ECHO: Funding Opportunity Announcements Webinar

Transcript

Presentation Period

Larry Tabak

Good afternoon everybody and thank you for joining us today to discuss the fiscal year 16 environmental influences on child health outcomes program, which we refer to as ECHO. We are excited about the potential opportunities this effort will provide and we certainly look forward to answering any questions you may have about the funding opportunity announcements. Here with me today is Dr. Janine Clayton, the Director of the Office of Research on Women's Health, who has been instrumental in helping me guide this effort and we also have a team of staff members from various institutes, centers, and offices from around NIH who have been equally helpful and important in working through this. So first thing I will do is describe a little bit about the program itself and then you will have of course an opportunity to ask some questions.

So as you can see in this slide, the ECHO Program is consistent with the goals of the former National Children's Study, but instead of a single longitudinal study, ECHO will support multiple synergistic longitudinal studies by tapping into existing cohorts. ECHO’s going to focus on the effect of pre-, peri-, and postnatal environment environmental exposures on pediatric development and health outcomes with high public health impact. Now by environmental exposures, we mean this in the broadest sense, that is behavioral, social, chemical, physical and beyond. Studies that are part of the ECHO Program will develop a multi-cohort protocol to address collaborative research questions and collect the same standardized targeted data – the so-called core elements. These core elements will include demographics, typical early health and development, genetic influences on early childhood health and development, environmental exposures, and patient/person reported outcomes. Some elements that may be considered, but will remain optional, are the microbiome and epigenetics. The core elements will help to gather longitudinal data and biospecimens from thousands of participants to build a repository on the trajectory of healthy development over childhood. These elements will also inform multiple areas of child health and development. The studies in ECHO will focus on four key pediatric outcomes that upper and lower airway; obesity; pre-, peri-, and postnatal outcomes, and neurodevelopment. Addressing these four key areas with significant public health impact will help address gaps in understanding and allow us to take advantage of this opportunity.

In addition the NIH will establish the IDeA States Pediatric Clinical Trials Network -- the acronym ISPCTN -- to provide opportunities for children in rural and medically underserved areas, some of whom may have rare conditions, to participate in state-of-the-art clinical trials and to enhance pediatric clinical trial expertise and capacity at a national level. Now, for those of you who are unfamiliar with it, the IDeA program was authorized by Congress to broaden the geographic distribution of NIH funding by enhancing the ability to compete for funding of institutions located in states in which the success rate for NIH grant applications has been historically low and currently 23 states and the Commonwealth of Puerto Rico are considered eligible for the IDeA program.

The next slide shows some potential research questions that could be addressed through this program and there are many -- for example one of the specific relative contributions of genetic and environmental influences on child health and again, I emphasize that we mean environment in the broadest sense – behavioral, biological, chemical, and social -- what are the inflection points at which the body's normal physiologic homeostasis becomes this regulated leading to chronic diseases and of course there are many others. I will now turn to Dr. Clayton, who will describe some of the specific program elements that will correspond to each of the funding opportunity announcements.

Janine Clayton

Thank you, Dr. Tabak. Good afternoon everyone. As Dr. Tabak mentioned, I will quickly run through the program elements, turn it back to Dr. Tabak to describe the structure and timeline, and then we will open up to questions. Last month, NIH released seven funding opportunity announcement to solicit applications for the ECHO Program. You can see the elements on your slide here. Each corresponds to one component of the program.

A main scientific component is the FOA soliciting applications from investigators with existing prenatal and/or pediatric cohorts. Investigators should propose hypotheses that can be answered within the extant cohort with outcomes for at least one of the four focus areas and how this cohort combined with others could answer research questions relevant to the goals of ECHO. The science should lead the justification for the cohort and the data to be collected. Characteristics of cohorts include, but are not limited to those initiated in pregnancy or postpartum that continue to follow offspring outcomes, those that ended data collection on pregnant women and offspring but can recontact, and those that are currently recruiting and/or assessing pregnant or postpartum women in their offspring. Other important items to note are that electronic health records, while encouraged, are not required and basic mechanistic studies that can only be done in humans are encouraged. Additionally, applicants are strongly encouraged to collaborate with biostatisticians when developing a research plan.

