Frequently Asked Questions | INCLUDE

Description of “deep phenotyping" in the NOFO.

Clinical data, imaging data, biospecimen collection for biomarker and omics studies, and any other elements proposed.

Is the total estimated $5M budgeted for 1) all years or 2) for each year?

$5 Million is the estimated costs for each year for the DS-CRS. This is an estimate and may be higher or lower depending on the final number of sites and awards made.

Can 3-6 partner institutions be made up of different departments from the same university, or should they be from the different universities?

The sites are intended as recruitment sites, so if two departments at the same institution will be recruiting together, they would count as one site.

How should U01 sites complete the Human Subjects section? Should it be specified for the hypothesis/common protocol that is proposed in the U01? Or as general compliance with the common protocol that will be agreed upon?

The Human Subjects section in the application should align with the approach proposed in the application. Applicants will not know the common protocol at the time you apply, so your application should focus on your proposal.

For DS-CRS, is each U01 required to propose a specific scientific hypothesis, or simply commit to performing “deep phenotyping” as determined by the consortium after funding?

Specify several hypotheses. The DS-CRS team considers it a priority for the DS-Cohort Development Program to test as a collaborative program. The hypotheses should be related to the proposed clinical and multi-omics data collection and allow for surveillance or follow-up of participants over time. 

The RFA mentions that phenotyping costs do not need to be included in the site budget, is this inclusive of all phenotyping costs, such as personnel?

No, the budgets for the DS-CRS are limited but need to cover key personnel and resources to perform phenotyping. The actual costs for doing the phenotyping will be covered by the DS-4C through a capitation model. 

Can more than one group of 6 sites point to the same 4C?

There will be a single DS-4C that will support the entire program of DS-CRS sites.

 Could behavioral data be part of the interest for U01?

Yes, behavioral data is considered a part of deep phenotyping.

Do partner sites need to recruit, or can they provide aspects of the phenotyping without directly recruiting? 

The cohort research sites are responsible for recruiting participants and involved in planning and collection of high-quality data, images, and biospecimens for multi-omics analyses.

Where should the "Table of Study Population" document be attached in ASSIST?

The Table is to be included in the 12-page research strategy section.

While phenotyping costs are not in the site budget, because estimates are requested, does this go in the justification, but not R&R forms?

We are requesting a general proposed budget, and the justification section would be a good place to put this, but the submitted R&R forms are just for the individual site costs (or subcontracted site if more than one is involved).

Does NIH have a target number for cohort size from each site?

There is no set number of participants expected to be collected by each site per year, since it depends on the site, its populations, and the number of partners involved. However, the number to be collected needs to be justified in the research strategy section.

How can we reach out other recruitment sites to co-apply for this grant? Should we contact each other by ourselves?

Reaching out is highly encouraged but there is a possibility of NIH forming those collaborations after review because this is a U award mechanism. If you really do not have contacts, please reach out to us. If we know of people who are thinking of applying, we might set that initial e-mail up. If you are looking for a limited partner, we have included hyperlinks in the NOFO to get you started to find some of those groups.   

Would you consider behavioral coding of observational videos to be behavioral data (for deep phenotyping)? If yes, I'm curious if that coding activity falls to the U01 sites, or to the U54 sites.

Collection of the data would be done by U01 CRS sites but U54 (4C) could be involved in data cleaning, curation, and harmonization. However, the U01s will work collaboratively with U54 to develop protocols for the first year of the awards. In the future, those codes will be integrated to U54 for data harmonization and shared through the Data Hub.  

The NOFO asks for a statistical plan and power analysis. Given that the purpose is to establish a longitudinal cohort with deep phenotyping, what outcome are we to power the analysis on?

Since this NOFO is focusing more on longitudinal cohort development and the common protocol will be established in the first year of the award, a statistical plan and power analysis is not required unless you’re proposing a specific research study.

Can you please provide some more detail on how you recommend discussing potential overlap between PIs and co-investigators who will be responding on the different NOFOs, particularly the clinical and biorepository coordinating centers? In similar efforts in other disease areas, there is considerable overlap in co-PIs and co-Is between biobanking and clinical research coordination.

There is no overlap among the functionalities covered by all three NOFOs, so if one specific PI is proposing to serve as one of the MPIs on different NOFOs, there should not be any overlap among different functionalities. However, it’s critical to keep in mind that the specific PI needs to make sure that enough effort would be contributed to all their applications.

