Released Date
Expiration Date
Activity Code
U01
Full Announcement
RFA-HL-21-015
Frequently Asked Questions for HeartShare RFA-HL-21-015
General Questions
- Can you provide an example of a program with similar organization to HeartShare?
- PVDomics is another NHLBI program that is designed as a deep phenotyping program and is a good model for HeartShare.
- See this link for a publication describing PVDomics.
- Can one investigator apply for both RFAs?
- Yes, there are no restrictions on applying to both RFAs.
- Please contact Dr. Sachdev or Dr. Wong if you are considering applying for both RFAs.
- Can an Early Stage Investigator (ESI) apply as PI for a Clinical Center (CC) or a Data Translation Center (DTC) application? If awarded, how will ESI/New Investigator status (NI) be impacted?
- Yes, an ESI can apply as a PI or co-PI for a CC or DTC application. If awarded, the ESI will lose his or her ESI/NI status as U01s and U54s are independent research awards that are R01 equivalent grants (see ESI FAQs). An ESI will not lose his/her ESI/NI status if he or she has a project role other than PI (e.g., co-investigator, collaborator, etc.).
- The NHLBI ESI R01 percentile advantage will not apply to a U01 or U54 application, which will receive priority scores only (i.e., no percentile scores).
- Applicants are encouraged to consider including early career investigators on the team and should carefully review the Investigator Review Criteria for each funding opportunity announcement.
- Can one site be awarded both a CC award to RFA-HL-21-015 and a DTC award to RFA-HL-21-016?
- Yes. If one institution has applications for a CC and DTC with different principal investigators, they may both be awarded if there is a clear firewall between the two groups.
- Yes. If one institution has applications for a CC and DTC with different principal investigators, they may both be awarded if there is a clear firewall between the two groups.
- Will co-investigators be included in the HeartShare Steering Committee (SC)?
- Yes, co-investigators will be included in the committee. The members of the SC will be defined to give each CC, DTC, NHLBI Program, and once selected, Core Laboratories representation in the SC. The SC is the governing body for the HeartShare program.
- Yes, co-investigators will be included in the committee. The members of the SC will be defined to give each CC, DTC, NHLBI Program, and once selected, Core Laboratories representation in the SC. The SC is the governing body for the HeartShare program.
- If the primary site has a different indirect rate for F&A than their collaborators that receive subcontracts, how is this handled?
- The subcontract indirect F&A rate will be honored for US institutions. For foreign components proposed as subcontracts, the NIH funds foreign F&A costs at a rate of 8 percent of modified total direct costs, exclusive of tuition and related fees, direct expenditures for equipment, and subawards in excess of $25,000 (see link). The subcontract budget should include direct costs and total costs using the secondary institution’s indirect F&A rate, which may be different from primary site’s indirect F&A rate. Note that the budget of the primary applicant should remain within the direct cost cap per year (excluding consortium F&A).
- The subcontract indirect F&A rate will be honored for US institutions. For foreign components proposed as subcontracts, the NIH funds foreign F&A costs at a rate of 8 percent of modified total direct costs, exclusive of tuition and related fees, direct expenditures for equipment, and subawards in excess of $25,000 (see link). The subcontract budget should include direct costs and total costs using the secondary institution’s indirect F&A rate, which may be different from primary site’s indirect F&A rate. Note that the budget of the primary applicant should remain within the direct cost cap per year (excluding consortium F&A).
- Is cost sharing allowed? That is, can institutions provide additional funds to support the HeartShare CCs and/or DTC)?
- Yes, cost sharing is allowed and institutional support is acceptable.
Clinical Center (CC) and Phenotyping Protocol Questions
- The RFA indicates that CCs are strongly encouraged to form multidisciplinary teams consisting of one HF investigator and one investigator from a complementary area of expertise, including but not limited to geriatrics, metabolic disease, and/or genomics. Is there a limit to the number of co-PIs on an application with one individual serving as contact PI?
- No, there is no maximum number of PIs on an application. Applicants should keep in mind that all PIs share the responsibility and authority for leading and directing a project, as well as contributing unique expertise that would not be possible with a single-PI proposal. A multi-PI plan is required, and more information can be found here.
