Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

NIH is establishing the new Environmental influences on Child Health Outcomes (ECHO) program to investigate the longitudinal impact of prenatal, perinatal, and postnatal environmental exposures on pediatric health outcomes with high public health impact. To do so, NIH will support multiple synergistic, prospective longitudinal studies using extant cohorts that represent variable environmental exposures (e.g., physical, chemical, biological, behavioral, social). These studies will collaborate on standardization and collection of core data elements to answer research questions of how environmental exposures impact one or more of four key pediatric outcomes. The program will be overseen by a Steering Committee (SC) of Investigators and an NIH Program Director and ECHO Program Team, and an External Scientific Board. A separate, but related research effort, will support an IDeA States National Pediatric Clinical Research Network to help address access gaps for rural children by leveraging the infrastructure at existing IDeA state centers.

ECHO will be established through 7 FOAs, including this FOA inviting applications for a Patient Reported Outcomes Research Resource Center Core (ECHO PRO Core). In addition, companion FOAs will support new research questions for existing cohorts (Cohort Sites), a Coordinating Center (CC), a Data Analysis Center (DAC), an IDeA States Pediatric Clinical Research Network Data Coordination and Operating Center, and IDeA States Pediatric Clinical Research Network Sites, as well as supplements to the Children's Health Exposure Analysis Resource (CHEAR).

Following the closure of the National Children's Study (NCS) in fiscal year (FY) 2015, Dr. Francis Collins, the NIH Director, emphasized the importance of and need for research addressing the links between the environment and child health and development. To make the best use of the NCS-appropriated funds for FY 2015, NIH established new programs and enhanced existing programs focusing primarily on the development of tools to enhance measurement of environmental exposures (e.g., physical, chemical, biological, psychosocial), and the study of environmental influences on placental and in utero development to identify the "seeds" of future diseases and conditions.

The new ECHO program for FY 2016 continues to leverage investments made in extant programs while providing the flexibility to investigate key questions of interest at the intersection of environmental health and pediatric research. NIH will support multiple synergistic, longitudinal studies using extant cohorts that represent a broad range of environmental exposures (e.g., physical, chemical, biological, behavioral, social). All longitudinal studies will test the hypothesis of how environmental exposures impact childhood health outcomes. Each applicant will propose a strategy for collection of a targeted set of data (Core Elements) as a part of the project and will agree to collaboration on standardization through Steering Committee participation. These Core Elements will include:

• Demographics [e.g., race, gender, ethnicity, socioeconomic status, geographic location/diversity]
• Typical Early Development [e.g., growth, milestones, sleep, nutrition, activity level]
• Optional Sub-Element: Microbiome
• Genetic Influences on Early Childhood Development
• Optional Sub-Element: Epigenetics [e.g., maternal "exposome"]
• Environmental Factors [e.g., physical, chemical, biological (in utero), psychosocial, natural and built environments]
• Patient Reported Outcomes (PROs) [e.g., PROMIS Adult and Pediatric Self- and Proxy-Reported Health representing Physical, Mental and Social Health Domains]

The cohort studies will focus on one to four key pediatric outcomes to assess range of functioning over time. These Focus Areas are:

• Upper and Lower Airway [e.g., asthma, allergies, sleep disordered breathing]
• Obesity [e.g., nutrition, diabetes, metabolic risk factors]
• Pre-, Peri-, and Postnatal Outcomes [e.g., birth defects, childhood outcomes]
• Neurodevelopment [e.g., autism, ADHD, depression, social/behavioral development, cognition]

The FY 2016 plan aims to provide the flexibility and opportunity to investigate key questions of interest at the intersection of environmental health and pediatric research, while also leveraging additional features and capabilities of the studies. For example, the studies could:

• Take maximal advantage of existing tissue banks collected across pregnancy (e.g., cervicovaginal secretions, maternal DNA, cord blood, placenta) and data sets by funding additional analyses
• Serve as a test bed for validating new technologies, tools, and approaches for efficient and effective environmental and pediatric monitoring
• Use systems approaches to develop multi-variable models to predict disease development
• Recruit future pregnancies and investigate outcomes of second children to serve as a comparison cohort to first pregnancy children

An additional opportunity for creating an IDeA States National Pediatric Clinical Research Network also will be supported. This national network for pediatric research will help address access gaps for rural children through a national network for pediatric research embedded at IDeA locations and link existing IDeA state centers with experts in clinical trials.

