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

Clinical Coordinating Center (CCC) for the NHLBI Prevention and Early Treatment of Acute Lung Injury (PETAL) Clinical Trials Network (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

  • August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications.

Funding Opportunity Announcement (FOA) Number

RFA-HL-14-015

Companion Funding Opportunity

RFA-HL-14-014, U01 Research Project – Cooperative Agreements

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

93.838

Funding Opportunity Purpose

This funding opportunity announcement (FOA) is for a Clinical Coordinating Center (CCC) for a new National Heart, Lung, and Blood Institute (NHLBI) Clinical Trials Network for the Prevention and Early Treatment of Acute Lung Injury (ALI) (PETAL Network).  The Network will consist of approximately 11 Clinical Centers and 1 CCC.  The Network will develop and conduct randomized controlled clinical trials to prevent, treat, and/or improve the outcome of adult patients with, or at risk, for ALI or the Acute Respiratory Distress Syndrome (ARDS).  This FOA solicits applications for a CCC and runs parallel with a separate FOA for the CCs (RFA-HL-14-014). These awards are expected to be for 7 years.      

Key Dates
Posted Date

May 15, 2013

Open Date (Earliest Submission Date)

June 25, 2013

Letter of Intent Due Date(s)

June 25, 2013

Application Due Date(s)

July 25, 2013, by 5:00 PM local time of applicant organization.

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

October-November 2013

Advisory Council Review

January 2014

Earliest Start Date

April 2014

Expiration Date

July 26, 2013

Due Dates for E.O. 12372

Not Applicable

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.

Table of Contents

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

Part 2. Full Text of Announcement


Section I. Funding Opportunity Description


Purpose

The NHLBI Clinical Trials Network for the Prevention and Early Treatment of Acute Lung Injury (PETAL) will conduct randomized controlled clinical trials to prevent, treat, and/or improve the outcome of patients with, or at risk for, Acute Lung Injury (ALI) or the Acute Respiratory Distress Syndrome (ARDS). PETAL will consist of 1 Clinical Coordinating Center (CCC) solicited under RFA-HL-14-015 and approximately 11 Clinical Centers (CCs) to be solicited under RFA-HL-14-014.  These awards are expected to be for 7 years. More than 1 trial will be conducted simultaneously, and it is expected that a minimum of 3-5 trials will be completed during the course of the award.  The CCC will be responsible for coordinating all aspects of the Network. 

Background and Objectives

This FOA builds on the demonstrated strengths and experience of the NHLBI Acute Respiratory Distress Syndrome Clinical Trial Network (ARDSnet), but shifts the focus towards prevention, earlier intervention, multidisciplinary collaborations, and new partnerships and approaches.

The goal of this new initiative will be very different from the current ARDSnet.  Numerous observational studies suggest that ALI and ARDS can be prevented and outcomes improved in patients at risk of, but without, established disease.  Recommendations from the critical care community stress the use of multidisciplinary approaches and studies of pre-ICU factors that will permit early identification and intervention in the emergency department (ED) or other locations within the hospital.   This new initiative will require a collaborative team approach that will bring together pulmonary/critical care investigators, with experts in other relevant specialties including, but not limited to, emergency, trauma, sepsis, and infectious disease medicine or other that will ensure early access to eligible patients. 

The scope of the Network studies will include patients at risk for ALI/ARDS including patients with shock or respiratory failure from sepsis as well as patients with established ALI/ARDS. Although the focus will be on early treatment and/or prevention, high-priority studies of novel treatments for established ALI and ARDS in ICU patients will be within the scope of this program. There will be latitude to propose and conduct clinical protocols that answer other significant questions that affect ALI/ARDS patients.  Study endpoints are expected to be mortality, but other longer-term endpoints may be considered, as long as they are shown to have relevance to heart, lung, and blood disorders. Purely mechanistic studies are not appropriate for this Network.

Protocols will be selected and written by the Steering Committee (SC), which will be composed of the Intensive Care Unit clinician-investigator and a second investigator from a different specialty (e.g., emergency medicine, surgery, anesthesia) from each of the 11 CCs, as well as the CCC and NHLBI.  The Network will be expected to consider protocol ideas from the wider critical care community from workshops and input from a PETAL public website.  Protocols will be reviewed for scientific merit, validity, and feasibility by an independent NHLBI Protocol Review Committee (PRC).  An independent NHLBI Data and Safety Monitoring Board (DSMB) will conduct interim reviews of trial data for patient safety and overall progress.