There will be two phases to this award. The UG3 phase will focus on issues such as re-contacting and re-consenting participants, retrospective data analysis, and multi-cohort protocol development. Data collection from the extant cohort could begin in this phase. The UH3 phase will shift to prospective data collection, analysis for the multi-cohort protocol, and risk modeling of altered exposures. The goal here is to reach a combined cohort size of approximately 50,000 participants.

To coordinate this considerable effort, the ECHO studies will be managed through a coordinating center, which will be responsible for essential activities such as developing the standardized data collection for the core elements, coordinating statistical analysis with the relevant cores, coordinating with existing biorepositories, and coordinating the functions of the steering committee and the external scientific board. The coordinating center will also work with the steering committee to administer and manage the opportunities and infrastructure fund, which will support pilot research projects led by investigators within the ECHO Program, and the introduction of new tools and technologies in the ECHO Program. The coordinating center will have four components to manage all its activities and responsibilities, such as the opportunities and infrastructure fund component and the core elements and scientific focus areas coordinating component. Applicants with appropriate expertise applying for the coordinating center are encouraged to consider applying for the data analysis center as well and vice versa.

The data analysis center will have the important task of developing and applying novel methods for combining and analyzing existing and new multiscale data across multiple cohorts. Additionally, its responsibilities include data quality control and assurance and validation, conducting multilevel analyses on longitudinal Consortium data, building and maintaining data dictionaries and databases, and developing data sharing security and dissemination plans with the coordinating center and Steering Committee. The data analysis center will not be responsible for analyzing individual cohort research data -- only those data collected using the multi-cohort protocols.

As one of the ECHO cores, the patient/person reported outcomes or PRO core will serve as a resource to the PIs and provide expertise on child PROs, including proxy measures and how they can best be incorporated into multi-cohort studies. The PRO core also will work to update existing and validate emerging child PROs, coordinate the mode of administration, assist the data analysis center with analysis of PRO data, and integrate PEPR-derived knowledge and resources into the ECHO Program. PEPR is a currently funded consortium designed to capitalize on recent advances in PROs to improve pediatric health and well-being by capturing the voice experience of children and their families living with a variety of chronic diseases and conditions.

Expanding upon another recently developed effort is the ECHO Children's Health Exposure Analysis Resource or CHEAR Core. This core will support the comprehensive exposure analysis of the ECHO core element multi-cohort protocol biological samples. Such biological samples include blood, urine, placenta, cord blood, as well as other bio specimens including hair, placenta, and deciduous teeth. The CHEAR core will also provide statistical and data support with the data analysis center and assist with incorporating exposure assessments into ECHOs of studies.

One additional component for which the FOA has not yet been released is a genetic core. This core will be supported in FY 17 and will work with the coordinating center and data analysis center to coordinate the standardized collection and measurement of genetic samples for SNP chip analysis for state-of-the-art techniques.

An additional component of the ECHO Program NIH is establishing an Institutional Development Award (IDeA) States Pediatric Clinical Trials Network. For those of you unfamiliar with the IDeA program, the IDeA program aims to broaden the geographic distribution of NIH funding for biomedical research by supporting research projects and institutions located in states with historically low NIH funding success rates. The goal of the IDeA States Pediatric Clinical Trials Network is to leverage the existing IDeA infrastructure and embedding clinical trials experts at IDeA state locations and facilitating the partnership with other academic institutions to increase access to clinical trials for children in IDeA states who often are unable to travel long distances to participate.

There are two components – the actual clinical sites, which are open to organizations in IDeA states and will focus on expanding pediatric clinical trials, and the data coordinating and operations center or DCOC, which will manage all the network sites’ activities. The data coordinating and operations center is open to all organizations with a partner in an IDeA state as the leader or co-PI. It is important to highlight how the IDeA network will link to the ECHO Program. Specifically, the Network will emphasize the four ECHO focus areas and PI's will encouraged to integrate the ECHO core elements in new studies. The data coordinating and operations center will have the primary responsibility of coordinating with the ECHO coordinating center and Steering Committee.

I will now turn this back to Dr. Tabak, who will briefly review the structure and timeline.

