National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Sudden Cardiac Death in the Young: Population Based Studies (U01)
U01 Research Project – Cooperative Agreements
The purpose of this FOA is to support mechanistic, genetic, and other studies to evaluate causes and consequences of and risk factors for sudden cardiac death in the young. Studies are required to use data and DNA samples from the Sudden Death in the Young Case Registry (described below) as foundations for their research.
February 25, 2015
May 15, 2015
May 15, 2015
June 15, 2015, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
June 16, 2015
Required Application Instructions
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
Sudden death in the young (SDY) is a critical public health and scientific issue. There is significant scientific disagreement, fueled by lack of evidence, about the best approach to prevent SDY. Some experts support the implementation of cardiovascular (i.e., electrocardiogram) screening programs for infants, athletes, or all children, to identify at-risk individuals and to prevent sudden cardiac death (SCD). However, rational policy development in the area of screening and prevention is currently limited by the lack of prospectively defined epidemiological data, including incidence rates and etiology for SDY.
The most common known diagnoses that increase risk for SDY include hypertrophic cardiomyopathy, coronary artery anomalies of wrong sinus origin, arrhythmogenic right ventricular cardiomyopathy, ion channelopathies, and genetic forms of epilepsy such as Dravet Syndrome. In up to 30% of cases of SDY, no specific diagnosis is found (autopsy negative). SCD has been documented at all ages and may be associated with competitive athletics. Approximately 10-15% of sudden unexpected infant death (SUID) cases may be due to ion channelopathies. Similarly, sudden unexpected death in epilepsy (SUDEP) has been documented at all ages, and several risk factors have been identified, including some cases originating with ion channelopathies. Noncompliance of antiepileptic medication usage and polytherapy in patients with refractory epilepsy are also risk factors for SUDEP.
The National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Neurologic Disorders and Stroke (NINDS) at the National Institutes of Health (NIH) are collaborating with the Centers for Disease Control and Prevention (CDC) to develop a two-phase initiative to provide a greater understanding of SDY.
During the first phase, the NHLBI, NINDS and CDC created the Sudden Death in the Young (SDY) Case Registry, a surveillance system and registry that will provide the first prospective, population-based data set compiled for the comprehensive evaluation of SDY in the United States. The SDY Case Registry is a surveillance system to comprehensively identify SDY cases for individuals =19 years of age in up to 10 states, create a registry of clinical information about cases, store DNA samples from registry cases, and establish a resource that will be used by NIH-funded researchers to investigate SDY.
The second phase of the initiative is composed of this FOA released and funded by NHLBI, which will support scientific research into sudden cardiac death in the young using the registry data and DNA samples. The CDC and NINDS are not providing funds for this FOA; however, in accessing data and conducting research, investigators funded by this FOA will interact with the CDC and NINDS staff as collaborating members on the SDY Case Registry Steering Committee.
To enhance the understanding of SDY, this FOA will support mechanistic, genetic, and other studies to evaluate causes and consequences of and risk factors for SDY. Studies are required to use the SDY Case Registry data and DNA samples as foundations for their research. Results of such studies are expected to be disseminated widely and to provide an evidence base to advance discussions about screening and prevention of SDY.
Selected Research Examples
Research supported by this FOA should fall within the NHLBI mission of heart, lung, blood, and sleep related disease.
Research questions of interest include, but are not limited to the following:
Applications that develop collaborations with the SDY Case Registry funded medical examiner's/coroner's offices and/or state public health agencies or their bona fide agents are of high programmatic interest. Applications that disseminate research findings promptly are also of high programmatic interest.
Applications which seek to determine the incidence of SDY are outside the scope of this FOA, will be considered non-responsive, and will not proceed to review. The CDC, NHLBI, NINDS and SDY Case Registry Steering Committee will be responsible for evaluating incidence.
The Program is a cooperative research program in which Research Centers will use phenotypic data and DNA samples from the SDY Case Registry. Collaborators in this effort include Research Centers, a DCC (funded separately from this FOA), the NHLBI, the CDC, the NINDS, the biorepository, state public health agencies or their bona fide agents, and medical examiner’s and coroner’s offices. The Research Committee, composed of funded Program Directors/Principal Investigators (PDs/PIs), NHLBI, NINDS, DCC, and the Biorepository PD/PI, will meet at the start of the project period to assess the needs of the Research Centers and develop a plan for supporting the Research Centers, achieve the research goals of each funded application, handle and share data, and ensure collaborations and minimize duplicative efforts across funded research projects.
