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.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section 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

There is an urgent need for development of new treatments and for testing of existing clinical management strategies in adult populations with chronic pulmonary diseases and obstructive sleep apnea. To facilitate efficient conduct of both inpatient and outpatient studies in "real world" settings, the NHLBI is establishing a novel structure: the Pulmonary Trials Cooperative (PTC). The PTC will carry out multiple clinical studies in a variety of chronic pulmonary conditions, including but not limited to interstitial lung disease (ILD), pulmonary hypertension (PH), chronic obstructive pulmonary disease (COPD), sarcoidosis, and obstructive sleep apnea. Asthma, and acute lung injury and critical care, are specifically excluded to avoid overlap with current programs. By studying multiple chronic pulmonary conditions in a single large program, the PTC will enable studies across a wide range of pulmonary diseases; encourage studies of patients with comorbid or intermediate conditions; involve a wide range of institutions, from major medical centers to community-based providers, in the recruitment, retention and follow-up of research subjects; and increase the efficiency of subject recruitment at individual sites by strongly encouraging the use of local medical information systems for the identification of potential research subjects.

This funding opportunity announcement (FOA) solicits applications to serve as the Network Management Core (NEMO), which will have primary responsibility for organizing and operating the multi-center PTC. The NEMO will cooperate with multiple Protocol Leadership Groups (PLGs) (see RFA-HL-15-015), which will develop and manage data for simple, pragmatic Phase 2 or Phase 3 clinical trials. PTC protocols will be selected through a process involving NIH-managed peer review of separate applications submitted in response to RFA-HL-15-015 or to other applicable FOAs.

NEMO will recruit and manage a network of 20-40 Clinical Centers, each of which may supervise several geographically-related secondary sites. Clinical Centers and secondary sites will be responsible for enrolling subjects with the various chronic pulmonary diseases and/or obstructive sleep apnea and carrying out the trial protocols approved by NHLBI. The Clinical Centers will transfer data and biospecimens to NEMO and contribute representatives to PTC committees. Clinical Centers will be offered uniform, fee-for-service reimbursement for per-patient costs according to budgets specified for each protocol. Clinical Centers will have the option to not participate in a particular trial.

The primary responsibility for implementation, oversight, continuing evaluation, and reporting of PTC studies will be vested in an Operations Committee (OC), consisting of the PIs of NEMO, rotating representatives of the Clinical Centers, the PI(s) of each PLG awarded (see RFA-HL-15-015), one program official from the NHLBI, and a Chair appointed by the NHLBI who may or may not be otherwise involved in the PTC. The PI(s) of each PLG awarded will vote only on general issues and on matters regarding their own protocol. Clinical Center representatives will serve for time-limited terms no longer than 2 years to allow adaptation of OC expertise to the evolving needs of the PTC. The Clinical Center representatives will be elected by the PIs of the Clinical Centers through a voting system implemented by NEMO. It is anticipated that the OC will meet approximately once per year in-person in the Bethesda, Maryland area and monthly by teleconference. Subcommittees and working groups will be established as needed by the OC to deal with specific issues. All recommendations of the subcommittees and working groups must be ratified by the OC before implementation or dissemination. Non-members may be permitted by invitation to participate in OC discussions, but these will not have a vote in OC decisions. A Data and Safety Monitoring Board (DSMB) will also be established in accordance with NHLBI policies (see http://www.nhlbi.nih.gov/funding/policies/dsmpolicy.htm) to act as an independent advisory group to the NHLBI Director on issues of human subject safety and privacy, study integrity, and study progress.

Responsibilities of NEMO

NEMO will carry out many of the functions that are typically performed by a Data Coordinating Center of a multi-center study. However, in the PTC all statistical, data management and data analysis responsibilities will reside in the PLG of a specific protocol implemented. NEMO will not receive individual level data for study participants. Activities of NEMO can be classified into three general areas of responsibility described in the following sections:

Clinical Center Supervision

The NEMO will recruit, assess, certify, and maintain a registry of Clinical Centers which will enroll participants, perform interventions, retain and follow research subjects; conduct protocol specific training of personnel at the Clinical Centers; reimburse the Clinical Centers for protocol costs, using pre-established, capitated rates, specific for each protocol; coordinate Clinical Center activities for the conduct of approved protocols; certify staff; track regulatory approvals and Clinical Center performance; and propose and implement corrective actions if deficiencies at the Centers are identified.

