport admissions

    o  Average daily census of the PICU

    o  Number of intubated, mechanically ventilated patients

    o  Race, gender, and ethnicity in the population of children admitted to the PICU during January 1, 2017 to January 1, 2019; race and ethnicity must be described as a percentage of the total PICU population as follows:

    § Ethnic Category (Female, Male, Sex/Gender Unknown or Not Reported)

    • ·    Hispanic or Latino
    • ·    Non-Hispanic or Latino
    • ·    Unknown (individuals not reporting ethnicity)

    § Racial Categories (Female, Male, Sex/Gender Unknown or Not Reported)

    • ·    American Indian/Alaska Native
    • ·    Asian
    • ·    Black or African American
    • ·    Native Hawaiian or Other Pacific Islander
    • ·    White
    • ·    More than one race
    • ·    Unknown or Not Reported
    Project/Performance Site Location(s) (Overall)

    Enter primary site only.  The primary site for all PL1 CPCCRN applications is the proposed Data Coordinating Center.

    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.

    For the PL1 application, all applicant PD(s)/PI(s) for the DCC and all Clinical Sites must be included.  The DCC PD/PI is the Contact PD/PI. Senior/Key Persons for each Clinical Site applicant must be included in that Site's specific section of the application.

    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:   Briefly describe the objectives/goals of the proposed Clinical Trial, including relevant scientific hypotheses and a statement of how the research and proposed Network will potentially advance the field and improve care for critically ill children and their families. 

    Research Strategy:  

    ·        Network Structure and Function

    Each application must include a description of the Network and the Steering Committee, which will be the main governing body of the Network.  Key roles, communication, and study governance structure should be described.  Plans for establishment of the Steering Committee and any anticipated subcommittees (e.g., writing subcommittee, publication subcommittee, etc.) should be included.

    A Family Network Collaborative (FNC), comprised of parents of children who have experienced critical illness or injury, should be included in the plan.  In brief, they assure that interests important to critically ill or injured children and their families are addressed in Network research.  All applications should address how they can incorporate family/participant input/feedback throughout the conduct of research within the Network.  Appropriate input and participation of the FNC (or similar group) are highly encouraged in all studies conducted by the CPCCRN.    

    A Data and Safety Monitoring Board (DSMB) will monitor the Network clinical trial.  As a part of its monitoring responsibility, the DSMB will follow any and all DSMB regulations outlined by the NICHD.  Funding for the functioning of the DSMB and the CPCCRN FNC (or equivalent) will be provided through the protocol funds (awarded to the DCC Core for distribution).  

    The application should address how the CPCCRN will incorporate junior investigators in the conduct of the research and/or scientific collaboration to encourage and provide opportunities for career development and training for the field of pediatric critical care.

    ·        Clinical Trial:  

    The Network must propose at least one multisite large-scale clinical trial that is designed to address an important clinical question in one of the high priority areas previously identified in this FOA.  Describe the research strategy for the R01-level Clinical Trial following the instructions in the SF424 (R&R) Application Guide and the NICHD Research Project Grant (R01-Clinical Trial Required) (PA-18-480).  Additional research projects may be proposed, as the research budget allows, but any such projects should be described under "Additional Research Projects."  If additional clinical studies are proposed in addition to the required clinical trial, those studies may or may not be clinical trials. 

    Letters of Support:   Include Letters of Support directly relevant to the proposed clinical trial, but not duplicative of other provided letters.  Include other letters of support if appropriate to the Overall section.

    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 CPCCRN is to facilitate discoveries by the broader 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, images, patient reported outcomes, 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 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.  The Data Sharing Plan must address the development of Public Use Datasets (PUDs) and the inclusion of posting PUDs to the NICHD DASH in a timely manner consistent with established recommendations.
    • ·    If the Clinical Trial project includes biospecimen storage, the application should discuss ownership of both data and biospecimens and a succession plan for ownership once federal support of the project has run out.
    • ·    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. (https://osp.od.nih.gov/scientific-sharing/genomic-data-sharing/) 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 human subjects research, clinical research, and/or NIH-defined 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 the clinical trial involves a common protocol across components (i.e., across the DCC and the individual Clinical Sites), applicants should include the PHS Human Subjects and Clinical Trials Information form(s) 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(s) in other components.  The Study Record must include sufficient information for all components that are involved in the particular study.  If human subjects are involved, add a Study Record for each proposed study involving human subjects.  There are no page limits for any attachments in the PHS Human Subjects and Clinical Trials Information form.

    The finalized protocol will require approval by NICHD.

    Section 2 - Study Population Characteristics

    2.7 Study Timeline

    The clinical trial is a 5-year effort.  The study timeline should list milestones that indicate progress at critical junctures of the clinical trial.  The timeline and milestones should be sufficiently objective to evaluate what will be achieved during the course of the project.  Prior to award, NICHD staff will negotiate with the PDs/PIs 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 Data and Safety Monitoring Board will make recommendations to the Network 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

    Data and Safety Monitoring Board (DSMB)

    In the Data and Safety Monitoring Plan, applicants must include the establishment of a Data and Safety Monitoring Board composed of subject matter experts who have no real or potential conflicts of interest with the Clinical Trial, and who report to the CPCCRN Steering Committee.  The DSMB must function in accordance with NICHD policy and 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 DSMB must include individuals with expertise in, at a minimum, clinical research, clinical trials, biostatistics, pediatrics, pediatric critical care.  Additional members with other specific expertise may be proposed.  NICHD must approve the DSMB 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, with the following additional instructions:

    Delayed Onset Studies are not allowed in response to this FOA; however, delayed start studies may be included as long as the delayed start study(ies) anticipate completion by the end of the 5-year funding cycle.