- No, there is no maximum number of PIs on an application. Applicants should keep in mind that all PIs share the responsibility and authority for leading and directing a project, as well as contributing unique expertise that would not be possible with a single-PI proposal. A multi-PI plan is required, and more information can be found here.
- What does the CC budget for RFA-HL-21-015 cover?
- The CC budget of $200K direct costs/year should only cover investigator time, coordinator time, and administrative costs. Phenotyping costs should not be included in the CC operational budget of $200K direct costs/year. Patient phenotyping and clinical research care costs will be distributed by the DTC to the CCs and cores by pre-determined capitation.
- The CC budget of $200K direct costs/year should only cover investigator time, coordinator time, and administrative costs. Phenotyping costs should not be included in the CC operational budget of $200K direct costs/year. Patient phenotyping and clinical research care costs will be distributed by the DTC to the CCs and cores by pre-determined capitation.
- Should phenotyping be proposed in the CC application to RFA-HL-21-015 and do budget details need to be included?
- Yes, the CC application should include a deep phenotyping protocol. Additional details and budget requirements are outlined as follows.
- CCs and cores will be reimbursed by the DTC per capitation. From the CC RFA: “Protocol funds to perform the deep phenotyping protocol will be awarded to the DTC and be distributed by the DTC to the CCs on a capitation basis in accordance with budgets approved by the Steering Committee and NHLBI. For planning purposes, it is estimated that $645,000 direct costs per year for years 1-2 and $1,345,000 direct costs per year for years 3-5 will be available for the study-wide phenotyping protocol(s). This will be finalized and agreed upon by the SC across HeartShare after funding. As the intent is to use existing NHLBI resources, such as TOPMed for omics, the cost of omics should not be included in budget totals.”
- The first part of the CC application should contain details of the operational budget and should not exceed $200K direct costs per year.
- The second part of the CC application should include your vision of a deep phenotyping protocol. Although the protocol funds for deep phenotyping are distributed to the CCs by the DTC, the approximate direct costs available are provided as a guide to help plan the scope and depth of testing. As noted under Section IV. Application and Submission Information and Deep Phenotyping Protocol, CCs will propose a preliminary baseline clinical examination protocol and budget. It is assumed that proposed studies would be conducted on the entire cohort, unless proposing an assessment that requires specialized resource(s) and small sample size.
- Per the RFA-HL-21-015, the applicants should only enter the operational budget related to Clinical Center activities on the ASSIST budget form. As the ASSIST platform does not have a secondary budget form to enter the phenotyping protocol expenses, applicants can detail the estimated annual expenses of the phenotyping protocols in the Budget Justification section. Note that omics should be included in the phenotyping protocol, however, as mentioned in the RFA, the intent is to use existing NHLBI resources, such as TOPMed for omics.
- The final phenotyping protocol will be determined after HeartShare funding in conjunction with the Steering Committee and the NHLBI.
- Should biomarker and multi-omics signaling pathway analyses be included in the itemized budget for a CC application to RFA-HL-21-015 or will that be part of the DTC budget for RFA-HL-21-016?
- Per the RFA HL-21-015, the budget of $200K direct costs per year is restricted to operational expenses such as salaries, travel, and appropriate administrative support. Please see the excerpt below describing the funds for the phenotyping protocol. These total estimates for deep phenotyping costs across all 4 sites are part of the DTC budget, but are provided as a guide for the CCs to help plan the research testing. As mentioned, however, the TOPMed resource should be used for omics whenever possible and this cost should not be included in proposed budgets.
“As discussed in the Research Strategy section below, CCs should describe their vision of a deep phenotyping protocol that will be standardized across all sites by the SC after funding. CCs will propose a preliminary baseline clinical examination protocol and budget. Protocol funds to perform the deep phenotyping protocol will be awarded to the DTC and be distributed by the DTC to the CCs on a capitation basis in accordance with budgets approved by the Steering Committee and NHLBI. For planning purposes, it is estimated that $645,000 direct costs per year for years 1-2 and $1,345,000 direct costs per year for years 3-5 will be available for the study-wide phenotyping protocol(s). This will be finalized and agreed upon by the Steering Committee across HeartShare after funding. As the intent is to use existing NHLBI resources, such as TOPMed for omics, the cost of omics should not be included in budget totals.”