The Clinical Centers assembled by NEMO should be capable of recruiting research subjects for trials in several disease areas and to have in place a means for contacting large numbers of subjects with specified clinical characteristics. NEMO will certify all Clinical Centers based on their access to potential trial participants and capabilities to carry out PTC protocols. NEMO will negotiate an arrangement with each for reimbursement of protocol costs according to agreed-upon capitated budgets. NEMO will develop master trial agreements and organize centralized IRB services to expedite the implementation of multiple protocols at many sites. NEMO will implement procedures for tracking the performance of Clinical Centers, and will implement criteria for dismissal of Clinical Centers whose performance does not meet pre-specified standards.

Network and Trial Administration

NEMO will assist in the development of study-specific documents and manuals of procedures, archive study documents, and distribute them through a secure PTC website accessible to the Investigators and NHLBI; organize meetings and teleconferences of PTC committees and boards; develop standard processes to expedite network operations, such as use of master trial agreements and a central Institutional Review Board (IRB) of record.

NEMO will coordinate protocol-specific training of staff at the Clinical Centers and sub-sites in the protection of human research subjects and their privacy and in study procedures, including completion of forms; administration of questionnaires; laboratory testing; bio-specimen procurement, processing, and shipping; data entry; quality control; and ascertainment and reporting of adverse events. NEMO will develop standards for testing and certification of staff, obtain OC concurrence, and maintain related records.

NEMO will provide a secure web-based portal for distribution of study documents, communications among investigators, and outreach to the public. Access to materials in development and other confidential information will be limited by password protection to authorized members of the PTC. NEMO will maintain an operations calendar; records of PTC activities; and a file of all study documents, including protocols, manuals of Standard Operating Procedures (SOPs), minutes of meetings, summaries of study progress, a log of OC decisions, dates of protocol approvals and modifications, IRB approvals at all sites, and staff training certifications. NEMO will implement procedures for backing up the program’s administrative data, including intermittent duplication of the database with storage at a remote facility. NEMO will contribute summaries of study progress to reports prepared for submission to the DSMB and NHLBI.

NEMO will schedule, organize, and accommodate all PTC committees and boards meetings and teleconferences. Payment for meeting rooms and consultant costs of the DSMB members will be the responsibility of NEMO.

Biospecimen Management

NEMO will create and operate a biospecimen repository for whenever biospecimen collection is necessary for a protocol, assuring linkage of biospecimens to clinical data in a manner that protects human subject privacy; and store and retrieve specimens under appropriate conditions and with provision for catastrophic events such as power failure. NEMO will be expected to coordinate with the NHLBI BioLINCC program to ensure that study procedures are compatible with that program's requirements for bio-specimen collection, labelling, and storage.

The following table summarizes and clarifies the complementary functions of NEMO and the PLGs.

Table: Summary of Functions

Network Management Core (NEMO)

Protocol Leadership Groups (PLG)

Organize a network of Clinical Centers capable of conducting the breadth of PTC trials. With approval from NHLBI, distribute funds to activate efficient processes for identifying and contacting potential research participants Train and certify Clinical Centers staff Verify IRB approvals Create and maintain a 508 compliant web-site Maintain official study documents, inclusive of manuals of Standard Operating Procedures (SOPs) Schedule, organize, and accommodate all PTC committees and board meetings and teleconferences Oversee process for review and selection of protocols Distribute protocol-specific funds to the Clinical Centers on a per-patient basis via master trial agreements Monitor clinical center activities with site visits as needed Distribute drugs/placebos Store biospecimens Generate periodic reports to the NHLBI and the DSMB Monitor participant retention, protocol adherence, research subject safety and protection according to NHLBI and other government and regulatory policies Report the demographic characteristics of enrolled populations and implement remediation plans imposed by NHLBI to ensure nationally representative participation of women and minorities in PTC studies Identify study outcomes or unanticipated problems that might compromise subject safety and necessitate changes or termination of the studies