    PHS Assignment Request Form (Overall)

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

    Data Coordinating Center

    When preparing your application, use Component Type ‘Data Coord Ctr.’

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

    SF424 (R&R) Cover (Data Coordinating Center)

    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 (Data Coordinating Center)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Data Coordinating Center)

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

    Project Narrative:  Provide a Project Narrative for this core.  Specific names provided for Other Attachments must be no more than 50 characters including spaces.

    Project /Performance Site Location(s) (Data Coordinating Center)

    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 (Data Coordinating Center)
    • ·    In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘DCC 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 Data Coordinating Center PD/PI must be the PD/PI for the PL1 application.
    • ·    The Data Coordinating Center is expected to have a scientifically and administratively qualified PD/PI with responsibility for providing administrative and operational support to the Steering Committee and the Network.  The DCC PD/PI should provide leadership, ensure interaction and collaboration among scientists and staff of the Network, and foster efficiency and synergies through effective organizational capabilities.  The following personnel are integral to ensuring successful operation of the Data Coordinating Center:

    o  PD/PI with the appropriate expertise as outlined in Section III. Eligibility.

    o  Because of the importance of the Data Coordinating Center functions, one of the Senior/Key Persons must be designated in the application to direct the DCC in the absence of the PD/PI.  This individual must possess similar qualifications as the PD/PI.

    o  Statisticians

    o  Clinical Trial Project Coordinators/Managers

    o  Programming and analytic staff (including supervisory staff and software expertise staff)

    o  Data processing staff

    o  Logistics and support staff

    Budget (Data Coordinating Center)

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

    Patient and protocol costs for studies and trials (i.e. capitation funds) will be supported with a budget of at least $700,000 total costs per year for distribution to the Clinical Sites, and support for required monitoring, DSMB visits and meetings, etc.  Actual costs should reflect the needs of the application protocol.  All protocol costs will be managed and allocated by the DCC, as previously described.  The capitation budget and plan for allocation of protocol funds should be described here, as should any budgetary items specific to the Clinical Trial not already discussed.

    It is expected that the DCC PD/PI will commit person months effort commensurate with the scope of work proposed.

    The base budget should not exceed $900,000 in direct costs for any given year, but should be commensurate with the scope of work proposed.  Allowable costs
     include: 

    • ·    Clinical Trial Project Coordinators/Managers
    • ·    Statisticians
    • ·    Logistics and support staff
    • ·    Programming and analytic staff (including supervisory staff and software expertise staff)
    • ·    Costs associated with data entry, management, collection and analysis
    • ·    Supplies and small equipment (itemized and justified)
    • ·    Travel (trips to Steering Committee meetings)
    • ·    Software
    • ·    Report generation
    • ·    Data analysis, manuscript preparation
    • ·    Arrangement of logistical services for protocol-specific costs, including subcontracts and supplies
    • ·    Support for the activities of the CPCCRN Steering Committee, the DSMB, FNC, etc. through provision of materials/documentation support, meeting planning and logistics and conference call/webinar coordination
    • ·    Other costs (itemized and justified)

    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 (Data Coordinating Center)

    Specific Aims: Include Specific Aims for the DCC.  Concisely describe how the Data Coordinating Center in the CPCCRN will coordinate and manage the activities of the CPCCRN and coordinate the interaction among the components.       

    Research Strategy:

    Applicants for the Data Coordinating Center (DCC) must present satisfactory evidence for all of the following capabilities (Applicants may refer to biosketches but should not duplicate biosketch information here).

    Evidence of Successful Past Performance

    The DCC PD(s)/PI(s) must demonstrate prior experience in the design, conduct, data analysis and management of major collaborative clinical research projects, preferably in pediatric critical care, and provide evidence of successful performance as a DCC for multisite 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 CPCCRN Clinical Sites and subcommittees, safety reports for the DSMB, and provision of support of data files.

    Academic Productivity

    The DCC PD(s)/PI(s) must describe their experience with previous or ongoing clinical trials, especially those of a cooperative or multisite design, in the field of pediatric critical care.  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.

    Staffing Plan and Capabilities

    The application should describe expertise and plans for staffing DCC functions from protocol design through analysis and provide evidence of multisite collaboration on recent clinical trials, especially those in pediatric critical care, including publications resulting from these studies.  The DCC should have some degree of flexibility in staffing to be able to respond to changing needs and seasonal variation in work effort of the CPCCRN.  For instance, meeting deadlines, trial startup and completion, and other variables occur which necessitate increases and decreases in staff effort from the DCC.  Logistical staff for day to day functioning of the Network and support staff to manage Clinical Site patient and protocol costs must be described and justified.  Active participation of the PD/PI is expected during all phases of a research study. 

    Capacity and Ability to Manage Data and Communications

    Ability to assist in protocol development with respect to design of manual of operations, data collection forms, data collection systems, electronic technology, and data entry systems must be demonstrated in the application.  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 as well as plans for a web-based system for participants of the CPCCRN.  Previous experience in pediatric critical care studies and FDA IND and IDE (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.  The DCC must develop/provide and maintain a website for both public access and private, secure investigator access.

