Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)
National Institutes of Health (NIH)

Components of Participating Organizations

National Heart, Lung, and Blood Institute (NHLBI)

Funding Opportunity Title
Limited Competition: Network Management Core (NEMO) for the Pulmonary Trials Cooperative (PTC) Disease Modifying Therapies for Chronic Lung Diseases (U24 Clinical Trial Required - Infrastructure)
Activity Code
U24 Resource-Related Research Projects – Cooperative Agreements
Announcement Type

Reissue of RFA-HL-16-016

Related Notices
July 26, 2019- Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-128

August 23, 2019- Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-137

Funding Opportunity Announcement (FOA) Number
RFA-HL-21-012
Companion Funding Opportunity

RFA-HL-21-013,UG3/UH3 Exploratory/Developmental Phased Award - Cooperative Agreement

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.838

Funding Opportunity Purpose

The purpose of this limited competition Funding Opportunity Announcement (FOA) is to support the continuation and expansion of the existing NHLBI Pulmonary Trials Cooperative (PTC) clinical trials network. This FOA requests applications for a cooperative agreement research grant (U24) to serve as the Network Management Core (NEMO) for the PTC. The PTC will include multiple Protocol Leadership Groups (PLGs) and a single Network Management Core (NEMO) and will conduct multiple simultaneous phase II clinical trials that will test innovative disease modifying therapies (DMT) for adult chronic lung diseases. NEMO will have primary responsibility for organizing and operating this multi-center cooperative. A companion FOA (RFA-HL-21-013) seeks Protocol Leadership Group (PLG) applications for specific phase II DMT trials.

Key Dates

Posted Date

May 01, 2020

Open Date (Earliest Submission Date)
June 24, 2020
Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

July 24, 2020 by 5:00 PM local time of applicant organization.

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review
December 2020
Advisory Council Review

January 2021

Earliest Start Date

April 2021

Expiration Date
July 25, 2020
Due Dates for E.O. 12372
Not Applicable
Required Application Instructions
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Most chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and asthma, currently have no cure, and available treatments are aimed primarily at symptom abatement. COPD affects at least 15 million people in the U.S. with >150,000 deaths yearly (and >60% of deaths are among those over 75 years of age). Although IPF is considered a rare lung disease (affecting 200,000 people or fewer), it causes about 40,000 deaths annually, with a median survival of only 3 years after diagnosis. Asthma affects >24 million people in the US, and >7% of these patients have a severe form of the disease. Other chronic lung diseases, including pulmonary sarcoidosis and lymphangioleiomyomatosis (LAM), are characterized by subversion of the lung architecture with progressive loss of functional lung tissue. Hence, there is an urgent need to develop innovative therapeutic approaches that, by interfering with underlying pathophysiological mechanisms, will significantly delay or permanently change the clinical progression of a chronic lung disease. Such a treatment may be considered a disease-modifying therapy (DMT).

This limited competition funding opportunity announcement (FOA) will promote the conduct of multiple clinical trials to test potentially disease-modifying therapies for chronic lung diseases. This FOA seeks an application to serve as the Network Management Core (NEMO) for the multi-center Pulmonary Trials Cooperative (PTC). The NEMO will have primary responsibility for organizing and operating the PTC and will cooperate with multiple Protocol Leadership Groups (PLGs) (see companion FOA RFA-HL-21-013) to conduct phase II clinical trials that test potential DMTs for chronic lung diseases.

The PTC is a network that includes multiple PLGs and a single Network Management Core (NEMO). The PTC is designed to simultaneously conduct multiple clinical trials in chronic pulmonary diseases, including but not limited to COPD, interstitial lung disease (ILD), asthma, adult cystic fibrosis (CF), adult primary ciliary dyskinesia (PCD), pulmonary hypertension (PH), sarcoidosis, and obstructive sleep apnea, but excluding acute lung injury and critical care and pediatric lung diseases. By studying multiple chronic pulmonary conditions in a single large program, the PTC enables studies across a wide range of chronic pulmonary diseases; encourages studies of specific subsets of patients; involves a wide range of institutions in the recruitment, retention and follow-up of research subjects; and increases the efficiency of subject recruitment at individual sites by strongly encouraging the use of electronic medical information systems for the identification of potential research subjects.