This set of companion FOAs aims to create a consortium of sites and investigators to conduct longitudinal studies of the effects that early environmental exposures (including in utero exposures) have on later child development and health outcomes. The consortium will consist of:

Cohort Sites: sites at which extant cohorts will be followed prospectively and where assessments of exposures and outcomes will be collected. Cohort sites will each conduct individual prospective longitudinal studies targeting at least one focus area and will participate with the other awardee clinical sites to conduct mutually agreed upon collaborative studies of a synthetic cohort of pooled sites. [RFA-OD-16-004]

Coordinating Center (CC): a central site responsible for organizing and managing activities and logistics for collaborative constituents of the consortium, including oversight and coordination of all ECHO programs, multi-cohort study design and protocol and informed consent development, data management system, administrative management of multiple-site/-project studies, evaluation of progress, data quality and completeness, and sample storage. [RFA-OD-16-006]

Data Analysis Center (DAC): responsible for developing and applying novel analytic methods for combining and analyzing existing and new longitudinal data from disparate extant cohorts, and for conducting multi-level analyses on pooled consortium data to address the impact of early life exposures on childhood health outcomes. [RFA-OD-16-005]

CHEAR: serve as a resource for analyzing personal environmental exposures from existing and prospective collections [PA-16-046]

PRO Core: responsible for maintaining and providing PROs, assisting with the incorporation of PROs into study design, coordinating the mode of administration, and updating existing and validating emerging child PROs [this FOA]

IDeA States Pediatric Clinical Research Network Data Coordination and Operating Center: a central site within the IDeA program that provides data coordination functions for pediatric clinical trials, technical instruction, adherence to state-of-the-art data standards, quality assurance, and an operational interface between the IDeA system and other entities. [RFA-OD-16-002]

IDeA States Pediatric Clinical Research Network Sites: sites at which teams of dedicated pediatric research staff will be established to augment geographic diversity of clinical trials [RFA-OD-16-001]

The purpose of this Funding Opportunity Announcement (FOA) is to invite applications for the ECHO Patient Reported Outcomes Research Resource Center Core (ECHO PRO Core). Working collaboratively with the other members of the ECHO Consortium and the PEPR Consortium (see below), the ECHO PRO Core will conduct research (including development and validation of new instruments) and provide research services and resources to all ECHO Cohort Sites and Centers and Cores. The ECHO PRO Core will provide psychometric and medical expertise in the development, selection and use of cPROs (or proxy measures) and PROs as appropriate to the goals and needs of the ECHO investigators and overall research program.

Patient-reported outcomes are assessments made by the person-or their proxy-that help to understand how a patient 'feels, functions or survives'-key outcome concepts in health care and clinical trials. Importantly, these same 'subjective' outcomes of feeling or functioning are most proximate to the patient (in this case a child) and their parents and other caregivers. PROs that involve children (e.g. cPROs) matter to them on a daily, monthly and yearly basis since they are reflective of their everyday life. In addition to environmental toxins or pollutants, other environmental factors such as school life, family situations, economic setting, gender, ethnicity all can impact children; these impacts can be assessed by cPROs. PROs are accepted by regulatory agencies such as the FDA to be sufficient evidence for approval, and included in labels as other outcomes, of therapeutics.

This effort is expected to leverage NIH funded health outcome measurement systems as appropriate:

• Patient Reported Outcomes Measurement Information System (PROMIS : http://www.nihpromis.org/)
• NIH Toolbox for Assessment of Neurological and Behavioral Function (NIH Toolbox: http://www.nihtoolbox.org/)
• Quality of Life (QOL) Outcomes in Neurological Disorders (Neuro-QOL: http://www.neuroqol.org/)
• Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me: http://www.air.org/files/4_pager_AIR_Health_Polict_2011_V10F.pdf
• Validation of Pediatric Patient Reported Outcomes in Chronic Diseases (PEPR) Consortium (http://niams.nih.gov/News_and_Events/Announcements/2015/PEPR_announcement.asp)

These measurement systems were developed using modern psychometric theory for question development, test construction, and scoring. For example, PROMIS, Neuro-QOL, ASCQ-Me, and NIH Toolbox (when relevant) used Item Response Theory (IRT) to develop "item banks," or groups of questions that measure a variety of health areas referred to as "domains" (e.g., physical functioning, pain, fatigue, depression, motor, sensory, and cognitive performance). In contrast to classically developed measures, item banks allow the creation of research instruments using any number of questions (items) in any order and ensuring greater consistency across the range of domains. All systems use a comparable metric to measure health domains in the general population as well as across various chronic diseases, and facilitate data harmonization with existing legacy scales (e.g. SF-36). These systems have also used computer adaptive testing (CAT) to reduce response burden by allowing researchers to obtain precise scores with a minimal number of items. These assessment systems can be used by researchers and clinicians in a variety of settings, with a particular emphasis on measuring outcomes in longitudinal and epidemiologic studies and prevention or intervention trials.

To date, investigators creating these systems, together with researchers using them, have developed, evaluated, and released (by the end of 2015) approximately 60 adult and 50 adult and pediatric (respectively) reliable, validated item banks, scales or profiles and performance-based measures assessing outcomes in a variety of health domains for child and/or adult respondents. Instruments are available in English and Spanish, with many translated into multiple other languages. The current web-based platform supporting PROMIS, NIH Toolbox, and Neuro-QOL has supported the work of additional investigators funded through other mechanisms, with over 800 active research studies using these measurement systems, and approximately 6.5 million participant responses collected. ASCQ-Me currently resides separately from the other three systems, and during this period of support, the Person-Centered Outcomes Research Resource (PCORR) (http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-13-008.html) will ensure the migration and integration of ASCQ-Me into the shared web-based platform used by the other three systems.