    Evidence of Reporting Capabilities

    Evidence of experience with generation of monthly reports on subject enrollment for multiple concurrent studies, reports for use by DSMB and Steering Committee meetings is required.  Documentation and dissemination of meeting minutes 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 and manuscripts for publication is to be described in the Research Plan.  The DCC PD/PI will provide a report to the NICHD and the Steering Committee, including a report of protocol fund distributions and outstanding invoices, as necessary and as requested. 

    Logistical and Other Support Services

    Applicants must describe experience and capabilities with respect to logistical and support services relevant to the Network.  The DCC provides arrangements for logistical support associated with Steering Committee meetings and conference calls, DSMB meetings, FNC meetings, webinars, and other meetings as needed by the Network.  The DCC also provides documentation in the form of minutes for the above-mentioned meetings.  On occasion, the DCC may handle travel arrangements for selected consultants as needed, and as resources permit.  The DCC will also provide infrastructure and support for the ongoing communication of the Network via email and teleconference.  Expertise in coordinating sample storage and study drug/equipment assignment is required.  The DCC oversees the patient and protocol funds for the studies and trials and maintains subcontracts with the Clinical Sites for disbursement. 

    On-Site and Off-Site Monitoring Ability

    Applicants for the DCC must provide evidence of experience in organizing and conducting both on-site and remote monitoring for research studies.  Generation of data errors and needed edits as queries to sites is required.  The DCC needs to ensure that Network Clinical Sites fully comply with NIH regulatory requirements, including Human Subjects Protections, informed consent, reporting of adverse events, human and animal safety and welfare provisions, and FDA requirements as indicated by specific studies.  As well, single IRB submissions and queries, including overall documentation and coordination of IRB approvals at Clinical Sites, is the responsibility of the DCC.

    Technology Transfer, Data Management and Protocol Training Capabilities

    Applicants are expected to describe capabilities in technology transfer, data management, and protocol training.  The DCC must be able to assist the Clinical Sites in data management and communication activities.  Training and technical expertise, as well as experience and resources, must be delineated.  Training sessions for scientific protocols, ongoing yearly certifications necessary for any CPCCRN study(ies) and data entry are arranged through the DCC.  The application should describe explicit plans, procedures, milestones, and timelines for adherence to the existing terms and conditions concerning Federal, Agency, and NICHD policies regarding research data sharing.  The applicant must describe protocols and processes for de-identifying research data and preparing and submitting datasets including specimens for archival in publicly available websites (e.g., the NICHD DASH, CPCCRN Biorepository).  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.

    Administrative and Management Capabilities

    The PD/PI should delineate his/her skills as a manager and administrator for a Data Coordinating Center.  The DCC must provide evidence of experience, ability, and organizational systems used to estimate the appropriateness and reasonableness of resources needed for individual projects and the ability to manage those resources efficiently during the course of the research.  Flexibility among personnel based on effort needed is required.  Prior experience with meeting formal deadlines (e.g., FDA reporting requirements, national meetings, Steering Committee meetings, DSMB meetings, and so forth) should be delineated in the application.

    The PD/PI and DCC must also demonstrate evidence of financial administrative capability.  The ability to efficiently process invoices from Clinical Sites and provide timely distribution of protocol funds is essential.  Experience with capitation for study subject recruitment by clinical sites is mandatory.  This includes providing and monitoring funds to the Clinical Sites for patient recruitment at regular intervals.  Experience with subcontracts is required, as there is anticipated need to supplement resources through arrangements with outside organizations, based on individual protocol requirements. 

    Special Strengths of the PD/PI and/or Institution

    Applicants are encouraged to describe special or unique strengths that may be relevant to CPCCRN research.  This 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 CPCCRN.   (Do not duplicate information included in Facilities and Other Resources).

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

    If the applicant DCC has substantial experience 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 multisite research in children, it should be summarized here.

    Intent to Participate

    There must be a clearly expressed intent to participate in a cooperative manner with other CPCCRN Clinical Sites, the CPCCRN at large, the DSMB and FNC in all aspects of research in a manner consistent with the terms of the award.  The prioritization of CPCCRN work at the DCC must be expressly stated in the application.  CPCCRN Clinical Sites are expected to participate in the study(ies), and the DCC provides logistic and data support for the project(s).  This may be covered in the letters of support, as appropriate, or in a separate statement.

    Letters of Support:  The departmental and institutional commitments to participate in CPCCRN-supported research must be clearly documented with letters of support from appropriate individuals, including the Chief Executive or Operating Official (or equivalent) of the applicant institution.  Evidence of past support can also be cited.  A description of the available and/or planned facility and how it has been used for multisite research as well as coordination of studies should be included.  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 should be described, as well as evidence of past research support.  Letters of support from appropriate leaders of institutional component services must be included in the application.

    ·        Applicants 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 (TIN) (https://trialinnovationnetwork.org), or other funded pediatric critical care research center as resources for conducting the proposed research must provide a letter of agreement that identifies the level and type of support from the CTSA program director, NCATS TIN director, or PD/PI of the pediatric critical care 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:

    All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.  The Data and Resource Sharing Plan for the Network as a whole should be described in the Overall component and should NOT be repeated here.  For the CPCCRN, preparation of data sets for public access and utilization will be carried out by the DCC.  The DCC should express their agreement with this policy.

    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 (Data Coordinating Center)

    When involving human subjects research, clinical research, and/or NIH-defined 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.  Human subjects study records should be provided as required in the Overall Section and Additional Research Projects section (if applicable), and not duplicated here.

