Frequently Asked Questions for New Approaches to Non-Viral Systems for Gene Transfer Applications for Heart, Lung, and Blood Diseases (R21/R33)

Questions for September 2007-2008

1. What is an R21/R33 grant mechanism?
2. What are the advantages of the combined R21/R33 Phased Innovation Award application?
3. What is the Budget and period of support?
4. When will the application be considered Non-responsive?
5. Do I need Preliminary data?
6. What should the milestones cover?
7. How will the application score be assigned?
8. SPECIFIC INSTRUCTIONS FOR PREPARING A COMBINED R21/R33 PHASED INNOVATION AWARD APPLICATION
9. What are the receipt dates for this PAR?
10. Is a letter of intent required?
11. If my application is not funded, can I submit an amended application?
12. Can an institution outside of the United States apply?
13. Can an application have a subcontract to Foreign Institutions?
14. Regarding eligible institutions, are Canadian and Mexican Universities/research centers considered as “foreign”?
15. How will NHLBI decide which applications to fund?
16. Who convenes the review committee?
17. Contact Information

Q: What is an R21/R33 grant mechanism
A: For the purposes of this PAR the R21/R33 grant mechanism is a phased innovation award mechanism that has an initial milestone-driven exploratory/feasibility “proof of concept” studies (R21 phase) followed by a transition to an expanded development  (R33 phase). Applicants will submit a single application organized into two phases, beginning with discussion of the R21 phase followed by discussion of the R33 phase.
The R21 phase must include:

• Well defined, preferably quantifiable performance targets (milestones) useful for judging the success of the proposed research, as well as a credible plan for development of technology in the R33 phase. 
• The Phased Innovation Award must have a section labeled Milestones at the end of the R21section of the Research Plan. This section must include well-defined objective performance targets (milestones) for completion of the R21 Phase/part of the application, a discussion of the suitability of the proposed milestones for assessing success of the R21 phase work, and a discussion of the implications of successful completion of these milestones for the proposed R33 study.
• The R21phase should demonstrate proof of concept that can be implemented for the R33 developmental phase.

The R33 phase must include: 

• A description of what will be accomplished to support the innovative exploratory and development research initiated under the R21 phase.
• Transition from R21 to R33 phase.

• Successful completion of R21 aims.

• Well defined milestones that will be accomplished in this R33 phase.
• The R33 defined milestones should reflect the next step of this phased innovation award (transition to an expanded development) 

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Q: What are the advantages of the combined R21/R33 Phased Innovation Award application?
A: The combined R21/R33 Phased Innovation Award application offers two advantages over the regular application process:         

• Single submission and review of both the R21 and R33 Phases as one application.
• Minimal or no funding gap between R21 and R33 phases.

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Q: What is the Budget and period of support?
A: The combined R21/R33 award is limited to five years in duration and neither the R21 phase nor the R33 phase can be longer than three years.

• R21 phase: Direct costs are limited to a maximum of $250,000 per year.
• R33 phase: Direct costs are limited to less than $500,000 per year.

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Q: When will the application be considered Non-responsive?
A: Applications that address the following: for example

• Cancer studies
• Viral vectors
• Phase-III Clinical trials
• RNAi-based methods using viral vector delivery
• R33 application alone
• Application without a plan for sharing data and model organism resource sharing plan

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Q: Do I need Preliminary data?
A: Preliminary data are not required for R21/R33 phased innovation applications. However, a compelling rationale for the proposed work is needed. 

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Q: What should the milestones cover?
A: The Milestones should provide well described objective performance targets, quantifiable if appropriate, with scientific justifications.  They should not be simply a restatement of the specific aims.  Discuss the milestones relative to judging the success of the R21 phase and their implications for R33 Phase.  If the application is fundable, the milestones will be reviewed and discussed by the Program Officer with the applicant.

The R21 section of the Research Plan must end with a section on objective performance targets (Milestones), quantitative if appropriate; to help evaluate the success of Phase I work after its completion.

If a copy or copies of a prototype will be needed for placement in one or more sites for pre-clinical or clinical testing, include a clear written justification for the funds requested in the Budget Justification Section, and make written reference to this instruction.

The transition from R21 funding to award of R33 funds will be based on program priorities, on the availability of funds and on successful completion of the R21 aims, including negotiated objective performance targets (milestones), as determined by NHLBI staff in the context of peer review recommendations.

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Q: How will the application score be assigned?
A: The R21/R33 application will be assigned a single priority score.  As discussed in the ADDITIONAL REVIEW CRITERIA section, the initial review panel has the option of recommending only the R21 phase for support. A Phased-Innovation Award application with a poorly prepared R33 plan  may not be recommended for support for the R33 phase or if the presentation of milestones are not sufficiently rigorous for proper validation of the R21 progress.. Thus clarity and completeness of the R21/R33 application with regard to milestones and specific goals for each phase are critical.