PEPR capitalizes on recent advances in the science of PROs to improve pediatric health outcomes by capturing the voice and experience of children and their families living with a variety of chronic diseases and conditions (e.g., asthma, atopic dermatitis, juvenile arthritis, lupus, type 1 diabetes, chronic kidney disease, inflammatory bowel disease, sickle cell disease) in clinical care and research by using the Patient-Reported Outcomes Measurement Information System (PROMIS ) tools and approaches coupled with detailed clinical phenotyping and/or biospecimen collection in well-characterized human cohorts.

PEPR will advance the science of cPROs at the individual as well as at a national level. The integration of PEPR derived knowledge and resources with the ECHO PRO Core would allow for a unique adaptive, responsive, synergistic environment to flourish between PEPR investigators and those in ECHO. Such an environment will subsequently push forward the science of synthesizing the vastly different kinds of data from all the other 'omics' (i.e. genomic, epigenomic, microbiomic) that constitute the ECHO Cores into forms usable to advance our understanding and implementation of these 'PROomics' data into personalized clinical care and research in pediatrics. The complementary nature of the 'subjective' PRO outcomes as collected by PROMIS cPROs to more traditional 'objective' outcomes will be meaningfully leveraged to improve health outcomes overall. The addition of cPROs, facilitated by the ECHO PRO Core, will offer new and exciting opportunities to understand the impact of environmental stressors on health outcomes.

The ECHO PRO Core would need to be facile with PROMIS instruments and methodology so that such integration would be as seamless and informative as possible to the ECHO investigators and participants. Since CAT best harnesses the power of Item Response Theory (IRT), which is at the core of PROMIS, the ECHO PRO Core needs to be able to have both CAT and traditional short forms as options for cPRO (self or proxy-report) collection.

The ECHO PRO Core will be expected to:

• Provide psychometric and medical expertise in the selection, development and validation (as appropriate) and the use of PROs , cPROs, and proxy PROs for the evaluation of health and disease in children and other subjects being studied by the ECHO Cohort Sites;
• Design and validate instruments to address important conceptual and assessment gaps as needed in collaboration with the PEPR consortium (e.g., parent proxy cPROs less than age 5);
• Work with the Steering Committee to finalize a research plan for the overall study during the first year of award, including the development of common data elements, metadata and data sharing agreements as appropriate;
• Propose a plan for selection of PRO instruments for adults (i.e. parents) and children to be included as part of the core element data collection and work with all ECHO Cohort Sites, the Coordinating Center, and the Steering Committee to devise the final plan for the optimum collection and analysis of PRO core element data;
• Advise and facilitate appropriate selection and seamless implementation of PRO instruments as part of evaluation of outcomes in specific clinical cohorts to maximize the transfer of PRO data into a common, harmonized and standardized metric;
• Develop the systems to link existing 'legacy' self-report data from the extant cohorts and conduct co-calibration with PROMIS instruments
• Provide an appropriate state-of-the-art set of mode of administration protocols for PROs that would be age and disease relevant, with special attention to setting, literacy level of participants and ethnic, racial and language considerations;
• Perform initial quality control and quality assessment of raw PRO data and work with Cohort Sites to resolve issues of missing data, etc.;
• Conduct preliminary analysis of datasets for evaluation of core element PRO data;
• Identify important trends in aggregate PRO data and work with the Cohort Sites and CC to design, and conduct analysis of PRO data and with the Data Analysis Center to facilitate the integration of PRO data into systems analysis plans. For additional useful information about the Pediatric Cohorts and the Data Analysis Center, see Environmental Influences on Child Health Outcomes Pediatric Cohorts (UG3/UH3), RFA-OD-16-004, and Environmental Influences on Child Health Outcomes Data Analysis Center (U24), RFA-OD-16-005.
• Carefully track all PRO data and metadata throughout the analysis, from Cohort Site data collection to final data deposit in an appropriate database;
• Contribute to overall data analysis and interpretation, and preparation of publications and resources originating in ECHO;
• Ensure that collection and reporting of individual data are compatible with EHR; and
• Provide consultation to Cohort Sites, the CC, the DAC, and the Steering Committee in all matters that relate to PROs and cPROs.

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

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 allowed.

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

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

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

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

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

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

Applicants must obtain the SF424 (R&R) application package associated with this funding opportunity using the "Apply for Grant Electronically" button in this FOA or following the directions provided at Grants.gov.

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

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

James Witter, M.D., Ph.D.
Telephone: 301-594-5032
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

• For this specific FOA, the Research Strategy section is limited to 30 pages.

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

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

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

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

Facilities & Other Resources

Team and Institutional Environment: The success of the application will depend on the expertise and experience of the team and the capabilities afforded by the institutional environment. Define the proposed site's capabilities relative to the current state-of-the-art of the field. Provide sufficient detail to allow reviewers to judge the contributions and interrelationships of relevant ongoing research. Briefly describe any additional features of the institutional environment that will contribute to the success of the ECHO PRO Core.

It is expected that the applicants have access to relevant, existing software that is already developed for the purpose of providing automated administration of item banks via both static (fixed-length) short forms and dynamic computer adaptive testing, as well as software and related materials for administration of instruments.

