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
The objective of this program is to investigate mechanisms of ventilatory control that contribute to instability of oxygenation and risk of morbidity and mortality in premature infants during and after the Neonatal Intensive Care Unit (NICU) using a prospective observational cohort. This is an important step toward the identification of new opportunities for preventive interventions for high risk premature infants.
Chronic respiratory disease impacts thousands of premature infants annually in the U.S. leading to prolonged stays in Neonatal Intensive Care Units (NICUs), increased mortality, and respiratory morbidity. With improved neonatal care, many survivors of extremely low gestational age birth develop bronchopulmonary dysplasia (BPD) defined by instability of oxygenation and persistent needs for respiratory support as they prepare for discharge home from the NICU at 36 weeks postmenstrual age (PMA). This inability to maintain oxygenation during the NICU course and at 36-40 weeks PMA is managed with a range of supportive measures including low to high flow nasal cannula, varying concentrations of oxygen, nasal continuous positive airway pressure, and mechanical ventilation.
Preterm birth can interrupt not only the rapid increase in surface area for alveolar-capillary gas exchange that takes place during the late stages of pregnancy, but also may interrupt neurodevelopment, and maturation of ventilatory (neurorespiratory) control. The ventilatory control system is required to regulate ventilation and provide oxygen to tissues and remove carbon dioxide. Neurons in the brainstem and higher centers in coordination with input from mechanoreceptors and chemoreceptors constitute the ventilatory control system. More than half of premature neonates have apnea of prematurity with significant episodes of interrupted breathing, resulting in significant hypoxemia and life-threatening bradycardias. Immature breathing mechanisms in the postnatal environment may contribute to BPD and/or result in respiratory decompensation, need for resuscitation, and mechanical ventilation. The trajectory of maturation of neurorespiratory control in premature babies is not clear, and how this contributes to acute and chronic respiratory outcomes of premature infants including BPD is unknown.
Despite the use of continuous cardiorespiratory monitoring in the NICU, episodes of periodic breathing and intermittent hypoxic periods are not captured even by the sophisticated monitors. Some episodes may accompany bradycardia. In premature infants, because of the intermittent nature of apnea, bradycardia, and desaturation episodes, events are infrequently recorded or reported. Clinical care givers often use physiologic responses to evoked challenges, such as titrating inspired oxygen concentrations to make a diagnosis of BPD, but better tests for this condition are lacking. Mathematical modeling algorithms that can utilize continuous recordings as input data from ICU monitors could inform the detection and analysis of breathing patterns in the premature. The ultimate goal is to gain greater insight into the pathogenesis of chronic respiratory disease of the premature, identify novel BPD phenotypes and physiological biomarkers, and discover targets for new prevention and treatment strategies to improve outcomes for very vulnerable children at the beginning of life.
Prospective observational cohorts from each research center will inform site-specific and multicenter investigation of mechanisms of ventilatory control in premature infants in the NICU and its role in respiratory outcomes to near term and 3 months corrected age. Multi-disciplinary teams are strongly encouraged with clinical research expertise in neonatology, respiratory and neural biology/physiology, sleep medicine, and/or computational modeling.
The program will consist of up to five Clinical Research Centers (CRCs) and one Leadership and Data Coordinating Center (LDCC) (described in RFA-HL-16-016). The first six months of the project period will be for intensive collaborative planning by the LDCC and CRCs to conduct the necessary activities, individually and as a cooperative program, so that enrollment of premature infants begins no later than the end of Year 1.
Clinical Research Centers (CRC): Each CRC applicant to this FOAshould investigate specific hypotheses of ventilatory control mechanisms (e.g. chemoreceptor, mechanoreceptor, developmental, etc.) that contribute to instability of oxygenation and risk of morbidity and mortality in premature infants. Methods to test these hypotheses should include novel approaches to examine how ventilatory control influences the inability to maintain oxygenation at 36 weeks postmenstrual age and acute/chronic respiratory compromise through at least 3 months corrected age. Applicants should include prospective assessment of control of breathing in a premature cohort at 2 or more time points to assess maturational changes of ventilatory control. Applicants are encouraged to include evoked phenotypes (e.g., medication induced, hypoxia/hyperoxia induced, etc.) to examine vulnerabilities and/or resilience of these respiratory control processes to the development of or resolved need for respiratory support at 36 weeks postmenstrual age and during infancy.