Develop a protocol, serve as Lead Investigator for that protocol, and manage and analyze study data Obtain Food and Drug Administration (FDA) regulatory approval for the trial, including Investigational New Drug/ Investigational Device Exemption (IND/IDE) or exemption as needed Develop and maintain a secure web-based data entry system and associated case report forms. To the extent possible, common data elements and re-usable forms that are applicable in trials of different interventions and in a variety of pulmonary diseases should be employed. Make forms available to NEMO for use in other trials Randomize subjects to different study arms Maintain updated status reports of the trial on ClinicalTrials.gov Procure drugs and placebos, test and label, as needed Manage protocol data; provide data quality assessment and quality control; perform data cleaning and statistical analyses of data; using a data system that protects patient confidentiality at all steps in the submission and analysis of clinical trials data and ensure the technical integrity and security of the dataset Analyze bio-specimens (if part of the protocol) Prepare manuscripts and publish results Prepare datasets for submission to an NHLBI data repository Process, tabulate, and report Adverse Events (AEs) in accordance with NHLBI policies Identify study outcomes or unanticipated problems that might compromise subject safety and necessitate changes or termination of the studies Generate periodic reports to the NHLBI and the DSMB

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

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

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

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.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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.

The PD/PI for the PTC NEMO should be a clinical trials expert with a track record in successfully supervising, managing, coordinating, and implementing complex, multi-center clinical trials in adults with chronic pulmonary diseases or obstructive sleep apnea.

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:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

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:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

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:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (express mail ZIP: 20817)
Telephone: 301-435-0270
Email: [email protected]

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 must identify professional staff and their qualifications needed to carry out all functions of NEMO, especially with regard to network management and clinical monitoring of pulmonary and sleep trials. Applicants are strongly encouraged to name an experienced research team that will support the project management and implementation of the network trials and to list additional clinical research expertise they could draw upon on an as-needed basis, as well as any research resources they have established at their institution. Personnel must provide expertise in study coordination, pulmonary medical expertise required for clinical and safety monitoring, and biospecimen storage. Applicants must describe the expertise and track record of the research staff, including a track record of achieving relatively short trial start-up times with regard to contract negotiations, IRB approval times, and study personnel training (provide examples and describe features of research team training they have conducted). Applicants must describe track record in chronic pulmonary diseases or sleep disorders trials clinical coordination. Applicants must also document experience in project management of recent trials and describe the collaborative leadership structure used in recent multi-center trials they have coordinated. Applicants are encouraged to describe any special expertise or unique strengths they can offer to the collaborative effort (e.g., experience in clinical trial management and collaborations with industry partners or patient groups

All instructions in the SF424 (R&R) Application Guide must be followed. A detailed budget for NEMO should be presented. The budget must reflect all activities delineated in the list of responsibilities included in this FOA. Activities related to coordinating multiple, simultaneous, clinical research studies should be budgeted, including: planning activities; start-up activities; implementation activities; close-out phase activities; participation in investigator meetings, OC and other leadership committee functions; site monitoring; communication, documentation and reporting; support of study drug management. Budgeting for the support of potential trial participant discovery and retention activities of Clinical Centers should be presented. The budget should also include costs for monthly PTC-wide teleconferences and travel costs for approximately one trip each year for two team members to attend OC meetings in Bethesda, MD, and other travel related to network operations (including 2-4 Clinical Center site visits per year).

Trial costs should be requested in Section F. Other Direct Costs and not co-mingled with other line items. Funding for trial costs in the PTC will be distributed to the Clinical Centers from NEMO on a per-patient basis (capitation) via master trial agreements. NHLBI expects to allocate sufficient funds for capitation costs for up to 3 simple, pragmatic trials over the course of the NEMO award period.

Core and recruitment system funds may be requested at up to $1.2m direct costs in year 1, $1.15m direct costs in year 2, $1.1m direct costs in year 3, $0.9m direct costs in year 4, and $0.8m direct costs in year 5, if needed for trial completion.

Protocol funds may be requested at up to $2.1m in year 1, $1.95m in year 2, $1.55m in year 3, and $1.4m in year 4.

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:

Specific Aims: Describe Specific Aims, including a summary of: 1) Leadership and Operations Plan; 2) Collaboration and Management of Clinical Centers Plan; 3) Training Plan; 4) Timeline for Management of Clinical Trials.

Research Strategy:

NEMO applicants should not propose a trial protocol because these protocols will be proposed through RFA-HL-15-015.