    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, with the following additional instructions:

    Delayed Onset Studies are not allowed in response to this FOA; however, delayed start studies may be included as long as the delayed start study(ies) anticipate completion by the end of the 5-year funding cycle.

    Clinical Sites

    When preparing your application, use Component Type ‘Clinical Sites.’

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

    SF424 (R&R) Cover (Clinical Sites)

    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 Sites)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Clinical Sites)

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

    Project Narrative:  Provide a Project Narrative for this Core for each Clinical Site in the application.  Specific names provided for Other Attachments must be no more than 50 characters including spaces.

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

    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 (Clinical Sites)

    • ·    In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Clinical Site 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.  
    • ·    Clinical Site PD(s)/PI(s) must be qualified as outlined in Section III.1.Eligibility.  The Clinical Site PD/PI 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 Clinical Site and any collaborating ancillary sites.  Diversity of Clinical Site PI(s)/PD(s), in terms of sex/gender, ethnicity, and under-represented minorities, is encouraged to be included in the application, if applicable.
    • ·    One Clinical Research Coordinator (CRC) for each Clinical Site (and subsites, if applicable) must be designated, with the biographical sketch included as part of the application.  Preference will be given to CRCs with clinical/nursing backgrounds, preferably in related practice areas, e.g. pediatric critical care, pediatrics, etc.
    • ·    Clinical Sites with multiple subsites/ancillary sites should identify the investigator responsible at each collaborating site(s).

    Budget (Clinical Sites)

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

    A Base Budget estimate for the Clinical Site should be included for all years.  The first year Base Budget will be limited to $175,000 in direct costs with allowances as follows:

    • ·    Clinical Site PD/PI:  Minimum 1.2 person months effort, yet commensurate with the scope of work
    • ·    Clinical Research Coordinator:  may request up to 1 Full-Time Equivalent (FTE), yet commensurate with the scope of work
    • ·    Travel:  The costs of travel to Network Steering Committee meetings for the PD/PI and Research Coordinator (at a minimum) should be included in the budget.  This includes a minimum of 2 to 3 meetings/year.
    • ·    Supplies and small equipment (itemized and justified): Not to exceed $5,000
    • ·    Start-up costs for any collaborating ancillary clinical sites:  commensurate with the scope of work
    • ·    Other costs (itemized and justified): Not to exceed $3,000

    The protocol budgets will consist of specific protocol-related allowances, capitated per subject enrolled in each study at the applicant Clinical Site.  The DCC will be responsible for issuing protocol fund payments to the Clinical Sites for the study(ies).

    Each CPCCRN Clinical Site will be awarded base costs (as listed above) from the NICHD.  The Clinical Site's F&A rates on the initial competitive awards will not be increased in future years due to changes in their negotiated rate agreements.

    Total funding for Clinical Sites depends on the base awards and reimbursements for approved protocol-related expenses from the DCC.  The overall provision of money for the CPCCRN is subject to the availability of NICHD funding.

    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 Sites)

    Specific Aims:  Briefly describe how the Clinical Site, as a whole, will contribute to the successful conduct and completion of the Clinical Trial, and additional Network studies, if relevant.  

    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 single unit.  Management plans, including supervision, training, in-service, certification, data handling, quality assurance, costs effective management, and communication are required for all Clinical Sites.  If a Clinical Site applies with more than one institution and/or facility (e.g. a consortium of sites applying together as one Clinical Site within the PL1), a separate plan of how the above issues will be handled for a multi-institution Clinical Site must be included.

    The Clinical Sites should address the following items (Applicants my refer to biosketches but should not duplicate biosketch information here):

    Collaboration

    Applicants should describe how the Clinical Sites will collaborate with each other and with the DCC as well as their participation on the Steering Committee.

    Academic Productivity

    Applicants must provide evidence of research productivity by the participating Clinical Sites in previous or ongoing clinical trials or descriptive studies of importance to the field of pediatric critical care, especially those of a cooperative or multisite design.  If a multisite group or consortium of sites has a long standing and productive collaboration and interaction among institutions, this should be clearly described in the application.  Contributions in the key areas of research development and design, patient recruitment, retention and study completion, data collection and analysis, and publications generated in collaborative activities should be included in the application.

    Pediatric Critical Care Staffing and Available Expertise

    Describe the staffing for the Clinical Site.  The Clinical Site should be a tertiary or quaternary care children's hospital with multiple full-time, board-certified, academically-oriented pediatric intensivists in a division of pediatric critical care medicine that admits both medical and surgical patients, and accepts transfers from outside facilities, including emergency departments, and pediatric inpatient services in the community setting.  The Clinical Site may include additional ancillary sites to assist with patient recruitment and the overall conduct of research.  A full description of any ancillary sites should also be included in the application.

    The Clinical Site PD(s)/PI(s) must be fully qualified as outlined in Section III.1 Eligibility.  The Clinical Sites PD(s)/PI(s)' clinical, academic, administrative, and research time commitments, and availability for CPCCRN research and management activities, should be clearly stated in the application.

    The application should describe additional multidisciplinary expertise available at the institution(s) for the research undertaken in this program, including (but not limited to) the areas of pediatric critical care medicine, pediatric surgical critical care, pediatric trauma, biostatistics, bioengineering, pediatric neurology and child development, genetics, pediatric rehabilitation, informatics, immunology, pulmonology, cardiology, pharmacology, therapeutic development, and clinical trials management.  Provide an explanation of how this expertise will be coordinated by Clinical Site leadership.