- Per the RFA HL-21-015, the budget of $200K direct costs per year is restricted to operational expenses such as salaries, travel, and appropriate administrative support. Please see the excerpt below describing the funds for the phenotyping protocol. These total estimates for deep phenotyping costs across all 4 sites are part of the DTC budget, but are provided as a guide for the CCs to help plan the research testing. As mentioned, however, the TOPMed resource should be used for omics whenever possible and this cost should not be included in proposed budgets.
- The 4 CCs are to recruit approximately 1,000 patients over 4 years. If satellite sites are needed to help with recruitment, should subcontracts be included in the application?
- Yes, satellite site subcontract(s) should be included in the CC application.
- Yes, satellite site subcontract(s) should be included in the CC application.
- Of the 1,000 deep phenotype subjects, will this include controls (nl, HFrEF, HFmrEF) and HFpEF or just HFpEF?
- Controls and comparators are needed for both the EHR and deep phenotyping portions. Investigators should propose patients numbers that they think are appropriate for both components assuming that the focus is on HFpEF. The final numbers for HFpEF patients, controls, and comparators will be determined later by the SC.
- Controls and comparators are needed for both the EHR and deep phenotyping portions. Investigators should propose patients numbers that they think are appropriate for both components assuming that the focus is on HFpEF. The final numbers for HFpEF patients, controls, and comparators will be determined later by the SC.
- Can existing NIH population studies (e.g., PVDOMICS, FHS, MESA) with data in TOPMed be included as controls in study design?
- Yes, existing NIH population studies can be used as sources for controls for HeartShare’s prospective component. NIH population studies can also be included in HeartShare’s retrospective component as a separate effort (i.e., Cohort Core) to harness existing data, images, and samples
- Yes, existing NIH population studies can be used as sources for controls for HeartShare’s prospective component. NIH population studies can also be included in HeartShare’s retrospective component as a separate effort (i.e., Cohort Core) to harness existing data, images, and samples
- Will there be uniform validation criteria for the EHR data HFpEF subjects across sites?
- Yes, there will be uniform EHR criteria to be determined later by the SC.
- Yes, there will be uniform EHR criteria to be determined later by the SC.
- How many subjects with EHR data only are a CC expected to enroll beyond the 250 per CC which will undergo electronic and prospective research studies type phenotyping?
- The final number of subjects will be determined later by the Steering Committee.
- The final number of subjects will be determined later by the Steering Committee.
- Can a PI collaborate with 1 or 2 other sites on a CC application to come in as a group?
- Yes, there is no restriction on sites applying together; however, one site will be the primary site (i.e., the institution submitting the application).
- Additionally, the operational budget for a CC is fixed at $200K direct costs per year so multiple sites applying together need to share this budget. Additional sites would be subcontracts to the primary site and would receive reimbursement for patient recruitment and phenotyping via the DTC.
- With this in mind, it would be helpful for applications to specifically discuss feasibility of completing study activities within the specified CC budget. A CC application proposing multiple sites should also provide evidence of successful coordination between the additional sites for EHR connectivity, data collection, and completion of the phenotyping protocol with the applicant budget serving as the lead site.
- What are the NHLBI expectations for diversity?
- Can a CC include its own retrospective cohort to HeartShare?
- Yes, existing cohort studies or trials are potential resources that may strengthen the HeartShare database. CCs may include extant resources if meeting the eligibility criteria of confirmed heart failure with broadly based phenotypic characteristics, imaging, outcome data, and any relevant biospecimens. Retrospective cohorts will be aggregated and curated such that the results of such analytics may inform prospective testing and analysis. Applicants may add cohort information in the deep phenotyping protocol of the CC application and also describe their prior research experience with respect to clinical phenotyping and multi-omics.
- Any NIH cohorts with adjudicated HFpEF patients can be a part of the HeartShare retrospective data as determined by the HeartShare Steering Committee. As described in the DTC Objectives section in RFA-HL-21-016, cohorts may include NHLBI-supported large cohort studies, NHLBI-sponsored ongoing clinical trials, and completed clinical trials, programs primarily supported by other NIH Institutes, and other federal and non-federal programs. The cohorts and trials do not have to be currently funded by the NHLBI, but must be aligned with the NHLBI’s Strategic Vision. HeartShare is intended to support research in the following cohort types:
- Epidemiological cohorts predominantly focused on U.S. populations and based on participants with HF in defined population groups (e.g., racial or ethnic minorities, geographic area)
- Cohorts established through either solicited or unsolicited awards, or through independent funding sources (e.g., industry, foundations).
