Phased Innovation and Phased Application (R21/R33) Awards
The R21/33 (exploratory/developmental grant) mechanism is used in program announcements requesting grant applications that are expected to have a high-risk proof of principle stage followed by a second, larger, scale-up or developmental phase.
How does the R21/R33 award differ from the standard R21 or R01 grant mechanism?
The R21 phase of an R21/R33 award is limited in budget and duration and is intended to support the high-risk initial stages of a research project. In these respects it is similar to a standard R21 grant. However, the R21/R33 mechanism provides for an R21 phase that is flexible in duration (12 to 24 months) and an expedited transition to the next phase of the project supported by the R33 award. R33 awards permit larger budgets and are typically two to four years in duration. Transition from the R21 to the R33 phase depends upon the successful completion of negotiated, peer-reviewed milestones as determined by an administrative review at the NCI. In some cases, applicants are allowed to apply directly for the R33 phase, the larger developmental phase, if they can show proof of concept or demonstrate feasibility in the grant application.
Does the NCI accept R21/R33 applications on any research topic?
R21/R33 and R33 applications are accepted only in response to specific program announcements that are intended to stimulate research in particular scientific areas. The NCI currently uses this mechanism to support the development of novel technologies and instrumentation and their initial applications, biomarker and assay development and early stage clinical correlative studies.
What is the significance of the milestones in an R21/R33 grant application?
The milestones are a critical aspect of the R21/33 mechanism. Milestones are concrete, quantitative measures of success of the feasibility phase (the R21 phase) of the grant. They are not the steps you plan to proceed through (the specific aims) nor are they lofty goals you may hope to reach under ideal circumstances. They are the set of criteria by which NIH staff will judge the success of your R21 phase and make the decision as to whether or not you may proceed to the larger R33 phase of your proposed work. You may want to consult with your program director (or the contact name listed in the program announcement to which you are applying) prior to writing the milestones section of your grant application.
How are the milestones negotiated?
Your application for an R21/R33 grant must include a set of proposed milestones. Reviewers will be asked, as part of the peer review process, to review your milestones and to make comments as to whether or not they are adequate tests of the feasibility of your proposed work and to make suggestions for improvements. When you receive your summary statement, you should read the section called “critique of milestones” and contact your program director if there are specific suggestions from the reviewers regarding your milestones. If your R21/33 grant will be funded, a program director may contact you and negotiate a final set of milestones which takes into account reviewer comments/concerns or NIH staff’s concerns.
How does the flexible R21 award phase work?
In your grant application you will specify the length of the R21 phase (usually either 12 or 24 months) that you consider necessary to meet your milestones. If your R21/33 grant is funded, you will be asked to provide an interim progress report directly to your program director (email is fine) which outlines how the project is proceeding, e.g., whether you are running ahead or behind schedule and which (if any) of the milestones have been accomplished. You should also feel free to contact your program director more often or at other times if you have questions or concerns about your project. For example, if your project is running significantly ahead of schedule, you may want to request transition to the R33 phase of the grant earlier than originally anticipated. You should contact your program director and discuss this possibility before sending in an official final progress report and request for transition: NIH staff need a minimum of 2 months to assess and process an R21 to R33 transition. If your project is running significantly behind schedule or you are having difficulty meeting your R21 milestones in the originally anticipated time-frame, you should contact your program director and discuss the possibility of allowing more time.
What is the process for administrative review and transition to the R33 phase?