All instructions in the SF424 (R&R) Application Guide must be followed. Applicants are encouraged to include expertise in PROs and cPROs (including proxy measures) research and development so that the application best captures the kinds of analyses likely to be valuable to describe the environmental influence in child health and development. The PD/PI, if a single individual, should be a pediatrician with documented expertise in the evaluation, development and validation of cPROs (or proxy measures) in health care and disease. He/she will likely be assisted by a program coordinator who will oversee day-to-day operations and manage budgets, travel, communication with the Consortium, etc. The applicants are expected to demonstrate expertise in the evaluation of outcomes in conditions in which there is emerging or established evidence of significant environmental influence. Key personnel should demonstrate strong scientific, administrative, technical, and management expertise in the areas that are critical to the success of the application, including experience with working productively in collaborative environments; and experience with administrative management of resource-based operations that serve the biomedical research community, such as service-providing consortia or centers.

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

The budget for the first year will be for Core planning activities, participation with the Steering Committee, in study planning activities, and preparation for sample analysis only. This should include personnel costs and travel to four Steering Committee Meetings.

The budgets for year 2 and following years will include costs incurred for full participation in ongoing longitudinal studies conducted by the ECHO Consortium. These include personnel, supplies, instrument/device preparation, and analysis, quality control and appropriate informatics, and any costs associated with data transfer to the CC and or DAC. Budgets for the second year and after of the award may be adjusted after the study has been completely planned in year 1.

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

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

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

Specific Aims: Describe each specific goal and the role of the applicant ECHO PRO Core in achieving the overall objectives of the ECHO Consortium.

Research Strategy

It is recognized that applicants will NOT know in advance with whom they will be collaborating because the members of the ECHO Consortium will not be known before award; therefore, applicants should make reasonable assumptions as to the types of collaborations that will be available and build flexibility into their research plans.

Project Structure: It is anticipated that at a minimum the ECHO PRO Core will have the following elements: Clinical Outcomes, Statistical/Psychometric, Administrative, and Technology elements, which would together enable the centralized collection and storage of PRO data.

Clinical Outcomes: This element will be focused on the evaluation of outcomes related to health and disease and on the longitudinal evaluation of affected children and their families. The application should include a discussion on the potential strategies to explore the relationship between environmental exposures and patient reported outcomes as part of the analysis of core element data and of data obtained longitudinally in the cohort studies supported by the ECHO Consortium. Staff will likely work closely with staff in the other sites as well as the CC and DAC to design the strategies to select, collect and analyze the data.

The description should include the following:

• Roles of staff;
• Proposed research strategies;
• Description of how the site intends to participate in data analysis and data interpretation of the entire ECHO dataset.

Statistics/Psychometric: This element will be focused on the standardization, organization, curation and feature assignment, and initial analysis of the data arising from the PRO core element data collection at the Cohort Sites. Staff will likely work closely with staff in the other sites as well as the CC and DAC to assemble, integrate, and analyze data.

The description should include the following:

• Roles of staff;
• Proposed data formats for each type of analysis;
• Plans and timelines for data management, protection, quality control, and movement to an appropriate site for access by the ECHO DAC;
• Plans for data analysis including curation, quality control, and statistical analyses;
• Description on how the site intends to participate in data analysis and data interpretation of the entire ECHO dataset.

Administrative: This element will be focused on the overall management of the work done by the ECHO PRO Core for coordination with the CC and other ECHO constituents.

The description should include the following:

• Roles of staff;
• Overall management plan including travel;
• Plan for communication and collaboration with the CC, DAC, and other Consortium Sites;
• Description of willingness to work with the Steering Committee to plan the entire study during the first year, to comply with any common protocols devised during the planning year, to work closely with other awarded Cohort Sites, and to share all data in a timely manner (defined by the Steering Committee) with the DAC and all members of the Consortium during the lifetime of the project, and with the greater public upon completion of the project, consistent with achieving the goals of the program;
• Management of all PRO Core elements.

Technology: This element will provide expertise and appropriate resources to conduct the technical work (i.e., software, hardware) of the ECHO PRO Core required to support the Consortium. The Technology element will provide an integrated platform for automated use of person reported outcomes measurement information systems. This platform must be compatible with various modes of information collection (including web/mobile-based entry, non-digital paper source data, and others). The platform must also be designed to allow Cohort Site users to access and use tools and instruments and tailor use to meet the specific study needs, while capturing and transmitting participant data securely. It is expected that staff will likely work closely with staff in the Cohort Sites, as well as the CC and DAC.

The description should include the following:

• Roles of staff;
• Expertise in the computer programming required for selection of existing and addition of new items and instruments;
• Expertise in automated administration of instruments with sufficient security and privacy capabilities;
• Experience with and/or expertise regarding computer adaptive testing (i.e. CAT) and administration of short forms via multiple modes (e.g. web applications, wireless devices, interactive voice response, pencil-and-paper);
• Plans for:
• Operations management;
• Database management;
• Hardware/server management;
• Software maintenance and upgrades;
• Data and systems backup; and
• Privacy and security management;
• Plans and timelines for data management, protection, quality control, and movement to an appropriate site for access by the ECHO DAC;
• Coordination of effort across all of the PRO Core elements and with the SC, CC and DAC;
• Description of how the site intends to participate in data analysis and data interpretation of the entire ECHO dataset.