Larry Tabak

Thank you, Dr. Clayton. So, this next slide shows the structure of ECHO and as you can see, everything and everyone ultimately will report to the NIH Director.  The components Dr. Clayton described a moment ago will have representation on the Steering Committee of which there will be a smaller executive committee with one representative from each core or center, one principal investigator representing all of the cohort sites, and the principal investigator of the IDeA Network DCOC. This executive committee will be composed of and report to the Steering Committee leadership, which will be the NIH ECHO Program Director and the principal investigators of the coordinating center and data analysis center. The ECHO Program team made up of NIH staff will assist the NIH ECHO Program Director in managing the program. External scientific input and recommendations will be provided by the external scientific board, which will be a working group of the NIH Council of Councils.

Going forward, with the timeline -- as I'm sure you are familiar -- letters of intent are due March 15. But perhaps more important to all of you is that the applications are due April 15. Review will occur this summer and we anticipate that funding decisions will be made after secondary review at the September 2016 Council of Councils meeting.

I hope you found this quick overview helpful. And that, if you did not before, you now appreciate that the goal of ECHO is to more efficiently and effectively utilize and leverage our current resources to address hugely important areas of research. At this point, we would like to open it up for comments and questions. Please note that those of you who are on the telephone will be limited to a two-minute period of time. So with that, I will turn it back to the operator and begin with the questions. Thank you.

Question and Answer Period

Dr. Tabak your first question is -- can international investigators and cohorts participate in ECHO?

So the answer is that applications from international organizations may only be submitted for the pediatric cohort RFA. However, the questions in the proposal have to be unique and compelling and importantly have to be able to provide justification of the scientific impact of non-US cohort data that currently is not possible among the US cohorts.

Dr. Clayton -- another question -- is the pediatric cohorts RFA that solicits applications from individual cohorts, consortia of cohorts, or both?

Actually both. Applicants with an individual cohort, as well as those that pre-assemble multiple cohorts, are invited to apply. No preference is given by NIH -- reviewers may consider cohort sizes in their evaluation.

Thank you. Dr. Tabak, is prior NIH funding of a pediatric cohort a requirement of receiving ECHO funding under the announcement RFA-OD-16-004?

There is no requirement for prior NIH funding -- although we assume that many of the cohorts will have some prior NIH funding or current NIH funding. But indeed, some cohorts -- some infrastructure had to be available to create the cohort, but it need not have been NIH funding.

Dr. Clayton -- are there specific criteria that apply to cohorts that are based outside United States for ECHO funding under the announcement?

The questions addressed in the proposal just have to be unique and compelling and able to provide justification of scientific impact of non-US cohort data that is not possible using US cohorts.

Dr. Tabak, we have a question that came in – can cohorts that are already started and have a great deal of infrastructure begin as a UH3?

The expectation is there's a lot of work to be done in the UG3 phase and member of the multi-cohort protocol development -- there should be no overlap in existing funds. To the extent that there are research questions that can be conducted and there's IRB approval for engaging those participants in the research questions proposed, it wouldn’t be possible to start as a UH3.

Dr. Tabak, can a cohort participate in more than one application?

I think that's possible. Of course, the key would be is the cohort being used to address different questions? And obviously we can't have duplication of effort -- but it certainly is conceivable that one group with expertise in one domain would ask a set of questions and then another group with a different set of expertise would ask a separate set of questions using the same cohort. So yes, it is possible for them to be used more than once.

Dr. Tabak, clarification -- 50,000 per cohort or are the subjects to be added over time? Essentially, what's a reasonable cohort size for an application?

I'm glad to be able to clarify this -- that's a number in aggregate. Across all studies and we may be being conservative -- we won't be unhappy if we hit 100,000 and the reason this is important to clarify is that there may be rather small cohorts that are studying rare diseases and conditions and we certainly would not want to dissuade people from considering posing questions related to those cohorts. So the number of individuals within each individual cohort is not really the issue. There is no threshold of numbers. Simply that the cohort has to be large enough to answer whatever the questions are at your posing. So sorry if that was not clear at the beginning.  

Dr. Clayton, should cohort applications cover all four of the key areas or can they focus on smaller subgroups therein?

An application need not cover all focus areas. Regardless, an application does not need to cover all focus areas. The science driving the resource questions will make it clear -- however applicants can propose to address more than one focus area -- but the budget must include no more than a $1200 total cost per subject per year for key focus area data.

Dr. Tabak, are multiple PI's possible or encouraged given the scope of the study?

Certainly they are. Obviously this is going to be a team sport and multiple PI's would be a good way of addressing them.

