December 18, 2015

Pediatric Cohort Sites FOAs

Why limit to extant cohorts? Extant cohorts may lack important samples/metadata/etc.

  • Initially, we are limiting the applications to extant cohorts. While we recognize there may be some limitations to this approach, we are confident that this is the best option at this time to make the most efficient use of funds, as we can leverage investments already made and extend resources further. For FY 16, we hope that leveraging extant cohorts will allow the program to begin to take shape and advance knowledge. We also will employ the latest methods in data science to address any concerns about combining and analyzing data from different studies. However, we are open to the possibility of including novel cohorts in future years.

What is the definition of “extant cohort”? What extant cohorts will be eligible? 

  • Extant cohorts have the data and infrastructure in place to recruit participants to the ECHO study or add a new component to the study. They can leverage their current participants, are currently recruiting, will begin recruitment prior to initiation of the ECHO consortium, and/or they have data and biospecimens from previous cohort studies that are available for analysis. Extant cohorts include those that have been consented previously for research.
  • Eligible cohorts include:
    • Those which are still actively collecting longitudinal follow up data or
    • Those which enrolled mothers before or during pregnancy that have the potential of collecting data on offspring or
    • Those which enrolled children at birth or in the first year of life
  • Previous federal funding of a cohort is not required for eligibility.

Does my cohort meet the criteria for applying?

  • The cohort has pre-, peri-, or post-natal data (prior to age 5 years)
  • The applicant is planning on collecting additional data or has the ability to recontact for additional data
  • The cohort has biospecimens of sufficient quality to measure early “exposures”, or personal/population-based exposure data, or is able to collect prospectively from early postnatal life (before age 5 years).
  • The applicant is willing to participate in standardized prospective Core Element data collection as part of a consortium protocol. Core Elements include:
    • Demographics (e.g. race, ethnicity, gender, socioeconomic status, geographic location)
    • Typical early development (e.g. growth, milestones, physical activity, sleep)
    • Environmental exposures (e.g. physical, chemical, in utero, microbial, psychosocial, natural and built environment)
    • Genetics (genotyping to be provided by an ECHO Genetics Core)
    • Patient (parent or surrogate) reported outcomes
  • The cohort is properly consented for recontact for prospective data collection, and data sharing.
  • The cohort must have data in one of the Focus Areas and detail how other Focus Areas could be incorporated prospectively:
    • Upper and lower airway (e.g. asthma, allergies, sleep-disordered breathing).
    • Obesity (e.g. nutrition, metabolic risk factors, activity level
    • Pre-, peri, and post-natal outcomes (e.g. birth defects, prematurity, neonatal/infant mortality)
    • Neurodevelopment (e.g. attention, cognition, emotion, social/language/behavioral development)

My cohort, which has been consented previously for research, could provide a wealth of additional information if expanded. As part of my ECHO application, can I propose to expand my cohort from 750 to 1000 children, for example, under the same protocol?

  • Yes, applicants may propose to expand an existing cohort, provided there is scientific justification. However, applications proposing to establish a completely new cohort will be considered non-responsive to the RFA.

I have a foreign cohort, can I apply?

  • Yes. However, the questions in the proposal have to be unique and compelling, and able to provide justification of the scientific impact of non-U.S. cohort data that currently is not possible using U.S. cohorts.

My cohort has terminated. Can I apply?

  • You are welcome to apply as long as you are able to recontact a sufficient portion of the sample for prospective data collection relevant to your research plan and sample size estimates needed for analysis, and are able to provide evidence that recontact would be possible.

Can I do a clinical trial?

  • You may not conduct a new clinical trial as a part of ECHO, but you may leverage data from an existing clinical trial if appropriate justification can be made for its inclusion in the ECHO Cohort.

What is “early life”?

  • Early life is defined as the period from preconception, fetal life, birth, and up to age 5 years old.

Is there an age limit for how old the cohort participants can be at the time of application?

  • There is no restriction on the current age range of cohort members, but all applicants must show that the proposed cohort already has early life exposure data and/or can collect high-quality data on early life exposure(s) among cohort subjects.

Do I need pregnancy data?

  • No.

What do I have to have measured in my cohort?

