Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
National Heart, Lung, and Blood Institute (NHLBI), (http://www.nhlbi.nih.gov)

Title: Phase II Clinical Trials of Novel Therapies for Lung Diseases (U01)

Announcement Type
New

Update: The following update relating to this announcement has been issued:

Looking ahead: As part of the Department of Health and Human Services' implementation of e-Government the NIH will gradually transition each research grant mechanism to electronic submission through Grants.gov and the use of the SF 424 Research and Related (R&R) forms. For more information and an initial timeline, see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-06-035.html. NIH will announce each grant mechanism change in the NIH Guide to Grants and Contracts (http://grants.nih.gov/grants/guide/index.html).

Request For Applications (RFA) Number: RFA-HL-10-003

Catalog of Federal Domestic Assistance Number(s)
93.838, 93.233

Key Dates
Release Date: February 23, 2009
Letters of Intent Receipt Date(s): May 18, 2009, December 30, 2009, and August 15, 2010
Application Receipt Dates(s): June 18, 2009, January 29, 2010, September 15, 2010
Peer Review Date(s): October 2009, June 2010, and January 2011
Council Review Date(s): January 2010, August 2010, and May 2011
Earliest Anticipated Start Date: April 2010, September 2010, and July 2011
Additional Information To Be Available Date (Url Activation Date): N/A
Expiration Date: September 16, 2010

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt, Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Arbitration Process
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

Purpose

The purpose of this FOA is to solicit research grant applications to conduct Phase II clinical therapeutic trials that have the potential to advance development of novel therapies for a lung disease or a cardiopulmonary disorder of sleep. Each application will propose one Phase II interventional trial that will most likely use physiological or biochemical rather than clinical endpoints along with at least one smaller basic ancillary research study that is tightly related to the clinical question. Although definitive Phase III trials will not be supported, the proposed studies must provide proof of concept for a novel intervention that has high potential for modifying current treatments and could be disease modifying.

Background

Acute and chronic lung diseases are a significant cause of mortality and morbidity in the United States, greatly affecting quality of life, as well as longevity. Many lung diseases are managed by controlling symptoms and lack proven pharmacologic or immuno-modulating treatments. Current treatments are often based on reducing inflammation or preventing cell proliferation with cytotoxic agents that have modest therapeutic efficacy and in most cases have substantial toxicities. Similarly, insufficient sleep and sleep disorders may contribute to cardiopulmonary diseases.

Novel and innovative treatments need testing in lung diseases and sleep disorders. Basic research studies in cells, tissues, and animal models, investigations of biomarkers and functional genomics have led to a better understanding of the pathogenesis of several of these diseases and suggest new ideas for treatment targets. Mechanistic insights into lung disorders suggest that already approved agents effective in other diseases (e.g., rheumatoid arthritis, diabetes, systemic lupus erythematosus) could be appropriate for treating lung diseases. Combinations of common drugs with low toxicities could be tested. Studies supported by this FOA are unlikely to be conducted by industry because of relatively small market shares, or changed or competing company priorities.

Despite the substantial progress made on identifying molecular mechanisms underlying lung diseases, there is little research supported by NHLBI for proof-of-concept, mechanistically-driven small clinical trials. These are important as they are key in translating basic research advances into clinical research, provide the foundation for larger efficacy trials, and can assist in the understanding of disease processes and perhaps disease sub-groups.

Research objectives

This program enhances opportunities for translational research with the central emphasis on clinical studies. Research conducted would provide high quality data that could lead to efficacy or Phase III trials in networks or investigator-initiated trials. Furthermore, this research will provide important pathogenetic understanding of responses to treatments. Close interaction between clinical and basic researchers required in this program should promote translation of basic science ideas into the clinical setting and expand on ideas from clinical observations that can be pursued in the basic laboratory.

Each application must propose one Phase II clinical treatment trial. In this context, Phase II trials are proof of concept studies that will most likely employ (surrogate) physiological (which can include imaging methods) or biochemical endpoints rather than mortality or major clinical endpoints. The trials should include data collection on well-characterized subjects. Novel clinical trial designs are encouraged.

Each application must also include at least one but no more than two tightly-related ancillary studies that will provide mechanistic understanding of the clinical question. The basic ancillary study can be bench-to-bedside or bedside-to-bench and will have budget restrictions (see Section II 2: Funds Available). The application must be led by the Principal Investigator of the clinical study. A separate investigator will lead each ancillary study. Co-principal investigators are encouraged in order to maximize the interaction and idea exchange. The ancillary study may be conducted by an investigator at a separate institution through a consortium agreement.