Preliminary Data: Preliminary data should indicate that the expertise of the staff and the resources available in terms of equipment and infrastructure are appropriate for the project. Preliminary data should indicate the feasibility of proposed, as well as the quality, reliability, and reproducibility of resulting data. In addition, data can be presented to illustrate proposed bioinformatics strategies for identifying important molecular fingerprints and strategies for identification of novel signals in those fingerprints.

It is appropriate to provide evidence that the site can function well in a consortium, adhere to agreed-upon common protocols, produce and transmit data in an accurate and timely fashion, and operate within the proposed organizational structure.

PRO Analysis Plan: The application should include a description of the proposed research strategy to collect core element PROs and cPROs. The application should describe approaches to collection and standardization, and analysis of PROs and or cPROs for the following ECHO Social and Behavioral Variables, and a discussion of their prioritization based on value to the goals of ECHO, time/effectiveness, and ease of administration.

• Location, measured via self-report of all places lived and when (and coded via address or zip code) able to estimate a range of environmental exposures including air, water, and lead exposure potential, violence exposure, neighborhood SES, school system data (parent to teacher ratios, percent on school lunch programs, etc.), and various policy variables (e.g., tobacco regulations). Improved Measures can be proposed, for example via apps on cell phones (smartphones);
• Parent (preferably mother and father) smoking status measured via standard survey self-report items (see PhenX) or the adult PROMIS smoking bank. The application should describe approaches to complement self report in special populations that may underrepresent smoking status;
• Physical Activity measured via self-report of minutes of moderate physical activity each day (PhenX). The application should include a description of potential improved measures such as use of smartphone accelerometry data as per location data above to estimate physical activity; or provide research grade actigraphs to subsample; or scrape data from commercial physical activity sensors that some may already have (e.g., Fitbit);
• Overall Health-Related Quality of Life (HRQOL) including PROMIS Global (8 items) or SF-12 (12 items), and/or longer versions such as the PROMIS pediatric profiles (25, 37 or 49 items);
• Stress, including Perceived Stress Scale and description of potential improved measures such as the PROMIS pediatric (psychologic, physical) stress experiences banks;
• Electrodermal Response (or galvanic skin response) wearable sensors could be used for intensive longitudinal tracking of a physiological response closely related to stress;
• Depression Measure: using PROMIS Depression or PHQ-9;
• Sleep Quality: using PROMIS Sleep Disturbance or Pittsburgh Sleep Quality Index;
• Perceived family and peer support using PROMIS social support banks;
• Parent-child relationship Measure: using Child-Parent Relationship Scale (15 items). The application should describe improved measures that could be considered such as use of smartphones, in a large or small subgroup of participants;
• Child data (parent proxy self-report below age 8 and child self-report thereafter);
• Cognitive function measure: using NIH Toolbox cognition battery (administered by tester via iPad from age 3 or later, as part of physical exam visit);
• Externalizing Behaviors using Achenbach Child Behavior Checklist, Conduct Disorder Rating Scale, and/or Conners Parent-Teacher Rating Scale and PROMIS PEPR items on anger, impulsivity, or other externalizing measures;
• Internalizing Behaviors: using PROMIS Child Depression and Anxiety Banks;
• Overall HRQOL Measure: using PedsQL or PROMIS Child Global or PROMIS Profiles;
• Peer relationships: using PROMIS Peer Relationships bank.

PROs and cPROs as Outcomes: The applicant should describe how they propose to provide technical and scientific input and expertise to enhance the selection of valid, reliable and time effective instruments to measure cPROs and PROs longitudinally in the clinical cohorts. The applicant should also describe approaches to translate the PRO data obtained with non PROMIS items/instruments into a common metric that will allow the comparison of outcomes among the different cohorts that will be part of ECHO.

Milestones and Timeline: Describe an approximate timeline for the proposed analyses, along with milestones. These should address at a minimum the time to full production and throughput at full production.

Letters of Support: Institutional commitments made to the ECHO PRO Core should be clearly documented.

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.

Resources generated by the ECHO Program are also expected to be widely shared with the Consortium and the broader scientific community for research. The Steering Committee will develop and implement Consortium-wide approaches for resource deposition and use, including submission to national repositories as appropriate. Resources include human and animal biospecimens, instrumentation and assays, special standards, protocols, bioinformatics tools, and animal models.

All applicants should name a responsible individual as contact for data sharing both within and outside the Consortium, and clearly identify support requested for data sharing.

Specific Plan for Sharing Software: A software dissemination plan, with appropriate timelines, is expected in the application. There is no prescribed single license for software produced in this project; however, reviewers will be asked to evaluate software sharing and dissemination plans. A dissemination plan guided by the following principles is thought to promote the largest impact:

1. The software should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories.

2. The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.

3. To preserve utility to the community, the software should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.

4. The terms of software availability should include the ability of researchers outside the Center and its collaborating projects to modify the source code and to share modifications with other colleagues as well as with the Center. An applicant should take responsibility for creating the original and subsequent "official" versions of a piece of software.

