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 Centers (CC) 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.
  • June 3, 2013 - See Notice NOT-HL-13-182. Notice of Correction to the Research Approach, R and R Budget & PHS 398 Research Plan Sections of this FOA.

Funding Opportunity Announcement (FOA) Number

RFA-HL-14-014

Companion Funding Opportunity

RFA-HL-14-015, 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 Clinical Centers (CC) 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 CCs and 1 Clinical Coordinating Center (CCC).  The Network will develop and conduct at least 3-5 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).  Each CC will be expected to enroll 220 patients over 5.5 years.  This FOA solicits applications for CCs and runs parallel with a separate FOA for the CCC (RFA-HL-14-015

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 Network) will develop and conduct randomized controlled clinical trials to prevent or treat, and/or improve the outcome of patients with, or who are at risk for, Acute Lung Injury (ALI) or the Acute Respiratory Distress Syndrome (ARDS). PETAL will be comprised of approximately 11 Clinical Centers (CC) and 1 Clinical Coordinating Center (CCC), which will be requested by a separate FOA.  More than 1 trial will be conducted simultaneously, and it is expected that at least 3-5 trials will be completed during the course of the award. Awards are expected to be for 7 years.  The CCs will work collaboratively to select, design, and conduct the trials.  Each CC is expected to recruit 220 patients over 5.5 years.

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 using multidisciplinary approaches and studies of pre-ICU factors that will permit early identification and intervention in the emergency department 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 department (ED) physicians, trauma, sepsis, surgery, hospitalist, or infectious disease that will facilitate early access to eligible patients. 

The scope of Network studies may 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 remain 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 clinically meaningful, such as 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 permitted.

The Network is expected to develop and participate in a collaborative, 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 the 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. 

Research Approach

The CCs will each include 1 (and only 1) other satellite recruiting institution that will participate in enrollment and study conduct but not on the Steering Committee (SC).  Each CC is expected to enroll a total of 220 patients over 5.5 years of recruitment (years 2 through 7).

The CCs will be expected to work closely with the CCC to participate intellectually in all aspects of the Network, including developing Network procedures and sub-committees, proposing and developing ideas for clinical trials, development of a collaborative IRB process, writing protocols and sample informed consent, protocol cost development, recruitment, and potentially serve as protocol PD/PI. The CC PD(s)/PI(s) will be expected to propose and conduct sub-studies and participate fully in Network committees.  CC PD(s)/PI(s) will be expected to develop regular communication within his/her CC staff, including investigators and clinical coordinators to discuss enrollment, screening, adherence to protocols, and other Network issues. 

Protocols will be selected and written by the 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, and the CCC and NHLBI.  The Network will be expected to consider protocol ideas from the wider critical care community engaged in 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.

In addition to the funds awarded directly to the CCs, protocol funds to conduct clinical trials (approximately $39 million over 6 years) will be part of the CCC’s grant award and will be distributed by the CCC to the Clinical Centers in accordance with protocol budgets (see RFA-HL-14-015). 

CCs will be responsible for the planning and collection of 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 scientific 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.

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

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.  Acute lung injury has several etiologies, and it is unknown whether different at-risk patients (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 and 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 transfusions strategies or changes in antibiotic management may need to be applied early to prevent acute lung injury. Although the focus of this program is on prevention and early treatment of acute lung injury, high priority studies of novel strategies for treating established ALI and ARDS still will be permissible. Studies that could optimize treatments for ALI/ARDS of different etiologies would be appropriate. There will be latitude to propose and conduct clinical protocols that answer other significant questions that affect ALI/ARDS patients.  

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. 

NHLBI intends to fund up to 11 awards for this program, with an estimated $29 million (Total Costs) over a 7-year period.

$1,610,000 (Total Costs) will be awarded in FY 2014 for up to 11 Clinical Centers.

Award Budget

Application budgets are limited to $93,841 (Direct Costs) for the first year and a maximum of $267,839 (Direct Costs) in each of the subsequent years (years 2 through 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.

This FOA requires two key investigators of different specialties (critical care and other) who may be designated multiple PDs/PIs.  If the multiple PD/PI structure is not used, the PD/PI must be an Intensive Care Unit clinician-investigator. The second investigator will be from a different specialty such as emergency medicine, surgery, anesthesia, or other that ensures and provides early access to patients at risk for lung injury. 

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 NHLBIHR-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  NHLBIHR-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
Division of Extramural Research Activities  
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
Telephone: (301) 435-0270
FAX: (301) 480-0730
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, with the following additional instructions:

Each CC is expected to include two Institutions, a primary site (the PD(s)/PI(s) institution) and one satellite recruiting site.