A CRC can be a single institution or group of institutions with the capability of recruiting and retaining at least 100 premature infants (at least 75 of which are <29 weeks gestation) during the NICU course and through at least 3 months corrected age to ensure robust pathophysiologic studies of ventilatory control maturation and its role in acute and chronic respiratory disease risk. Each CRC should be comprised of a multidisciplinary team including at least one clinician scientist with expertise in neonatology and one expert in ventilatory control neurobiology/physiology. Additional key personnel such as recruiters, nurse coordinators, biomedical informatics, biostatisticians, and others should be included.
Each CRC will not only propose and conduct unique research with measurements of ventilatory control at the CRC site, but must also be committed to contribute clinical and NICU-cardiorespiratory monitor data to the LDCC for the multicenter collaborative proposal. Each CRC will designate one PD/PI to serve on the Steering Committee.
Multicenter Collaborative Project: In addition to individual CRC studies, this collaborative program will develop a LDCC-coordinated multicenter project that will investigate ventilatory control mechanisms in outcomes of instability of oxygenation, acute and chronic morbidity. The multicenter protocol will leverage readily available NICU cardiorespiratory monitor data from at least 500 premature subjects (75% of which are below 29 weeks gestation) enrolled across participating sites. To investigate the role of maturation of ventilatory control on outcomes of premature infants, the LDCC will include a computational modeling expert to develop a protocol, which will be finalized with Steering Committee member input, that utilizes at a minimum respiratory rate and rhythms, pulse oximetry, and heart rate. The multicenter project will answer whether algorithms using readily available clinical NICU cardiorespiratory monitoring data can detect ventilatory control instability and predict acute or chronic respiratory disease after 36 weeks PMA. This could lead to a new strategy for detection of ventilatory control contributions to chronic respiratory outcomes of the premature that could be implemented widely for research and clinical care.
Steering Committee (SC): The SC is composed of CRC PDs/PIs, the LDCC PDs/PIs, SC Chair, and the NHLBI Program Scientist. The SC will have responsibility for developing the overall scientific direction of the program; assuring compliance with program policies and procedures; selecting topics for investigation; designing study protocols; implementing studies; ensuring data quality and completeness; participating in the analysis and interpretation of data; and reporting results in presentations and publications. The SC will be chaired by an outside expert selected by the NHLBI. The Chair will have one vote, as will each of the CRCs, the LDCC, and the NHLBI Project Scientist.
Each SC member must work intensively in a cooperative and interactive manner with the LDCC awardee so that enrollment begins no later than the end of year 1. The awardee is expected to attend an in-person 2-day Steering Committee meeting on July 28-29, 2016 in Bethesda, MD, in order to develop the multicenter protocol. The SC will meet by conference call monthly, and the CRC PD/PI will meet in-person at least twice a year throughout the project period.
Within 6 months of award, the SC will 1) identify harmonized clinical data to be collected, 2) develop common respiratory phenotypes at approximately 36 weeks PMA, 3) develop common respiratory outcomes to 3 months corrected age, 4) develop a protocol for cardiorespiratory monitor data transfer to the LDCC for analysis, 5) determine what biospecimens will be collected and stored on subjects for later analysis through additional funding outside this FOA, and the procedures for collection, storage, and access of the biospecimens, and 6) develop a data sharing plan for the data and biospecimens collected, including a long-range plan for subsequent studies of the cohort as it ages to maturity. Note that biospecimen collection will not be permitted until the final protocols are reviewed and approved by the Observational and Safety Monitoring Board (OSMB) and IRBs.
Single CRC protocols have unique study objectives and are likely to include distinctive data collection that may not be required by the multicenter protocol and will be supported by CRC funds. These should be harmonized with and not conflict with multicenter objectives. SC members must reach the following milestones in the first year before enrollment begins: finalize the multicenter protocol within 6 months, OSMB and IRB review and approval, development of Manual of Operations, data management system launched, and staff training.