  • At the outset, you should propose outcome measures relevant to least one of the Focus Areas:
  • Upper and lower airway (e.g. asthma, allergies, sleep-disordered breathing).
  • Obesity (e.g. nutrition, metabolic risk factors, activity level)
  • Pre-, peri, and post-natal outcomes (e.g. birth defects, prematurity, neonatal/infant mortality)
  • Neurodevelopment (e.g. attention, cognition, emotion, social/language/behavioral development)
  • Prospectively, you’ll need to include in your application measures for each of the Core Elements.
  • Demographics (e.g. race, ethnicity, gender, socioeconomic status, geographic location)
  • Typical early development (e.g. growth, milestones, physical activity, sleep)
  • Environmental exposures (e.g. physical, chemical, in utero, microbial, psychosocial, natural and built environment)
  • Genetics (genotyping to be provided by an ECHO Genetics Core)
  • Patient (parent or surrogate) reported outcomes

What measures will I be collecting prospectively?

  • Prospective measures will be standardized by the ECHO consortium in the multi-cohort protocol, led by the Coordinating Center and recommended by the Steering Committee. The prospective measures will be focusing on the Core Elements:
  • Demographics (e.g. race, ethnicity, gender, socioeconomic status, geographic location)
  • Typical early development (e.g. growth, milestones, physical activity, sleep)
  • Environmental exposures (e.g. physical, chemical, in utero, microbial, psychosocial, natural and built environment)
  • Genetics (genotyping to be provided by an ECHO Genetics Core)
  • Patient (parent or surrogate) reported outcomes

Do we have to commit extant data and biospecimens to ECHO?

  • Any new data/biospecimen collection supported with ECHO funds would be subject to NIH data sharing procedures/policies.
  • There is not an expectation that data and specimens generated previously on/by the cohorts as part of the original study will be part of ECHO. However, data and specimens gathered under the ECHO multi-cohort protocol will be part of the ECHO Consortium data/specimens, and will be reasonably accessible to other ECHO investigators and the research community. Additional details will be worked out by the Steering Committee in the first year of the program. 

Can investigators work together on an application? Can multiple cohorts come in together on one application?

  • Absolutely! In terms of sites, the ideas will be investigator-initiated, and we have no preference for single or multi-site proposals. The number of sites will depend on the questions in the study, and the most appropriate means of addressing them, but pre-assembly of cohorts is encouraged.

Are there ideal numbers of PIs and Co-Is that NIH has in mind for these applications?

  • No, whatever is necessary to have the appropriate expertise. NIH encourages applicants to include biostatistician effort and/or a data center that will be able to handle work that will be done outside the main ECHO multi-cohort study or the ECHO within-focus area multi-cohort studies.  

How many applications can our cohort be a part of?

  • While applicants may submit more than one scientifically appropriate application using this cohort, carefully consider the feasibility and the scientific questions that could be addressed. That said, the applications must address distinct specific aims/research questions. Applicants are encouraged to consider the best science (i.e., the questions with the highest impact) when putting together the applications and determining how to apply with this cohort.

How much money can I request?

  • You should request the amount needed to complete both the cohort specific study as well as consortium-related studies. Keep in mind that the per subject, per year allowable budget for costs related to the Common Element data collection is up to $1000 in total costs. There is a $1 million DC cap to the budget in year 1 (planning Phase UG3), but any budget should be well-justified.

If I plan to address more than one focus area, do the allowable costs per subject per year increase accordingly?

  • No, regardless of how many focus areas will be addressed in an individual application, budgets must include no more than $1,200 total costs/subject/year for Key Focus Area specific clinical data and exposure assessments (non-overlapping with existing funding).

Can we examine other non-key outcomes (focus areas), such as pain?

  • ECHO expects outcomes to be in one or more key outcome focus areas – upper and lower airway; obesity; pre-, peri-, and postnatal development; and neurodevelopment.

To whom should the letter of intent be sent and by when?

  • Letters of intent are due by March 15, 2016

Will all funded studies be converted from a UG3 to a UH3?

  • It is possible, but will not necessarily be the case. In order for conversion to occur, all milestones must be met, which the PI has proposed and have been negotiated with NIH staff. If they are not met, the study will not be converted.