The SDY Case Registry: The SDY Case Registry is operated under the guidance of the CDC, NHLBI, and NINDS. Its goals are to: identify all pediatric sudden deaths (= age 19) based on precise case definitions in a population-based sample in 9 jurisdictions; document the circumstances of the sudden deaths with death scene investigation and multidisciplinary case analysis, including review of medical records, reports from a standardized autopsy, and family history; and collect biospecimens (blood for DNA extraction) and store them in a central biorepository. Participating state public health agencies or their bona fide agents include: Georgia, Minnesota, New Hampshire, New Jersey, Wisconsin, Delaware, Tennessee, the city of San Francisco and the Tidewater region of Virginia.
The Registry broadens and enhances the activities of the National MCH Center for Child Death Review the Sudden Unexpected Infant Death (SUID) Case Registry. Phenotypic data is collected and entered into a central database by state-based child death review and advanced review teams. The data is extracted from death certificates, medical records, death scene investigations, and pathology reports. State public health agencies or their bona fide agents participating in the SDY Case Registry have proprietary rights over the data they enter into the Registry; however, under a specific agreement, data from individual states is combined into a single de-identified dataset. The DCC will facilitate the initiation of data use agreements between investigators and state public health agencies (or their bona fide agents) to access the dataset. A blood sample for DNA extraction is collected from a subset of cases and stored in the biorepository. Families are given the option to consent to have the decedent's data that was collected during Child Death Review and Advanced Review and/or a DNA sample be entered into the SDY Case Registry for research use. In addition, families are given the option to consent to re-contact by investigators for the purposes of obtaining additional information or returning clinically actionable results.
Data Coordinating Center (DCC): The SDY Case Registry’s DCC at the Michigan Public Health Institute is funded separately from this FOA via an Interagency Agreement between the NIH and CDC. The DCC provides administrative support to the SDY Case Registry, creates case report forms for phenotypic data, develops consent forms for participation in the Registry, maintains the SDY database, and subcontracts to a biorepository at the University of Michigan for DNA extraction and storage of samples. The DCC works closely with research teams to establish data use agreements with the SDY Case Registry data collection sites (state public health agencies or their bona fide agents) for access to phenotypic data and DNA samples for study. The DCC does not provide statistical support or conduct data analysis for each funded research project. Rather, they facilitate access to the data and act as liaisons between investigators and the jurisdictions that collect the data.
Research Centers: Research teams will work collaboratively with NHLBI, NINDS, CDC, the Registry’s DCC, biorepository, other Registry participants (state public health agencies or their bona fide agents, and medical examiner’s and coroner’s offices) and the other funded Research Centers. Through the DCC, research teams will access the phenotypic data and DNA samples of interest to their study.
It is possible that research applications from the funded research centers will have overlapping aims, patient populations, and/or methodologies. NHLBI's goal is for funded research teams to work collaboratively with each other and NHLBI to minimize overlap and increase efficiency of the research process (i.e. working collaboratively to recruit and characterize control subjects). Achieving such collaboration may involve investigators adapting their research plans after funding to maximize efficiency among funded applications.
Research centers will be responsible for developing a process to return clinically-actionable results to subject’s families in an efficient manner (if consent has been given by the family to do so).
NHLBI: The National Heart, Lung, and Blood Institute is responsible for organizing the program, and provides funding for the SDY Case Registry via an Interagency Agreement and an Interdepartmental Delegation of Authority with the CDC. In addition to regular award oversight, the NHLBI Project Scientists will be involved substantially with the awardees as a partner, consistent with the Cooperative Agreement mechanism, described below. NHLBI will also work with the CDC and NINDS to evaluate the incidence of SDY using Registry data.
CDC: The Centers for Disease Control and Prevention supervise the daily operations of the SDY Case Registry. CDC subcontracts with the DCC at the Michigan Public Health Institute and oversees and provides technical support to grantees at state public health agencies or their bona fide agents participating in the SDY Case Registry. CDC also collaborates with NHLBI and NINDS to provide scientific oversight for the Registry and to evaluate the incidence of SDY. The CDC also provides subject matter expertise in SUID and epilepsy.