SF424(R&R) Other Project Information

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

Facilities and Other Resources: Institution descriptions should include information about the intensive care units (for example, open/closed, numbers of beds, staffing model, screening ability) and a description of the emergency department (ED) or the other clinical service that will facilitate early identification of patients at risk for, or with, ALI/ARDS.

Other Attachments: Provide the following information as a single PDF file with the name “(PD/PI name) PETAL.pdf.”

SF424(R&R) Senior/Key Person Profile

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

This FOA requires two key investigators of different specialties (critical care and other) who may be designated multiple PDs/PIs. If the multiple PD/PI structure is not used, PD/PI must be an Intensive Care Unit (ICU) clinician-investigator; the second key investigator (who may be designated as a  PD/PI) is expected to be from a different specialty such as emergency medicine, surgery, anesthesia, or other that ensures and provides early access to patients at risk for lung injury.

R&R Budget

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

Clinical Center Budget: The CC budget consists of core support only and is expected to cover the effort required for Network participation, including regular teleconferences for protocol development and other Network committees including regular SC conferences, CC group meetings, and activities related to IRB approval and updates, manuscript preparation, and travel costs for in-person meetings.

The first year budget should be lower than subsequent years.  In year 1, core support is expected to consist of the following:  the two key investigators are expected to devote a total of 3 person months (25% full-time professional effort) (combined) with one clinical coordinator at 3 person months (25% full-time professional effort).  When patient recruitment begins (years 2-7), coordinator effort may increase to 12 person months (100% full-time professional effort). A budget may be proposed for the satellite recruiting center including 1.2 person months (10% full-time professional effort) and up to 3.6 person months (30% full-time professional coordinator effort). 

Effort needed for protocol execution should NOT be included here.  Protocol effort will be a part of protocol budgets reimbursed by the CCC as recruitment occurs. One page sample protocol budgets which include effort for proposed protocols will be provided as an attachment as described above.

As each CC application requires one (and only one) satellite recruiting site, the application should use the traditional subcontract model. 

Other costs may include a travel budget for two SC meetings (2 days, 1 night) per year for two investigators.  Year 1 and Year 5 should include one additional meeting for an international research priorities workshop that will be organized by the CCC in conjunction with the SC and NHLBI.   Applicants may budget for one trip per year for one research coordinator and one trip per year for one junior faculty member.  Modest administrative support and supply budget may be proposed.

Clinical Protocol Budget: A one-page budget for each protocol must be provided in the SF 424 (R&R) Other Project Information form. A spreadsheet rather than the SF 424 budget page forms should be used and a format is suggested below.  The budget should indicate the total direct costs of implementing the protocol on a per patient basis.  This should include separate entries for estimated hours for enrollment (screening and consent) for PD/PI and coordinator, estimated hours for protocol implementation and data collection, and clinical costs (including tests, drugs, supplies) required for research protocol that are not a part of usual care.  If limited biospecimens are required by the protocol, the costs of obtaining and shipping them to CCC biorepository, as well as the estimated cost of analyzing the specimens should be included in a line item.  Costs associated with equipment that may be unique to the proposed protocol should also be provided as a line item. A format with some of the suggested elements is below; details will depend on the protocol proposed and may likely not include all elements.

Suggested format for Clinical Protocol Budget:

PROCEDURE

Investigator effort (hrs)

Coordinator effort (hrs)

Other clinicians (hrs)

Screening

Consent

Day 1 Launch

Protocol execution

Data collection and QI

CRF review

Specimen handling

SAE reports

AE reviews

IRB communication

TOTAL hrs

Salary

Salary x Hours

OTHER:

Equipment

Protocol specified tests

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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 traditional Research Strategy, with the usual headings, the application should use the following two subsections:  

Subsection 1:  Clinical Center Organization and Recruitment plan (maximum 4 pages).

Subsection 1 should describe the organizational plan for the CC.  This will include:

 (a) A description of the roles of the Critical Care physician and the second key clinician-scientist who will assure early access to patients with, or at risk for, ALI/ARDS who may be designated co-PD(s)/PI(s).  The required second key investigator may be employed by the satellite recruiting site but does not have to be. This FOA requires two key investigators of different specialties (critical care and other).

(b) A description of the one satellite site including leadership and research nurse coordinator support.  Previous collaborations/interactions should be described. 

(c) A discussion of the challenges and solutions to early identification of appropriate patients.  Importantly, the application should describe plans to capture patients at-risk for ALI/ARDS from other departments and transfer to ICU. 

(d) A description of a plan for regular communication within the CC to include coordinators.   Describe methods and frequency for communication and review of screening and recruitment.

