NOTICE OF LIMITED COMPETITION REQUEST FOR COMPETING APPLICATIONS: NHLBI 
PROGRAMS OF EXCELLENCE IN GENE THERAPY FOR HEART, LUNG AND BLOOD DISEASES

RELEASE DATE:  April 23, 2004
 
NOTICE: NOT-HL-04-110

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

APPLICATION RECEIPT DATE:  October 21, 2004

The NHLBI is requesting competing renewal applications from the four NHLBI 
Programs of Excellence in Gene Therapy (PEGTs) 
(http://www.med.cornell.edu/pegt/).  These programs were awarded as 
a result of Request for Applications (RFA) HL-00-008, 
Programs of Excellence in Gene Therapy 
(http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-00-008.html).  
This re-competition will continue to facilitate clinical gene therapy studies 
and provide unique ongoing resources and education 
programs to the NHLBI investigators for a one time renewal cycle.

The following four activities in the PEGTs will be emphasized in the renewal 
period:

o   Preclinical projects to facilitate the translation of gene therapy into 
clinical studies

o   Clinical Phase I/II studies to test safety and efficacy of gene therapy 
studies in cardiovascular, pulmonary and hematological disorders

o   National Cores to provide resources and services to NHLBI-supported 
investigators at no cost

o   Training positions in clinical projects to train MD,MD/PhD and PhD 
scientists in conducting gene therapy clinical trials

Each PEGT must provide a multidisciplinary structure that will coordinate 
activities between basic science investigators and clinicians in order to enable 
the translation of basic research to clinical application.  

Preclinical Projects: Each PEGT must consist of preclinical projects that will 
generate sufficient data to support the movement of the project to the next clinical 
phase.  For example: 1) experiments addressing the safety and evaluation of the 
vector and the toxicity of the expressed protein(s); 2) experiments verifying that 
the administration route successfully transports the gene of interest to the target 
site; 3) experiments evaluating the immune response against the gene therapy product; 
and 4) experiments evaluating the biodistribution of the gene of interest.

Clinical Projects: Each PEGT must have two or more clinical projects (Phase I and/or 
Phase II studies).  Clinical projects that were initiated and supported as 
preclinical projects during the previous award cycle and not completed are expected 
to be included in the competing renewal application.  If previous clinical studies 
were completed or terminated, new clinical studies may be proposed.  Clinical 
projects can be proposed as preclinical studies in years 06 and/or 07 in order to 
meet the requirements for an Investigational New Drug (IND) application prior to 
initiating the clinical studies.  However, by the beginning of year 08, these 
clinical projects must plan to initiate Phase I and/or Phase II clinical studies.  
Phase III studies will not be considered.  Foreign collaborations for clinical 
studies may be included if they have fulfilled all the regulatory requirements as 
required in the United States ie. IRB, IBC, DSMB, RAC and OHRP.

National Cores: All National Cores should continue in this new cycle.  However, if 
investigators do not wish to continue a specific National Core due to the lack of 
interest from the community, they may propose a new National Core with prior approval 
from NHLBI.  Each National Core must be submitted as a separate section with its own 
budget.  The progress report section should include a description of all the services 
performed in the previous cycle with a detailed budget for these services.  If the 
PEGT has a similar core for the PEGT itself, it is not considered a National Core and 
should only be included in the PEGT local Core section.

Training Program: Each PEGT must have two clinical training positions associated with 
the proposed clinical trials.  Trainees will be supported by the PEGT for up to two 
years at which time the trainees will be expected to apply for other support.  The 
National Cores may propose courses and training in state of the art gene transfer 
technology.  

All PEGTs may compete for the “Administrative Coordinating Center” (ACC) that 
replaces the “Data Coordinating Center”.  This must be submitted as a separate 
application from the PEGT application.  The ACC will maintain the PEGT website, 
manage and administer the service requests for the National Cores and arrange 
meetings such as Steering Committee meetings, Grantees’ meetings and NHLBI Data and 
Safety Monitoring Committee meetings.  