Are recruitment milestones to be set for the entire U01 or by partner site within a U01? For example, an RLI may have small numbers, but important diverse enrollment.

There should be an overall timeline for the U01 main site. For the partner sites, there should be specific milestones which can be negotiable. An RLI will probably have different milestones.

Will the U54 cover the cost of a central IRB, or will that need to be budgeted by each U01 coordinating center?

We will need to establish a central IRB for this effort, and it may be funded in other ways.

Can you please elaborate on what the structure of a “Component” for the DS-CRS site could look like if it’s not a traditional sub-contract?

A multi partner application could have each enrollment site included as a partner site and budgeted as a subaward/consortium. NIH application instructions for subawards should be followed, including budget pages for each subaward.  The budget for the main site is $300K in direct costs as well as $300K for partner sites. Each of the sites will be adequately funded, recognizing the main site may have somewhat more responsibilities.

Could you clarify which components of the budget will be covered by the Cohort sites, and which will be covered by the coordinating center? Could you also elaborate - the request requires estimates of all costs, including costs that would be covered by the coordinating center during the award as part of the capitated budget?

We would like for applicants to propose a phenotyping budget, but it is not required to be added in the proposal. Please do feel free to describe the phenotyping cost per individual or what may be a standard cost per individual. We are looking to use these forecasts to develop a future budget for the larger cohort. The budget request is for the personnel costs which should be much smaller.

Can one "site" do all the recruitment and additional "sites" provide necessary collaborative support and expertise needed but not be separately recruiting (e.g., one site for recruitment, one site for clinical review, one site for phenotyping)?

It could be separated but we would encourage resource-limited institutions to develop infrastructure for deep phenotyping. We want to encourage creation of research infrastructure, particularly for resource limited institutions. If there is an opportunity to incorporate some of the phenotyping in each of the sites that is doing the recruitment, that could be perceived as a strength because that would allow a larger number of institutions and sites that would have the capacity to do this protocol and perform deep phenotyping. This is a U mechanism so there is a possibility of NIH putting some collaborations together.

Is the common protocol focused on the repository or will a proposed CRs' aims/procedures be potentially adopted for a common protocol?

The common protocol is going to be for both phenotyping and biospecimen so both should be included in the protocol proposed under each application. We are trying to make these coordinated and related programs, so that the common protocol would then be instituted under the auspices of DS-4C in partnership with all the CRS sites, as well as the biorepository when that award is made for collection and storage of biospecimens.

 In terms of cohort size, could an application propose a large cohort for one aspect of phenotyping, with a smaller subset undergoing a more resource-intensive aspect of phenotyping?

Yes, they are open for different options; it is good to leverage different resources from different sites. Ultimately, we want a common protocol that all the sites can follow. While there may be some specific aspects of one site that may speak to a particular sub population of individuals with Down syndrome, ultimately a common protocol needs to be something that can be broadly instituted across the entire program. Think innovatively and have a strong justification for your proposal. The proposal must include a common protocol that could be adopted broadly.

For rich phenotyping from areas of under-resourced areas, is the plan to submit support for travel/lodging to institutions with CTSAs or is the thought to set up an infrastructure for rich phenotyping in areas that do not typically conduct patient-oriented research?

The goal is to try to bring some of these research phenotyping protocols to intuitions that do not have it. at least some of the baseline should be implementable in some research limited institutions.  

Regarding the biobanking resource NOFO (RFA-OD-24-004), how many awards does this grant support in FY2024?  Should we apply for the DS-4C and biobanking resource award?

The goal is to make one award for the DS-4C and one award for the DS-Biorepository.

 How many hypotheses should be included in the proposal? Should this be written to the rigor of aims in a standard R01 or as justified proposed ideas to be considered by the network?

We recognize this is not a standard RO1/UO1 that is hypothesis driven however you can develop some hypotheses for the cohort you are focused on. We do not expect everybody to be recruiting their entire cohort across the life span. There might be some hypotheses on a subset of individuals you are recruiting, based on demographic features or age range, etc. Nevertheless, the focus is on a common prototyping. The NOFO research strategy section does specify several priorities to consider for a group of common protocols.

As the U01s are recommended to have a Community Advisory Board, how will the CAB connect with the Outreach Core of the U54?

