ECHO Program Webinar

Transcript

Environmental influences on Child Health Outcomes (ECHO) Program Webinar

February 1, 2016

Presentation Period

Larry Tabak

Good afternoon and thank you for joining us today. We will discuss the fiscal year 2016 Environmental influences on Child Health Outcomes program. We have called it ECHO. We are excited about the potential opportunities. Here with me today is Dr. Janine Clayton, Director of the Office of Research on Women's Health. She has been instrumental. We also have a number of staff from different institutes from across NIH, who have been helpful in working through this with us. We will discuss the program itself and then we will have an opportunity to ask questions.

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 several synergistic longitudinal studies by tapping into existing cohorts. ECHO will focus on the effect of pre-, peri- and postnatal environmental exposures on pediatric development and health outcomes with high public health impact. We mean this in the broadest sense – namely 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 core elements, across all studies. These core elements will include demographics, typical early health and development, genetic influences on child health and development, environmental exposures, and patient/person reported outcomes. Two sub-elements that may be considered, but remain optional depending upon the research questions, are the microbiome and epigenetics. While they are not required, these are areas of great potential importance. The core elements will help gather longitudinal data and bio specimens from thousands of participants to build a repository on the trajectory of healthy development over childhood. These elements also will inform multiple areas of child health and development. The studies in ECHO will focus on four key pediatric outcomes – 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 to provide opportunities for children in rural and medically underserved areas, some of which may have rare conditions, to participate in the state of the art clinical trials, and to enhance pediatric clinical trial expertise and capacity at a national level. For those of you unfamiliar with it, the IDeA program was authorized by to broaden the geographic distribution of NIH funding by enhancing the ability to compete for funding of institutions located in states in which a historical success rate for NIH grant applications has been low. Twenty-three states and the Commonwealth of Puerto Rico are considered eligible for the IDeA program.

Here are some examples of potential research questions that could be addressed through this program. These are only meant to be illustrative and these include: what are the specific relative contributions of genetic and environmental – again, in the broadest context, behavioral, biological, chemical, social etc. – influences on child health. And what are the inflection points at which the body's normal homeostasis becomes dis-regulated leading to chronic diseases.

Dr. Clayton will now describe the specific program elements of ECHO which correspond to each of the

funding opportunities announcements. Janine.

Janine Clayton

Thank you. Good afternoon. As Dr. Tabak mentioned, I will run through the program elements and then turn back to Dr. Tabak to describe the timeline. Last month, NIH released seven funding opportunity announcements for the ECHO program. Listed here you can see that each corresponds to one component of the program.

The main scientific component is the funding opportunity announcement soliciting applications from investigators with existing prenatal and/or pediatric cohorts. Investigators should propose hypotheses that can be answered within the cohort with outcomes for at least one of the four focus areas, and how this cohort combines with others to answer research questions relevant to the goals of ECHO. The science should lead the justification for the cohort and data to be collected. Characteristics of such cohorts include, but are not limited to, those initiated in pregnancy or postpartum that continued to follow outcomes. Those that ended data collection on pregnant women and offspring, but can recontact them. Those that are currently recruiting and/or assessing pregnant or postpartum women and their offspring. Other 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 the research plan.

There will be two phases to this award. The UG3 phase will focus on recontacting and reconsenting 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, analyses for the multi-cohort protocol, and risk modeling of multi-exposures. The overall goal is to reach a combined cohort size of 50,000.

To coordinate this effort, the ECHO studies will be managed through a Coordinating Center. It will be responsible for central activities such as developing standardized data collection of core elements with the Steering Committee, coordinating statistical analyses 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 Opportunity and Infrastructure Fund, which will support pilot research projects led by young investigators and the introduction of new tools and technologies into the ECHO program. The Coordinating Center will have four components to manage all its activities and responsibilities, such as the opportunities infrastructure fund component, and the Core Elements and scientific focus areas coordination component. Applicants with appropriate expertise who are applying for the Coordinating Center are encouraged to consider applying for the Data Analysis Center 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, conducting multilevel analyses on longitudinal consortium data, building and maintaining data dictionaries and databases, and developing a data sharing, security, and dissemination plan 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 protocol.