MECHANISM OF SUPPORT

The PEGTs use the cooperative agreement (U01) administrative and funding mechanism of 
support.  Under the cooperative agreement, the NIH assists, supports, and/or 
stimulates, and is substantially involved with recipients in conducting a study by 
facilitating performance of the effort in a "partner" role.  Details of the 
responsibilities, relationships, and governance of a study funded under this 
cooperative agreement will be the same as in the current terms and conditions of the 
award.  Organization, Operation, and Oversight, as well as Terms and Condition of 
award remain unchanged from the original RFA
(http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-00-008.html).

The total project period for an application submitted in response to this Notice may 
not exceed five (5) years.  This program will end as of August 31, 2010.  No renewal 
of the program will occur.  The anticipated award date is September 1, 2005.

FUNDS AVAILABLE

The NHLBI intends to commit approximately $14 million total costs per year to support 
4 Programs of Excellence in Gene Therapy (PEGT), 6 National Cores, and 1 
Administrative Coordinating Core. 

The Programs of Excellence in Gene Therapy (PEGT) applicants may request a project 
period of 5 years.  The requested budget for each PEGT should include direct costs 
and associated facilities and administrative (F&A) costs and may not exceed 10% over 
the total costs awarded in the year 05 budget.    

The National Core applicants may request a project period of 5 years.  The requested 
budget for each National Core should include direct costs and associated facilities 
and administrative (F&A) costs and may not exceed 10% over the total costs awarded in 
the year 04 budget.   

The Administrative Coordinating Core (ACC) must request a project period of up to 5 
years.  The requested budget for the ACC should include direct costs and associated 
facilities and administrative (F&A) costs, and the cost for the biannual NHLBI Gene 
Therapy DSMB meetings.  The total costs for this budget may not exceed $500 thousand 
per year.

A composite budget representing all components for the entire project period is 
required.  Budget Form pages 4 and 5 of PHS Form 398 should be completed for each 
component listed in the composite budget.  A separate budget is required for each 
pre-clinical, clinical, local core, national core and any subcontracts.  The budget 
pages must be clearly labeled as to which component activity they address.  
Applicants should provide adequate budget justification, and all applicable direct 
costs, and facilities and administrative (F&A) costs.  In addition, the utilization 
relationships between research projects and any cores that serve those projects 
should be presented.

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  Applications must have a DUN and Bradstreet 
(D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when 
applying for Federal grants or cooperative agreements.  The DUNS number can be 
obtained by calling (866) 705-5711 or through the web site at 
http://www.dunandbradstreet.com/.  The DUNS number should be entered on line 11 of 
the face page of the PHS 398 form.  The PHS 398 document is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format.  
For further assistance contact Grants Info, Telephone (301) 435-0714, Email: 
GrantsInfo@nih.gov.
 
SUPPLEMENTAL INSTRUCTIONS: Only competing renewal applications which were funded as 
part of RFA HL-00-008, Programs of Excellence in Gene Therapy for Heart, Lung and 
Blood Diseases will be considered.  For each clinical study, there must be a 
timeline, a detailed monitoring plan and a copy of all RAC communications, IRB and 
IBC communications or approvals and pre-IND or IND number. 

For every application, Item 2 on the Face Page should be checked "Yes"; after 
"Number:" enter "NOT-HL-04-104" and after "Title:" enter "Competing Applications for 
PEGTs".

SENDING AN APPLICATION TO THE NIH: 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
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application plus all five 
collated sets of appendix material must be sent to:

Chief, Review Branch
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924
Bethesda, MD 20817 (for express/ courier service)
Telephone: 301-435-0270
FAX:  301-480-0730

APPLICATION PROCESSING: Applications must be received on or before the 
application receipt date listed in the heading of this Notice.  If an application is 
received after that date, it will be returned to the applicant without review. 

Although there is no immediate acknowledgment of the receipt of an 
application, applicants are generally notified of the review date within 8 weeks.
 
PEER REVIEW PROCESS 

Applications that are complete will be evaluated for scientific and technical merit 
by an appropriate peer review group convened by the NHLBI in accordance with the 
process stated below. 

PROGRAMS OF EXCELLENCE IN GENE THERAPY APPLICATIONS
 
Each project will receive a priority score.  The scientific merit of each preclinical 
and clinical project will be evaluated using the standard review criteria 
(Significance, Approach, Innovation, Investigator, and Environment).  