A key characteristic of the PTC is its focus on core milestones. A core milestone is defined as a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones are performance-based and designed to ensure completion of each PLG trial on time and on budget. Milestones are aligned with the bi-phasic mechanism of each PLG award, being established for both the first year (coinciding with the R61 phase of each PLG award) and subsequent years (coinciding with the R33 phase of the PLG award). Satisfactory completion of the milestones for the first year will be assessed administratively at about 9 months (i.e., progress report will be due) to determine eligibility to continue the award related to a specific PLG. These clinical trials are expected to be conducted with a high degree of efficiency, with streamlined administrative procedures wherever possible. The NEMO grantee will support each specific PLG grantee for meeting core milestones, and the NEMO applicant is strongly encouraged to propose project management principles and to address contingency plans that proactively confront potential delays or disturbances in meeting the anticipated milestones.

Phases of Award

The first year of each awarded PLG (RFA-HL-21-013) will have a corresponding milestone-driven period with the NEMO. NEMO will be expected to use this period to support the development of the resources necessary for the performance of the phase II clinical trial; develop study partnerships; obtain approvals of Institutional Review Board and Data and Safety Monitoring Board for the trial protocol; and develop informed consent(s)/assent(s), a manual of operations, data management systems, randomization procedures, and a final integrated project management plan. Successful completion of the R61 phase of a specific PLG application will support a decision by NHLBI to proceed beyond the first year for that specific PLG award, subject to the availability of funds. An administrative decision will be made after review of the progress made by both the NEMO and the specific PLG for each phase II trial. These reviews will be conducted approximately 9 months into award, with particular attention paid to the extent to which agreed-upon milestones have been met. Due to the collaborative and parallel nature of NEMO and PLG awards, NHLBI will enter into negotiation with the NEMO to achieve revision or early phase-out of the portion of the award related to a specific phase II trial if progress is deemed inadequate upon administrative review.

The roles of the NEMO are distinct from but interactive with those of the PLGs. Applicants should examine the companion FOA (RFA-HL-21-013 and the Table below for information regarding roles of NEMO and the PLGs). It is expected that the PLGs will be responsible for their own milestones completion and will be responsible for recording their milestones completion through eConnect , a platform that facilitates transfer of electronic information regarding clinical trials to NHLBI. NHLBI policies regarding milestones and relevant clinical research/studies policies are described in the following: NHLBI Accrual of Human Subjects (Milestones) Policy NHLBI Policy for Inclusion of Women and Minorities in Clinical Research, NHLBI Policy for Data and Safety Monitoring of Extramural Clinical Studies, and NHLBI Data Sharing Policy .

Scope

The new focus of this renewal differs from the previous PTC program by exclusively supporting investigations of DMT.

PTC Structure and Governance

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 carrying out the PLG trial protocols approved by NHLBI. The Clinical Centers will transfer data and biospecimens (the latter if applicable) to the PLG biostatistical core 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. Due to the exploratory nature of the research to be completed, it is envisioned that each trial will enroll up to 400 participants total. Clinical Centers will have the option not to participate in any 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, the PI(s) of each PLG awarded (see RFA-HL-21-013), 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. 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 will not have a vote in OC decisions. A Data and Safety Monitoring Board (DSMB) will also be established in accordance with NHLBI policies 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 multicenter 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 in collaboration with each PLG, protocol specific training of personnel at the Clinical Centers; reimburse the Clinical Centers for protocol costs, using pre-established, capitated rates, specific for each PLG 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 chronic lung diseases as specified in the FOA description and to have in place 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, together with each specific PLG, 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 coordinate 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.

Data Harmonization. Each PLG will have primary responsibility for developing study forms and implementing a data management system for the specific protocol they propose. PLGs are also tasked, in concert and coordination with each other and the NEMO, with establishing a data-harmonization committee aimed at promoting common measures and forms that can be used by researchers across the PLG studies within and across particular lung research fields. By using these common measures, researchers in and outside the PTC will be able to more easily compare and combine datasets to detect more subtle and complex associations among variables, thereby promoting greater collaboration, efficiency, and return on investment.

Table: Summary of Functions

Network Management Core (NEMO)

Protocol Leadership Groups (PLGs)

  • 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 website
  • Maintain official study documents, inclusive of manuals of Standard Operating Procedures (SOPs)
  • Schedule, organize, and accommodate all PTC committees, board meetings, and teleconferences
  • Manage and 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
  • Generate NEMO-specific periodic reports for distribution to the NHLBI and the DSMB
  • Distribute to the NHLBI and the DSMB the PLGs reports in an agreed-upon format among all the PLGs and the NEMO
  • 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, provide the 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 other 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
  • Register the trial and 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
  • Store and analyze biospecimens (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 and submit to NEMO periodic reports, in an agreed upon format among all the PLGs and the NEMO, for the NHLBI and the DSMB that NEMO will forward to those entities
See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument
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. See Section VI.2 for additional information about the substantial involvement for this FOA.
Application Types Allowed
Renewal

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?
Required: Only accepting applications that propose clinical trial(s)

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NHLBI intends to commit total costs up to $2,000,000 in FY2021 to fund one new award.