As one of the ECHO cores, the patient/person reported outcomes core (PRO) will serve as a resource to the PI's and provide expertise on child PROs including proxy measures and how they can be best incorporated into multi-cohort studies. The PRO core also work to update existing and validate emerging child PROs, coordinate 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 by capturing the voice and experience of children and families living with a variety of chronic diseases and conditions.

Expanding on another recent effort is the CHEAR core. This will support the comprehensive exposure analysis of the ECHO Core Element biological samples which will be on the multicore protocol. Such biological samples include lead, urine, placenta, as well as other biospecimens including hair and deciduous teeth. The CHEAR core will also provide statistical and data support with the Data Analysis Center, and assist with incorporating exposure assessment into ECHO. While its use will not be required, it is strongly encouraged to promote the use of standardized methods across the studies. As an incentive, use of the CHEAR core will be low-cost, essentially free to ECHO investigators.

One additional component is the genetic score. This core, which will be supported in fiscal year 2017, will work with the Coordinating Center and Data Analysis Center to coordinate the standardized collection and measurement of genetic samples for analysis through state-of-the-art techniques.

As an additional component of the ECHO program NIH is establishing an Institutional Development Award (IDeA) States Pediatric Clinical Trials Network (ISPCTN). For those of you unfamiliar with the IDeA program, it aims to broaden the geographic distribution of NIH funding, by supporting research projects at 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 by embedding clinical trialists at IDeA state locations and facilitating their partnership with other academic institutions to increase access to clinical trials for children in IDeA states who are often unable to travel long distances to participate. There are two components – the actual clinical sites, which are open to organizations in IDeA states and they will focus on expanding pediatric trials; and the DCOC – Data Coordinating and Operations Center, which will manage all the network’s activity. The DCOC is open to all organizations with a partner in an IDeA state as the lead or co-lead.

An important point is how the IDeA program fits into the ECHO program. Specifically, the network will emphasize the four focus areas, and PIs will be encouraged to integrate the ECHO core elements into their study. The Data Coordinating and Operations Center will have the primary responsibility of coordinating with the ECHO Coordinating Center and Steering Committee. Now, I will turn it back to Dr. Tabak.

Larry Tabak

Thank you, Dr. Clayton. As you can see displayed on this slide is the structure of ECHO. Importantly, this effort will report ultimately to the Director of NIH. The components 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 PI representing all the cohort sites, and the PI 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 the 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 an external scientific board, which will be a working group of the National Institutes of Health Council of Councils. One key function of the Steering Committee will be to work collaboratively with the Coordinating Center to further define the core elements and develop the details of the multi-cohort protocol. Additionally, subcommittees of the Steering Committee will be formed to determine specific items such as data sharing, publication policies, and to facilitate collaborations amongst and between the four focus areas and the IDeA States Pediatric Clinical Trials Network.

Going forward, dates to remember include, letters of intent which are expected by March 15. Applications, which are due April 15. The review will occur this summer and we anticipate that funding distribution will be made after secondary review at the fall Council of Councils meeting.

I hope you found this brief overview helpful. If you did not before, I hope you appreciate that the goal of ECHO is to more efficiently and effectively utilize and leverage current resources to address a hugely important area of research. We will now open it up for comments and questions. If anyone calls in, please note that your call will be limited to two minutes. We will try our best to address all questions, but if we run out of time, there is an email address that is displayed that you can contact us for follow-up information. With that, we will turn it over for questions.

Question and Answer Period

There were several questions about the budget cost limits in the ECHO program. Are costs like staff salaries, the salary of the primary investigators, data management support expected to be covered in those costs? Or would those be over and above the percent the cost?

You should request the amount you need to complete both the cohort specific study as well as any consortium related studies. The per subject per year allowable budget for costs related to the common element data collection is up to $1000. And there is a $1 million direct cost limit to the budget in year one because that is the planning phase. But any other budget requested needs to be well justified.

And also a CHEAR lab has indicated [that analyses] cannot be provided free of charge until the UH3 phase.

Let me turn to our colleagues at NIEHS.

This is Claudia. The answer to that is you are correct. In the UG3 phase, if you're proposing to do analysis, those costs need to be borne by the PI. There will be some funds available for feasibility testing for a limited number of samples, and again in the second phase the cost for analysis decided upon by the entire group will be covered free of cost.

Thank you. Will project proposals that cover all four focus areas be prioritized for funding over projects that focus on only one or two or three?