Can the UG3 phase be one year instead of two?

  • No, the UG3 will be 2 years. 

Can prospective data collection begin during the UG3 phase?

  • Yes, provided there is an IRB approved protocol to do so. Keep in mind the need for alignment with Core Data Elements that will be developed in the ECHO multi-cohort protocol.

Does NIH have a preference for institution-IRB approvals vs. central IRBs?

  • The ECHO FOA has no stated preference, but 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. The applicant should propose how IRB oversight will be managed, particularly if multiple institutions/sites are included in an application.

Do we need to propose our own Data and Safety Monitoring Board (DSMB) or will there be a DSMB for all ECHO cohorts?

  • In the event the ECHO activities include clinical trials, an independent Data and Safety Monitoring Board (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.

Who will do the review?

  • The Center for Scientific Review at NIH will be doing the review.

What are the roles of Coordinating Center vs. individual projects (e.g., data management, quality control, data distribution inside and outside ECHO)?

  • The Coordinating Center will serve as the hub for communication, collaboration, and interaction amongst the studies. ECHO will be overseen by NIH staff and a Steering Committee, which will be co-chaired by the NIH ECHO Program Director, the PI of the Coordinating Center, and the PI of the Data Analysis Center. The Steering Committee will also include the PIs of the Cores (i.e., the PRO Core, the CHEAR Core, and the Genetics Core), the PIs of the pediatric cohorts, and the PI of the IDeA States Pediatric Clinical Trials Network Data Coordinating and Operations Center. 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 collectively representing the cohort sites.
  • The individual projects will investigate the key questions of import to their study, but also include measurements of the Core Elements. Further, all studies within each Focus Area will coordinate collection of standard disease-specific questions, as identified by the Focus Area cohort community, in addition to the study-specific questions and Core Elements.

How will decisions be made about common measurements and project-specific measurements?

  • Decisions about the Core Elements will be managed through the Coordinating Center and have input/recommendations from the Steering Committee. Project-specific measurements will be left up to the individual investigators.

How does the IDeA state network fit with the overall program?

  • The IDeA States Pediatric Clinical Trials Network will be an additional related, but separate, opportunity. This network will consider the four ECHO Focus Areas a priority, and all prospective data collection will be encouraged to utilize the ECHO standardized research measures – the Core Elements. The PI of the Data Coordinating and Operations Center (DCOC) will be a member of the Steering Committee, and they will also participate, with the PIs from all the IDeA state sites, as a member of an ECHO Steering Committee subcommittee.

What services will CHEAR provide to ECHO through the ECHO CHEAR Core? 

  • During the UG3 phase, the CHEAR labs will support the feasibility assessment of conducting exposure analysis on the samples provided without cost to the UG3.  It is expected that during the UG3 phase the CHEAR and ECHO steering committees will develop a standardized set of common analytes that will be measured on samples from the UH3 phase; this decision will be based on a combination of factors including the analytical capabilities of CHEAR, the scientific rationale for the analyses, and the cost of the analysis.

Do we need to include a budget for analyses by CHEAR or for environmental exposures in our ECHO Pediatric Cohort RFA (RFA-OD-16-004) application? 

  • In the UG3 phase, applicants should budget for analysis of exposures which are central to their hypotheses.  During the UG3 phase, CHEAR will support limited analysis to support feasibility assessment without cost.  For instance, if a UG3 is proposing to assess an association between pesticide exposures and neurological development, CHEAR will support the analysis of a small number (10 to 20) of urine samples to demonstrate feasibility, but will not be able to support the analysis of large numbers (hundreds) of samples to verify the association.
     
  • ​In the UH3 phase, CHEAR will support the analysis of the agreed upon common measures (Core Elements) for all samples without costs.  Additional analytes may be measured beyond this set, but UH3 investigators will need to include a budget for such analysis.

Will ECHO investigators need to apply for access to CHEAR? 

  • CHEAR is dedicating analytical capacity to ECHO – the ECHO CHEAR Core. There will be a streamlined process for ECHO investigators that focuses on clarifying issues related to sample numbers and analytical needs as well as consent/IRB approvals.

Where can I learn more about CHEAR?

This page last reviewed on February 24, 2016