The CAB for each U01 CRS proposal will work locally for the recruitment sites, with engagement and synergy with the DS-4C outreach core. The community advisory board will work together with the core to make guidelines for the outreach core. The community advisory board will be local boots-on-ground for individual CRS sites and help with local recruitment but our goal would be to integrate the CABs with the outreach for DS-4C so they can share best practices and enhance work; there will be opportunities for synergy.

Can you speak to the longitudinal goals of the NOFOs?  Should the DS-CRS sites propose collecting data longitudinally (for the 5 years of the grant) or is the idea that the data will be combined across all DS-CRS sites and used to infer longitudinal results?

Each site will collect deep phenotyping data under a common protocol, but all the data will be ingested by DS-4C for a comprehensive look at Down syndrome across the lifespan--this will inform longitudinal results.

About estimating level of effort for investigators, is it only the main application PI who attends the steering committee meetings to come up with the common protocol, or is it the site PI’s as well?

There will need to be a representative from each site and that should be reflected in your budget. Most of the meetings will be held virtually, at most two meetings will be held in person.

Should a CRS “focus” on one phenotype in the application? Could we focus on ~3 and note that we’ll collect others based on the common protocol? And if we focus on ~3 phenotypes - can we propose different sample sizes based on the intensity of phenotyping?

Applicants need to address all the phenotypes for the DS sample proposed, although you can highlight areas of specialty. Remember that the proposed protocol needs to be comprehensive for the age of subjects proposed.

Are you hoping to line up the U54 and U01 start dates? It sounds like the U01s will not be able to do a lot of planning if their start date is 6 months prior to the U54's start date.

The reality is that the awards are likely to be made near each other so there won't be a 6-month lag. We set up different application due dates because we want to give DS-4C applicants more time to prepare applications since it’s a multi -component proposal that requires a lot of effort and teamwork. There will not be much of a lag between awards for the CRS and 4C.

Is the partner site’s $300K cost direct or total cost?

It is direct cost.

If a partner site is doing aspects of phenotyping but not recruiting participants directly, what would the budget be for that partner site?

Whatever the needs are for that site, up to $300K direct costs per year.

I assume we won’t include funds for incentives?

This is a little tricky because we anticipate that the outreach core for the 4C is going to be helping with outreach and that capitation cost will be some incentive for individuals recruited. Keep in mind there may be variable rates depending on location, ages, and other types of factors for the individuals recruited into this common protocol. We suggest proposing what you think would be a reasonable incentive in your budget justification.

Does the biobank award applicant need to have Down syndrome expertise?  If we have expertise in biobanking but not in DS, does that qualify?

The applicant may not need Down syndrome expertise per se but should have expertise in biobanking.

Is longitudinal assessment encouraged or is the idea to do a single assessment for phenotyping?

Longitudinal assessment is encouraged, with a proposed periodicity and justification for that frequency.

Would recruited cohort participants be recruitable to other studies?

Yes, that is a possibility. We plan to implement a GUID system to track individuals across studies without releasing PII, under the direction of the INCLUDE DCC. It is the choice of participants if they want to enroll into other studies. It is best to add a question in the consent form asking if the participants are enrolled in other studies as well.

Will all the sites in a CRS U01 application sink or swim together or do you envision pulling certain sites out of individual U01s?

I think this is the benefit of the U-mechanism. If milestones will not be met, we should discuss this before that time point comes. If there is a site that is unable to meet recruitment numbers, there will be a process to add additional sites later if needed.

At one place in the U54 DS-4C NOFO, it states that the Call Center would be under the Outreach core; at two other places, it states that this would be part of the Administrative Core, would you clarify that?

It’s more natural for the Call Center to be hosted by the Outreach Core, please include the Call Center in the Outreach Core in your application.

What is the purpose of the Down Syndrome Cohort Development Program (DS-CDP) and the Down Syndrome Federated Biobanking Resource (DS-Biorepository)?

The purpose of the DS-CDP is to establish a cooperative program committed to the assembly of a longitudinal, diverse cohort of people with Down syndrome (DS) across the lifespan to better understand the co-occurring conditions that impact them and their quality of life though deep phenotyping and multi-omics analysis of biospecimens. There are 2 components to the DS-CDP:

• The Down Syndrome Cohort Research Sites (DS-CRS) will identify and enroll people with DS to participate as part of a diverse cohort under a common protocol to be developed after award.
• The Down Syndrome Clinical Cohort Coordinating Center (DS-4C) will provide overall project coordination and outreach, support development of new cohorts of people with DS, and curate metadata from the new cohorts.