The Network will plan for and collect high-quality biospecimens that will permit the longitudinal molecular analysis of disease pathogenesis and recovery, as well as disease stratification in critically ill patients.  These samples will be available to the wider research community for mechanistic work conducted under other funding mechanisms.   Samples will be stored at a central laboratory repository at the CCC or at a subcontractor to the CCC and transferred to the NHLBI biorepository at the end of each trial.

The Network is expected to develop and participate in a cooperative, central, or shared IRB that will streamline IRB approval while maintaining patient safety.

In year 1, the PETAL Network is expected to be devoted to establishment of Network structure and procedures (including a cooperative IRB model), and selection and design of at least two clinical trial protocols. Years 2-7 will include protocol conduct, additional protocol designing, and routine Network functions.  The last half of year 7 should be dedicated to Network closeout.

Scope of Activities for the CCC

The CCC will be responsible for coordinating all aspects of PETAL. The CCC is expected to be experienced and highly competent in the coordination of complex clinical trials. The CCC will have a key role in trial design and analysis, and be responsible for oversight and monitoring, data collection, data integrity, reporting, training, and all PETAL Network operations. In addition to the usual varied responsibilities associated with organizing and overseeing a clinical trials Network, the CCC in cooperation with the NHLBI will (1) organize conferences in Year 1 and Year 5 with the broader critical care community to discuss priorities for prevention or early treatment clinical trials and developing a method to routinely welcome ideas for trials from the critical care community; (2) oversee development and storage of a biospecimen collection for molecular phenotyping of patients from samples collected by CCs at a central laboratory and transfer to the NHLBI biorepository in accordance with their guidelines at the end of trials; and (3) oversee development of an efficient, streamlined IRB review process which could be a collaborative, central, or shared IRB or some other method that will increase efficiency of trial reviews while maintaining safety and quality.

Research Topics

There are several new strategies that might prove beneficial in reducing the burden of ALI.  This Network is expected to emphasize prevention and early treatment.  New Food and Drug Administration (FDA) guidelines for testing combination therapies in serious illnesses open new possibilities.  There may be novel treatment opportunities emerging through increasing understanding of the lung microbiome and the role of the host response in initiating, maintaining, and resolving lung injury.  ALI/ARDS has several etiologies, and it is unknown whether different patients at risk (for example patients with sepsis, pneumonia, aspiration, or trauma) develop the same degree or type of lung injury, or whether treatments can be tailored and targeted to individual patients to either alleviate or prevent ALI/ARDS from developing.  Initial studies of regenerative medicine approaches, such as using stem cell therapies, may be ready for testing in larger studies by this Network.  Ventilation and blood transfusion strategies or changes in antibiotic management may need to be applied to early intervention of acute lung injury.  Although the focus of this program is on prevention and early treatment of ALI/ARDS, high-priority studies of novel strategies for treating established ALI and ARDS will be permissible.  Studies that could optimize treatments for ALI/ARDS of different etiologies would be appropriate. There will be latitude to propose clinical protocols that address other significant questions that affect patients with ALI/ARDS that have the potential to substantially improve clinical outcomes.  .

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.

Application Types Allowed

New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications

It is estimated that approximately $53 million (Total Costs) will be awarded to the CCC over a 7-year period.

One CCC will be funded by this award.

Award Budget

Application budgets are limited to a maximum of $857,142 (Direct Costs) for the first year excluding patient care costs.

Budgets for years 2 through 7 are limited to a maximum of $1,123,809 (Direct Costs) related to core activities.

Budgets should also include patient care costs for $7,280,000 in each of years 2 through 6 and $3,300,000 in year 7.

Budgets need to reflect the actual needs of the proposed project.

Award Project Period

The total project period for an application submitted in response to this funding opportunity may not exceed 7 years.   

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

Section III. Eligibility Information


1. Eligible Applicants


Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

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 not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not 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.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

The CCC will have two key investigators (PDs/PIs).  The PDs/PIs must be a senior statistician with demonstrated experience in coordinating clinical trials, preferably in critically ill patients. The second key investigator will have demonstrated experience in clinical trials in critically ill patients, appropriately Board-certified and actively involved in the care and study of pulmonary and critically ill patients, especially those with ALI/ARDS. 

2. Cost Sharing

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

3. Additional Information on Eligibility


Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

Proposals submitted in response to contract solicitation NHLBI-HR-14-03  do not violate the above prohibition on submission of essentially same applications within 37 months.  NHLBI cancelled the contract solicitation and is instead issuing this cooperative agreement mechanism, thus proposals submitted to NHLBI-HR-14-03 will not be reviewed.