Dr. Clayton, are there specific criteria that apply to cohorts based outside the US for funding?

Could you repeat the question please?

Are there specific criteria for cohorts based outside the US for ECHO funding?

Applications from international organizations -- they can only be submitted to the pediatric cohort RFA. However, the questions in the proposal have to be unique and compelling and able to provide justification of the scientific impact of non-US cohort data that currently is not possible -- Cohort data that is currently not possible.

Dr. Clayton, what is expected age range for ECHO participants?

The expected age range is preconception to five years of age.

Dr. Tabak, are the submission of both coordinating center and data analysis center applications encouraged and will the coordinating center and the data analysis center applications be reviewed and scored separately?

So each application is to be self-contained because they will undergo independent review and in the cover letters to your applications you can indicate that you're submitting both coordinating center and a data analysis center but be sure to address coordination between the coordinating center and the data analysis center in addition to the coordination of other aspects of the ECHO program.

Dr. Tabak, will ECHO support collection of new subjects and supplement an existing cohort?

So yes it's possible. Again, the applicant will have to justify what unique questions will be made possible to answer by adding an additional subject.  

We have several questions about personnel costs -- what does the $1200 per subject cover?

The $1200 total cost per subject per year should cover the activities for specific clinical data and exposure assessment of those cohort subjects and they should not cover what's already funded with other resources.

Dr. Tabak, little more clarification on the ages of the participants – the RFP talks about early exposures being under age 5. Does this mean some or all the cohort children should be under age 5 during the UH3 and UG3 phases and is it anticipated that some of the ECHO cohorts can continue to enroll pregnant women during the UH3 phase?

Gets a two-part question. The answer is that the subject participants’ exposure data relevant to that should have been collected in some way when the participants were less than five years of age. However, some cohorts may have children that are aged beyond that period -- school-age adolescence -- that would be acceptable in response to the funding opportunity announcement. Cohorts that are still actively enrolling and collecting data through other resources, such as a pregnancy cohort -- additional subjects that are part of that cohort design can certainly be continued but the emphasis is on gathering data on the childhood health outcomes.

All right Dr. Tabak, so the proposal should be driven by the science they are interested in pursuing and the overarching goals of the ECHO consortium?

Well I hope they are complementing one another that the scientific goals that you have align with the overarching goals of the program. This is really not meant to be a license to do basic inquiry. We really are trying to focus this towards enhancing our understanding of early childhood development and what that manifest later in life. So I hope you don't find those things in contradistinction to one another and I hope that clarifies things.

And Dr. Tabak, are cohorts funded with intramural NIH contracts eligible to apply?

So intramural investigators are not eligible to apply for ECHO funding and may not serve as principal investigators of these grant applications. They can be listed as collaborators, additionally -- NIH intramural cohorts may be included in application to the ECHO Program provided they beat criteria for applying as outlined in the ECHO pediatrics cohort funding opportunity announcement. But it is important for you to recognize that ECHO funds cannot be used to support NIH intramural personnel salaries or any other expenses with managing intramural cohorts.

This investigator understands that applicants are encouraged to apply for both the coordinating center and the data analysis center if they are appropriately qualified but the question is -- will there be any special consideration and the awards given to applicants who apply to both?

We are encouraging that an applicant apply to both -- and we certainly mean by that that let's say if the score of an application who has only applied to one of them is exactly the same as the score for somebody who has applied to both, we may -- we may decide to fund the one that has applied to both. And the reason is because we want to have strong collaboration between these two components.

Dr. Clayton, different subject. How will the data sharing work? For example, when do data have to be shared relative to publication?

I will turn that question to my colleague.

The Steering Committee is the group that will lead the discussion on this matter and is going to make some decisions which will come up relatively early hopefully during the first year of the awards. That's when there will be discussions about exactly when data are going to become public. This is something that hopefully will constitute a data sharing policy that will be adopted by all awardees of the ECHO Program.

If I could add to that, all the applications should address a data sharing plan and we would certainly encourage applicants to refer to the NIH data sharing plan, sharing genomic data, sharing plan for additional information so we are not starting all over again. We are going to build upon the existing principles here.