In addition, the DS-Biorepository is a related resource that will establish an infrastructure to facilitate coordination, collection, management, and dissemination of biospecimen materials from individuals with DS who are part of the DS-CDP and other INCLUDE-funded clinical research projects to advance clinical research of co-occurring conditions in individuals with DS.

How will diversity be promoted within each Funding Opportunity?

Each proposal in response to any of the NOFOs will be expected to include a Plan for Enhancing Diverse Perspectives, as described in NOT-MH-21-310, submitted as an attachment in Other Project Information to ensure the diversity and representation of the cohort collected as well as the investigator team. In addition, the DS-CRS applications will be encouraged to include partners that represent low-resourced institutions or those serving groups underrepresented in biomedical research, as well as local DS and community groups.

Where can I turn for additional information about these funding opportunities? Will there be a pre-application webinar to answer questions in real time?

Yes, return to this page or the Funding Opportunity notice for details about the timing of the pre-application webinar and other resources. In addition, NIH program staff, as designated in the NOITPs, are available to answer questions.

Can the same site propose both a DS-4C and a DS-CRS? What about a DS-Biorepository?

Yes, the same site can propose to be 2 or 3 of the components represented by the 3 funding opportunities. However, each proposal needs to ensure that there is adequate level of effort and expertise to support the functions required by each component.

Are foreign sites allowed?

One or more foreign sites can be included as a subaward or a component of a DS-CRS, DS-4C, or DS-Biorepository application but cannot serve as the primary application site.

How will the ‘omics evaluations proposed as part of the DS-CDP common protocol be funded? Should I describe the ‘omics I think should be collected under the DS-CDP with a justification for each? Should I propose a budget for ‘omics evaluations as part of my proposal for a DS-CRS or DS-4C?

Each DS-CRS proposal application should describe, justify and budget accordingly for proposed biospecimen collections and ‘omics evaluations for cohort participants.  The costs for ‘omics evaluations will be supported through separate awards to NIH-funded sequencing resources such as those that support the NIH Common Fund Kids First Research Program (https://commonfund.nih.gov/kidsfirst) or the NHLBI Trans-Omics for Precision Medicine (https://topmed.nhlbi.nih.gov/) initiatives.

Does each site apply individually to be a DS-CRS, or do we submit as a group of sites to form the cohort? Will each site be part of a larger cohort that NIH selects?

Under the U01 to be published in response to NOT-OD-23-134 , individual sites can apply to be a DS-CRS, or groups of up to 6 total partners can apply to be a collaborative team of DS-CRS with a single proposed protocol for phenotyping and biosample acquisition. Applicants are strongly encouraged to include at least 3 partner institutions, with a maximum of 6 total institutions as part of an application, with an emphasis on including at least one partner from low-resourced institutions or institutions serving groups underrepresented in biomedical research, such as Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCU), other Minority Serving Institutes (MSIs), and states eligible under the Institutional Development Award (IDeA) program . In addition, sites are encouraged to work with their local DS and other community partners when they propose a recruitment plan. NIH will select several DS-CRS applications to fund, some of which may represent a single site and others that may represent collaborative teams made up of several partner sites.

What are the goals and structure of the Down Syndrome Clinical Cohort Coordinating Center (DS-4C)?

The DS-4C, as described in NOT-OD-23-135, is conceived as a coordinating center that will be responsible for overall Down Syndrome Cohort Development Program (DS-CDP) coordination and outreach to support development of new cohorts of people with Down syndrome, and curate the metadata from the new cohorts. The DS-4C will provide resources that will support cohort development, to include longitudinal deep phenotyping and biospecimen collection. The research questions will be focused on activities of the four cores: (1) Administrative Core, to oversee the study operations, to support a call center that facilitates acquisition of outside records, additional data collection, and longitudinal contact with patients, and to provide capitation costs to the Cohort Research Sites (DS-CRS) for each recruited subject; (2) Outreach Core, to oversee communication with the DS community and address issues of diversity, equity, inclusion, and accountability (DEIA) among research subjects and/or investigators; (3) Cohort Core, to coordinate and lead the implementation of the common protocol developed in conjunction with the DS-CRS awards and the DS-Biorepository and oversee data collection and data quality; and (4) Data Management Core, to ingest, aggregate, integrate, harmonize, and curate data collected by the DS-CRS and ensure they are shared through the INCLUDE DCC (https://includedcc.org(link is external)) Data Hub.