Leadership and Operations Plan

Describe in detail plans for assembling and supervising a network of Clinical Centers capable of conducting multiple, pragmatic Phase 2 or Phase 3 clinical trials in chronic lung diseases and obstructive sleep apnea (including a mechanism for recruiting additional Clinical Centers to the PTC during the initial period of the program), administering network activities and clinical trials, and managing a biospecimen repository. Describe SOPs currently in place and planned; how tasks will be delegated and supervised; and how the management team will be directed and will communicate among themselves, with the Clinical Centers, and with the PLGs (e.g., clearly describe how interactions and communications between NEMO and the clinical sites will be managed).

Describe planned support for all aspects of complex multi-center trials, oversight of the Clinical Centers, and the organization and functioning of the PTC OC. Applicants must state their willingness to participate in a collaborative and interactive manner with the PLGs, NHLBI, and potential partners (including academic, foundation, and industry partners) in all aspects of the network program. Describe plans to achieve successful collaboration). Plans for distribution of capitated funds, including plans for master trial agreements and to organize centralized IRB services, should be described.

Training Plan

Describe plans for general training of Clinical Center personnel as needed for implementation of protocols involving multiple chronic lung diseases and/or obstructive sleep apnea and participants with co-morbid conditions..

Timeline for Management of Clinical Trials

Describe schedule for completion of the target number of studies within the 5-year project period, and methods for quickly establishing the procedures and tools necessary for launching trial protocols, activating the Clinical Centers assembled, and ensuring study progress.

Milestones for protocol initiation should be described in the grant application. As an illustration, the early goals listed below would yield approval for implementation of the first protocol within the first year of the project period.

• Three months after award - Publish templates for master trial agreements. Have an operational website that lists the NEMO and Clinical Centers operations, begin awarding start-up costs to qualifying Clinical Centers, describe the procedure for patient recruitment, and provide written operating procedures for the PTC operations. Begin steps of the launching of PLG trial protocol(s).
• Six months after award - Negotiate capitated costs of trials. Convene first meeting of OC. Schedule first DSMB meeting and distribute materials. Finalize budget for first protocol. Publish forms and procedures for protocols to be launched.
• Nine months after award - DSMB review and NHLBI approval of the first protocol(s). Submission of first protocol(s) to IRBs.
• Twelve months after award - Enrollment of first subjects. DSMB review and NHLBI approval of additional protocol(s). Submission of additional protocol(s) to IRBs.

Letters of Support: Provide letters of support as needed to document commitments of institution and other parties involved.

Applicants are encouraged to provide letters of support from potential Clinical Centers willing to participate in the PTC.

Institutions should document commitment to the PD/PI by providing departmental and institutional support letters and are encouraged to demonstrate appropriate commitment such as protected time, departmental research leadership position, facilities, space, or resources for the PD/PI).

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide.

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.

Important reminders:
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 by the Center for Scientific Review and responsiveness by the National Heart, Lung, and Blood Institute (NHLBI), NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

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.

Significance

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?

Investigator(s)

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? Does the PD(s)/PI(s) have a track record of successfully designing and implementing the management aspects of multi-center clinical trials or coordinating multi-center clinical trials? Does the PD(s)/PI(s) have a successful track record in chronic pulmonary diseases or sleep disorders trials clinical coordination? Are the investigators prepared to carry-out the key tasks in a timely manner, including, but not limited to establishing procedures, the web site, and specific training?

Innovation

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?

Approach

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? Are plans adequate for assembling and supervising a network of Clinical Centers capable of performing Phase 2 or Phase 3 simple pragmatic trials in multiple chronic pulmonary diseases and obstructive sleep apnea? Are interactions and communications between NEMO and the clinical sites clearly described and administratively feasible? Does the applicant have a track record of achieving relatively short trial start-up times with regard to contract negotiations, IRB approval times, study personnel training?

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?

Environment

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? Does the institution provide departmental and institutional letters that demonstrate appropriate commitment for the PD(s)/PI(s) such as protected time, departmental research leadership position, facilities, space, or resources? Does the application demonstrate that the institution will be able to coordinate and utilize standardized network master trial agreements for per patient cost of clinical programs?

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.

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Children

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.

Vertebrate Animals

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.