What will drive the decision-making is the quality and creative innovation of the questions being asked. And so there is no strategic advantage to cover all the areas. I assume it's possible that there are some groups out there that are sufficiently broad, but I think in most instances folks would be best suited to focus on their specialty areas.

Here's another question about CHEAR. How does coordination with CHEAR work with the budget? Should fees be included in the per subject budget?

Again I will turn that over to Claudia or Kim.

I understand the question is that in the $1200 per person cost doesn't need to include cost for analysis of any environmental exposures? And I would say the answer is probably yes.

So we will need to huddle on this. Could you repeat the question – there is a timing piece? During the UG3 phase. We are doing this in real time in different locations. Kim, during the UG3 phase, you had indicated that it would only be some resources available to do feasibility testing.

That is correct.

So is the question related to if we want to go beyond feasibility testing? Maybe if the person who posted it could resend the question and clarify what it is that there trying to get the information for.

Is there anywhere I can find more details about the core elements?

In the frequently asked questions and also in the funding opportunity announcement there is more description. For example, under demographics, examples provided include race, ethnicity, socioeconomic status, geographic location. Typical early development core element examples might be growth, milestones, physical activity, sleep, depending again on questioning context of the cohort. Genetic elements as you heard will be provided by the ECHO genetics core.

Can cohorts or potential cohorts that are already under recruitment be expanded if needed to address our new cohort specific gains and/or extend recruiting to new sites to broaden the diversity of the cohorts?

The answer to both questions is yes. Again, obviously driven by the scientific questions that are being posed. But in both instances that could be an appropriate use of funds from ECHO.

For the IDeA clinical trials site, what should we ask our potential collaborators to state in their letter of support?

I'm going to ask my colleague.

Great question. I think the biggest thing is the ready access to underserved and rural population of patients and the ability to enroll them in critical trials.

Is it acceptable for PI's and/or investigators on the Data Analysis Center and Coordinating Center to overlap?

I will turn it over.

Yes, the answer is it is acceptable that they can overlap.

How many people are expected to sit on the Steering Committee and Executive Committee?

There is no preassigned number. We don't know how many awards will openly be made so therefore we do not know how many PIs there will be. But, in terms of the Executive Committee, there will be only one representative of all the cohort PIs. The actual Steering Committee leadership will consist of the ECHO program director, with the principle investigator of the Coordinating Center, and the principle investigator for the Data Analysis Center. That is the only thing that is fixed, if you will. But the remaining parts, that will be dependent upon how many different PI's there are.

So, the Steering Committee will have a representative from each of the cohort sites that are supported by ECHO. And that is why the number is undetermined. The executive committee will have not only representatives from the Coordinating Center and the Data Analysis Center as well as ECHO program director, but it also will have one PI that represents all of the cohort sites, and a PI from the IDeA States Data Coordinating and Operations Center, as well as one representative from each of the cores – so the CHEAR core, genetic core, and PRO Core.

And I'm going to assume this is referring to the ECHO application. Is there a minimum number of subjects per proposal that would be considered appropriate?

I think that really depends on the questions that are being posed. There is no magic number here we are looking for. One could envision a very small, but highly specialized cohort that is studying a rare disease or condition, which would enable the investigator to pose very important and interesting questions. That is perfectly appropriate. Alternatively, one could envision the other extreme, a cohort of many thousands, tens of thousands of people asking a more generalized question for a more common disease. Each are perfectly reasonable and appropriate to propose. Again, driven by the scientific basis of the questions that are under study.

During the last session there were many questions that were listed on the screen, but were not included in the download after the webinar added. Is this information accessible and will be available?

From last time, the webinar itself has been posted on line, and many of the questions were answered in the Q&A section. There were several redundancies in the questions and we have also updated the FAQ to reflect some other questions that were not answered. I would like to reiterate that you can always contact the email on the screen if you have specific questions.

May companies outside the IDeA state submit within in-state network participant?

The only people eligible for the IDeA program are people in the IDeA state.

For clinical sites, it has to be an individual institution within an IDeA state. Any institution within an IDeA state can apply to be a clinical site. The DCOC does not necessarily be need to be from an IDeA state, but needs to partner with an institution within an IDeA state.