    The application should address how the Clinical Site will incorporate junior investigators in the conduct of the research and/or scientific collaboration to encourage and provide opportunities for career development and training for the field of pediatric critical care.

    Research Staff

    A Clinical Research Coordinator who is qualified by training, background, and research experience, should be clearly identified and included in the biographical sketch section of the application.  As stated, preference is for CRCs with clinical/nursing backgrounds, preferably in related practice areas, e.g. pediatric critical care, pediatrics, etc.  Additional research staff should be available, as the Network protocol(s) may require patient recruitment at night and on weekends, so evidence of coverage will be needed to ensure maximal Clinical Site participation.  The application should describe plans for training staff and managing their responsibilities and activities.

    Evidence of Follow-Up Capabilities

    Evidence of commitment to following children for up to two years after discharge from the PICU must be prominent at all Clinical Sites.

    Critical Care Data System

    An established electronic data system must be in place to collect and analyze patient information.  A detailed description of the variables to be collected, quality control, and management of the data system must be provided.  An illustration of the use of the system for a recent clinical research study should be included in the application.  All successful applicants, as a condition of the award, must provide complete, accurate, and timely transmission of data to the Network DCC.  Applicants should describe their processes for responses to data entry edits, queries and audits.

    Additional Clinical Capabilities

    Applicant Clinical Sites are expected to have a full range of pediatric subspecialists, state-of-the-art facilities, clinical capabilities, and excellent support staff.  Laboratory facilities, imaging capabilities, research pharmacists, and qualified staff in nursing and respiratory therapy are essential requirements that should be documented in the application.

    Special Strengths of the Clinical Site PD(s)/PI(s) and/or Institution

    Applicants are encouraged to describe special or unique strengths that may be relevant to CPCCRN research.  This can include state-of-the-art scientific capabilities such as modern imaging techniques, proteomics, genomics, microanalysis, clinical pharmacology, respiratory therapy, and so forth, which may be shared or may be available to develop and expand the scientific productivity of CPCCRN.  (Do not duplicate information included in Facilities and Other Resources).

    In addition, special administrative strengths or experience, as well as participation in administrative aspects of clinical research (institutional review board, data and safety monitoring committee, advisory board for clinical research, clinical research committees, etc.) should be highlighted.  Level and support of clinical trials can be described.

    Applications from institutions that have a Clinical and Translational Science Award (CTSA) or other funded pediatric critical care research centers must describe the type and amount of support available from those resources for conducting research at the Clinical Sites.

    Intent to Participate

    There must be a clearly expressed intent to participate in a cooperative and collaborative manner with other CPCCRN Clinical Sites and the DCC in all aspects of research as outlined in this FOA.  Clinical Sites are expected to participate fully in the Network trial(s)/project(s).  This may be addressed in the Letters of Support, as applicable, or in a separate statement here.

    Letters of Support:

    Strong institutional commitment, as well as evidence of past research support, must be clearly documented with letters of support from appropriate individuals at the Clinical Site(s) (including any ancillary sites).  Evidence of support in areas of grants management, personnel management, space allocation, electronic data systems management, procurement, equipment as well as general support for the research should be provided.

    Letters from the Service or Division Chief of Pediatric Critical Care Medicine, the Chair of Pediatrics, and the Chief Operating or Executive Officer of the Clinical Site must be included in the application.  These letters must indicate support for the application and clearly state that appropriate clinical time commitments and schedule modifications will be made as needed to assure the applicant and Clinical Site's full participation in Network studies, as well as writing and administrative responsibilities as part of the Steering Committee. Assurance of cooperation with the policy for capitation of research costs should also be provided from the departmental and institutional offices of sponsored research programs.

    The Chief Executive or Chief Operating Officer of the Clinical Site (and any ancillary sites) must provide a letter of assurance that staff resources in pharmacy, nursing, respiratory therapy, and administrative support and language translation will be available to support the activities of CPCCRN.

    Applications from institutions that have a CTSA funded by the NIH or other funded pediatric critical care research centers as resources for conducting the proposed research must provide a letter of agreement that identifies the level and type of support from the PD/PI or the CTSA program director.

    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.  For the CPCCRN, preparation of data sets for public access and utilization will be carried out by the DCC, but applicant Clinical Sites should express their agreement with this policy, as well as the plan for storage of biospecimens and data, if applicable.  

    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. (https://osp.od.nih.gov/scientific-sharing/genomic-data-sharing/) 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.   

    Additional Research Project (OPTIONAL)

    When preparing your application, use Component Type ‘Addtl Res Project.’

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

    SF424 (R&R) Cover (Additional Research Project)

    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 (Additional Research Project)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Additional Research Project)

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

    Project Narrative:  Provide a Project Narrative for each additional research project in the application. Specific names provided for Other Attachments must be no more than 50 characters including spaces.

    Project /Performance Site Location(s) (Additional Research Project)

    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 (Additional Research Project)

    • ·    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.   

    Budget (Additional Research Project)

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

    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.

    Note: The DCC will distribute patient and protocol funds (i.e. capitation funds) to the Clinical Sites as previously described, and support for required monitoring and DSMB visits and meetings.  Actual costs should reflect the needs of the application protocol and must fit within the allotted overall budget for this FOA.  The capitation budget and plan for allocation of protocol funds should be described here, as should any budgetary items specific to the Additional Research Project not already discussed.

    PHS 398 Research Plan (Additional Research Project)

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

    Specific Aims:  Briefly describe the goals of the Additional Research Project, including relevant scientific hypotheses, as applicable, including a statement of how the research will potentially advance the field and improve care for critically ill children and their families.  The Additional Research Project may or may not be an NIH-defined clinical trial (i.e. clinical trial optional).