(e) A narrative to defend ability to enroll 40 patients/year.  Experience in other clinical trials, ICU and ED capacity and staffing may be part of this narrative. (Detailed description of experience in critical care clinical trials will be provided as an attachment as described above in the SF 424 (R & R) Other Project Information section.)  Applicants that do not have prior experience enrolling critically ill patients at the projected rate should describe plans to meet the target enrollment goals.  This could include documenting volume of ED admissions with an estimate of the proportion of patients at risk for ALI. Institutions that are tertiary referral centers should discuss the challenges and solutions regarding capturing eligible patients early or before the development of ALI.

Subsection 2:  Clinical Trial Proposals (maximum 4 pages each)

Propose TWO network clinical research trials in patients with, or at risk for, ALI/ARDS that have the potential for improving clinical outcomes of critically ill patients.  At least one proposal should address prevention of ALI/ARDS in an at-risk population, early treatment or a trial that highlights the two disciplines represented by the PD(s)/PI(s). 

Each clinical trial proposal should include the hypotheses or questions to be addressed, background, rationale, and significance of the anticipated results, preliminary data, patient group to be studied, the number of patients per group, the interventions and methods (including power and statistical analysis of endpoint to be studied).  Clinically meaningful endpoints are expected.  If the end point is other than mortality, the significance to heart, lung, and blood disorders should be explained.  Although mechanistic studies are not expected to be conducted within the PETAL Network, if the proposed clinical protocol requires a protocol-specific clinical test or blood or tissue sample, these should be described.

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 and departmental (ICUs, ED, etc.) and institutional support letters indicating willingness to participate in PETAL clinical trials as a single PDF file with the name “(PD/PI name) PETAL.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, with the following modifications: 

Clinical data collected by the CCs will be deposited with the CCC which will be responsible for adhering to the NIH data sharing policy.

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.

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? 

Do the trials proposed address important clinical problems?

Does completion of the proposed clinical trials have the potential to improve outcomes for patients with, or at risk, for ALI/ARDS and respiratory failure change concepts, method, or treatment for prevention?   

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?

Do the PD(s)/PI(s) have experience conducting clinical trials in critically ill or at risk patients? 

Do the PD(s)/PI(s) have a track record of working together? 

Do the PD(s)/PI(s) have history of working on collaborative projects?

Does the applicant have a research coordinator identified by name and is there a track record of working together and achieving successful recruitment?

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?

Does the clinical trial address an important question that has not been asked before?  

Were novel clinical trial designs proposed?   

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

Are the clinical trials feasible from ethical, organizational, and budgetary perspectives? 

Are the trials proposed adequately powered and feasible? 

Were efficient clinical trial designs proposed?

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?

Does the plan for recruiting patients at-risk or early in the course of critical illness propose feasible and effective approaches to overcome this challenge?  

Is the plan for capturing and transferring at risk patients within the hospital or from another hospital for tertiary care centers feasible and efficient?

If a center is a tertiary center, have barriers and solutions to early recruitment been described?

Do the applicants demonstrate a high likelihood of achieving recruitment goals?   

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?

Do the PD(s)/PI(s) have a good communication and collaboration plan between themselves AND the research coordinator to review screening practices?

Have the leaders of clinical units to be used for patient recruitment provided letters stating commitment to enrolling in PETAL trials?   

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 Councill. 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 PD(s)/PI(s) of the CC will have the primary responsibility for all aspects of the PETAL studies, including proposing protocols, participating in their development, preparing protocol budgets in collaboration with the CCC, modifying proposals if indicated, leading studies, recruiting study participants, conducting the research, assuring quality of study participant care and protocol adherence, assuring the accurate and timely transmission of data collected to the CCC, analyzing and interpreting data, and preparing publications. 

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 and sharing 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 project scientist (PS) will participate in SC 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 SC and 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 SC.

The NHLBI reserves the right phase out a PETAL study (or an individual award) in the event of (1) failure to develop or implement mutually agreeable collaborative protocols; (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 each Clinical Center 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 SC.  Two investigators from each site and the Clinical Coordinating Center (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 CCC, 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’s two PD(s)/PI(s) (one with expertise in critical care, one with expertise in emergency medicine or some other specialty with early access to patients) are expected to participate in all SC meetings, each Clinical Center has 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 may be involved in reviewing and prioritizing protocol ideas for significance.  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 Program Scientist, and scientists with expertise in clinical trial design, biostatistics and CCC management, critical care, 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 Scientist, will serve as Executive Secretary to the DSMB.

Members of the SC will be required to accept and implement policies approved by the SC.

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 SC 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.

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.HarabinA@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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