Biohazards

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.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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).

Resource Sharing Plans

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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

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 NHLBI Advisory Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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 Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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 primary 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:

• All aspects of their study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. The awardee agrees to accept close coordination, cooperation, and participation of NIH staff in those aspects of scientific and technical management of the study including those outlined under "NIH Responsibilities".
• Awardees will participate in regular meetings and teleconferences and will support any committees, task forces, and advisory panels as needed.
• Support or other involvement of industry or any other third party in the study--e.g., participation by the third party; involvement of project resources or citing the name of the project or the NIH support; or special access to project results, data, findings, or resources--may be advantageous and appropriate.
• Award recipients will own the rights in any tangible work products created under the terms of the cooperative agreement. Work products may include such things as research reports, papers, research, findings, training curricula, data sets, books, patient tools, and other materials. All such products shall be made accessible to the public and are subject to Government rights of access, as appropriate, in accordance with NIH’s legal directives and authorities.

NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• The NHLBI Project Scientist will have access to the data and work with the PD(s)/PI(s) to ensure the objectives of the program are being met. The primary responsibility for the program resides with the awardee, although specific tasks and activities will be shared among the awardee and the NIH Project Scientist.
• The NHLBI reserves the right to phase out or curtail the award (or an individual component of the award) in the event of inadequate progress.
• The NHLBI Project Scientist will act as a resource and facilitator for activities of the awardee with other NIH, DHHS, or other federally-sponsored research networks that may be relevant to this effort.
• The NHLBI Project Scientist will serve as a resource to provide scientific/programmatic support during the accomplishment of the clinical trial by participating in the design of the activities, advising in the selection of sources or resources, advising in management and technical performance, or participating in the preparation of publications.
• The NHLBI Project Scientist will participate in the monitoring of recruitment, retention and follow-up of study participants, and monitoring of data integrity and quality control through consideration of annual reports, site visits, patient logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting patient enrollment targets, adherence to uniform data collection procedures, gender and minority representation and the timeliness and quality of data reporting.
• The NHLBI Project Scientist will assist in the development and modification of study protocols, meeting regulatory requirements, and monitoring patient safety.
• The NHLBI Project Scientist will interact with the PD(s)/PI(s) on a regular basis to monitor progress. Monitoring may include: regular communication with the PD(s)/PI(S) and her/his staff, periodic site visits, fiscal reviews, and other relevant stewardship matters.
• NHLBI will establish a Data and Safety Monitoring Board (DSMB) in accordance with NHLBI policies to provide expert advice to the institute regarding study performance and human subject protection. Members of the DSMB will be independent of the study and free of conflict of interest. The NHLBI Project Director will operate as the executive secretary for all DSMB meeting attending both open and closed sessions.
• Additionally, an NHLBI Program Official will be responsible for the normal scientific and programmatic stewardship of the award, and will be named in the award notice.

Areas of Joint Responsibility include:

• The PD(s)/PI(s) provide, in concert with the NHLBI Project Director, support necessary to ensure that sites and investigators, and NHLBI and other research partners fully comply with federal regulatory requirements, including but not limited to those relating to human subjects protections, informed consent, and reporting of adverse events.
• Awardees and NHLBI will jointly develop appropriate confidentiality procedures for data collection, processing, storage and analysis to ensure the confidentiality of data on individual health care provider organization patients, health care providers and other institutions.
• All awardees and NHLBI will cooperate to ensure the timely and broad dissemination of lessons learned, to inform researchers and health care systems engaged in research in health care settings.
• An Operations Committee (OC) composed of three Clinical Center PIs on a rotating basis (as described in the Network Structure management section), the NEMO PD/PI(s), the PLG PDs/PIs who originated the trial idea, and the NHLBI Project Scientist will be the main governing body of the network. The NHLBI will appoint an OC Chair who may or may not be independent of the Clinical Centers and NEMO, to preside over OC meetings and serve as the OC representative to DSMB.

Dispute Resolution:

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 investigator chosen without NIH staff voting from among the PI of the FOA, 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.

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

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: http://grants.nih.gov/support/index.html
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
Email: [email protected]

Antonello Punturieri, M.D., Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0230
Email: [email protected]

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: [email protected]

Catherine Sanchez
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-402-3839
Email: [email protected]

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.