Should hypotheses be answerable by data already collected in the cohort or can we propose new hypotheses that would be answerable by additional data collection in the UH3 or second phase?

It's designed as a phase approach and he will give you more detail.

The new hypothesis can be addressed certainly in a second phase of the proposal. The first phase is meant to really set up the system, set up the cohorts into one common protocol that will address the core elements retrospectively. It also will be to create a protocol that will address prospective elements as well. At the same time as all of this is moving, each cohort as well as each focus area could develop their own hypothesis to move the science forward.

Along similar lines, will groups submitting applications with multiple cohorts have an advantage over group's submitting applications with a single cohort?

It depends on the scientific question. Again, this is not about numbers, this is about the quality and creativity of the questions that are being posed and the research plan to address those questions. That really is the driver, not the number of cohorts, the sizes of cohorts, etc.

What leeway will each cohort have to do analyses based on the data they collect from the cohort? Will some approval of analyses be needed from one of the coordinating centers?

If the cohort has its own hypotheses, and is going to collect data to address that hypothesis, there is no need for approval and no need for coordination with the Coordinating Center. The Coordinating Center and the Data Analysis Center only deal with collaborative protocols. Anything where more than two or three cohorts get together and decide to analyze something or to conduct a particular protocol.

To add to that, obviously the more opportunity to do those cross collaborative questions, presumably the stronger the application be.

Is there a list of currently available CHEAR measures or requisite sample details to conduct essays?

Let's turn it over to our colleagues at NIEHS.

Currently, the CHEAR side is working on a list of analytes that they can handle, but for the most part the majority of analytes that one could consider being measured, like those collected in NHANES, there are capabilities within CHEAR to do those. In addition, it includes many different biological responses and indicators as well as a table omics and on targeted analysis. The CHEAR website is being developed now to do that. As far as what is relevant to ECHO, as the Steering Committee and others get together to decide to bring forward what will be the exposures of measure for the UH3 component, those will be identified. But many different metals, a lot of different pesticides are all within the ability of the CHEAR labs to analyze.

Foreign institutions either on their own or in collaboration with US partners are eligible to apply but should offer something unique that may not be present in the US cohort. Can you please expand on this and would a multiple PI application with a US PI and a foreign PI be acceptable?

The short answer is it would be acceptable. But again, if there is a foreign component proposed, you need to hit the bar as to what the unique opportunity is. And it typically that means that it would be very difficult if not impossible to do a similar study using a domestic cohort. But yes, we are not limiting this only to domestic centers.

The RFA states that the participant in cohort demonstrates an 80% retention rate. Can you clarify the timeframe for which this rate is to be calculated? For example, is this the overall retention from birth hike it age 12 or from each annual visit? Uniform definition seems to be needed.

I think that when we included an 80% retention rate we started using that as a guide so that we might get the largest quantity of participants possible as well as the most diverse sample. I think we should consider using 80% for retention.

Do cohort applicants need to budget for this statistical and data relating research that is not collaborative across cohorts?

Yes. The answer is yes they do. Because the Coordinating Center and the Data Analysis Center as I mentioned before, will only support collaborative research projects.

I'm going to assume this is going to and NIEHS. Who is the best contact to identify CHEAR costs during the UH3 phase?

For the UH3 phase? So as far as costs, you could contact David Balshaw. But I think whatever will be in the UH3 phase will be decided by the Steering Committee. And the cost to CHEAR to do the analysis will be free of charge to ECHO.

Should a concept proposal be included as part of an application to the IDeA state clinical trial network?

That is an interesting question. As far as the network application, we are not requesting a concept proposal.

For ECHO, should each individual project applying have a cohort sample size of 50,000? What about smaller cohorts?

Again, there is no reconceived number that we are aiming for. It is possible that small targeted cohorts that are studying a rare disease or condition could prove to be very valuable and very important and questions might be able to be framed around such cohorts. Conversely, you could have a very large cohort setting a more common disease or condition. Either or both are absolutely appropriate and there is no advantage to either. It is the quality of the scientific question that you are addressing.

Can we propose new variables within the core elements? Are new variables allowed?

I gave some examples and there are other variables that might be proposed as long as those are in those core elements that have been described. Regarding PRO and that range of variables that might be represented there, I would encourage the investigator to contact the PRO point of contact and I will give you the name in the moment to get more information about the specific range of PROs – Jim Witter.