Section IV. Application and Submission Information


1. Requesting an Application Package

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.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, 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.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

The letter of intent should be sent to:

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 7214, MSC 7924
Bethesda, MD 20892-7924 (Express zip: 20817)
Telephone: (301) 435-0270
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.

Required and Optional Components

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

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.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

The CCC will have two key investigators.  The PD/PI will be a senior statistician with demonstrated experience in coordinating clinical trials. The second key investigator will have demonstrated experience in clinical trials in critically ill patients, appropriately Board-certified and actively involved in the care and study of pulmonary and critically ill patients, especially those with ALI/ARDS.

R&R Budget

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

To justify the personnel component of the budget, in addition to the standard biosketches including the tailored individual statement for key personnel, the applicant should include a table outlining the expertise and effort proposed for the CCC.  Effort should differ during Year 1 startup (protocol writing, Network operations, data base preparation) and Year 7 close down (finalizing data bases, final manuscripts, transferring data and biospecimens to NHLBI). Expertise typically needed for a CCC includes project management, nurse coordinator, biostatistics, computer expertise including data base creation and management, website development.  For this FOA, expertise in biobanking is needed.  

Suggested travel:

Year 1: 

Years 2 through 7:

Other costs to be included but not limited to:

Biospecimen lab

A budget should be proposed to support a central biospecimen lab.  This should include sufficient labor to establish procedures that meet quality standards of the NHLBI Biorepository (BioLINCC https://biolincc.nhlbi.nih.gov/home).   Costs include sample collection kits assuming several types of biospecimens that would be useful for molecular phenotyping (e.g., inflammatory and other biomarkers, expression analysis, and tissue analysis), shipping containers and shipping costs for the CCs, costs for storage at the CC biorepository, and costs for final shipping to the NHLBI biorepository.  Costs for Q/A should be described.  This biospecimen collection plan will be finalized by the SC, but the CCC should present a vision and budget for the biospecimen collection.

A subcontract may be proposed for the biospecimen repository.  

PHS 398 Cover Letter

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:

In lieu of a Research Strategy with the usual headings, the applicant should describe their experience and plans for carrying out the duties involved in overseeing a complex clinical trials network.  Some of the duties are listed below.

This CCC will have four additional roles that should be addressed:  (1) methods to routinely solicit/welcome research ideas from the wider critical care community (e.g., public website), (2) overseeing development of more efficient IRB process by the SC, and (3) development and operation of a biospecimen lab.  This plan should outline a vision for the types of samples that would support molecular phenotyping appropriate for critically ill patients. 

The Research strategy section may include any other information that the applicants deem important for determination of merit.

Letters of Support: Provide letters of support, including letter indicating institutional willingness to participate in cooperative, central, or shared IRB model developed by the SC, as a single PDF file with the name “PETAL support.pdf.”

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.  

3. Submission Dates and Times

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. 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.

Funds budgeted for protocol capitations and SC chair effort will be restricted for these purposes.

6. 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 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 NHLBI, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.  

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information


1. Criteria

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.

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.

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?

Is the PD/PI a senior statistician with experience managing complex clinical trials, especially ALI/ARDS?

Is the PD/PI knowledgeable about clinical trial design and analysis?

Does the staff of the CCC have experience and qualifications in clinical trial management?

Is the Critical Care key investigator (one of the PDs/PIs) experienced in working with clinical trials in critically ill patients?

Is there an investigator associated with the proposed biospecimen lab who is knowledgeable about biomarkers and biospecimens?

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?

Have innovative, cost-effective approaches to clinical trial design, data collection, training, CC oversight and information sharing been described?  

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 economical and efficient means for communication with and among CCs described?

Is there a good plan for obtaining clinical trial ideas from the wider critical care community?

Is the plan for the biospecimen repository sufficient to result in high quality specimens?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion 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? 

Has the Institution indicated a willingness to participate in a cooperative, central, or shared IRB?

Are facilities available for secure data and biospecimen storage?

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.

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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

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.   

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NHLBI in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the NHLBI Advisory Council. The following will be considered in making funding decisions:

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

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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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.

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 prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

The Clinical Coordinating Center PD/PI will be responsible for the overall function of all PETAL research activities.  The CCC PD/PI will be responsible for oversight of protocol development, drug acquisition and distribution, data collection, data safety and confidentiality, quality assurance, data analysis, coordination of data distribution, and implementation of all data sharing plans. The CCC PD/PI will be responsible for the distribution of protocol funds to the Clinical Centers (see “Funds Available” in Section II. 2. RFA-HL-14-014).  The CCC PD/PI will be responsible for coordination of manuscript preparation, activities of the Steering Committee, Protocol Review Committee, and Data and Safety Monitoring Board.