5. Given the long-term goals of this initiative to create software and tools for ECHO research that will serve as a resource to biomedical researchers across the nation, applicants are expected to propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others. This proposal may include a plan to incorporate the enhancements into the "official" core software, may involve the creation of an infrastructure for plug-ins, or may describe some other solution.

6. Any software dissemination plans represent a commitment by the institution (and its subcontractors as applicable) to support and abide by the plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

See more tips for avoiding common errors.

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

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

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

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

Specific to this FOA: Does the project support the overall goals of the ECHO Program? Will successful completion of the aims bring unique advantages to the ECHO Program?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

Specific to this FOA: Do the investigators have experience with existing PRO instruments, as well as their development, measurement and harmonization with other large collaborative efforts?

Have the investigators demonstrated their willingness to collaborate with NIH scientists and staff, and with investigators and staff from other constituents of the ECHO Consortium?

Have the investigators demonstrated a willingness to participate in planning the study and to use common protocols?

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

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

Specific to this FOA: Is there a sound rationale for the selection of cutting edge technologies?

Is there evidence of technical excellence and capacity for the proposed analysis, demonstrating general feasibility of the proposed approaches? Are proposed mode of administration approaches efficient in terms of cost and time use? Is the projected capacity of the site adequate? Are there plans for standardization and validation? Are procedures in place to ensure quality of data and consistency as well as adequate data management and statistical plans for the proposed analyses?

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

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

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

For research that involves human subjects but does not involve one of the six 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 six 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.

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 children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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

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

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS). Reviewers will comment on a software sharing plan and whether investigators have demonstrated a willingness to share all data, biospecimens, and protocols in a timely manner with ECHO members during the project period, and with the broader research community after the completion of the ECHO project, as appropriate and consistent with achieving the goals of the program.

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Compliance with resource sharing policies.

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

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

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

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

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

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

• Grants funded under this FOA will not be awarded with the Streamlined Noncompeting Award Process (SNAP) authorities (NIH Grants Policy Statement 8.4.1.2 Streamlined Non-Competing Award Process).
• Grantees will not be able to submit a modified progress report.
• Grantees will not be provided the authority outlined in the NIH Standard Terms of Award to extend the final budget period of the previously approved project period one time for up to 12 months beyond the original expiration date shown in the Notice of Award. All extensions, including the first extension, will require NIH prior approval.
• Grantees will not have authority to automatically carryover funds. All carryover actions require NIH prior approval.
• Grantees must submit annual Federal Financial Reports (FFRs).
• All grant funds must be expended within the approved project period on a first-in, first-out basis. Unobligated funds reported on the FFR must be returned to NIH.

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person's race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator's scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other DHHS, PHS, and NIH grant administration policies.

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

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

• Directing the activities of the ECHO PRO Core, including: (i) establishing and implementing processes for decision-making, communication and collaboration; (ii) establishing and implementing processes and systems for tracking the implementation of Center support functions, identifying problems/deficiencies, and determining the need for and implementing corrective actions; (iii) assessing and allocating resources, reviewing their adequacy, and determining needed adjustments; (iv) establishing and implementing financial management capacity and systems to track and project Center resources and expenditures; (v) implementing and managing an information system to support day-to-day Center activities; (vi) establishing and managing portals for study-specific documents/materials; (vii) reporting to and obtaining input from the ECHO Steering Committee (including the Executive Committee), the External Scientific Board, the ECHO Coordinating, Center PD/PI, the ECHO Data Analysis Center PD/PI, the ECHO Genetics Core PD/PI, the ECHO CHEAR Core PD/PI, the ECHO Pediatric Cohort site PDs/PIs, and the IDeA States Pediatric Clinical Trials Network PD/PI; and (viii) establishing procedures and metrics for assessing Center progress and productivity.
• Providing the full scope of ECHO coordination support including standardization, quality assurance and quality control for the collection of core outcomes by all ECHO Pediatric Cohort sites; ensuring appropriate and effective coordination and collaboration with the NIH ECHO Program Director and the NIH ECHO Team, the ECHO Steering Committee, the ECHO Coordinating Center PD/PI, the ECHO Data Analysis Center PD/PI, the ECHO Genetics Core PD/PI, the ECHO CHEAR Core PD/PI, and the ECHO Pediatric Cohorts PDs/PIs (across all ECHO cohorts and within ECHO scientific focus areas); and ensuring that the performance of support functions complies with all Federal and, where appropriate, country-specific regulatory requirements and guidelines for the conduct of human subjects research, as well as NIH policies and procedures.
• Providing reports to the NIH ECHO Program Director and the NIH ECHO Team regarding Coordinating Center and overall ECHO activities (e.g. tabular summaries of study progress, protocol deviation and site monitoring reports), as well as budgetary summaries as requested.
• Ensuring the appropriate training/certification of Coordinating Center staff designated to provide coordination support, and including a list of all training programs and written assessments in the Annual Progress Report.
• Ensuring that data generated under the support of ECHO will become publicly accessible to outside investigators, through the ECHO database, within a pre-specified period that will be negotiated with the NIH ECHO Program Director before the award is issued.