NINDS: The National Institute of Neurologic Disorders and Stroke collaborates with CDC and NHLBI in the scientific oversight of the Registry. NINDS focuses on gathering data on cases of Sudden Unexpected Death in Epilepsy (SUDEP).
Research Committee: The Research Committee will consist of the Research Center PDs/PIs; the NHLBI, CDC, and NINDS Project Scientists; the DCC PD/PI, and the Biorepository PD/PI. The Research Committee will oversee research progress, help to minimize scientific overlap between the Research Centers, facilitate coordination and collaboration between the Research Centers, the DCC, and the SDY Case Registry jurisdictions, develop any relevant policies (e.g., data sharing) and subcommittees, recommend improvements to the Registry, and ensure expeditious reporting of study results, among other tasks. The Research Committee will interact with the SDY Case Registry Steering Committee on an as-needed basis. The Research Committee will meet by conference call at least quarterly. The Research Committee will also meet in-person at the start of the project period for an implementation meeting, and in-person up to twice a year throughout the remainder of the project period.
SDY Case Registry Steering Committee: The SDY Case Registry Steering Committee consists of NHLBI, CDC, and NINDS Project Scientists, the DCC PD/PI and the Biorepository PD/PI. This committee oversees the operation and data collection of the SDY Case Registry and is separate from the Research Committee.
External Advisory Committee (EAC): Activities of both the SDY Case Registry as well as the Research Teams will be overseen by an EAC, which has already been established by the NHLBI, NINDS and CDC. This EAC will monitor patient safety (in studies that involve siblings of the deceased or other live subjects), review program performance, and offer advice on future scientific directions. As part of its monitoring responsibility, the EAC will submit recommendations to NHLBI leadership regarding the conduct and continuation of each study. The EAC will meet every six months, and on an as-needed basis.
SDY Case Registry Jurisdictions: Nine jurisdictions have been funded via cooperative agreements with the CDC to compile data and DNA samples for the SDY Case Registry. These jurisdictions include: Georgia, Minnesota, New Hampshire, New Jersey, Wisconsin, Delaware, Tennessee, the city of San Francisco, and the Tidewater region of Virginia. State public health agencies, or their bona fide agents, have formed teams of medical examiners/coroners, pathologists, death scene investigators, child death review teams, cardiologists, and neurologists in each jurisdiction to compile phenotypic data and DNA samples for the SDY Case Registry on cases of sudden death in individuals = 19 years of age.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
NHLBI intends to fund up to 3 awards.
NHLBI expects to commit up to $2.5 million total costs per year for fiscal years 2016, 2017, 2018, and 2019.
Application budgets are limited to $540,000 direct costs per year.
The scope of the proposed project should determine the project period. The maximum project period is 4 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
Non-domestic (non-U.S.) Entities (Foreign Institutions) are
not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:
Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Director, Office of Scientific Review
National Heart, Lung, and Blood Institute, NIH
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed. Applicants should describe qualifications and experience with collaborative research efforts in the Biographical Sketch. Research Center PDs/PIs will be required to declare a minimum effort of 2.4 calendar months per year. Applications proposing Multiple PDs/PIs must have a minimum combined PD/PI effort of 2.4 months.
All instructions in the SF424 (R&R) Application Guide must be followed. Budgets should include costs for the PDs/PI(s) to travel to an initial kick-off meeting for funded investigators in Bethesda, MD and to two in-person Research Committee meetings per year in Bethesda, MD.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Projects should demonstrate that the completion of their aims will advance discussions about screening and prevention of SDY.
Investigators should describe their plans for developing research protocols using registry data; finding, ascertaining, and characterizing appropriate controls, if needed; and performing additional phenotyping of cases, analyzing data, and performing genetic and other evaluations of the DNA samples as required by their study question(s). Investigators should also describe in their application IRB-approved plans for re-contacting families for attaining additional information or consenting of siblings or relatives and communicating clinically-actionable results of genetic studies to families, if applicable.