And since we are on that subject -- another person asked, the ECHO data analysis center RFA states that the RFA will not support data analyses of studies conducted within each ECHO pediatric cohort that do not represent collaborative work between the ECHO cohorts. For the studies within a cohort, where will statistical support or funding come from?

We expect that if you're going to have studies within a cohort, those studies will be supported by funds that you'll be requesting and that you will actually include funds to cover statistical support within your own cohort. The DAC will only as stated support studies that involve collaboration.

Dr. Tabak – will the CHEAR Core be at reduced or no cost to the ECHO participants?

I think Kim is on the phone would you like to handle that please. Kim, maybe you can type the…she has now so that the cost is quite good. It is free -- doing this by typing bear with us for a moment and the answer is yes I did get that correct thank you.

Dr. Tabak, can more than one cohort be included in a given application depending on the research question?

I think the expectation is that you could have multiple cohorts. We have heard through the grapevine that some investigators have actually contemplated merging at least intellectually their cohorts for the purpose of submitting these applications. So yes we would certainly encourage if appropriate to the research questions being asked that multiple cohorts be employed.

Something of a related question -- how will the cohort PI's participate in the decision-making about ECHO core assessments?

So let's try that once more we are having technical glitch here could you repeat the question.

How will the cohort PI's participate in the decision-making about ECHO core assessments?

So again, the Steering Committee will ultimately be responsible for rendering decisions of this type and as I mentioned briefly a few moments ago, the Steering Committee leadership will be composed of the ECHO Program Director, the principal investigators of the coordinating center and the data analysis center. The Steering Committee will be different subgroups represented by the different principal investigators so various components as well as the different sides the IDeA site and the different cores so all of this will be up to the Steering Committee and leadership that ultimately will be responsible for adjudicating any questions of this type. This will ultimately go up to the Director of NIH and all along will be informed to very important ways. The ECHO Program team that are the staff from the Institute centers and offices many of whom are seated around this table with me and in North Carolina, and an external science advisory board and I think that we have discovered in multiple complementary ways.

Dr. Tabak, the next investigator’s asking how the review process for the series of our phase will work?

           We have a review guru in the room who would like to cover this

So it would be done by special emphasis panels and with the exception of the IDeA application which my understanding is will be reviewed by child health -- I'm getting nods -- it would also be a special panel so that Center for Scientific Review will do everything else.

We are planning -- operate separately with a specific panel but the specific decisions about how the review will be handle will be made once we see the nature of the applications and numbers.

Thank you. That's our representative from the center for scientific review. Thank you. The technology worked there. Good.

Do the IDeA states clinical trials applications need to include an existing cohort?

No. The IDeA states clinical trials could be performed on any study relevant to the pediatric population but preference given to the four focus areas of ECHO. It does need to be an existing cohort.

 Dr. Tabak, did or can we use other labs that we have established relationships with?

So you can use any lab. The advantage to using the CHEAR Core set up is the fee structure is quite favorable because it's no cost but if for some reason you think you need to use a different lab, then again you would have to be able to do this in a standardized way because the ultimate goal is to be able to synthesize all the data that is collected and so as part of the application plan. You will have to make a fairly compelling case as to A) why you would want to use a separate laboratory -- and B) how you would ensure that whatever analytics emerge are in fact merge of all with virtual with everybody else so if you are measuring from something that for some reason CHEAR is not looking at then I suppose you could make that argument. But if it is a sort of standard exposure I think it would be difficult to argue successfully. I don't know if anybody wants to --

For further clarification for your individual cohort specific research question where you have preliminary data and expertise to measure the exposures that you propose for your hypothesis, you certainly would be encouraged to use your expertise that you have in hand. The CHEAR resource would likely be more evident to you once ECHO becomes conjoined and CHEAR will likely support the multi-cohort protocol scientific questions which will be developed after the program is initiated.

 Great thank you.

Dr. Clayton, folks on the phone asked if we could go over again the definition of existing or exiting cohort?

Extant cohorts are those that have an infrastructure in place to recruit participants to their study or add a new component to the study. They can leverage their current participants in maybe currently recruiting -- perhaps will begin recruitment prior to initiation of the ECHO consortium and/or they have data in biospecimens from previous cohort studies that are available for analysis. Cohorts consented previously for research. ECHO examples of eligible cohorts include those that are still actively collecting longitudinal follow-up data or those which involve mothers before or during pregnancy that have the potential of collecting data on offspring or those who enrolled children at birth or the first year of life.