    Research Strategy:  Describe the research strategy for the Additional Research Project following the instructions in the SF424 (R&R) Application Guide using an NIH/NICHD-appropriate parent FOA (i.e. R01 (clinical trial required), R01 (clinical trial not allowed), R21 (PA-18-482 clinical trial optional), R03 (PA-18-481 clinical trial optional).

    Letters of Support:  Include Letters of Support directly relevant to the proposed Additional Research Project, but not duplicative of previously provided letters.

    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.  The Data Sharing Plan will be considered during peer review and by program staff as award decisions are being made as appropriate and consistent with achieving the goals of the program.  It is expected that the results of NICHD-funded research will be shared with the wider scientific community in a timely manner.
    • ·    Awardees should submit datasets to the NICHD Data and Specimen Hub and other equivalent broad-sharing data and/or biospecimen repositories.
    • ·    If the Clinical Trial project includes biospecimen storage, the application should discuss ownership of both data and biospecimens and a succession plan for ownership once federal support of the project has run out.
    • ·    The following resource describing Common Data Elements may be helpful during the planning phases of a project when considering ways to optimize data collection in order to facilitate broad data sharing: https://www.nlm.nih.gov/cde/.

    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 (Additional Research Project)

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

    The finalized protocol will require approval by NICHD.  If the Additional Research Project meets the NIH definition of a clinical trial, the following requirements for study timeline and Data and Safety Monitoring Board apply and must be included in the application.

    ·        Section 2 - Study Population Characteristics

    ·        2.7 Study Timeline

    The clinical trial is a 5-year effort.  The study timeline should list milestones that indicate progress at critical junctures of the clinical trial.  The timeline and milestones should be sufficiently objective to evaluate what will be achieved during the course of the project.  Prior to award, NICHD staff will negotiate with the PDs/PIs 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 Data and Safety Monitoring Board will make recommendations to the Network 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

    Data and Safety Monitoring Board (DSMB)

    In the Data and Safety Monitoring Plan, applicants must include the establishment of a Data and Safety Monitoring Board composed of subject matter experts who have no real or potential conflicts of interest with the Clinical Trial, and who report to the CPCCRN Steering Committee.  The DSMB must function in accordance with NICHD policy and 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 DSMB must include individuals with expertise in, at a minimum, clinical research, clinical trials, biostatistics, pediatrics, pediatric critical care.  Additional members with other specific expertise may be proposed.  NICHD must approve the DSMB 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, with the following additional instructions:

    Delayed Onset Studies are not allowed in response to this FOA; however, delayed start studies may be included as long as the delayed start study(ies) anticipate completion by the end of the 5-year funding cycle.

    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 NICHD Scientific Review Branch, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

    Pre-Application Technical Assistance Webinar
     

    An informational pre-application technical assistance webinar, addressing the scientific and administrative issues associated with this initiative, is anticipated.  The purpose of this webinar will be to (1) familiarize the potential applicant with established NIH guidelines and criteria for review, (2) discuss the areas of NICHD programmatic emphasis, and (3) facilitate the submission of a well-organized application. 

    Applicants interested in the pre-application technical assistance webinar should contact Ms. Tammara Jenkins (tjenkins@mail.nih.gov) to request further details.  Individuals planning on participating in the webinar are requested to submit specific questions to Ms. Jenkins at least one week in advance of the webinar.  Participation in the webinar is not required to submit an application in response to this announcement.  Individual telephone consultation, separate from the pre-application webinar, is also available upon request and encouraged for all interested applicants.    

    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 FOA, review of applications will include 2 (two) categories.  The first category for review is the overall structure and function of the proposed Network.  The second category for review is the common clinical trial to be conducted by all members of the Network.

    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 - Overall

    Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the overall Network and proposed clinical trial 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 overall Network and clinical trial 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 clinical trial that by its nature is not innovative may be essential to advance a field.

    Significance

    Do the overall Network and proposed clinical trial 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 overall Network and proposed clinical trial 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 Network?  Is the proposed overall Network likely to successfully complete a rigorous clinical trial (as proposed)?

    Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported in the clinical trial research plan 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 overall Network and the proposed clinical trial? 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 overall Network PD(s)/PI(s) have the ability to contribute to the overall Network 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 clinical trials, including experience in research design, particularly in pediatric critical care?  Is there adequate commitment of time and effort for the research and administrative functions of the overall Network?  As a group, are the investigators well-suited to the clinical trial/project(s)?  Is there evidence of multidisciplinary backgrounds and interests among the investigators?  Does the application propose a structure that will optimize the number and distribution of participating investigators?  Does the application demonstrate the commitment, availability, and flexibility of staff time for satisfactory conduct of the proposed Clinical Trial (and additional research project(s), if applicable)?

    Is there evidence of the quality of the investigators' participation in randomized clinical trials or seminal observational and translational studies in the recent past? 

    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? 

    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?

    Is there evidence that the overall Network will be a source of innovation in scientific design?

    Does the overall Network propose innovative ways to communicate, to allocate resources, to promote collaborations, to recruit and retain research subjects, or other research activities? 

    Does the proposed Clinical Trial offer an innovative approach to conducting multisite pediatric critical care research?  Does the proposed Clinical Trial hold the potential to transform care of critically ill or injured children in one of the identified high-priority areas of pediatric critical care?