How are you envisioning the collaboration between the DS-4C and the DS-CRS? Are DS-CRS sites encouraged to be engaged in the 4C and thus, submitted as companion applications?

It is not necessary for DS-CRS applicants to coordinate with a DS-4C applicant as part of the submission process. The two programs will be competed separately, but the successful awardees will be brought together to collaborate on a shared phenotyping protocol and biospecimen collection effort, known as the common protocol.

What details can you provide about the DS-4C Administrative Core? Will it include training of DS-CRS to collect data? Will it include costs for associated phenotyping (purchasing of supplies for sites such as protocols, kits, vials, etc.)?

The Administrative Core will include activities associated with recruitment and enrollment costs as well as training of staff to administer the phenotyping protocol, along with costs associated with materials for testing, evaluation, and subject evaluation as part of the common protocol. However, biospecimen collection will be coordinated by the DS-Biorepository, which will cover the costs of assembling biospecimen sample collection kits, as well as their distribution and tracking, including payment of shipping costs for submission of samples from the DS-CRS sites to the DS-Biorepository.

What details can you provide about the DS-4C Outreach Core? Will it include a call center and longitudinal data collection? How are you envisioning outreach to promote diversity, equity, inclusion, and accessibility (DEIA) nationally?

The Outreach Core will coordinate outreach activities for the entire DS Cohort Development Program, including a call center to triage incoming requests from researchers, participants, and families. The call center will direct referrals and follow-ups of enrolled participants in partnership with the DS-CRS sites that perform the actual recruitment. We expect the Outreach Core to facilitate longitudinal follow-up of enrolled subjects with periodic data collection appropriate to the age range of subjects being recruited. Outreach to diverse communities is described in responses to questions about the DS-CRS above; essentially, each CRS application is encouraged to include at least one partner from low-resourced institutions or institutions serving groups underrepresented in biomedical research, as well as members of local Down syndrome and other community partners.

What details can you provide about the DS-4C Cohort Core? Will the Cohort Core dictate the common protocol to the DS-CRS? As data collection of neurobehavioral or medical records is very different than data collection of biospecimens, are you envisioning co-leads for this core?

The Cohort Core will partner with the DS-CRS sites and the DS-Biorepository during the first year of the awards to develop a common protocol based on the protocols proposed by the DS-CRS applicants. We recognize that data collection of medical records, neurodevelopmental tests, and biospecimens vary; thus, we expect that a DS-4C application is likely to have a multidisciplinary leadership team to direct the program. Subsequently, staff from this core will guide the implementation of the common protocol.

What details can you provide about the DS-4C Data Management Core? How is this core distinct from the current roles of the INCLUDE DCC? Or is it intended just to collect data coming from DS-CRSs as an aid to the INCLUDE DCC separate from their role in aggregating data from other DS studies?

The Data Management Core will help coordinate the data ingest and transfer to the INCLUDE DCC. We expect the DS-4C to develop productive and efficient connections with the INCLUDE DCC to facilitate such linkages and enhance data harmonization and integration to promote sharing with the broader DS community, consistent with the goals of the NIH Data Management and Sharing Policy (https://sharing.nih.gov/data-management-and-sharing-policy). Applicants are encouraged to reach out to the INCLUDE DCC for guidance and a letter of support for their proposal.

What is the role and function of the DS-Biorepository?

The DS-Biorepository will be a resource to support the collection, storage, distribution of, and linkage of biosamples from DS clinical research. The aim is to facilitate the coordinated receipt and distribution of biospecimens, from future and previously funded clinical research studies. As a federated system, the DS-Biorepository will also provide linkages to existing and legacy biospecimen repositories housing specimens from DS-focused clinical research. The DS-Biorepository should include a cost-recovery estimate for sample collection, storage, and distribution.

What do you mean by a “federated” biorepository?

In addition to collecting and storing biospecimens, the DS-Biorepository will develop a centralized system that links and/or connects, through a web-based user interface, distributed networks of existing biorepositories to facilitate the search of all publicly accessible biospecimens relevant to the study of DS. This model does not require existing biorepositories to relinquish their collections of biospecimens.