Thank you, Dr. Tabak, NIEHS is back on the line -- where do we find out what exposures the CHEAR resource is able to measure?

Back on the line.

Well if they are back in line.

Sorry this is Kimberly Gray. I’m just filling in for David Balshaw. The CHEAR website will be live soon and you can always go to the CDC analytical site for their environmental measures and we will -- our capacity should be to replicate most of the environmental samples in CHEAR. 70% of the funds are really being used to do environmental characterization of biological samples and it does have the availability and capacity to also measure some other biological elements like cytokines, immune markers of inflammation. To get back to the original question -- I think there's some through CHEAR through ECHO, it is free for service in it would be those ECHO awards, but as CHEAR stands -- as itself NIH funded grants that don't have environment and also request to use it not as a part of ECHO but separate so that's where the NIH cohorts or funded grants can use the CHEAR service outside of the ECHO Program.

Dr. Tabak, does the ECHO application cover both UG3 and UH3 or just UG3?

Yes, the applicant should propose both UG3 and UH3 phases in their response to this funding opportunity announcement for the pediatric cohorts.

Dr. Tabak, one more clarification question on the age ranges -- the expected age range was the conception to age 5, but if an existing cohort has already collected data within that age range and would like to continue to follow those participants, is that permissible basically?

That would be permissible as long as there are data already existing that can measure exposures prior to the age of five and the child health outcomes can be done over any period of childhood.

Dr. Clayton, it is my understanding that an ECHO cohort applicant will need to request funding for what is proposed. If the ECHO Program decides to adopt these plans across multiple cohorts, how will this be handle in terms of conversion of the responsibilities of staff and budget from the individual cohort group to the data analysis center?

I will turn the question to my colleagues. That's a little difficult question.

Let's think about it from the start. If you have, if you are proposing research that relates to your own cohort, the funds that you request should cover that research. Once we have a common ECHO protocol, then the funds you have requested for that common ECHO protocol which are supposed to be about $1200 per person or a thousand dollars per person per year and those funds will be used to the execution of that common ECHO protocol, so there will be no need theoretically to make any transitional changes that will change your budget. It will be you will have to have already incorporated the work that you are doing independent of the ECHO common protocol in your budget.

Another participant is wondering if this is a one-time opportunity for applications or will there be more calls for applications later on?

No specific plans to offer any renewals of these funding opportunity announcements.

                Now is the time folks.

Another couple more data related questions. Dr. Tabak, can you elaborate on how data will be transmitted to the data analytics Center?

So what would happen is the data analytics center together with the coordinating center will create appropriate databases, which are going to be used by the sites by the PDs at each site to upload the data that will be required for the common ECHO protocol. So that will be primarily the responsibility of the data analysis center to put together those databases and the coordinating center will help in training the staff at the sites to enter the data into these databases.

Dr. Tabak, will those funded through this program be free to submit or to address other research questions with the cohort going forward?

So again assuming that there is no overlap, sure. But obviously applicants will have to be mindful to articulate why their new application does not represent duplication of current efforts.

And related question about existing cohorts -- is it preferable to have a healthy large cohort with less detail or well-characterized but small disease-related court with lots of longitudinal follow-up?

Answer is yes.  Meaning that it depends on the scientific question that you're posing. And so I could imagine questions which would require a very large healthy cohort -- I can also imagine many questions that would require a more specialized cohort looking intensely at a unique disease or condition. Either are valuable it just depends on the nature of the scientific question that the team which is to explore.

There seems to be some questions about the $1200 amount -- is the $1200 amount for the common ECHO protocol but not for the research question?

The 1200?

The $1200 total cost per subject per year is for the work to collect clinical and exposure data in the longitudinal phase of your specific cohort application toward a key focus area or areas. There will be an additional $1000 total cost per subject per year to cover the cost of the determined core elements that must be collected as a member conducting a multi-cohort protocol. The specific elements will be determined by the steering committee. Under the budget section of section 4 of the funding opportunity announcement, you will also find that there is an expectation for salary, for an FTE if no less than 2.4 calendar months for the PI's -- for multiple PI's collectively -- and that there are expectations for travel to steering committee meetings four times a year that should be built into the budget.