- If investigators work with a particular colleague or lab for tissue or omics analysis, should this be included in the application or should budget details for this type of collaboration be worked out after the award?
- Yes, your experience with tissue and/or omics analysis should be detailed in the section of the application describing the deep phenotyping protocol. This should include a description of which core labs you think are necessary. If you feel that your current collaborator could function as a core lab for the HeartShare program, please describe the capabilities of the site to function as a specific core in the phenotyping protocol.
- Yes, your experience with tissue and/or omics analysis should be detailed in the section of the application describing the deep phenotyping protocol. This should include a description of which core labs you think are necessary. If you feel that your current collaborator could function as a core lab for the HeartShare program, please describe the capabilities of the site to function as a specific core in the phenotyping protocol.
- Can collaborations/subaward budget contracts with external investigators be included in a CC application to RFA-HL-21-015?
- Yes. If you have collaborators that have specific expertise that may benefit the overall HeartShare program, you may describe this experience and propose in the phenotyping protocol that this group function as a core for the entire program. As mentioned above, TOPMed resources should be used whenever possible for omics since that resource is separate from the total HeartShare budget.
Data Translation Center (DTC) Questions
- What type of leadership structure is recommended for the DTC?
- Expertise in heart failure, epidemiology, bioinformatics, statistical support, machine learning/artificial intelligence, omics, and systems biology are recommended for the DTC. Multi-disciplinary expertise is acceptable as long as the teams have the necessary capability to achieve HeartShare goals
- Expertise in heart failure, epidemiology, bioinformatics, statistical support, machine learning/artificial intelligence, omics, and systems biology are recommended for the DTC. Multi-disciplinary expertise is acceptable as long as the teams have the necessary capability to achieve HeartShare goals
- The RFA states that the DTC should budget for 15% effort for the Chairs/Co-Chairs. Will this 15% effort be shared among each Chair/Co-chair, or should the budget include 15% for each of the multiple chairs/co-chairs?
- The 15% effort will be shared among each Chair/Co-Chair. That is, a single Chair should dedicate or two co-Chairs should each have 7.5% effort. The salary support will be part of the DTC’s $300K direct costs/year study operations budget.
- The 15% effort will be shared among each Chair/Co-Chair. That is, a single Chair should dedicate or two co-Chairs should each have 7.5% effort. The salary support will be part of the DTC’s $300K direct costs/year study operations budget.
- The RFA states that $50K is included and restricted for a consultant budget as part of the study operations budget for the DTC’s Admin Core. Is the $50K consultant budget separate from the budget for the 15% effort for the Chairs/Co-Chairs?
- Yes, the $50K consultant budget for the External Advisory Committee (EAC) and Observational Study Monitoring Board (OSMB) consultants is separate from the budget for the 15% effort for the Chairs/Co-Chairs. Both budgets will be supported by the Admin Core’s study operations budget of $300,000 direct costs/year.
- Yes, the $50K consultant budget for the External Advisory Committee (EAC) and Observational Study Monitoring Board (OSMB) consultants is separate from the budget for the 15% effort for the Chairs/Co-Chairs. Both budgets will be supported by the Admin Core’s study operations budget of $300,000 direct costs/year.
- Will NHLBI appoint an independent study chair separate from the DTC?
- Yes, NHLBI will appoint an independent study chair, External Advisory Committee (EAC), and Observational Study Monitoring Board (OSMB). Only the Chair has a salary support. The EAC and OSMB will receive honorarium and have a travel budget. It is anticipated that most meetings will be virtual. Funding for these roles will come from the DTC.
- Yes, NHLBI will appoint an independent study chair, External Advisory Committee (EAC), and Observational Study Monitoring Board (OSMB). Only the Chair has a salary support. The EAC and OSMB will receive honorarium and have a travel budget. It is anticipated that most meetings will be virtual. Funding for these roles will come from the DTC.
- Will only one abstract be needed and included in the Overall section or will each core need an abstract?
- An abstract will be needed for each DTC component (i.e., Overall and cores).
- An abstract will be needed for each DTC component (i.e., Overall and cores).
- Are Resource Sharing Plans, as well as Facilities and Other Resources sections, required for the Overall component and all 4 cores?