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SPECIFIC INSTRUCTIONS FOR PREPARING A COMBINED R21/R33 PHASED INNOVATION AWARD APPLICATION:

An R21/R33 application must include specific aims that are relevant to each phase and include objective performance targets (feasibility milestones) that would justify transition to the R33 phase.  Applications must include a specific section labeled Milestones following the Research Plan for the R21 phase.  Milestones should describe objective performance targets--preferably
quantifiable and scientifically justified, and not simply restate the R21 specific aims.  Discuss the suitability of the proposed milestones as targets against which to measure R21 progress, as well as the implications of their successful completion for the R33 phase.  List this section in the Table of Contents as "Milestones."  Applications lacking this information, as determined by NHLBI program staff, may be returned to the applicant without review.  For funded applications, completion of the R21 objectives as presented in a progress report with data on how well the milestones were met will elicit an NHLBI expedited review that will determine whether or not R33 funding should be awarded.  The release of R33 funds will be based on program priorities, availability of funds, and successful completion of Phase I objectives and results of the negotiated milestones.  The expedited review may result in additional negotiations of award.

The R21/R33 Phased-Innovation Award application must be submitted as one application with one Face Page, and with its Research Plan clearly organized into two phases of work.  To accomplish a clear distinction between the two phases, applicants are directed to complete a two-phase Research Plan.  Complete Sections a-d of the Research Plan for the R21 Phase 1, including a Milestones section, and Sections a-d for the R33 Phase II plan.  It is not necessary to repeat information, e.g., there may be little or nothing more to add to the R33 Section b. Background and Significance; likewise R33 Section c. Preliminary Studies/Progress Report, is prospective.  The Form 398 Table of Contents should be modified to show Sections a-d for each phase as well as the R21 milestones.  There is a page limit of 25 pages for the composite a-d text, i.e., Sections a-d and milestones for the R21 and Sections a-d for the R33 phase must be contained within the 25 page limit.

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Q: Is a letter of intent required?
A: No, but it helps the Institute staff to plan the review. Applicants are encouraged to send a letter of intent, which must be received by August 12, 2007 or August 12, 2008 and which should include the following information:

• Descriptive title of proposed research
• Name, address, and telephone number of the Principal Investigator
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

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Q: What are the receipt dates for this PAR?
A: Contingent on the availability of funds and programmatic priorities, the anticipated receipt dates for this initiative are September 12, 2007, and September 12, 2008.

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Q: If my application is not funded, can I submit an amended application?
A: Yes, an amended application will be accepted for applications submitted on the first or second receipt dates. Applications submitted on the first receipt date (September 12, 2006) may submit an amended application to either the second (September 12, 2007) or third (September 12, 2008) receipt dates. Applications first submitted on the second receipt date (September 12, 2007 may submit an amended application on the third receipt date (September 12, 2008).

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Q: Can an institution outside of the United States apply?
A: Yes, institutions from foreign countries are eligible to apply. Several special provisions apply to applications submitted by foreign organizations: Charge back of customs and import fees is not allowed. Format: every effort should be made to comply with the format specifications, which are based upon a standard US paper size of 8.5" x 11." Funds for up to 8% administrative costs (excluding equipment) can now be requested (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-028.html) Organizations must comply with federal/NIH policies on human subjects, animals, and biohazards. Organizations must comply with federal/NIH biosafety and biosecurity regulations. See Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award." Proposed research should provide a unique research opportunity not available in the U.S.

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Q: Can an application have a subcontract to Foreign Institutions?
A: Yes.

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Q: Regarding eligible institutions, are Canadian and Mexican Universities/research centers considered as “foreign”?
A: Canadian and Mexican institutions are considered to be foreign with respect to submitting an application in response to this solicitation. A foreign institution is defined as “an organization located in a country other than the United States and its territories that is subject to the laws of that country, regardless of the citizenship of the proposed PI.” This is defined in the Glossary Section of Part I of the NIH Grants Policy Statement, dated 12/03, and located on the Internet at address: http://grants1.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part2.htm#_Toc54600040.

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Review

Q: How will NHLBI decide which applications to fund?
A: The decision to fund will be based on three criteria: the scientific merits of the projects described within an application, the availability of funds, and program priorities. These decisions are made at two levels of review. In the first level of review, applications are evaluated for scientific merit by a tailored committee known as a Special Emphasis Panel, or SEP. This committee is composed of scientists and clinicians, like you. The committee is tasked with the difficult job of stratifying the responsive applications by assessing their scientific merit.

The committee’s critiques are incorporated into summary statements that are then made available to both the applicants and members of the National Heart, Lung, and Blood Advisory Council (NHLBAC). In addition to identifying the strengths of applications, the SEP is also asked to identify deficiencies/weaknesses of the various applications so that applicants may use these critiques if they choose to resubmit an amended application.

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Q: Who convenes the review committee?
A: The Scientific Review Administrator (SRA) assigned to the review is responsible for selecting and recruiting the consultants that comprise the Special Emphasis Panel. Global areas of expertise, as well as specific project needs are also considered.

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For further information contact:
Pankaj Qasba, Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
Bethesda, MD 20892
Telephone: (301) 435-0055
FAX: (301) 480-0867
Email:qasbap@nhlbi.nih.gov

Sonia I. Skarlatos, Ph.D., FAHA 
Acting Director
Division of Cardiovascular Diseases
NHLBI Gene Therapy Coordinator
National Heart, Lung and Blood Institute
Tel: 301-435-0477
Fax: 301-480-7971
Email: skarlats@nhlbi.nih.gov

Susan Banks-Schlegel, Ph.D.
Division of Lung Diseases
National Heart, Lung and Blood Institute
6701 Rockledge Drive
Rockledge II, Room 10220
Bethesda, MD 20892-7952
Tel: 301-435-0202
Fax: (301) 480-0202
Email: schlegels@nhlbi.nih.gov

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Last update: July 9, 2007