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

NIH assistance to the ECHO operations will be provided by the ECHO Project Director and the NIH ECHO Team, as well as by NIH Project Scientists or other NIH staff that may be assigned to cross-ECHO studies or studies within one of the four ECHO scientific focus areas. NIH staff will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond the normal program stewardship role for grants. It is anticipated that decisions regarding the ECHO PRO Core activities will be reached by consensus and that the NIH staff members will participate in this process. In various matters related to study approval and oversight, the NIH staff will have final decision authority, as described below.

• Concept Proposals and Study Protocols: NIH Project Scientists will: (i) participate in the development, review and approval of the concept proposals and research protocols of all cross-ECHO studies and of ECHO-supported studies that will entail a particular ECHO scientific focus area; (ii) provide final approval prior to initiation for cross-ECHO studies as well as for ECHO-supported studies within each ECHO scientific focus area; (iii) approve timelines for protocol development, implementation and completion; (iv) participate in the data analysis process and the development of manuscripts resulting from ECHO-supported studies.
• Study Monitoring and Management: (i) The NIH ECHO Team and NIH Project Scientists, through the ECHO Coordinating Center, will monitor compliance with OHRP and NIH requirements for human subject research, accurate protocol implementation and internal quality assurance across all ECHO-supported studies. This includes: participating in the development of and approving Data and Safety Monitoring Plans prior to study initiation; determining the need to conduct for-cause clinical site visits, participating in such visits, and approving recommendations for remedial actions. (ii) NIH staff will participate in ECHO Study Management Teams to manage the day-to-day implementation of ECHO-supported studies that will be conducted across all ECHO Pediatric Cohorts or cross-Cohort studies that address an ECHO scientific focus area.
• IND/IDE Sponsorship: Aside from the IDeA States Pediatric Clinical Trials Network, the ECHO Pediatric Cohort sites are not likely to conduct clinical trials requiring IND/IDE sponsorship. However, in the rare event that this becomes a necessity, the ECHO NIH Program Director will determine on a case by case basis whether the regulatory sponsor for a clinical trial conducted under IND/IDE will be an NIH IC or an ECHO Pediatric Cohort Investigator. If the regulatory sponsorship responsibility is assigned to an NIH IC, NIH Project Scientists/Medical Monitors will obtain, through the ECHO Coordinating Center and the ECHO Data Analysis Center, regular reports on serious adverse events and protocol deviations, and will decide on the final disposition of SAE Reports for all IND/IDE studies.
• Study Termination: NIH reserves the right to terminate, curtail or suspend an ECHO-supported study for any reason, including but not limited to risks to subject safety, occurrence of unforeseen safety or ethical issues, scientific question is no longer relevant or the objectives will not be met, failure to comply with Federal regulations or Terms and Conditions of Award, and reaching a major study endpoint before schedule with persuasive statistical significance.
• Access to Data: The NIH ECHO Team and NIH Project Scientists will have the right of access to all data (raw and analyzed) generated under this cooperative agreement and may periodically review these data.
• Grant Stewardship: Additionally, an NIH program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

The ECHO NIH Program Director, with approval by the NIH Director, will establish an ECHO External Scientific Board. The External Scientific Board will submit its recommendations to the ECHO NIH Program Director, who will then inform the members of the ECHO Steering Committee. Recommendations by the External Scientific Board are advisory.

Areas of Joint Responsibility include:

• The NIH ECHO Program Director and the NIH ECHO Team, in collaboration with the PDs/PIs of all ECHO awards, will participate in deliberations and decision-making regarding the multiple substantive, operational, financial and administrative responsibilities of this NIH initiative.
• NIH Project Scientists and/or their designees will collaborate with ECHO PRO Core staff to ensure the provision of appropriate information, materials and training regarding NIH policies and procedures for the conduct of human subject research.
• Close interactions among the awardee, awardees from the companion FOAs, and NIH will be required. Shortly after the award, the PDs/PIs and NIH program staff will form the ECHO Steering Committee, which ultimately will report to the NIH Director.