Award Budget

Direct costs may not exceed $1,605,000 in FY2021, $2,430,000 in FY2022, $2,595,000 in FY2023, $2,745,000 in FY2024, $2,745,000 in FY2025, $2,485,000 in FY2026, and $2,835,000 in FY2027.

All future year commitments are subject to the availability of funds. Actual funding will depend on annual appropriations. Application budgets need to reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is 7 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Required Registrations

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) – 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.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons.Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. 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.

Eligible Individuals (Program Director/Principal Investigator)
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.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

 

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)

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guideexcept 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.

 

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
Email: NHLBIChiefReviewBranch@nhlbi.nih.gov

Page Limitations
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed
Instructions for Application Submission
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.
SF424(R&R) Cover
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Project/Performance Site Locations
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Other Project Information
All instructions in the SF424 (R&R) Application Guide must be followed.

Facilities and Other Resources: Describe the facilities and resources available for the coordination of multi-site simultaneous phase II clinical trials of disease-modifying therapies (DMT) in adult chronic lung diseases, including project management tools that will be used. Describe how the infrastructure at the NEMO and performance sites will facilitate the efficient operation of multiple, simultaneous phase II clinical trials of disease-modifying therapies (DMT) in adult chronic lung diseases.

Other Attachments: Both attachments listed below must be provided.

1. Trials Management Plan

A description of how the proposed trials will be managed must be provided as an attachment using the filename "Trials Management Plan.pdf" and may not exceed 5 pages.

Describe the strategy that will be used throughout the project to ensure good management of multiple phase II clinical trials of disease-modifying therapies (DMT) in adult chronic lung diseases, including support for the scientific study leadership to identify barriers, make timely responses, and optimize the allocation of limited resources to meet pre-defined study objectives. This description should include:

  • The roles of the project manager
  • A risk assessment plan
  • A risk management plan including plans for remediation in the event that there is inadequate progress toward achieving the core milestones for a particular phase II trial. The plan should identify a range of contingencies that could threaten a single phase II trial progress or feasibility and propose solutions using study resources.
  • Key methodology and standard operating procedures for resource management, study deployment, operations/execution, and study closure.
  • How the clinical trial management team, in collaboration with a specific PLG, will resolve fiscal and logistical issues in a timely manner including plans to pro-actively evaluate and prioritize study risks and issue corrective responses.
  • Processes required for orderly project closure .
  • The trial management plan should provide sufficient detail to demonstrate the ability of NEMO to assure the reach of the goals of each phase II clinical trial on-budget and on-time and to successfully manage and mitigate risks.

2. PTC Network Description

The phase II clinical trial will be conducted using the infrastructure of an existing Network, the pulmonary trials cooperative (PTC). A PTC Network Description Plan should be provided as an attachment using the filename "PTC Network Description.pdf" and may not exceed 6 pages. This description should include:

  • Brief description of the PTC and history of trials conducted in the PTC, including number of years of operation, funding that supported each trial conducted and plans for continuation and modification of the PTC.
  • Initial and continuing plans to replace sites that are poorly-performing or that are removed through the PTC re-competition process. These plans should include contingencies for funding, data recovery, and the follow-up of enrolled trial participants.
  • Infrastructure capacity and availability of patient populations based on current ongoing trials within the PTC.
  • Plans to utilize the current PTC infrastructure in PLG trials, including participant recruitment, trial implementation, and central coordination through each of the PLGs and data management, data analysis, or statistical analysis through the NEMO.
  • Plans to utilize master clinical trial agreements and a single IRB.
  • Plans to promote communication and cooperation among the PLGs, the NEMO, and the NHLBI.
SF424(R&R) Senior/Key Person Profile
All instructions in the SF424 (R&R) Application Guide must be followed.

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 research resources they have established at their institution. Personnel must provide expertise in study coordination, pulmonary medical expertise required for clinical and safety monitoring, data security and IT infrastructure management (including development of public and secure study websites). Without duplicating information already provided in the biosketches, applicants must describe/document:

  • 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)
  • the track record in chronic pulmonary diseases trials clinical coordination
  • experience in project management of recent trials and describe the collaborative leadership structure used in recent multi-center trials they have coordinat

Again, without repeating information provided in the biosketches, 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 Key Personnel who are major scientific contributors to the study must provide an NIH Biosketch whether or not they are budgeted. The PD/PI (or Multi-PDs/PIs) for the NEMO cannot be Key Personnel on a PLG application.