Leadership and Data Coordinating Center (LDCC) (described in RFA-HL-16-016): The LDCC will provide statistical leadership and expert assistance in concept development and feasibility assessment of the multicenter protocol, but will not be responsible for statistical leadership of CRC specific proposals. The LDCC will facilitate all aspects of recruitment including harmonization of data collection and cardiorespiratory monitor download and transfer across sites, consent form templates, development and programming of case report forms, preparation of materials for submission to local IRBs, manuals of operation, oversight of protocol and protocol amendments, web-based data entry, serious adverse event reporting, coordinator and other staff training, common phenotyping elements, and clinical database management. The LDCC will provide the data management system that facilitates multicenter and single center data collection, retrieval, data sharing, and analysis. The LDCC will provide an open data system so that single research centers can add data elements/case report forms needed for single center projects and ensure the data are readily accessible. The LDCC will create and manage a DNA biorepository (trios of subject and parents) of samples from multicenter subjects and facilitate access for future genetic projects. The LDCC will also organize meetings and calls of the Steering Committees, OSMB, and program joint bi-annual meetings; design and maintain written materials and a website to support the program.
Safety Oversight: Protocols (single CRC and multicenter) will be reviewed by Institutional Review Boards and an OSMB with expertise to evaluate risk and current accepted clinical practices. The OSMB will provide overall monitoring of progress, interim data and safety issues and will be appointed by NHLBI. Therefore, applicants should not appoint OSMB members in advance of the peer review, or even inquire about the interest of possible OSMB members, because anyone so contacted would not be eligible to serve as a member of the peer review committee that will evaluate the applications for scientific merit. An NHLBI scientist other than the NHLBI Pre-Vent Program Scientist will serve as the Executive Secretary to the OSMB. The OSMB will meet approximately semi-annually by teleconference call or in-person meetings in the Greater Washington D.C./Baltimore region.
The NHLBI will be substantially involved with the awardees in a partnership. The NHLBI Program Scientist will monitor patient recruitment and study progress, ensure a policy for the disclosure of conflicts of interest, and assure adherence to NHLBI policies.
Selected Research Examples:
Research examples include, but are not limited to:
This FOA is intended to support only human studies and test a hypothesis. Descriptive studies alone will not be considered responsive. Applications that include animal studies or model systems will not be considered responsive. Patient registries and retrospective studies will not be considered responsive. Clinical trials are not the intent of this FOA.
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 5 awards, corresponding to total costs up to $948,000 in FY 2016, and up to $3,002,000 total costs per year for fiscal years 2017, 2018, 2019, and 2020.
Application budgets may not exceed direct costs of $120,000 in FY 2016 and may not exceed direct costs of $380,000 in FY 2017, FY 2018, FY 2019 and FY 2020.
Application budgets should reflect the actual needs of the proposed project.
The scope of the proposed project should determine the project period. The maximum project period is 5 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 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.
PD(s)/PI(s) must possess a doctoral degree in a relevant field such as neonatology, neurophysiology, sleep medicine and is/are required to commit no less than 2.4 person-months (20 percent) combined effort to the CRC activities of the Pre-Vent program. PDs/PIs must have clinical research expertise. Active participation of the PDs/PIs is expected during all phases of a clinical research study.
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:
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
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
Telephone: (301) 435-0270
Fax: (301) 480-0730
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 with the following additional instructions:
Facilities and Other Resources: Institution descriptions should include information about the neonatal intensive care units (for example, open/closed, numbers of beds, staffing model, screening ability), description of the NICU cardiorespiratory equipment used and the standard settings used (pulse oximetry, heart rate, respiratory rate, other); description of equipment available for physiological measures of ventilation; Information Technology/Institutional support and experience with data transfer for multicenter project participation.
Other Attachments: Provide the following information as a single PDF file with the name “(PD/PI name) Pre-Vent (Census & Clinical Studies).pdf.”
All instructions in the SF424 (R&R) Application Guide must be followed.
One individual must be designated as an alternate PD/PI who is able to serve in the absence of the PD/PI. Multi-disciplinary teams are strongly encouraged with clinical research expertise in neonatology, respiratory and neural biology/physiology, and/or sleep medicine. Key personnel for the CRC should include Biostatistics expertise.
All instructions in the SF424 (R&R) Application Guide must be followed
Applications should budget for the following:
Multicenter Data Collection [Biospecimens & Cardiorespiratory Monitor Data (CRM)]
Budgets must include $100,000 direct costs over years 2-5 for DNA biospecimen and cardiorespiratory monitor data collection and transfer to the LDCC for the multicenter protocol and if awarded will be restricted and may be renegotiated based on performance, and will not be re-budgeted without NHLBI prior approval. This may include personnel costs including information technology support.