Investigators should describe their plans to work closely with the participants in the SDY Case Registry, including state public health agencies or their bona fide agents, medical examiners and coroners, the Data Coordinating Center (DCC) at the Michigan Public Health Institute, the biorepository at the University of Michigan, the CDC, the NINDS, and the NHLBI to ensure coordination of activities and collaborative transfer of information. Investigators should describe their plans for entering into data use agreements with the SDY Case Registry state public health agencies or their bona fide agents.
Applicants should describe partnering, where applicable, with SDY Case Registry-funded medical examiners and coroners and the state public health agencies or their bona fide agents in the development of their applications. For instance, if an investigator proposes to obtain specific tissues (other than blood) from autopsy cases, that investigator may consider partnering with one or more medical examiner’s or coroner’s offices in a state/jurisdiction that participates in the SDY Case Registry. If an applicant proposes to interview family members or to obtain DNA from family members, describe plans to partner with members of the medical examiner’s or coroner’s offices or state public health agencies or their bona fide agents.
If the population of interest is limited in number in the SDY Case Registry, describe alternative populations, approaches or strategies to manage that limitation.
Research Design and Methods: This section should propose a project consistent with the objectives of the FOA that can be completed (i.e., results ready for publication) by the Research Center within the project period. The research strategy should describe activities required to ensure that research activities can begin promptly at the beginning of the funding period, such as choosing appropriate control populations, working out processes for recruiting control subjects, obtaining necessary regulatory approvals (IRB), and ordering necessary supplies, among other activities. The research design should also include a description of the anticipated data, the control population, and the research methodology, including return of clinically-actionable results to families in an efficient manner.
The research strategy should also include specific milestones that could be used to evaluate success of the project throughout the duration of funding. Depending on the application, such milestones may include, but are not limited to, study development, data analysis, IRB approval, submission to dbGAP, and enrollment targets.
Collaboration: Applicants should state their general support of collaborative research and their willingness to participate in a collaborative and interactive manner with other Research Centers and the key members of the SDY Case Registry, including the DCC, the biorepository, the NHLBI, NINDS and CDC, and jurisdictions. Applicants should include evidence in their applications of prior successful collaborative research projects.
Letters of Support:
Applications are required to include a letter of support from the SDY Case Registry and biorepository to acknowledge feasibility of the study and availability of data and samples. Investigators should contact the DCC to request a letter of support. The process may take up to 2 months, so investigators are encouraged to contact the DCC early. To request a letter of support, investigators will be required to fill out a data request form and provide a description of the proposed study and data/biospecimen needs.
Sudden Death in the Young Case Registry Data
c/o Michigan Public Health Institute
2455 Woodlake Circle
Okemos, MI 48864
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.
Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
To be considered responsive, compliant, and complete to this FOA, applications must:
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? How will successful completion of the aims advance discussions about screening and prevention of SDY?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Have the applicants demonstrated a commitment to collaborating with other Research Centers and the key members of the SDY Case Registry, including the DCC, the biorepository, the NHLBI, NINDS and CDC, and participants in the SDY Case Registry? Have the applicants demonstrated a track record of scientific collaboration?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?
How well have investigators described their plans for developing research protocols using registry data; finding, ascertaining, and characterizing appropriate controls, if needed; and performing additional phenotyping of cases, analyzing data, and performing genetic and other evaluations of the DNA samples as required by their study question(s)?
Where applicable, how well have applicants outlined procedures for returning clinically-actionable genetic results to families in a timely manner?
Have the applicants acknowledged that they will be required to execute agreements with each of the state or jurisdiction-level grantees in the SDY Case Registry to obtain access to the Registry data?
How well developed is the plan for partnership between the investigators and medical examiners or coroners, if applicable to the research question?
How well have the applicants described alternative populations, approaches or strategies to manage the possible limitation that the population of interest to the investigator is limited in number in the SDY Case Registry?
How likely is the project to be completed (i.e., results ready for publication) by the Research Center within the project period, with research activities starting promptly at the beginning of the funding period, such as choosing appropriate control populations, working out processes for recruiting control subjects, obtaining necessary regulatory approvals (IRB), and ordering necessary supplies, among other activities?
What is the quality of the specific milestones that could be used to evaluate success of the project throughout the duration of funding?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NHLBI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Heart, Lung, and Blood Advisory Council. The following will be considered in making funding decisions:
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Cooperative Agreement Terms and Conditions of Award
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
The Research Center PDs/PIs will be responsible for all aspects of the study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the Research Committee.