 

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, phase II 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 video-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). Protocol costs should be requested in Section F, Other Direct Costs, 8. Other 1 and not co-mingled with other line items. Funding for protocol costs in the PTC will be managed and distributed to the Clinical Centers by NEMO on a per-patient basis (capitation) via master trial agreements. NHLBI expects to allocate sufficient funds for capitation costs for up to 5 disease-modifying therapies (DMT) phase II trials over the course of the NEMO award period.

Core and recruitment system funds may not exceed direct costs of $0.705M in year 1, $0.830M in year 2, $0.895M in year 3, $0.895M in year 4, $0.895M in year 5, $0.830M in year 6, and $0.770M in year 7.

Protocol funds may not exceed direct costs of $0.9M in year 1, $1.6M in year 2, $1.7M in year 3, $1.85M in year 4, $1.85M in year 5, $1.655M in year 6, and $2.07M in year 7.

R&R Subaward Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Cover Page Supplement
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy:

Leadership and Operations Plan

Describe in detail plans for assembling and supervising a network of Clinical Centers capable of conducting multiple, disease-modifying therapies (DMT) focused Phase II clinical trials in adult chronic lung diseases (including a mechanism for recruiting additional Clinical Centers to the PTC during the initial period of the program), with plans for administering network activities and clinical trials. Describe SOPs currently in place and planned; how tasks will be delegated and supervised; and how the management team will communicate among themselves, with the Clinical Centers, and with the PLGs.

Describe planned support for all aspects of complex multi-center trials, oversight of the Clinical Centers, and the organization and functioning of the PTC Operations Committee (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 protocol funds, including plans for master trial agreements and for funding of centralized IRB services, should be described.

NOTE: Applications will address planned approaches to carry out many of the functions that are typically performed by a Data Coordinating Center of a multicenter study. However, in the PTC all statistical, data management and data analysis responsibilities will reside in the PLG of a specific protocol implemented, unless specifically agreed between a PLG and the NEMO that these should reside at the NEMO. In general, NEMO will not receive individual level data for study participants.

Training Plan

Describe plans for general training of Clinical Center personnel as needed for implementation of protocols involving multiple adult chronic lung diseases.

Timeline for Management of Clinical Trials and NEMO Milestones

Propose and justify milestones that will be subject to peer-review. A milestone is defined as a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones should be relevant, measurable, achievable, results-focused and time-bound, and should address timing of overall recruitment/enrollment and retention goals. The milestones must address accrual goals for women, minorities and individuals of all ages, including older adults (as applicable to the populations targeted in the trials), and any other identified requirements for completion of the approved research.

Describe schedule for completion of the target number of studies within the 7-year project period, and methods for quickly establishing the procedures and tools necessary for launching trial protocols, activating the Clinical Centers, and ensuring study progress.

Early Milestones (Year 1)

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 a specific PLG project period.

Three months after award: Publish templates for master trial agreements. Have an operational website that describes the NEMO and Clinical Centers operations, begin awarding start-up costs to qualifying Clinical Centers, define the procedure for patient recruitment, and provide written operating procedures for PTC operations. Begin steps of the launching of PLG trial protocol(s).

Six months after award: Negotiate protocol costs of the trials awarded. 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.

Eleven months after award: Enrollment of first subjects. DSMB review and NHLBI approval of additional protocol(s). Submission of additional protocol(s) to IRBs.

Trial Milestones (Year 2 and Beyond)

Enrollment of 25%, 50%, 75% and 100% of the projected recruitment for all study participants, including women and minorities (as appropriate).

Study closure and completion plans.

Collection of data related to primary and secondary endpoints and database lock.

Submission of primary manuscript to peer-reviewed scientific journal(s) and dissemination of results.

Clinical Center Supervision

Describe how 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 in collaboration with each PLG, protocol specific training of personnel at the Clinical Centers; reimburse the Clinical Centers for protocol costs, using pre-established, capitated rates, specific for each PLG 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.

Describe how the Clinical Centers assembled by NEMO should be capable of recruiting research subjects for trials in chronic lung diseases as specified in the FOA description and have in place means for contacting large numbers of subjects with specified clinical characteristics. How NEMO will certify all Clinical Centers based on their access to potential trial participants and capabilities to carry out PTC protocols. How NEMO will negotiate an arrangement with each for reimbursement of protocol costs according to agreed-upon capitated budgets. How NEMO will develop master trial agreements and organize centralized IRB services to expedite the implementation of multiple protocols at many sites. How 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

Describe how 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.