- Yes, these materials are required for Overall component and all 4 cores.
- Yes, these materials are required for Overall component and all 4 cores.
- Is part of the DTC responsibilities to build the database and platform for analysis of omics and imaging data (and if so, will the funding come out of our budget)?
- The DTC should use NIH resources to complete the data portal core and data management core activities. Specifically, TOPMed will support omics and BioData CATALYST infrastructure will support the data platform. The DTC is tasked with specific responsibilities that include creating an interface for HF investigators to access data and an interface for patients.
- The DTC should use NIH resources to complete the data portal core and data management core activities. Specifically, TOPMed will support omics and BioData CATALYST infrastructure will support the data platform. The DTC is tasked with specific responsibilities that include creating an interface for HF investigators to access data and an interface for patients.
- RFA-HL-21-016 has itemized costs for the Administrative and Outreach Core budget. Should the cost for the Study Chair(s) (1.8 calendar month effort) and travel costs for PIs and Core Leaders be considered as part of that cost for Study Operations ($300K direct costs/year limit)?
- Yes, the cost for the study chair and travel costs are a part of the study operations budget of $300K direct costs per year.
- Yes, the cost for the study chair and travel costs are a part of the study operations budget of $300K direct costs per year.
- RFA-HL-21-016 has suggested budgeting amounts for years 1 and 2 only for the Cohort Core. Does this mean that the function of the Cohort Core is phased out after year 2?
- Yes, the work of the Cohort Core is planned for years 1 and 2 only.
- Yes, the work of the Cohort Core is planned for years 1 and 2 only.
- Per RFA-HL-21-016, the NHLBI “intends to commit total costs of up to $3.765M in FY2021 to fund 1 new award.” If an institution’s indirect F&A rate plus the direct cost cap exceeds the $3.765M total cost amount, how should this be handled?
- For RFA-HL-21-016, application budgets may request up to $2.445M in direct costs (excluding consortium F&A) per year for 5 years. Applicants are encouraged to not exceed the $3.765M total costs per year.
- For RFA-HL-21-016, application budgets may request up to $2.445M in direct costs (excluding consortium F&A) per year for 5 years. Applicants are encouraged to not exceed the $3.765M total costs per year.
- For the DTC Cohort Core, can other cohorts from NIH-funded work be part of HeartShare retrospective data?
- Yes, any NIH cohorts with adjudicated HFpEF patients can be a part of the HeartShare retrospective data. As described in the DTC Objectives section in RFA-HL-21-016, cohorts may include NHLBI-supported large cohort studies, NHLBI-sponsored ongoing clinical trials, and completed clinical trials, programs primarily supported by other NIH Institutes, and other federal and non-federal programs. The cohorts and trials do not have to be currently funded by the NHLBI, but must be aligned with the NHLBI’s Strategic Vision. This FOA is intended to support research in the following cohort types:
- Epidemiological cohorts predominantly focused on U.S. populations and based on participants with HF in defined population groups (e.g., racial or ethnic minorities, geographic area)
- Cohorts established through either solicited or unsolicited awards, or through independent funding sources (e.g., industry, foundations).
- Yes, any NIH cohorts with adjudicated HFpEF patients can be a part of the HeartShare retrospective data. As described in the DTC Objectives section in RFA-HL-21-016, cohorts may include NHLBI-supported large cohort studies, NHLBI-sponsored ongoing clinical trials, and completed clinical trials, programs primarily supported by other NIH Institutes, and other federal and non-federal programs. The cohorts and trials do not have to be currently funded by the NHLBI, but must be aligned with the NHLBI’s Strategic Vision. This FOA is intended to support research in the following cohort types:
- Will the DTC have any decision making about SOPs/QC for the core labs ?
- Yes, the DTC will solicit and establish necessary cores and the DTC will have oversight of core activities.
- Yes, the DTC will solicit and establish necessary cores and the DTC will have oversight of core activities.
- Will there be core labs (e.g., imaging, omics) and if so will they be selected by NHLBI? Will the DTC have any decision making about SOPs/QC for the core labs? Will they have funding from a separate mechanism or will those be funded from DTC funds?
- Yes, both the DTC and CCs should propose necessary cores. Core services will be reimbursed by the DTC budget. Final decisions for cores will be made by the Steering Committee. DTC will have oversight of core activities and cores will be supported by DTC funds.