Support or other involvement of industry or any other third party in the PETAL studies may be advantageous and appropriate.   Awardees must follow NHLBI policy concerning third party agreements.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

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

The PETAL program scientist (PS) will participate in Steering Committee activities.  Several procedures are in place to manage potential conflicts of interest by PS administering the cooperative agreement.  PS adhere to stringent NIH ethics rules and financial disclosure; staff are prohibited from observing scientific review of competing applications from an investigator with whom they have published in the last three years; recommendations from PS about budgetary requests (e.g., carryover, administrative supplements, no-cost extensions) are reviewed and approved by supervisors (e.g., Branch Chiefs, Division Director, and, Institute Director); recruitment progress is reviewed by study independent staff (quarterly within the Division; semi-annually or quarterly by the DSMB and supervisory staff, and annually by the NHLBI Director; PS will generally be asked to leave the room during DSMB reviews of study results; recommendations made by PS in annual progress reports are reviewed by grant specialists in a separate Division (Office of Grants Management); PS will not seek lead authorship of primary publications and will obtain approval by Branch Chief to participate in secondary publications.

Program staff may work with awardees on issues coming before the Steering Committee and, as appropriate, other committees (e.g., recruitment, intervention, follow-up, quality control, adherence to protocol, assessment of problems affecting the study and potential changes in the protocol, interim data and safety monitoring, final data analysis and interpretation, and preparation of publications).  NHLBI Program staff, on behalf of the NHLBI, will have the same access, privileges, and responsibilities regarding the collaborative data as the other members of the Steering Committee.

The NHLBI reserves the right to phase out a PETAL study (or an individual award) in the event of (1) failure to develop or implement mutually agreeable collaborative protocol; (2) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (3) major breach of a protocol or substantive changes in the agreed-upon protocol with which NHLBI cannot concur; (4) attaining of a major study endpoint before schedule with persuasive statistical significance; or (5) human subject ethical issues that may dictate an early phase out of a trial or the program.

Annual continuation and level of funding for the CCC will be based on NHLBI review of actual recruitment and overall performance, determined as part of the NHLBI review of the annual non-competing continuation grant progress reports submitted by awardees.

Additionally, an agency program official or IC program director 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:

Awardees agree to the governance of the study through a Steering Committee (SC).  Two investigators from each CC and the CCC, a Chairperson, to be appointed by the NHLBI, and an NHLBI representative will comprise the SC.  All major scientific decisions will be determined by majority vote of the SC.  Each Clinical Center, the Clinical Coordinating Center, and the NHLBI Program Office will have one vote; the Chair will have one vote in case of a tie.  Note that although each Clinical Center is expected to have two representative participants (one with expertise in critical care, one with expertise in emergency medicine or some other specialty with early access to patients)  in all SC meetings, each Clinical Center has only one vote.  It is anticipated that SC meetings will be held at least once a month by conference call and two times a year in person.  The first year during Network establishment and initial protocol selection, may require more frequent contact

An independent Protocol Review Committee (PRC) will provide peer review for each PETAL protocol.  The PRC will be appointed by and be advisory to the NHLBI.  It will consist of a chairperson, and Executive Secretary who is an NHLBI scientist other than the NHLBI Project Scientist, and scientists with expertise in clinical trial design, biostatistics and clinical coordinating center management, asthma clinical management and research in adults and pediatrics, bioethics, and other areas of expertise as needed.  Because the Board serves as an independent group advisory to the NHLBI, study investigators will not communicate with Board members regarding study issues, except as authorized by PRC Executive Secretary.  The PRC will evaluate protocols proposed by the SC based on the significance of the questions to be addressed, scientific merit and innovation of the experimental design and approach, feasibility, appropriateness for the Network and consistency with NHLBI missions and policies.  The PRC will provide a written critique of each proposal and a final recommendation to the NHLBI.   All study protocols performed by PETAL will be recommended by the PRC and approved by the NHLBI before initiation. 

An independent Data and Safety Monitoring Board (DSMB) will be appointed by the Director, NHLBI to provide overall monitoring of study performance, interim data, and safety issues.  An NHLBI scientist, other than the NHLBI Program Scientists, shall serve as Executive Secretary to the DSMB.

Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

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 Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

Funds budgeted for capitation reimbursement to CC and salary for SC chair will be restricted for these purposes.

3. Reporting

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. 

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 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)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Phone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

Scientific/Research Contact(s)

Andrea L. Harabin, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0222
Email: andrea.harabin@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)

Gayle Jones
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0140
Email: jonesgt@nhlbi.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 Parts 74 and 92.


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