The PD(s)/PI(s) are required to declare a minimum effort of 2.4 calendar months per year.
Awardee(s) agree to the governance of the study through a Research Committee and to accept and implement policies approved by the Research Committee. The Research Committee voting member for the Awardee will be the PD/PI. For Centers with multiple PDs/PIs, the contact PD/PI will serve as the voting member.
Awardee(s) will assure that all members of the research team are aware of SDY Case Registry policies and procedures and kept informed of SDY Case Registry activities, meetings, and results.
Awardee(s) agree to publicly release data and other products of the study as appropriate in a timely manner and publish results in peer-reviewed journals, in accordance with SDY Case Registry policies and governance and consistent with achieving the goals of this program. Genomic data are expected to be shared through dbGaP consistent with the NIH data sharing policies and achieving the goals of this program.
Awardee(s) agree to follow best practice in clinical research and to follow procedures to protect and ensure the privacy of medical and genetic data and records of individuals.
Awardee(s) agree to develop a mutually agreed upon patient reporting plan for all studies involving human research (example first patient in and on-going recruitment).
Awardee(s) agree to develop a mutually agreed upon DNA sequencing reporting plan for any genomic studies supported by this funding announcement.
Awardee(s) agree to develop a mutually agreed upon, IRB-approved Genetic Family dissemination plan for the return of any and all clinically-actionable results.
Awardee(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
NIH staff members have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The NHLBI is responsible for organizing and providing overall support for the SDY Case Registry Investigators. The NHLBI Program Office and Office of Grants Management are responsible for the overall management.
The NHLBI Project Scientists will serve on the Research Committee; he/she or other NIH scientists may serve on other study committees, when appropriate. The NHLBI Project Scientist (and other NIH scientists) may work with awardees on issues coming before the Research Committee and, as appropriate, other committees, e.g., recruitment, intervention, follow-up, quality control, adherence to protocol, assessment of problems affecting the study and possible changes in protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and dissemination of clinically actionable results to families.
The NHLBI Project Scientists, on behalf of the NIH, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the Research Committee.
The NIH reserves the right to withhold funding or curtail the study (or an individual award) in the event of (a) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (b) major breach of the protocol, substantive changes in the agreed-upon protocol, or SDY Case Registry policies with which NHLBI cannot concur; or (c) human subject ethical issues that may dictate a premature end of the award.
The NIH will appoint members of the Advisory Committee. These members will have varying expertise, such as cardiology, neurology, pathology, public health, research and genomics. The members will be independent of the funded Research Centers. The Committee will monitor patient safety, review program performance, and offer advice on future scientific directions. As part of its monitoring responsibility, the Advisory Committee will submit recommendations to NHLBI regarding the conduct and continuation of each study.
Support or other involvement of industry or any other third party in the study - e.g., participation by the third party; involvement of study resources or citing the name of the study or NIH support; or special access to study results, data, findings or resources - may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NIH.
Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property issues is assigned to NHLBI staff other than the Project Scientist. The responsibility for final decision making may reside with Senior Institute management, separate organizational components and/or oversight committees.
Areas of Joint Responsibility include:
The Research Committee has primary responsibility for the general organization of the SDY Case Registry Investigators, development of policies, managing and eliminating overlap between funded research studies, and expeditious reporting of study results. All major scientific and administrative decisions are determined by majority vote of the Research Committee.
The Research Committee voting membership shall consist of the Research Center PIs, the NHLBI, CDC, and NINDS Project Scientists, and the DCC PI and the Biorepository PI. Meetings of the Research Committee will ordinarily be held by telephone conference call or in-person. Budgets should include costs for the PI to travel to an initial kick-off meeting for funded investigators in Bethesda, MD and to two in-person Research Committee meetings per year in Bethesda, MD. The Research Committee Chair will be appointed by NHLBI from the Research Committee membership. Additional members may be added by majority vote of the Research Committee.
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Research Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Commons Help Desk (Questions regarding eRA Commons
registration, submitting and tracking an application, documenting system
problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: https://grants.nih.gov/support/index.html
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
Kristin M. Burns, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
National Heart, Lung, and Blood Institute (NHLBI)
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.