- Yes, both the DTC and CCs should propose necessary cores. Core services will be reimbursed by the DTC budget. Final decisions for cores will be made by the Steering Committee. DTC will have oversight of core activities and cores will be supported by DTC funds.
- What type of omics are possible through TOPMed? What proteomics platform does TOPMed use? Is an Omics Core needed if TOPMed is doing all the omics?
- See this link for omics, including WGS, RNA-seq, methylation, metabolomics, and proteomics.
- TOPMed has used both the Somascan and Olink proteomics platforms in previous years.
- Yes, an Omics Core can be included in the phenotyping proposal in case the Steering Committee decides that additional omics capabilities are required. Personnel with relevant expertise and previous omics experience can be described in the phenotyping protocol.
- Should the DTC propose a deep phenotyping protocol?
- The deep phenotyping costs are provided as guidance for a deep phenotyping protocol and the CCs will be using these estimates for the second half of their application in which they describe the phenotyping protocol in detail. For the DTC applicant, a detailed phenotyping protocol or budget is not required at this stage since the program coordination and oversight, cohort core, and data management and analytics are the key responsibilities. The final phenotyping protocol will be determined by a Steering Committee that will consist of CCs, NHLBI Program staff, and the DTC investigators. The DTC will play a large role in this.
- For the many DTC roles, it is expected that applicants use the suggested budgets for each core and describe key aspects of each and their associated budgets. As an example, for the research skills program, the organization, recruitment strategies, deliverables or expectations for the trainees, and specific roles of the DTC and CC investigators, as well as budgets for these activities, may be described.
- For the DTC application, should we list the given budgets for deep phenotyping and for the research skills program and other components, or do we need more detailed budgets for each activity?
- For the many DTC roles other than deep phenotyping, it is helpful to use the suggested budgets for each core and describe key aspects of each and their associated budgets. As an example, for the research skills program, the organization, recruitment strategies, deliverables for the trainees, and specific roles of the DTC and CC investigators, as well as budgets for these activities, may be described.
- For the many DTC roles other than deep phenotyping, it is helpful to use the suggested budgets for each core and describe key aspects of each and their associated budgets. As an example, for the research skills program, the organization, recruitment strategies, deliverables for the trainees, and specific roles of the DTC and CC investigators, as well as budgets for these activities, may be described.
- For the Research Skills Program, the RFA requires that applicants budget for salary support for early career investigators. Should that line item go in Other Personnel expenses (section B of application budget) with to be determined (TBD) for the personnel, or should it go as a separate line item under Section F - Other Direct Costs?
- If applications are providing salary support for a TBD early career investigator, they should include the budget in section B. They should also provide a written budget justification to describe in detail what the TBD early career investigator will be doing on the project.
- If applications are providing salary support for a TBD early career investigator, they should include the budget in section B. They should also provide a written budget justification to describe in detail what the TBD early career investigator will be doing on the project.
- Should DTC applicants assume that any costs for additional studies in the retrospective cohort (e.g., additional omics) come out of the deep phenotyping funds?
- No, all costs for the retrospective cohort are covered by the DTC’s $200K direct costs per year budget for years 1-2 allocated to supported the Cohort Core. Omics costs are covered through TOPMed or through the Cohort Core budget.
- No, all costs for the retrospective cohort are covered by the DTC’s $200K direct costs per year budget for years 1-2 allocated to supported the Cohort Core. Omics costs are covered through TOPMed or through the Cohort Core budget.
- Is the DTC expected to oversee a central biorepository with central collection of specimens or to catalogue with each CC on collecting their own specimens and then facilitating transfer to core laboratories for specific omics platforms?
- The DTC would be expected to do the latter. That is, collaborate with the CCs on inventorying biospecimens collected by each CC and coordinating the samples for core analyses.
HeartShare Information Webinar
On October 27, 2020, NHLBI held a HeartShare technical assistance webinar to inform potential applicants about RFA-HL-21-015 and RFA-HL-21-016. This included a review of the purpose and objectives of the RFAs, application and peer review requirements, and budget considerations.
The webinar slides and recording are posted below.
HeartShare Technical Assistance Webinar - slides (pdf)
HeartShare Technical Assistance Webinar - video