    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 Network and the proposed clinical trial? 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 trial or additional study(ies) 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 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, Statistical Analysis, and Data and Specimen Storage

    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 site 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?

    If the Clinical Trial project includes biospecimen storage, is there discussion of ownership of both data and biospecimens and a succession plan for ownership once federal support of the project has run out?

    In terms of the overall organization of the proposed Network:

    • ·    Does the application clearly demonstrate the feasibility of the organizational structure?
    • ·    Does the organizational structure have clear lines of authority that allow for efficient implementation of the proposed clinical trial?  Are the individual components well-integrated into the Network?  Does the application demonstrate willingness to work and cooperate with other Network Clinical Sites, ancillary sites (if applicable) and the DCC to achieve CPCCRN goals?
    • ·    Is appropriate administrative organization proposed for establishing and maintaining communication and cooperation between the Network investigators? 
    • ·    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 DSMB? 
    • ·    Is the plan for use of a single IRB adequate? 
    • ·    Does the overall Network research team have the institutional supports and capabilities, including the patient populations, to participate fully in a collaborative effort? 
    • ·    Is it likely that the overall Network, as described, has the ability to recruit, retain, and follow up with subjects in a clinical trial?  Are appropriate populations available at the Clinical Sites and is there evidence of commitment to prioritize CPCCRN studies?  Are appropriate administrative, clinical, and data organizational management facilities available at the overall Network Clinical Sites and DCC?
    • ·    Is there a well-developed and justified overall system for administration and disbursal of capitation funds?
    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?

    Does the overall Network environment provide adequate high-quality data analytic capacity, database facilities, coordination, and data resources?

    Are the Data Coordinating Center and Clinical Site environments (including ancillary sites) appropriate for the trial(s)/research proposed?

    Do the applicant institutions have access to diverse subject populations, including racial, ethnic, socioeconomic, and geographic diversity?

    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?

    Additional Review Criteria - Overall

    As applicable for the overall Network and clinical trial 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 proposed clinical trial 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 overall Network and proposed clinical trial 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 Network and clinical trial 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 .  Reviewers should also comment on whether the plan for creating Public Use Datasets and their deposition into the NICHD DASH in a timely manner, as well as continuation or development of the CPCCRN Central Biorepository are reasonable.


    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.

     
    Review Criteria - Data Coordinating Center

    As applicable for the Data Coordinating Center proposed, reviewers will evaluate the following items, while determining scientific and technical merit, and in providing an impact score for the Data Coordinating Center but will not give separate scores for these items.  For the application as a whole, the criteria below will be considered in addition to those presented above for the Overall section.

    • ·        Does the application demonstrate the scientific, administrative, statistical, and academic qualification of the DCC PD(s)/PI(s), the individual identified as backup to the DCC PD(s)/PI(s), and the research team at the DCC, as well as the qualification of the applicant institution to participate fully as the DCC for the CPCCRN Network?  Does the DCC PI have clinical experience in the fields of pediatrics, critical care, or preferably, pediatric critical care?
    • ·        Does the DCC demonstrate experience and an ongoing record of accomplishments in coordinating and managing multisite clinical trials research, especially in pediatric critical care patients, either as an independent DCC, or as part of an individual Data Coordinating Center in the past five years?
    • ·        Does the application demonstrate the appropriate commitment, availability, and flexibility of staff and PD/PI time for the DCC for the satisfactory conduct of the study(ies) and Network activities?
    • ·        Do the key personnel possess appropriate and adequate knowledge and experience in areas relevant to the conduct of collaborative clinical research, especially multisite clinical trials, including experience in biostatistics, research design, execution, data management and quality control, preferably in pediatric critical care medicine, institutional review boards (IRBs), project management, staff site training, as well as the special needs of pediatric subjects?
    • ·        Does the DCC application demonstrate adequate evidence of management capability, including assessment of the PD/PI's ability to estimate appropriate and reasonable resources for research studies, to manage research resources efficiently during study execution, to oversee capitation systems to Clinical Sites and manage sub-awards during an ongoing study, and to budget and administer support for Steering Committee and DSMB meetings and communication systems?
    • ·        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 webinars, conference calls and support the complexity of workflow within the Network?
    • ·        Does the application provide adequate quality and examples of procedures for communication of relevant information among investigators during the conduct of the clinical trial, adequate quality of reporting capabilities in multisite trials with respect to regular reports, trial subject enrollment, and DSMB experience, adequate quality of procedures for on-site and remote monitoring, and adequate quality of protocol training and data entry training capabilities?
    • ·        Does the application provide 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?
    • ·        Is there evidence of technology transfer capabilities and capability and support of publicly utilizable datasets?
    • ·        Will the institutional environment and supports (both administrative and organizational management), equipment and other physical resources available to the DCC contribute to the probability of success in facilitating the Network and proposed research?  Are there unique resources that enhance the site's probability of success as the Network DCC?
    Review Criteria - Clinical Sites

    As applicable for the Network Clinical Sites proposed, reviewers will evaluate the following items, while determining scientific and technical merit, and in providing an impact score for the Network Clinical Sites but will not give separate scores for these items.  For the application as a whole, the criteria below will be considered in addition to those presented above for the Overall section.