Another person was wondering -- the $1200 limit may be more difficult in studies focusing on neurodevelopment. Are there exceptions to that dollar limit?

 We've given a guide of what is appropriate given the need to spread these funds to reach objectives. If there is justification for additional funds, that will be reviewed at the peer review panel relative to the scientific impact and justification of fitting into the budget.

Dr. Tabak, here’s a question related to this program -- will ECHO have some input when it comes to selecting IDeA state Network pediatric clinical trials network research projects?

That's a great question. I think it will. Only to the extent that the priority will be given to the four areas of the ECHO Program so come down to the Steering Committee the IDEA states clinical sites so --

Related to the IDeA program, will institutions located within the IDeA eligible states and Puerto Rico be permitted to apply for this funding opportunity to service clinical sites for this Network?

Yes. In a word yes. The DCOC can be a site outside the ideas state-eligible networks but it would have to partner with an institution within the IDeA state eligible areas.

 Dr. Clayton, if funded and the multi-cohort protocol is in place, how much flexibility will there be to evaluate novel questions for the cohort separate from the multi-cohort protocol?

We refer to the opportunities and infrastructure fund component -- that element will allow support of private projects on top of those within the ECHO pediatric cohort, and introduce new tools and technologies is another topic that could be funded. Recommendations regarding the distribution of those opportunities and infrastructure funds will be majorly by the ECHO Steering Committee which will assess ECHO’s needs and will request applications for pilot projects within the ECHO community.

And related to that -- are all ECHO PIs encouraged to participate in the new cohort data collection protocol?

There will be core data elements that will be standardized for all participants of ECHO data collection. There may be some data elements that are specific to a focus area -- so that is also a possibility that there would be conjoining of cohorts toward a particular key focus area where those data elements are relevant for that health outcome in children not necessarily relevant for all focus areas.

And is the collection of prospective data expected and if so at how many points in time?

Prospective data collection is essential to ECHO, and the primary work will be done in the UH3 phase of this funding opportunity announcement for the cohorts.

Do we need to include specific aims about the core elements as well as the specific research project in the application?

The specific aims for the pediatric cohorts funding opportunity announcement should be targeted to the research that the applicant proposes to conduct -- hypothesis testing research questions. We've also asked for some visioning about what the contributions could be towards answering questions for you to have available as many as 50,000 subjects in the focus area of your interest. That will give us an idea of where the multi-cohort protocol may develop.

Is the microbiome currently a priority focus area or not?

So it depends again on the question the applicant wishes to pose. For certain domains, the microbiome will be crucially important and now some experts will tell you it doesn't matter what domain it is the microbiome is crucially important, so I'm willing to accept that provided that the applicant is able to make the scientific justification the scientific case for that. So whilst we do not want to make it a mandatory element and we determine optional, we certainly recognize the emergent importance and excitement about this type of research and if there is a link is to be made, then surely applicants should take advantage of that.

There is a question who would count as a participant in the ECHO Program.

I concede I don't understand the question

Participants will need to include Child Health Outcomes

So funding would not go to support the grandmothers of the children unless they were key to the data that are needed for the analyses and the scientific hypothesis has been tested.

So I think we have time for one final question

Could we clarify how many cohorts do you anticipate awarding?

We have no preconceived notion of the number. This is going to be driven by the rigor and creativity of the applications that we received. My hope is that the program team will have a very, very difficult time deciding among just remarkable applications and we will just figure it out once we are able to survey what is available. So there is no preconceived number. We are giving you guesstimates of 50,000 participants only just to give you a ballpark. We might end up with many more -- that's great but again the science is going to drive this.

So I think at this point I'd like to first thank the participants of this Webinar for excellent questions. It really actually helps us in a great way because it informs us as to what areas might need additional clarification and we are delighted to be able to provide some clarity on these topics. I think that we are going to really look forward to seeing the ideas that the community will bring forth.

We will host one additional Webinar, which is currently scheduled for February 1 at 2:30 -- the link to the ECHO website is found on this rotating slide that has appeared before you. And with that, I want to thank all of my colleagues here in the room and my colleague at the NIEHS and my colleague at the CSR who is also off-site -- for their participation and again to all the members of the community for participating. Dr. Clayton any last final words here -- I'm getting a shaking no. So, thank you for your help and we are adjourned. Thank you.