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:
Research Strategy: Each CRC applicant should propose specific hypotheses of ventilatory control mechanisms (e.g., chemoreceptor, mechanoreceptor, developmental, etc.) that contribute to instability of oxygenation and risk of morbidity and mortality in premature infants. Methods to test these hypotheses should include novel approaches to examine how ventilatory control influences the inability to maintain oxygenation at 36 weeks postmenstrual age and acute/chronic respiratory compromise through at least 3 months corrected age. Applications should include prospective assessment of control of breathing in 100 or more premature neonates (at least 75 of which are <29 weeks gestation) at 2 or more time points to assess maturational changes of ventilatory control. Applications are encouraged to include evoked phenotypes (e.g., medication induced, hypoxia/hyperoxia induced, etc.) to examine vulnerabilities and/or resilience of these respiratory control processes to the development of or resolved need for respiratory support at 36 weeks postmenstrual age and during infancy.
The CRC research application should include the hypotheses or questions to be addressed, background, rationale, and significance of the anticipated results, preliminary data, patient group to be studied, the number of patients per group, the interventions and methods (including power and statistical analysis of endpoint to be studied). Clinically meaningful acute and/or chronic respiratory endpoints to at least 3 months corrected age are expected.
Each CRC will not only propose and conduct unique research with physiological measurements of ventilatory control at the CRC site, but must also be committed to contribute clinical and NICU-cardiorespiratory monitor data to the LDCC for the multicenter collaborative application (RFA-HL-16-016).
Applications should include a timeline with the following minimum milestones in the first year before enrollment begins: finalize the CRC single center protocol and the LDCC-led multicenter protocol within 6 months, OSMB and IRB review and approval, development of Manual of Operations, and staff training on CRC specific protocol, multicenter protocol, and LDCC data management system.
Applications should include a detailed plan and timeline for prospective enrollment, retention, and analyses from a premature cohort of at least 100 premature neonates (at least 75 of which are <29 weeks gestation) enrolled by no later than end of year 4.
In addition, the CRC applicant should include as recommendations for harmonization across sites in the LDCC-led multicenter protocol: 1) proposed perinatal and postnatal data elements that will be acquired for the single center protocol that can be standardized for a multicenter protocol, 2) a rationale for a comparative group of infants = or > 29 weeks gestational age (GA), 3) proposed common respiratory outcomes near term and at 3 months corrected age that will be acquired for the single center protocol that can be standardized for a multicenter protocol, and 4) identify a strategy and institutional commitment for NICU cardiorespiratory monitor data download and transfer to the LDCC. These proposed approaches (1-4) will serve as recommendations for harmonization across sites when the Steering Committee convenes to finalize the multicenter proposal.
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.
The application should state agreement to collaborate on Steering Committee development and implementation of multicenter protocols for standardized clinical data, electronic cardiorespiratory monitor data, biospecimen collection, training, and data entry into a central data management system and biorepository.
Applicants are encouraged to include a protocol and informed consent form in the appendix, but are not required.
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.
Human subjects' restrictions apply until final multicenter protocol developed and OSMB and IRB approval. Restrictions of multicenter activity funds may be renegotiated in subsequent years 2-5 based on performance.
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, NIH. Applications that are incomplete or non-compliant will not be reviewed.
This FOA is intended to support only human studies. Applications that include animal studies will not be considered responsive. Patient registries alone, without a hypothesis to be tested, will not be responsive. Retrospective studies will not be considered responsive. Agreement to participate in protocol development and implementation must be stated.
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? To what extent is the strategy proposed likely to reveal new insights into ventilatory control maturatation of premature infants?
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? To what extent do key personnel have research experience in neonatal clinical studies, ventilatory control, prospective observational design and analysis? Is there biostatistical expertise for analysis of the single center research proposal?
Pre-Vent is designed to engage multidisciplinary expertise to examine ventilatory maturation of premature infants and its role in respiratory outcomes, so evidence of prior collaboration is not a requirement of the research team.