Each core (except the National Cores) will be Recommended or Not Recommended based on 
whether the core is essential to the program and has the capability to fulfill the 
proposed function.  Reviewers will evaluate the number of projects serviced by the 
core; strengths and weaknesses of the proposed approaches, resources, and 
interactions; and whether the investigators are qualified for their role(s). 

Each National Core will be assigned a priority score using the review criteria listed 
below; this score will have no effect on the overall score of the application.

REVIEW CRITERIA FOR A PEGT APPLICATION

1)  Scientific merit of the preclinical and clinical projects, including the progress 
and proposed plans.

2) Multidisciplinary nature of the proposed studies, the coordination and synergy 
between basic and clinical researchers, and the likelihood that the application will 
enable the translation of basic research to clinical application.

3) Quality of the training program, including whether the trainees have been 
adequately trained, and whether there are plans for assessing the quality and benefit 
of the educational opportunities offered.

4) Access to patients for collaborative clinical research, and demonstrated 
willingness of the investigators to work as part of the collaborative clinical 
research component with the NHLBI Project Scientist.

REVIEW CRITERIA FOR NATIONAL CORES

National Cores will be evaluated as to the services provided and their accessibility 
to NHLBI-supported investigators.  The evaluation of each National Core includes the 
following: 

1) Significance: Does the National Core address an important area, and have the 
potential to provide an impact?

2) Progress: Have the services and/or resources produced by this Core been beneficial 
to the scientific community?

3) Plans: Are the proposed plans adequately developed and feasible?   Are the plans 
for assessing the quality and benefit of these services and/or resources reasonable? 

REVIEW CRITERIA FOR THE ADMINISTRATIVE COORDINATING CENTER

1) Quality of the plans for coordination and collaboration of the activities with 
NHLBI Gene Therapy by setting up meetings for the Programs of Excellence in Gene 
Therapy (including activities of the Steering Committee, NHLBI Gene Therapy Data 
Safety and Monitoring Board, and Grantees’ Meeting); the adequacy of the proposed 
plan to organize communications within the program via websites, e-mail listserves, 
and conference calls.

2) Quality of the administrative, supervisory, and collaborative arrangements for 
achieving the goals of the program, including willingness to cooperate with the 
participating Centers and the NHLBI; quality of the proposed organizational structure 
and management plan.

3) Availability of the facilities and equipment to effectively
coordinate the activities of the Programs in Excellence in Gene Therapy, and assist 
customers in providing National Core services.

ADDITIONAL REVIEW CRITERIA FOR ALL APPLICATIONS: In addition to the above criteria, 
the following items will be considered in the determination of scientific merit and 
the priority score:

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human subjects 
and protections from research risk relating to their participation in the proposed 
research will be assessed.
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of plans to 
include subjects from both genders, all racial and ethnic groups (and subgroups), and 
children as appropriate for the scientific goals of the research.  Plans for the 
recruitment and retention of subjects will also be evaluated.

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to be used 
in the project, the five items described under Section f of the PHS 398 research 
grant application instructions (rev. 5/2001; updated 09/09/2003) will be assessed.

BUDGET:  The reasonableness of the proposed budget and the requested period of 
support in relation to the proposed research.

AWARD CRITERIA

Factors that will be considered in making awards include: 

o Scientific merit (as determined by peer review)  
o Availability of funds  
o Programmatic priorities.

SCHEDULE

Application Receipt Date: October 21, 2004
Peer Review: February - March 2005
Council Review: June 16, 2005
Start Date: September 1, 2005

INQUIRIES

o Direct your questions about scientific/programmatic issues to:

Sonia I. Skarlatos, Ph.D.
Deputy Director
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
Rockledge II, Room 9158
6701 Rockledge Drive
Bethesda, MD 20892-7940
Telephone: (301) 435-0477
FAX: (301) 480-7971
email: skarlats@nhlbi.nih.gov

o Direct your questions about peer review issues to:

Chief, Review Branch
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924
Bethesda, MD 20817 (for express/ courier service)
Telephone:  301-435-0270
FAX:  301-480-0730

o Direct your questions about financial or grants management issues to:

Ms. Vicki Maurer
Grants Operations Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Rockledge II, Room 7164, MSC 7926
6701 Rockledge Drive
Bethesda, MD 20892-7926
Telephone: (301) 435-0185
FAX: (301) 480-0422
email: maurerv@nhlbi.nih.gov

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