How will the Cohort Development Program (DS-CDP) integrate with the Federated Biospecimen Repository (DS-Biorepository) described in NOT-OD-23-136?

The DS-CDP will coordinate the collection of biospecimens from registered participants in the longitudinal cohort study to be deposited in the DS-Biorepository. The DS-CRS applicants will propose a phenotyping protocol, but the final common protocol will be developed collaboratively by the DS-4C, DS-CRS sites, and DS-Biorepository during the first year of the awards. As part of the proposed protocol, the DS-CRS sites will describe the biospecimens to be collected and recommended ‘omics evaluations.’ The DS-Biorepository will have the capacity to collect and distribute a variety of biospecimens, including, but not limited to blood, plasma, skin, biopsy or surgical tissues, brain (whole or sections), spinal cord, cerebrospinal fluid, and amniotic fluid. In addition, the DS-Biorepository will be responsible for the assembly, distribution, and tracking of biospecimen collection kits to the DS-CRS sites along with any shipping costs for submission of samples back to the DS-Biorepository.

We have an existing biospecimen repository funded by an entity other than NIH. Are we eligible to apply?

Yes, existing biospecimen repositories that are not currently receiving NIH funding are eligible to apply.

We have an existing biospecimen repository focusing on a specific type of tissue collection (e.g., brain collection or blood collection). Are we eligible to apply?

An existing biobank can apply, but it needs to demonstrate proficiency with collection of more than one tissue type (e.g., plasma, skin, and biopsy tissues, etc.).

Will the biorepository be enrolling patients along with the clinical centers or will the biorepository just be responsible for accepting the samples to be processed from the clinical centers?

The DS-Biorepository NOFO is a resource grant, and it will support the infrastructure for this biorepository, and will not focus on enrolling participants. If an applicant who is applying for the biorepository NOFO as well as one of the other two NOFOS (DS-4C, DS-CRS), then they would be considered eligible to enroll participants. This biorepository NOFO is a resource grant.

Does this funding cover the sample processing – (i.e., PBMC processing costs and transport)?

Yes, it will cover costs for required processing of the samples. Those applying to the DS-Biorepository NOFO would be expected to recover the costs for transporting samples from clinical sites and processing those samples.

It would be helpful to know the number of sites (and projected total number of participants) as this relates to budget for arranging/training staff for processing at sites, as well as shipping costs back to the central biorepository.

The number of participants will depend on the study that has been proposed. The function for this Biorepository includes taking samples from studies that are from INCLUDE as well as other Down syndrome studies that are not necessarily part of INCLUDE. In terms of sites, this biorepository will be the primary one for the Cohort Development Project (CDP) program, which is why it is highly encouraged that the DS-4C and DS-CRS NOFOS are also read. For the CDP program, 3 to 6 sites per application, and 3 to 8 awards total are allowed. It is assumed that the best estimate will be presented.

For budgeting and planning purposes, what is a ballpark number of stored samples per year to plan for storage? Also, the number of samples to be processed and what type of processing they will undergo?

For budgeting purposes, there is no ballpark number of samples stored per year, but the sample numbers will have a limit in terms of the budget. Samples can be processed based on the overall budget. It will be different for different sites because costs are going to be unique to the institution.

How many other INCLUDE programs will utilize the biorepository for storage and processing and if so, how do we know the volume to expect for budgeting purposes?

It is anticipated that in the future other INCLUDE projects will also utilize this biorepository. INCLUDE Projects are not required to use this biorepository as there are alternatives also available currently. The focus should be on the CDP for this repository and if it needs to be scaled, we will consider additional funding in the future to meet that need. The intent is to direct project leads to the availability of the biorepository once it is in place prior to requesting additional funding to utilize another repository.

How many pages do we need to write for this grant?

The page limit is twelve (12) pages. All page limitations are described in the SF424 Application Guide, and the Table of Page Limits must be followed.

Existing biospecimen repositories that are not currently receiving NIH funding are eligible to apply?

It is not necessary to be an NIH supported biorepository to apply for this grant, however NIH supported biospecimen repositories can also apply.

Is this award a standalone submission?

Yes.

Does NIH maintain a complete list of existing biospecimen repositories?

Through the NIH-wide Biomedical Informatics Coordinating Committee (BMIC), NIH has a listing of NIH-supported repositories available through: https://www.nlm.nih.gov/NIHbmic/domain_specific_repositories.html

Is there a minimal set of specimen types anticipated?

