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General FAQs for Down Syndrome Cohort Development Program (DS-CDP) and Down Syndrome Federated Biobanking Resource (DS-Biorepository)
The following FAQs are for , and .
Description of ādeep 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 ādeep phenotypingā 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.Ā
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.Ā
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.
Ā 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?Ā
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.Ā Ā Ā
Would you consider behavioral coding of observational videos to be behavioral data (for deep phenotyping)?Ā 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. Ā
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 youāre 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?Ā 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, itās 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 āComponentā for the DS-CRS site could look like if itās 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.Ā 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.
Ā 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.Ā 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.Ā 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.Ā Ā
Regarding the biobanking resource NOFO (RFA-OD-24-004), how many awards does this grant support in FY2024?Ā 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.
Ā 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?Ā 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 PIās 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 āfocusā on one phenotype in the application? Could we focus on ~3 and note that weāll 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 itās 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 siteās $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 wonāt 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?Ā 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?
Itās 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 , 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 āomics evaluations proposed as part of the DS-CDP common protocol be funded? Should I describe the āomics I think should be collected under the DS-CDP with a justification for each? Should I propose a budget for āomics 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 āomics evaluations for cohort participants.Ā The costs for āomics 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 () or the NHLBI Trans-Omics for Precision Medicine () initiatives.
This page last reviewed on January 8, 2024