Describe plans for NEMO coordination, together with each specific PLG, of 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. How NEMO will develop standards for testing and certification of staff, obtain OC concurrence, and maintain related records. How 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. How 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. How NEMO will implement procedures for backing up the program’s administrative data, including intermittent duplication of the database with storage at a remote facility. How NEMO will contribute summaries of study progress to reports prepared for submission to the DSMB and NHLBI. NEMO will schedule, organize, and coordinate all PTC committees and boards meetings and teleconferences. How payments for meeting rooms and consultant costs of the DSMB members will be made.

Data Harmonization

Describe how the NEMO in concert and coordination with all the PLGs, will establish a data-harmonization committee aimed at promoting common measures and forms that can be used by researchers across the PLG studies within and across particular lung research fields. Describe how researchers in and outside the PTC will be able to more easily compare and combine datasets to detect more subtle and complex associations among variables, thereby promoting greater collaboration, efficiency, and return on investment with the use of data harmonization.

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 site 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 site PD/PI).

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.

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
  • Awardees are expected to comply with the NHLBI Data Sharing Policy.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information
When involving human subjects research, clinical research, and/or NIH-definedclinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form
All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. 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. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day.

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 and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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 How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

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 and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact
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).
Scored Review Criteria
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? Is the prior research that serves as the key support for the proposed project rigorous? 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?

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

 

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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?

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Specific to this FOA:
How strong is the track record of the PD(s)/PI(s) regarding successfully designing and implementing the management aspects of multi-center clinical trials or coordinating multi-center clinical trials? How strong and successful is the track record of the PD(s)/PI(s) in chronic pulmonary diseases trials clinical coordination? How likely are the investigators to be prepared to carry-out the key tasks in a timely manner, including, but not limited to establishing procedures, the web site, and specific training?

How strong is the Trials Management Plan in regard to the roles/responsibilities of the Project Manager?

How strong is the project management expertise represented among the key personnel?

How strong are the experience and capability of the PDs/PIs and key personnel in multidisciplinary NEMO functions including, tracking, logistics and administration, communications, data security and IT infrastructure (including development of public and secure study websites), and regulatory support?

 

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?

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

 

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA:

Where appropriate, how strong are the strategies presented in the proposed NEMO to utilize current best practices for the conduct of the multi-site clinical trials it will support? How well does the PTC Network Description address plans for: continuation and modification of the PTC, replacement of poorly-performing sites or sites removed via the PTC re-competition process, use of the current PTC infrastructure in PLG trials, utilization of master clinical trial agreements and a single IRB, and promotion of communication and cooperation among the PLGs, the NEMO and NHLBI?

 

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?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed? Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate? If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial? If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Specific to this FOA:
To what extent do the support letters from the institution, department, and other partiesdemonstrate appropriate commitment for the PD(s)/PI(s) such as protected time, departmental research leadership position, facilities, space, or resources? To what extent does the application demonstrate that the institution will be able to coordinate and utilize standardized master trial agreements for per patient cost of clinical programs?

Additional Review Criteria
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.

Study Timeline
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Core Milestones
To what extent are the proposed milestones appropriate for the NEMO in that they arerelevant, measurable, achievable, result-focused and time-bound?

 

For research that involves human subjects but does not involve one of thecategories 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 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 individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

 

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

 

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

 

Not Applicable

 

For Renewals, the committee will consider the progress made in the last funding period.

 

Not Applicable

Additional Review Considerations
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.

 

Not Applicable

 

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 Data Sharing Plan (GDS).

 

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

 

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Heart, Lung, and Blood Institute, 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 on the basis of established PHS referral guidelines 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 appropriate national Advisory Council or Board. 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.

3. Anticipated Announcement and Award Dates

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.Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

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.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain "applicable clinical trials" on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 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 will designate an executive secretary for all DSMB meetings who will attend 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 Scientist, 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 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.

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final RPPR, 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 agreementsare 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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM)about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings.Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
Application Submission Contacts
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threatensubmission by the due date, and post-submission issues)

Finding Help Online:http://grants.nih.gov/support/(preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email:GrantsInfo@nih.gov(preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support(Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email:support@grants.gov

Scientific/Research Contact(s)

Antonello Punturieri, MD, PhD
Division of Lung Diseases
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0233
Email: punturieria@nhlbi.nih.gov

Peer Review Contact(s)

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: NHLBIChiefReviewBranch@nhlbi.nih.gov

Financial/Grants Management Contact(s)

Laurel Kennedy
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-4777
Email: laurel.kennedy@nih.gov

 

Section VIII. Other Information

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.
Authority and Regulations
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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