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? To what extent does the clinical research proposal address an important question that has not been asked before? To what extent were novel clinical study designs to evaluate maturation of ventilatory control and its role in respiratory outcomes of premature infants 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? To what extent will the analyses proposed inform the role of ventilatory control in a BPD outcome? Based on the timeline provided, how likely is the analysis of ventilatory measurements and clinical data collection to be completed within the project period? To what extent are the respiratory outcomes at 36 weeks postmenstrual age and at 3 months corrected age appropriate?
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?
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? Given the NICU census provided, to what extent is there demonstration of feasibility of new subject recruitment and sample/data collection? Is there institutional/NICU support for the proposed project? Are there resources/equipment to measure ventilatory control in premature infants?
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.
To what extent are the timeline and milestones proposed likely to lead to feasible enrollment in the first year?
To what extent is there demonstration of feasibility of electronic cardiorespiratory data collection from CRCs and transfer to the LDCC?
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.
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 overall function of all Pre-Vent research activities. The Clinical Research Center (CRC) PDs/PIs will be responsible for oversight of protocol development, data collection, data safety and confidentiality, quality assurance, data analysis, coordination of data distribution, and implementation of all data sharing plans. The CRC PDs/PIs will be responsible for the collection and transfer of NICU cardiorespiratory monitor data and biospecimen collection and transfer to the Leadership and Data Coordinating Center. The CRC PDs/PIs will be responsible for single center and multicenter protocol preparation and IRB submission, activities of the Steering Committee, data collection and completion, quality review, and Observational Safety Monitoring Board.
Support or other involvement of industry or any other third party in the Pre-Vent studies may be advantageous and appropriate. Awardees must follow NHLBI policy concerning third party agreements.
Awardees 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 HHS, PHS, and NIH policies.
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The NHLBI Pre-Vent Project scientist (PS) will participate in Steering Committee activities. Several procedures are in place to manage potential conflicts of interest by PS administering the cooperative agreement. PS will not seek lead authorship of primary publications and will obtain approval by Branch Chief to participate in secondary publications. Program staff may work with awardees on issues coming before the Steering Committee and, as appropriate, other committees (e.g., recruitment, intervention, follow-up, quality control, adherence to protocol, assessment of problems affecting the study and potential changes in the protocol, interim data and safety monitoring, final data analysis and interpretation, and preparation of publications). NHLBI Project scientist, on behalf of the NHLBI, will have the same access, privileges, and responsibilities regarding the collaborative data as the other members of the Steering Committee.
The NHLBI reserves the right to negotiate milestones for study conduct in each year of an award and the right to phase out an individual award in the event of: (1) failure to develop or implement a mutually agreeable collaborative protocol; (2) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (3) major breach of a protocol or substantive changes in the agreed-upon protocol with which NHLBI cannot concur; (4) attaining of a major study endpoint before schedule with persuasive statistical significance; or (5) human subject ethical issues that may dictate an early phase out of a trial or the program. Annual continuation and level of funding for the CRC will be based on NHLBI review of actual recruitment and overall performance, determined as part of the NHLBI review of the annual non-competing continuation grant progress reports submitted by awardees.
Additionally, the NHLBI Program Official will be responsible for the programmatic stewardship of the award and will be named in the award notice
Areas of Joint Responsibility include:
Awardees agree to the governance of the study through a Steering Committee (SC). Up to two investigators from each CRC and the LDCC, a Chairperson, to be appointed by the NHLBI, and an NHLBI representative will comprise the SC. All major scientific decisions will be determined by majority vote of the SC. Each Clinical Research Center, the Leadership and Data Coordinating Center, and the NHLBI Project Scientist will have one vote; the Chair will have one vote in case of a tie. Note that although each Clinical Center may have multiple PIs, each Clinical Research Center has only one vote. It is anticipated that SC meetings will be held at least once a month by conference call and two times a year in person. The first year during Pre-Vent program establishment and initial protocol selection, may require more frequent contact
An independent Observational Safety Monitoring Board (OSMB) will be appointed by the Director, NHLBI to provide overall monitoring of study performance, interim data, and safety issues. An NHLBI scientist, other than the NHLBI Project Scientist, shall serve as Executive Secretary to the DSMB.
Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering 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 Steering 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 Service Desk (Questions regarding ASSIST, 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)
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Carol J. Blaisdell, 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 Part 75.
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