I just want to add that with the core elements, the Steering Committee will determine these in more detail. The core elements that are outlined in the RFA are more broad topics that NIH has identified as important. They will be described in detail once the projects get funded and the Steering Committee starts meeting.

If we are collaborating plan to collaborate with federal partners what role may they play?

That is a broad question. I think I can only give you a broad answer. It really depends on the nature of that effort. For example, intramural cohorts that are supported by NIH can be included in the ECHO program provided they meet the criteria for applying as outlined in the cohorts funding opportunity announcement. But the funds cannot be used to support any intramural personnel salaries or other expenses managing the intramural cohort. There is that limitation. While on the topic, intramural investigators are not eligible to apply for ECHO funding – they may not serve as PIs.

Will the Data Analytics Center need capability of receiving electronic data electronically or will they be required?

We have suggested that it is a good idea to try to get electronic health records as part of the data that will be collected primarily in the core protocol. Primarily however this is not necessary. The way that the data will be transferred to the Data Analysis Center will be through a database system and electronic entry that the Data Analysis Center will have to put together to fit all of the needs of the various cohorts and the way that will be operating. That is part of their tasks to be accomplished as soon as possible.

Is there an upper age limit for cohorts that have been followed from pregnancy or birth into the third decade?

Again it depends on the quality of the existing data. Keep in mind that the main goal is to understand pre-, peri- and post postnatal exposure/ genetics on development of disease maintenance of health resiliency to disease and so forth. And so, if you had a cohort that has been in existence for three decades, if you have the appropriate data, bio specimens, etc., that is 30+ years old, that would be a wonderful resource. But conversely, if you lack those resources, but only have more recent information, then it would be, I would be hard-pressed to understand how that could be used to address questions related to pre-, peri-, and postnatal development.

There is a question about if a particular cohort site includes multiple cohorts, can you clarify how the data coordinating for the site-specific project and the ECHO coordinating center are expected to work together?

This is an interesting example. Yes, the possibility that there may be multiple cohorts within a single application is there, and is certainly something that we encourage. But that will require coordination within that application. Within that cohorts that will allow for those cohorts that are coming together as a single application to appear at the end of the day as a single cohort. Because it is going to be very difficult for the Coordinating Center to go to each one of these sub cohorts and get information. It will be much more effective for an application to have its own coordination within the multiple cohorts to come in. That level of coordination will be certainly a positive element in the application. Reviewers are going to look at this and they will offer their opinion.

Is it permissible for an entity in the IDeA state to submit applications to both ECHO and IDeA?

Sure, an Institute within an IDeA state can apply to both the IDeA state and if they have an extant cohort also apply to the ECHO program.

If we are having trouble with accessing the grant application for the Coordinating Center who should we contact for help?

So contact the Commons. The helpline at the ERA Commons. I'm sorry to hear that is a problem.

A follow-up question, it seems that from what was said a few moments ago that we cannot use ECHO funds for data collection during the UG3 phase. What portions of our birth cohort need interim assessment so the early data is not lost?

There must being a misunderstanding. You can certainly continue to collect data during the UG3 phase as long as you are also meeting your milestones and working on those things during the UG3 phase in anticipation to transition to UH3.

What will the frequency and venue for Steering Committee meetings be? This is necessary to propose travel budgets.

The Steering Committee will meet in person quarterly for the first year, at least annually thereafter, and there will be monthly teleconferences as well.

Also regarding the cohorts, my cohort has terminated, can I still apply?

You can. Again, assuming that you have the requisite data / bio specimens available, that you are able to recontact participants, and of course are posing questions that are creative, interesting and so forth.

You said earlier that applications were encouraged to apply to both the Coordinating Center and Data Analysis Center, how can those applications be linked?

The simple thing to do is to clearly indicate in each application that it is linked to application X on the other side. However you need to make sure that each application is complete and does not depend on the other. Because reviewers are not going to be able to go from one application to the other to see to what extent every element is there. They will not do that and this will hurt an application that is not complete by itself.

How does the IDeA State Pediatric Clinical Trials Network – could you clarify how it fits again with the overall ECHO program?

It fits in a number of ways. The PI of the DCOC will serve on the Steering Committee of the overall ECHO program. Additionally, the priority areas of study for the IDeA state network will be the same core for priorities of the overall ECHO program. And finally the IDeA state steering committee subcommittee -- that will be the three ways.