    • ·        Do the Clinical Sites have experienced leadership, the necessary patient populations and organizational capacities to make an important contribution to the CPCCRN Network, including demonstration of successful experience with managing multisite clinical trials/research projects, including the participation of ancillary sites?
    • ·        Are the Clinical Site PDs/PIs, collaborators, and other researchers well-suited to the CPCCRN Network?  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)?
    • ·        Do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the Clinical Sites and the Network? 
    • ·        Do the Clinical Site PDs/PIs and other Key Personnel have demonstrated expertise in pediatric critical care, and the scientific, administrative, clinical and academic qualifications to conduct a successful clinical research study(ies) in a high-priority area of pediatric critical care?
    • ·        Do the Clinical Site PD(s)/PI(s) have significant track records of productivity in clinical research in the recent past?
    • ·        Is there commitment of staff time for the satisfactory conduct of the study(ies) and are there qualified team members who would be responsible for data quality and management activities?
    • ·        Does the application reflect commitment on the part of the Clinical Sites to collaborate with the other Network components and the Steering Committee?
    • ·        Do the research teams at the Clinical Sites have the institutional support and capabilities including the patient populations to participate fully in a collaborative effort?  Are they capable of enrolling a large cohort of patients for the clinical trial, and achieving adequate follow up and retention rates for up to 2 years? 
    • ·        Do the applicant Clinical Sites have the necessary diversity (including geographic, race/ethnicity, and sociodemographic diversity) of patient populations required for the project including at least 1,500 admissions per year (this patient population may include admissions from any designated ancillary sites)? 
    • ·        Will there be competition with other studies for enrolling eligible children and will the proposed clinical trial have precedence?  Have the Clinical Sites discussed plans for maintaining enrollment in the event of competing studies?
    • ·        Are staffing levels at the Clinical Sites and any subsites appropriate to cover the proposed clinical trial schedule of enrollments?
    • ·        Are there institutional assurances to provide support to the study in such areas as fiscal administration, personnel management, space allocation, procurement, planning, and budgeting?
    • ·        Do the Clinical Sites (and associated ancillary sites) have the necessary electronic data collection systems to participate in the CPCCRN study(ies)?
    • ·        Do the research teams at the Clinical Sites have the institutional support and capabilities to participate fully in the CPCCRN Network?  Does that institutional commitment include cooperation with the policy for capitation of research costs as outlined?
    • ·        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/ (https://trialinnovationnetwork.org/)), or other funded pediatric critical care research centers available to leverage as resources for conducting the proposed research?
    • ·        Do the applicant Clinical Sites demonstrate a commitment to career development and training of junior investigators and how they might incorporate this into the scientific efforts of the Network?
     
    Review Criteria - Additional Research Project (If applicable)

    As applicable for the Additional Research Project proposed, reviewers will evaluate the following items, while determining scientific and technical merit, and in providing an impact score for the Additional Research Project but will not give separate scores for these items.  For the application as a whole, the criteria below will be considered in addition to those presented above for the Overall section.

    • ·        Are the scientific rationale and need for an Additional Research Project well supported by preliminary data, clinical and/or preclinical studies, or information in the literature?  For trials or projects focusing on clinical or public health endpoints, is this additional research project necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice?  For trials or projects focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
    • ·        Are the DCC and Clinical Site PDs/PIs, collaborators, and other researchers in the Network well-suited to the proposed Additional Research 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 proposed Additional Research Project and the Network?
    • ·        With regard to the proposed leadership for the project, do the DCC and Clinical Site PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial/research project and meet milestones and timelines, as necessary? Do they have appropriate expertise in study coordination, data management and statistics? For a multisite trial, is the organizational structure appropriate and are the DCC and Clinical Sites well-suited to conduct the proposed research?
    • ·        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?  
    • ·        Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Additional Research Project?  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 Additional Research Project involves human subjects and/or NIH-defined clinical research, are there 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 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, Statistical Analysis, and Data and Specimen Storage  

    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 site 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?

    • ·        If the Additional Research Project includes biospecimen storage, is there discussion of ownership of both data and biospecimens and a succession plan for ownership once federal support of the project has run out?
    • ·        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?
    • ·        Are the Data Coordinating Center and Clinical Site environments (including all ancillary sites) appropriate for the proposed project?
    • ·        Does the application adequately address the capability and ability to conduct the research project at the proposed site(s)? Are the plans to add ancillary recruitment sites, as needed, appropriate?
    • ·        If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
    • ·        Is there evidence of the ability of the individual site 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? 
    Additional Review Criteria - Additional Research Project (if applicable)

    Study Timeline

    Is the proposed clinical trial 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

    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.

    Additional Review Considerations - Additional Research Project (If applicable)

    As applicable for the Network and 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

    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 .  Reviewers should also comment on whether the plan for creating Public Use Datasets and their deposition into the NICHD DASH in a timely manner, as well as continuation or development of the CPCCRN Central Biorepository are reasonable.


    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.

    Additional Review Considerations - Overall

    As applicable for the Network and clinical trial 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 .  Reviewers should also comment on whether the plan for creating Public Use Datasets and their deposition into the NICHD DASH in a timely manner, as well as continuation or development of the CPCCRN Central Biorepository are reasonable..


    Authentication of Key Biological and/or Chemical Resources

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

    Budget and Period of Support

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

    2. Review and Selection Process

    Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the NICHD Scientific Review Branch 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.

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

    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).   

    Prior Approval of Pilot Projects

    Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation. 

    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

    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.

    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)

    Tammara Jenkins, MSN, RN, PCNS-BC, FCCM
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
    Telephone: 301-435-6837
    Email: tjenkins@mail.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

    Financial/Grants Management Contact(s)

    Bryan Clark, MBA
    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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