Two months prior to the anticipated R21-to-R33 transition date, you should receive a 2590 form in the mail: this is the form you will use to write your final progress report and request the transition. The form suggests a two page limit for the progress report: IGNORE that 2 page limit. Use as many pages as you need to adequately describe your progress and accomplishment of the milestones. Provide data and figures to support your claims (as you would in the preliminary data section of a grant application). Also briefly describe the work you plan for the R33 phase of the grant, highlighting any changes in approach, etc. from the original grant application. Do NOT send this form directly to your program director, send it to
Records Management Center
Grants Administration Branch, NCI
Executive Plaza South, Suite T-42
6120 Executive Boulevard
Bethesda, Maryland 20892-7107
Telephone Number (301) 496-9438
FAX Number (301) 496-8662
During the approximately two months between when you submit your final progress report/transition request and when, if successful, you receive an award for the R33 phase of the grant, you may be contacted by your program director or other NIH staff with requests for additional information, clarification of the science, additional data, or administrative details (e.g. updated other support, confirmation of IRB approval, etc). If NIH staff determine that you have met your R21 milestones, you will be awarded the R33 phase of the grant. If NIH staff cannot determine, from the data provided, whether you have successfully completed all R21 milestones, your program director will contact you for more information or clarification. If the R21 milestones have not been met and feasibility has not been shown, your program director will contact you and discuss whether additional time or other resources are needed for the completion of the milestones or other whether other options for you to continue related work are appropriate.
If I apply for an R21/R33 grant, is it possible that only the R21 portion will be funded?
Some program announcements offer the option of applying for the standard R21 grant as well as the R21/R33 or R33; other program announcements are restricted to the R21/R33 or R33. You should apply for the type of award that makes the most sense for your project, taking into account the scope of the work and the amount of preliminary data that you can present. You should also consider whether or not it will be possible to design concrete, quantitative milestones to serve as benchmarks for the success of an R21 project. If not, then the standard R21 is the more appropriate option.
In rare instances reviewers may recommend that only the R21 portion of an R21/R33 application be funded. This may occur in unusual cases when there is very strong enthusiasm for the research proposed in the R21 phase but reviewers cannot agree on a set of appropriate milestones. It is much more likely that an application with a weak R33 proposal or a set of inadequate milestones will receive a poor priority score.
It is also possible that a funded R21/R33 project may be terminated at the conclusion of the R21 phase if it becomes clear that the milestones cannot be met within a reasonable time.
What are the budget limitations on R21/R33 grants?
The specific limitations on the number of years and the level of direct costs that can be requested are spelled out in the program announcement. A typical R21 phase is limited to two years and $100,000 in direct costs per year, but announcements do vary. Usually there is no specific budget limit on the R33 phase, but the duration may be limited to four years or less.
Are R21/R33 applications reviewed in regular study sections?
Applications in response to NCI program announcements designated “PAR” are reviewed in special review groups convened by the NCI Division of Extramural Activities. R21/R33 and R33 applications in response to NIH-wide “PAs” are reviewed in ad hoc study sections at the Center for Scientific Review.
Is an R21/R33 grant renewable?
There is no option for a competitive renewal of an R21/R33 or R33 award. Results from a successful R21/R33 project may be used as preliminary data to support a subsequent new grant application.
How much in the way of preliminary data are needed for an R21/R33 grant application?
As for other kinds of exploratory grant applications, the answer to this question is determined on a case-by-case basis in peer review. Although reviewers are reminded that preliminary data are not required for an exploratory grant application, they must still find some basis for evaluating the significance, innovation and feasibility of the proposed research. Thoughtful and well-crafted milestones can help convince reviewers that you have a clear idea of what proof of feasibility entails and are prepared to achieve it.
How are R21/R33 and R33 grant applications scored?
R21/R33 and R33 applications receive priority scores from peer reviewers on a scale of 1.0-5.0, or they may be unscored. Percentile rankings are not calculated for R21/R33 or R33 applications. NCI funding decisions are made on the basis of priority scores, and separate funding cut-offs are established for each type of grant.
How long are program announcements active?
NCI program announcements may be active for up to two years. The NIH Guide announcement will specify the expiration date and any special receipt dates. If you cannot find an expiration date in the announcement, especially if the announcement is more than two years old, check the DEA Web site to make sure the PA is still active.
What are the page limits for an R21/R33 or R33 application?
The program announcement will include detailed modifications to the standard PHS 398 application instructions. Read and follow them carefully.
What are the receipt dates?
The program announcement will specify particular receipt dates. A letter of intent may be requested.
Are the budgets for R21/R33 grants modular?
They usually are not, but in some cases the program announcement might specify otherwise.