Could someone elaborate on age requirements for subjects participating in a UH3 phase? Do they have to be under some minimum age at the time of the initial primary data collection?

There is no boundary to the age. Simply the availability of the requisite data and bio specimens. And so one could envision a cohort that has been in place for a number of years where those materials exist. But now the members of the cohort have gone beyond a certain age. Or vice versa. There is no boundary to the age. But again, the focus has got to be on the role of exposures and genetics on pre-, peri- and post postnatal development. And you don't want a cohort that is so far removed from that crucial period of time that you cannot address those important areas.

And just to add on, we've defined the pre-, peri- and post postnatal time period as anything under the age of five.

Could someone talk about the issue of overlap? If you have a current grant focused on specific aims, does the ECHO application need to be differentiated from that set of hypotheses?

Absolutely. And of course you'll need to be very careful in delineating what is different and unique about the current efforts. Certainly it’s in support of the other, but the questions, and anything you're proposing to do have to be separate and distinct.

Will the Steering Committee meeting be in or around the DC area?

We assume it will be, but actually had you asked that question last week, we would've said last week -- No. With 2 feet of snow and only one snowplow for the whole area. That is not true actually. There's more than one snowplow.

If you can submit linked Data Analysis and Coordinating Centers applications, can you submit linked applications for the pediatric cohorts?

The linked applications to pediatric cohorts are not recommended. It is better to have these as separate entities, as was described earlier. Certainly groups can work together and submit one coherent application where you do what will be very intense work up to the application, but that the review panel will need to see a great deal of evidence that the group has already come together, whether it is two cohorts or 30 cohorts, that does not matter. So no, we are not encouraging linked applications for the cohort phase.

Let me clarify. Even for the Data Analysis Center and Coordinating Center, each application has to be self-contained. As was mentioned, they will be linked in a way that they can be mentioned, but anything that you mention about the other application in the other application needs to be all inclusive of any information you need to get across to the reviewers. They will not have access directly to both applications.

This relates back to the CHEAR Core. And they do work to address creative research questions in year one of the grant and at what cost?

Let's turn to the NIEHS for that.

This is Kim. This is going back to the original question about the use of CHEAR within ECHO. For the first phase, CHEAR will be up and running and will determine what priority analyzed biomarkers will be used in the UH3 phase. There may be some available.

Again I will clarify. The intent for the first phase is just that. Preparatory. It is an opportunity for everyone to do their due diligence. And while we certainly appreciate the enthusiasm wanting to get going, the experience around the table suggests that the one year phase is really important to get everyone on very firm ground. So the complexities of putting together some number of cohorts to do what is being proposed.

Will the IDeA State Network conduct their own studies?

Initially, our anticipation is that other investigators outside of the network will bring trials to the IDeA states network to be conducted through the network. Hopefully, as we approach deeper into the cycle and towards the end of the cycle, the network will be able to develop their own projects.

If an investigator with an established cohort are posing to study obesity and mental health disorders in ECHO can they also propose the measurements?

They can certainly use the same for more than one application; however, the application should be distinctive terms of the hypothesis you're proposing and the actual research that is being undertaken.

Are there specific requirements for the 30 page research plan limit?

So if you look at the funding opportunity announcement, section 4.2 that will answer the question about page limitations.

For the DCOC application, what funds need to be included in the budget submission? Should sample studies and associated costs be proposed?

I am assuming that is for the IDeA states. In putting together the budget I think there will be two aspects. One will be for the infrastructure which requires it to effectively operate the DCOC. The other will be for costs for individual particles. I think the individual capitation cost for the protocol will vary by what is being required to conduct clinical trial. Did that answer the question?

Larry Tabak

I think we're coming to the hour where we need to wrap things up. Again, I want to thank all of my colleagues in the room for answering all of the tough questions. I think the community really has responded to this in a wonderful way. We encourage you to ask any additional questions that we did not get to today via the email address that has been on the website. I think that we are really looking forward to seeing what creative and novel ideas the community is going to come up with in response to the ECHO FOA. Again, thank you. I know we did not get to every question, but we hopefully hit at least many of them. And for those of you whose questions were not answered, please post them. With that, we will sign off and thank you.