There is not a minimal list of the types of specimens that will be banked, but applicants should have the capability to handle the brain biopsy, skin, plasma sample types, and the other types of samples listed in the NOFO (RFA-OD-24-004)

Is the expectation that the samples are processed at the selected biorepository, or can you contract with another laboratory?

The cohort studies will be utilizing the selected biorepository for the cohort. The biorepository itself will need to be performing those functions as a resource for the INCLUDE project.

Any restrictions on where the samples are processed (i.e., outside of US) prior to contribution to the biobank?

As part of this NOFO, foreign components are allowed, so there are no restrictions from NIH. Please take into consideration any restrictions specific to the countries where the samples will be sent.

Beyond storing and processing the biospecimens, can we propose to sequence some samples and get genetic data of these samples in this grant? Will this grant cover this cost of sequencing?

No, the sample sequencing and plans for collecting genetic data would be covered by other INCLUDE Project grants and not from this grant.

Are the samples anonymized at the site? If so, is the biorepository responsible for developing a common system for that across sites?

Yes, all samples will be de-identified at the clinical site before being sent to the biorepository. The biorepository is part of the federated user interface, web-based, system that will develop a common system for matching across various sites. Cross site linking is being developed with the DCC and will be rolled out when ready via NIH approved applications. Linkages will be limited to the approved protocol and will be between the research sites and the DS-4C. This limitation will ensure that a participant is enrolled to just one site.

Is a premortem clinical evaluation a prerequisite for accepting a specimen?

The actual protocol practices and SOP for that will be developed together with the CDP program and the NIH. Having clinical data linked to biospecimen will be key.

Could we get some more detail about how the biospecimen request approval process might work and how will tissue dissemination be managed? Would generation of certain data types be prioritized?

Because this is a resource grant, the approval process and related SOPs will be provided by the CDP program. This will be happening once awards are made. A steering committee with representation from the CDP, staff from the clinical research sites, the cohort center, and the biorepository will be developed and approve the common protocol.

Will this biobank be considered human subject research if the biobank site does not intend to enroll DS patients and collect samples? Or must the biobank site also enroll DS patients and collect samples?

The biobank is only for human subject research or human participant research. If the institution that houses the biorepository is located at one of the institutions that is awarded as a clinical core site, then it can enroll DS patients.

Will the biobank work only with deidentified samples for purposes of the human subject’s research exception, or will they also have the full PHI and require a full study record?

The Biorepository should only work with de-identified samples.

If we are already enrolling in our own DS biobank, would we not be expected to continue to do that for this biorepository?

If another existing biorepository is being used, it can be linked to the INCLUDE Project, but it is not required.

For this biobank, do you expect to merge with other DS biobanks?

A goal of this NOFO is to create a federated system that will link with existing Down syndrome biorepositories and existing repositories with Down syndrome samples. So, in addition to linking to other existing resources, this Biorepository will collect and process samples from the DS-CRS cohort NOFO that is part of DS-CDP, and other INCLUDE research projects. If an existing Down syndrome biorepository does not apply to this NOFO, it is requested that the Biorepository be able to link to that external, existing biorepository as the information is better publicly shared. This allows the ability to know where requests and access these bio samples can be made.

For material transfer, is the biorepository responsible for creating the material transfer and data use agreement or just to follow the regulations?

The Biorepository should establish the Material Transfer Agreements (MTAs) and any data use agreements, in collaboration with the other participating grantees for the CDP, as part of the Common Protocol. This is a primary repository for the CDP program; however, there may be other sites or DS studies that may use this biorepository. If that is the case, then the MTAs and data use agreements should also be done in collaboration with the PIs of those studies.

Do you expect this new web interface to also disseminate biospecimen requests to repositories or only query ability?

Yes. The specimens should be made available through the web interface. The query function is also available on the INCLUDE data hub. There will be cost coverage for sending samples and receiving samples.

Creating a web system and linking datasets may take a long time, how long do you expect it to take to establish this system? What is the role of the INCLUDE DCC in this web-based interface?

The INCLUDE Data Hub currently has a portal where you can access the metadata, phenotypic data, and genomic data. The intent is to provide a new function about specimens which will be linked to the biobanking website once ready. The expectation is to use the first year to prepare for the landing page of the website. Awardees should coordinate with the INCLUDE DCC to set up the linkage.