ECHO Steering Committee

• The ECHO Steering Committee will be co-chaired by the NIH ECHO Program Director, the PI/PD of the Coordinating Center, and the PI/PD of the Data Analysis Center. It also will be composed of the PIs/PDs of the PRO Core, CHEAR Core, the Genetics Core, the IDeA States Pediatric Clinical Trials Network DCOC, and each of the cohort sites, who all will have one vote. The NIH ECHO Program Director and the NIH ECHO Team will serve as non-voting members of the ECHO Steering Committee.
• An Executive Committee of the Steering Committee also will be established, and will be composed of the three co-chairs and a representative from each of the funded elements one each from the PRO Core, the Genetics Core, CHEAR Core, and the IDeA States Pediatric Clinical Trials Network DCOC, as well as one PI/PD collectively representing the cohort sites.
• The Executive Committee will invite expert consultants as needed, coordinate with the External Scientific Board, assist as necessary with annual progress reports, and appoint and charge members of subcommittees.
• These subcommittees will facilitate development, implementation, and monitoring of specific ECHO functions as needed. Suggested subcommittees include:
• Data Measurement and Sharing: members from each cohort site, the CC, the DAC, and the PRO Core; responsible for selecting core measures and establishing protocols for data collection, quality control (QC), and sharing; CC and DAC would implement the protocols, conduct training and QC, etc.
• Biostatistics and Design: members from each cohort site, the CC, the DAC, and the PRO Core; responsible for (1) developing analysis plans for each of the core measures, including biospecimens and environmental samples, (2) reviewing and providing advice on the analysis plans for each of the participating cohorts, (3) conducting methods research based on issues that arise during the course of the project, (4) serve as a consulting body for any of the PDs/PIs seeking input on analysis issues
• Publications: members from each cohort site, CC, DAC, and the PRO Core; responsible for developing publication policies and procedures, review of abstract and manuscript proposals for cross-project papers and presentations, review of proposed ancillary studies, and review of proposed pilot studies
• Focus Areas: members from the cohorts in each Focus Area and the CC; separate subcommittees for each of the 4 Focus Areas to support regular interactions among investigators interested in the same Focus Areas
• Project Coordinators: members would include the coordinators from the cohort sites and a CC representative; meet regularly for exchange of information about their studies, and help each other identify best practices for a variety of logistical issues including retention, training, data collection, etc.
• IDeA States Network: members from the participating IDeA states sites, IDeA states DCOC, and the CC; meeting regularly for exchange of information about their projects, best practices, etc.
• Key personnel will be expected to serve on subcommittees, as appropriate, according to their expertise.
• The Steering Committee will meet in person quarterly during the first year and at least annually thereafter. Monthly teleconferences will be held for the Steering Committee and its subcommittees, and these may be more frequent at times to facilitate planning, etc. The Coordinating Center (CC) will be responsible for arranging and facilitating the meeting and teleconferences. Applicants should plan to attend an initial planning meeting of the Steering Committee in Bethesda, Maryland in fall 2016.
• The Steering Committee will have responsibility for developing the overall scientific direction of the program; assuring compliance with program policies and procedures; designing study protocols; implementing studies; ensuring data quality and completeness; planning for analysis and interpretation of data; and reporting results in presentations and publications.
• The Steering Committee must work cooperatively and interactively during the first year to develop the final protocols and all of the materials necessary to begin the prospective human studies within 12-18 months after award. The final plan, with a study timeline and milestones, will be submitted and must be approved by the NIH ECHO Program Director and the NIH Director, with involvement of the NIH ECHO Team and relevant IC program staff, before the second year of funds will be awarded.
• First year planning activities include, but are not limited to:
• Developing clinical and laboratory protocols and plans for data collection and management
• Standardizing collection of core data elements
• Overseeing plans to address the various bio-ethical issues and concerns (e.g., handling of sensitive data, participatory risk, involvement of vulnerable populations, incidental findings) that are likely to arise during the conduct of the research
• Obtaining approvals as needed at the ECHO Pediatric Cohort site institutions, such as IRB approvals
• Preparing a Manual of Operations with primary responsibility residing with the CC
• Developing a detailed plan for storage and shipping of all biospecimens
• Developing detailed plans for the thorough analysis of data
• Agreeing to abide by a common data sharing plan
• Developing a detailed timeline with concrete milestones for the entire study

External Scientific Board

• Five to seven external experts will serve as the External Scientific Board (ESB), and will be selected and appointed by the NIH ECHO Program Director and NIH Director.
• The ESB will review and offer input on ECHO structure, function, and studies, both during protocol development and during the analysis of results. Members of the Board will provide input based on their individual areas of expertise, as needed over the course of the program. They will assist the NIH regarding processes and substantive issues that arise during the project and will help ensure that the resources to be delivered by the program are as useful as possible for the end users.
• External Scientific Board members may be invited to attend some ECHO Steering Committee meetings.

Data and Safety Monitoring Board

• In the event the ECHO activities include clinical trials, an independent DSMB will be established to monitor and provide recommendations to the NIH regarding participant recruitment/enrollment, safety, data quality, and other issues, as appropriate. The DSMB will also review the Steering Committee-approved common protocol, informed consent templates, milestones, and monitoring plans prior to the start of recruitment. It is recommended that, if possible, a single central Institutional Review Board (IRB) is used to streamline the protocol approval process and to standardize the monitoring of human subjects' protection in the ECHO program.

Development of Milestones

• Because this Consortium will require specific achievable goals (e.g., timely recruitment of participants, expected annual throughput), milestones should be proposed by the applicant. Milestones are goals that are quantifiable for measuring success, and include associated annual or semi-annual quantitative criteria.
• Final milestones will be designed during the first year in the planning phase. After review and approval by the NIH, the final set of approved milestones will be specified in the Notice of Award.
• Progress towards achieving the final set of milestones will be evaluated by NIH program staff on an annual basis. If justified, future year milestones may be revised based on data and information obtained during the previous year. If, based on the progress report, the project does not meet the milestones, funding for the project may be either restricted or discontinued.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the ECHO awards) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. The panel members will be a designee of the ECHO Steering Committee, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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 progress report, 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.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)

Telephone: 301-710-0267

James Witter, M.D., Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: [email protected]

Valerie Durrant, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-827-6390
Email: [email protected]

Donna R. Sullivan
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2979
Email: [email protected]

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

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