Consortia with other sites that will assist with patient recruitment are highly recommended.

Research topics: Clinical studies must include trials of novel drugs, devices, or management practices for treatment of lung diseases that will provide proof of concept or early testing for efficacy that have the potential to change clinical practice and modify disease. Where possible, the clinical trial will be a double-blinded placebo-controlled design. Given the scope of this FOA, it is most likely that appropriate physiological or biochemical endpoints rather than clinical endpoints will be used. Some examples that may or may not be feasible include but are not limited to those listed below:

Examples of ancillary studies:

Examples of research that would NOT be responsive to this FOA:

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information


1. Mechanism of Support

This funding opportunity will use the cooperative agreement (U01) award mechanism.
The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses Just-in-Time information concepts.It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award." There is no intention to renew these awards.

2. Funds Available

Future year awards will depend on annual appropriations. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size of each award will also vary. The clinical study budget is expected to be a majority of the budget. An ancillary study may not exceed $150,000 direct costs/year and the sum of two ancillary studies cannot exceed $250,000 direct costs/year. Although the financial plan of NHLBI provides support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. There will be a rigorous administrative evaluation of recruitment and scientific progress before non-competing renewals are awarded. In addition, NHLBI intends to establish a translational oversight committee who will review progress. The metrics for success and continued funding will be based on achievement of research milestones. Completion of the proposed clinical studies, new insights into disease mechanism or treatment efficacy, and progression to Phase III efficacy will constitute ultimate success of this program.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation; see NOT-OD-05-004.

NIH grants policies as described in the http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically.Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

The PI of the application must be the leader of the clinical trial. This individual should have demonstrated experience in design and recruiting into clinical studies or trials. Each ancillary study must be led by a separate individual who may be either a Co-Investigator or a Co-Principal Investigator on the the application for the phase II clinical trial network. This individual should have demonstrated expertise in the proposed field of basic science. Multiple PD/PIs are encouraged.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Resubmissions. Applicants may submit one revised application (resubmission); revised applications must include a one page introduction that addresses issues raised in the previous review (Summary Statement).

Renewals. Renewal applications are not permitted in response to this FOA.

Number of Applications. Applicants may submit more than one application, provided each application is scientifically distinct.

Applications from foreign institutions are not eligible for this program.

Section IV. Application and Submission Information


1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form, and the YES box must be checked.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PD/PIs are proposed, use the Face Page-Continued page to provide items 3a 3h for all PD/PIs. NIH requires one PD/PI be designated as the contact PD/PI for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the Contact PD/PI, et. al. The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan entitled Multiple PD/PI Leadership Plan must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts.The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Additional information is available in the PHS 398 grant application instructions.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date(s): May 18, 2009, December 30, 2009, August 15, 2010.
Application Receipt Dates(s): June 18, 2009, January 29, 2010, September 15, 2010.
Peer Review Date(s): October 2009, June 2010, and January 2010.
Council Review Date(s): January 2010, August 2010, and May 2011.
Earliest Anticipated Start Date: April 2010, September 2010, and July 2011.

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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 NIH staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Chief, Review Branch
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 7214, MSC 7924
Bethesda, MD 20892-7924 (Express zip: 20817)
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov


3.B. Sending an Application to the NIH

Applications must be prepared using the forms found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Chief, Review Branch
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 7214, MSC 7924
Bethesda, MD 20892-7924 (Express zip: 20817)
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov


3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time(of the applicant institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s) and time, the application may be delayed in the review process or not reviewed. All applications must meet the following criteria to be considered on-time:

Please visit http://era.nih.gov/electronicReceipt/app_help.htm for detailed information on what to do if Grants.gov or eRA system issues threaten your ability to submit on time.

Submission to Grants.gov is not the last step - applicants must follow their application through to the eRA Commons to check for errors and warnings and view their assembled application!

3.C.2 Two Day Window to Correct eRA Identified Errors/Warnings

IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond. As of January 25, all corrections must be complete by the due date for an application to be considered on-time. See NOT-OD-10-123.

Once an application package has been successfully submitted through Grants.gov NIH provides applicants a two day error correction window to correct any eRA identified errors or warnings before a final assembled application is created in the eRA Commons. The standard error correction window is two (2) business days, beginning the day after the submission deadline and excluding weekends and standard federal holidays. All errors must be corrected to successfully complete the submission process. Warnings will not prevent the application from completing the submission process.

Note that the following caveats apply:

3.C.3 Viewing an Application in the eRA Commons

Once any eRA identified errors have been addressed and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday Friday, excluding Federal holidays) to view the assembled application before it automatically moves forward to NIH for further processing.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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